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Gregory, Simon Gray

Overview:

My principal area of research involves elucidating the molecular mechanisms underlying multi-factorial diseases. My lab is primarily interested identifying the complex genetic factors that give rise to multiple sclerosis, autism and cardiovascular disease. We are using targeted approaches to identify differential methylation of the oxytocin receptor gene (OXTR) in individuals with autism, and applying these data to an NICHD funded ACE award, SOARS-B, to assess long term use of oxytocin nasal spray to improve social reciprocity in 300 children with autism, and for which we are developing e/genetic and transcriptomic predictors of response and effects of long term drug exposure. My MS laboratories at Duke University and the David H Murdock Research Institute (DHMRI) are using cell signaling and immune cell flow sorting to establish the role of IL7R signaling in the development of MS; we have developed three novel mouse strains to induce EAE susceptibility and to investigate allele and splicing specific effects of IL7R in these novel MS models; I am PI of the MURDOCK-MS collection, a cross sectional MS cohort of ~1000 MS patients that will provide the basis for genetic, genomic and metabolomic biomarker identification of MS disease development and progression. I am also Director of the nascent Duke Center for Research in Autoimmunity and MS within the Duke Department of Neurology.

Positions:

Professor in Neurology

Neurology, MS & Neuroimmunology
School of Medicine

Research Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of Duke Molecular Physiology Institute

Duke Molecular Physiology Institute
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.A.Sc. 1990

B.A.Sc. — RMIT University (Australia)

Ph.D. 2003

Ph.D. — Open University, Milton Keynes (U.K.)

News:

Grants:

Postdoctoral training in genomic medicine research

Administered By
Duke Center for Applied Genomics and Precision Medicine
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
June 14, 2017
End Date
May 31, 2022

Copper Homeostasis in Mammals

Administered By
Pharmacology & Cancer Biology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
February 01, 2004
End Date
February 28, 2022

Characterizing the (epi)genetics of oxytocin response in clinical and animal models

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 14, 2017
End Date
January 31, 2022

Bioinformatics and Computational Biology Training Program

Administered By
Basic Science Departments
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2005
End Date
June 30, 2021

Transfusion Medicine and Hematology

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
July 01, 1975
End Date
June 30, 2021

Genetics Training Grant

Administered By
Basic Science Departments
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 1979
End Date
June 30, 2020

Epigenomics in insulin resistance associated overactive bladder

Administered By
Obstetrics and Gynecology, Urogynecology
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
June 01, 2017
End Date
May 31, 2020

Specific and Pervasive Symptoms in Adults with Multiple Sclerosis Using the MURDOCK-MS Dataset: A Secondary Analysis

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Significant Contributor
Start Date
September 01, 2017
End Date
August 31, 2019

Systems Biology Approaches for Predicting Cardiometabolic Risk in Persons Living with HIV

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 03, 2015
End Date
August 31, 2018

Identifying Genetic and Epigenetic Signatures of Treatment Response to Oxytocin in Humans and Mice

Administered By
Duke Molecular Physiology Institute
AwardedBy
Autism Speaks
Role
Principal Investigator
Start Date
September 01, 2016
End Date
August 30, 2018

Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Administered By
Medicine, Medical Oncology
AwardedBy
Prostate Cancer Foundation
Role
Investigator
Start Date
August 01, 2014
End Date
August 01, 2018

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

Administered By
Radiology, Cardiothoracic Imaging
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 01, 2015
End Date
July 31, 2018

SOARS-B

Administered By
Psychiatry, Child & Family Mental Health and Developmental Neuroscience
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 04, 2012
End Date
May 31, 2018

Integration of CT imaging features with cell-free plasma DNA as biomarkers for early lung cancer detection in patients with indeterminate pulmonary nodules

Administered By
Radiology, Cardiothoracic Imaging
AwardedBy
Society of Thoracic Radiology
Role
Collaborator
Start Date
January 01, 2016
End Date
January 15, 2018

SRA for Stephanie Arvai

Administered By
Duke Molecular Physiology Institute
AwardedBy
University of Texas Medical Branch
Role
Principal Investigator
Start Date
February 01, 2016
End Date
November 30, 2016

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1998
End Date
August 31, 2016

Metabolomic Quantitative Trait Locus (mQTL) Genetic Mapping in Human CVD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 15, 2009
End Date
May 31, 2016

A role for pathogen-induced IL-10 production in susceptibility to MS

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Multiple Sclerosis Society
Role
Co Investigator
Start Date
September 01, 2014
End Date
August 31, 2015

Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

Administered By
Duke Molecular Physiology Institute
AwardedBy
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
September 04, 2012
End Date
August 01, 2015

Defining the Functional Role of a Novel MS Susceptibility Gene, IL7R alpha chain

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2009
End Date
June 30, 2015

Linkage and candidate gene analysis in non-syndromic Chiari type I

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
June 01, 2009
End Date
March 31, 2015

Study of Genetic Basis of Fuchs Corneal Dystrophy

Administered By
Ophthalmology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
September 15, 2007
End Date
August 31, 2013

Genetic Mediators of Metabolic Cardiovascular Disease Risk

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2009
End Date
May 31, 2012

Candidate Genes and Longitudinal Disability Phenotypes

Administered By
Center for the Study of Aging and Human Development
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
May 15, 2006
End Date
April 30, 2012

Molecular mechanisms of altered calcium sensing in human parathyroid disease

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
June 01, 2010
End Date
January 31, 2012

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 15, 2005
End Date
August 31, 2010

Hereditary basis of neural tube defects

Administered By
Medicine, Medical Genetics
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 1999
End Date
April 30, 2010

Genotyping - Illumina Methylation Analysis of DNA Samples

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institute of Environmental Health Sciences
Role
Principal Investigator
Start Date
September 16, 2008
End Date
February 28, 2010

Genotyping - Methlylation Infinium Chips

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institute of Environmental Health Sciences
Role
Principal Investigator
Start Date
September 16, 2008
End Date
February 28, 2010

Molecular Dissection of Cardiovascular Disease: From Genes to Models to Function

Administered By
Medicine, Medical Genetics
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
August 15, 2007
End Date
July 31, 2009

GENECARD: Gene identification in Early-Onset CAD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2003
End Date
March 31, 2009

Molecular Genetics of Coronary Artery Disease

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 2006
End Date
July 31, 2007

High-Resolution CGH Characterization of Brain Tumors

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 15, 2004
End Date
July 31, 2006
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Publications:

Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin.

The balance of myeloid populations and lymphoid populations must be well controlled. Here we found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct effects in shifting this balance through cell-type-specific regulation of apoptosis. Intracellular OPN (iOPN) diminished the population size of myeloid progenitor cells and myeloid cells, and secreted OPN (sOPN) increase the population size of lymphoid cells. The total effect of OPN on skewing the leukocyte population balance was observed as host sensitivity to early systemic infection with Candida albicans and T cell-mediated colitis. Our study suggests previously unknown detrimental roles for two OPN isoforms in causing the imbalance of leukocyte populations.

Authors
Kanayama, M; Xu, S; Danzaki, K; Gibson, JR; Inoue, M; Gregory, SG; Shinohara, ML
MLA Citation
Kanayama, M, Xu, S, Danzaki, K, Gibson, JR, Inoue, M, Gregory, SG, and Shinohara, ML. "Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin." Nature immunology 18.9 (September 2017): 973-984.
PMID
28671690
Source
epmc
Published In
Nature Immunology
Volume
18
Issue
9
Publish Date
2017
Start Page
973
End Page
984
DOI
10.1038/ni.3791

Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome.

Although circulating microRNA (miRNAs) have emerged as biomarkers predicting mortality in acute coronary syndrome (ACS), more data are needed to understand these mechanisms. Mapping miRNAs to high-risk traits may identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We aim to investigate the relationship between circulating miRNAs and high-risk traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of 199 patients with NSTE-ACS. Generalized linear models were used to test associations of miRNAs and 13 high-risk clinical traits, including the Global Registry of Acute Coronary Events (GRACE) score, a widely validated risk score for mortality in NSTE-ACS.There were 205 nominally significant miRNA-risk factor associations (p < 0.05) observed. Significant associations occurred most frequently with chronic heart failure (HF) (43 miRs), GRACE risk score (30 miRs), and renal function (32 miRs). In hierarchical cluster analysis, chronic HF and GRACE risk score clustered most tightly together, sharing 14 miRNAs with matching fold-change direction. Controlling for a false discovery rate of 5%, chronic HF was significantly associated with lower circulating levels of miR-3135b (p < 0.0006), miR-126-5p (p < 0.0001), miR-142-5p (p = 0.0004) and miR-144-5p (p = 0.0007), while increasing GRACE risk score inversely correlated with levels of miR-3135b (p < 0.0001) and positively correlated with levels of miR-28-3p (p = 0.0002).Circulating miRs clustered around two powerful traits for mortality risk in NSTE-ACS. MiR-3135b, which was under-expressed in chronic HF and increasing GRACE risk score, and miR-28-3p, which has no known association with cardiovascular disease, warrant further investigation.

Authors
Wang, A; Kwee, LC; Grass, E; Neely, ML; Gregory, SG; Fox, KAA; Armstrong, PW; White, HD; Ohman, EM; Roe, MT; Shah, SH; Chan, MY
MLA Citation
Wang, A, Kwee, LC, Grass, E, Neely, ML, Gregory, SG, Fox, KAA, Armstrong, PW, White, HD, Ohman, EM, Roe, MT, Shah, SH, and Chan, MY. "Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome." Atherosclerosis 261 (June 2017): 19-25.
PMID
28437675
Source
epmc
Published In
Atherosclerosis
Volume
261
Publish Date
2017
Start Page
19
End Page
25
DOI
10.1016/j.atherosclerosis.2017.03.041

Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.

Authors
Afshari, NA; Igo, RP; Morris, NJ; Stambolian, D; Sharma, S; Pulagam, VL; Dunn, S; Stamler, JF; Truitt, BJ; Rimmler, J; Kuot, A; Croasdale, CR; Qin, X; Burdon, KP; Riazuddin, SA; Mills, R; Klebe, S; Minear, MA; Zhao, J; Balajonda, E; Rosenwasser, GO; Baratz, KH; Mootha, VV; Patel, SV; Gregory, SG; Bailey-Wilson, JE; Price, MO; Price, FW; Craig, JE; Fingert, JH; Gottsch, JD; Aldave, AJ; Klintworth, GK; Lass, JH; Li, Y-J; Iyengar, SK
MLA Citation
Afshari, NA, Igo, RP, Morris, NJ, Stambolian, D, Sharma, S, Pulagam, VL, Dunn, S, Stamler, JF, Truitt, BJ, Rimmler, J, Kuot, A, Croasdale, CR, Qin, X, Burdon, KP, Riazuddin, SA, Mills, R, Klebe, S, Minear, MA, Zhao, J, Balajonda, E, Rosenwasser, GO, Baratz, KH, Mootha, VV, Patel, SV, Gregory, SG, Bailey-Wilson, JE, Price, MO, Price, FW, Craig, JE, Fingert, JH, Gottsch, JD, Aldave, AJ, Klintworth, GK, Lass, JH, Li, Y-J, and Iyengar, SK. "Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy." Nature communications 8 (March 30, 2017): 14898-.
PMID
28358029
Source
epmc
Published In
Nature Communications
Volume
8
Publish Date
2017
Start Page
14898
DOI
10.1038/ncomms14898

Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer.

Purpose: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of tumor biology and enable a precision medicine approach.Experimental Design: CTCs and paired leukocytes from men with metastatic castration-resistant prostate cancer (mCRPC) were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on EpCAM/CD45 expression. We next performed whole genomic copy number analysis of CTCs and matched patient leukocytes (germline) using array-based comparative genomic hybridization (aCGH) from 16 men with mCRPC, including longitudinal and sequential aCGH analyses of CTCs in the context of enzalutamide therapy.Results: All patients had mCRPC and primary or acquired resistance to abiraterone acetate or enzalutamide. We compiled copy gains and losses, with a particular focus on those genes highly implicated in mCRPC progression and previously validated as being aberrant in metastatic tissue samples and genomic studies of reference mCRPC datasets. Genomic gains in >25% of CTCs were observed in AR, FOXA1, ABL1, MET, ERG, CDK12, BRD4, and ZFHX3, while common genomic losses involved PTEN, ZFHX3, PDE4DIP, RAF1, and GATA2 Analysis of aCGH in a sample with sequential enzalutamide-resistant visceral progression showed acquired loss of AR amplification concurrent with gain of MYCN, consistent with evolution toward a neuroendocrine-like, AR-independent clone.Conclusions: Genomic analysis of pooled CTCs in men with mCRPC suggests a reproducible, but highly complex molecular profile that includes common aberrations in AR, ERG, c-MET, and PI3K signaling during mCRPC progression, which may be useful for predictive biomarker development. Clin Cancer Res; 23(5); 1346-57. ©2016 AACR.

Authors
Gupta, S; Li, J; Kemeny, G; Bitting, RL; Beaver, J; Somarelli, JA; Ware, KE; Gregory, S; Armstrong, AJ
MLA Citation
Gupta, S, Li, J, Kemeny, G, Bitting, RL, Beaver, J, Somarelli, JA, Ware, KE, Gregory, S, and Armstrong, AJ. "Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 23.5 (March 2017): 1346-1357.
PMID
27601596
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
23
Issue
5
Publish Date
2017
Start Page
1346
End Page
1357
DOI
10.1158/1078-0432.ccr-16-1211

Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk.

Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk. Importantly, this DDX39B variant showed strong genetic and functional epistasis with allelic variants in IL7R exon 6. This study establishes the occurrence of biological epistasis in humans and provides mechanistic insight into the regulation of IL7R exon 6 splicing and its impact on MS risk.

Authors
Galarza-Muñoz, G; Briggs, FBS; Evsyukova, I; Schott-Lerner, G; Kennedy, EM; Nyanhete, T; Wang, L; Bergamaschi, L; Widen, SG; Tomaras, GD; Ko, DC; Bradrick, SS; Barcellos, LF; Gregory, SG; Garcia-Blanco, MA
MLA Citation
Galarza-Muñoz, G, Briggs, FBS, Evsyukova, I, Schott-Lerner, G, Kennedy, EM, Nyanhete, T, Wang, L, Bergamaschi, L, Widen, SG, Tomaras, GD, Ko, DC, Bradrick, SS, Barcellos, LF, Gregory, SG, and Garcia-Blanco, MA. "Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk." Cell 169.1 (March 2017): 72-84.e13.
PMID
28340352
Source
epmc
Published In
Cell
Volume
169
Issue
1
Publish Date
2017
Start Page
72
End Page
84.e13
DOI
10.1016/j.cell.2017.03.007

A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.

Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk.

Authors
Ward-Caviness, CK; Neas, LM; Blach, C; Haynes, CS; LaRocque-Abramson, K; Grass, E; Dowdy, ZE; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Miranda, ML; Gregory, SG; Shah, SH; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, CK, Neas, LM, Blach, C, Haynes, CS, LaRocque-Abramson, K, Grass, E, Dowdy, ZE, Devlin, RB, Diaz-Sanchez, D, Cascio, WE, Miranda, ML, Gregory, SG, Shah, SH, Kraus, WE, and Hauser, ER. "A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic." PloS one 12.3 (January 2017): e0173880-.
PMID
28355232
Source
epmc
Published In
PloS one
Volume
12
Issue
3
Publish Date
2017
Start Page
e0173880
DOI
10.1371/journal.pone.0173880

Human centromere repositioning within euchromatin after partial chromosome deletion.

Centromeres are defined by a specialized chromatin organization that includes nucleosomes that contain the centromeric histone variant centromere protein A (CENP-A) instead of canonical histone H3. Studies in various organisms have shown that centromeric chromatin (i.e., CENP-A chromatin or centrochromatin) exhibits plasticity, in that it can assemble on different types of DNA sequences. However, once established on a chromosome, the centromere is maintained at the same position. In humans, this location is the highly homogeneous repetitive DNA alpha satellite. Mislocalization of centromeric chromatin to atypical locations can lead to genome instability, indicating that restriction of centromeres to a distinct genomic position is important for cell and organism viability. Here, we describe a rearrangement of Homo sapiens chromosome 17 (HSA17) that has placed alpha satellite DNA next to euchromatin. We show that on this mutant chromosome, CENP-A chromatin has spread from the alpha satellite into the short arm of HSA17, establishing a ∼700 kb hybrid centromeric domain that spans both repetitive and unique sequences and changes the expression of at least one gene over which it spreads. Our results illustrate the plasticity of human centromeric chromatin and suggest that heterochromatin normally constrains CENP-A chromatin onto alpha satellite DNA. This work highlights that chromosome rearrangements, particularly those that remove the pericentromere, create opportunities for centromeric nucleosomes to move into non-traditional genomic locations, potentially changing the surrounding chromatin environment and altering gene expression.

Authors
Sullivan, LL; Maloney, KA; Towers, AJ; Gregory, SG; Sullivan, BA
MLA Citation
Sullivan, LL, Maloney, KA, Towers, AJ, Gregory, SG, and Sullivan, BA. "Human centromere repositioning within euchromatin after partial chromosome deletion." Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 24.4 (December 2016): 451-466.
PMID
27581771
Source
epmc
Published In
Chromosome Research
Volume
24
Issue
4
Publish Date
2016
Start Page
451
End Page
466
DOI
10.1007/s10577-016-9536-6

An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage.

Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-like receptor protein 3 (NLRP3) inflammasome-independent and interferon-β (IFNβ)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNβ treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-β receptor (LTβR) and CXC chemokine receptor 2 (CXCR2), is involved in type B EAE development, and type B EAE is ameliorated by antagonizing these receptors. Relative expression of Ltbr and Cxcr2 genes was indeed enhanced in patients with IFNβ-resistant multiple sclerosis. Remission was minimal in type B EAE due to neuronal damages induced by semaphorin 6B upregulation on CD4+ T cells. Our data reveal a new inflammatory mechanism by which an IFNβ-resistant EAE subtype develops.

Authors
Inoue, M; Chen, P-H; Siecinski, S; Li, Q-J; Liu, C; Steinman, L; Gregory, SG; Benner, E; Shinohara, ML
MLA Citation
Inoue, M, Chen, P-H, Siecinski, S, Li, Q-J, Liu, C, Steinman, L, Gregory, SG, Benner, E, and Shinohara, ML. "An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage." Nature neuroscience 19.12 (December 2016): 1599-1609.
PMID
27820602
Source
epmc
Published In
Nature Neuroscience
Volume
19
Issue
12
Publish Date
2016
Start Page
1599
End Page
1609
DOI
10.1038/nn.4421

Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs.

Authors
Zeng, Y; Chen, H; Ni, T; Ruan, R; Nie, C; Liu, X; Feng, L; Zhang, F; Lu, J; Li, J; Li, Y; Tao, W; Gregory, SG; Gottschalk, W; Lutz, MW; Land, KC; Yashin, A; Tan, Q; Yang, Z; Bolund, L; Ming, Q; Yang, H; Min, J; Willcox, DC; Willcox, BJ; Gu, J; Hauser, E; Tian, X-L; Vaupel, JW
MLA Citation
Zeng, Y, Chen, H, Ni, T, Ruan, R, Nie, C, Liu, X, Feng, L, Zhang, F, Lu, J, Li, J, Li, Y, Tao, W, Gregory, SG, Gottschalk, W, Lutz, MW, Land, KC, Yashin, A, Tan, Q, Yang, Z, Bolund, L, Ming, Q, Yang, H, Min, J, Willcox, DC, Willcox, BJ, Gu, J, Hauser, E, Tian, X-L, and Vaupel, JW. "Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages." Rejuvenation research 19.3 (June 2016): 195-203.
Website
http://hdl.handle.net/10161/14659
PMID
26414954
Source
epmc
Published In
Rejuvenation Research
Volume
19
Issue
3
Publish Date
2016
Start Page
195
End Page
203
DOI
10.1089/rej.2015.1737

Novel loci and pathways significantly associated with longevity.

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

Authors
Zeng, Y; Nie, C; Min, J; Liu, X; Li, M; Chen, H; Xu, H; Wang, M; Ni, T; Li, Y; Yan, H; Zhang, J-P; Song, C; Chi, L-Q; Wang, H-M; Dong, J; Zheng, G-Y; Lin, L; Qian, F; Qi, Y; Liu, X; Cao, H; Wang, Y; Zhang, L; Li, Z; Zhou, Y; Wang, Y; Lu, J; Li, J; Qi, M; Bolund, L; Yashin, A; Land, KC; Gregory, S; Yang, Z; Gottschalk, W; Tao, W; Wang, J; Wang, J; Xu, X; Bae, H; Nygaard, M; Christiansen, L; Christensen, K; Franceschi, C; Lutz, MW; Gu, J; Tan, Q; Perls, T; Sebastiani, P; Deelen, J; Slagboom, E et al.
MLA Citation
Zeng, Y, Nie, C, Min, J, Liu, X, Li, M, Chen, H, Xu, H, Wang, M, Ni, T, Li, Y, Yan, H, Zhang, J-P, Song, C, Chi, L-Q, Wang, H-M, Dong, J, Zheng, G-Y, Lin, L, Qian, F, Qi, Y, Liu, X, Cao, H, Wang, Y, Zhang, L, Li, Z, Zhou, Y, Wang, Y, Lu, J, Li, J, Qi, M, Bolund, L, Yashin, A, Land, KC, Gregory, S, Yang, Z, Gottschalk, W, Tao, W, Wang, J, Wang, J, Xu, X, Bae, H, Nygaard, M, Christiansen, L, Christensen, K, Franceschi, C, Lutz, MW, Gu, J, Tan, Q, Perls, T, Sebastiani, P, Deelen, J, and Slagboom, E et al. "Novel loci and pathways significantly associated with longevity." Scientific reports 6 (February 25, 2016): 21243-.
Website
http://hdl.handle.net/10161/14652
PMID
26912274
Source
epmc
Published In
Scientific Reports
Volume
6
Publish Date
2016
Start Page
21243
DOI
10.1038/srep21243

Integrated metabolomic and transcriptomic profiles of males with multiple sclerosis

Authors
Cote, SA; Gregory, SG; Winnike, J; Knagge, K; Ilkayeva, O; O'Connell, T; Bain, J; Muehlbauer, M; Maichle, S; Newby, LK; Zhang, X
MLA Citation
Cote, SA, Gregory, SG, Winnike, J, Knagge, K, Ilkayeva, O, O'Connell, T, Bain, J, Muehlbauer, M, Maichle, S, Newby, LK, and Zhang, X. "Integrated metabolomic and transcriptomic profiles of males with multiple sclerosis." February 2016.
Source
wos-lite
Published In
Multiple Sclerosis
Volume
22
Publish Date
2016
Start Page
9
End Page
10

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.

Authors
Ward-Caviness, CK; Neas, LM; Blach, C; Haynes, CS; LaRocque-Abramson, K; Grass, E; Dowdy, E; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Lynn Miranda, M; Gregory, SG; Shah, SH; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, CK, Neas, LM, Blach, C, Haynes, CS, LaRocque-Abramson, K, Grass, E, Dowdy, E, Devlin, RB, Diaz-Sanchez, D, Cascio, WE, Lynn Miranda, M, Gregory, SG, Shah, SH, Kraus, WE, and Hauser, ER. "Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease." PloS one 11.4 (January 2016): e0152670-.
PMID
27082954
Source
epmc
Published In
PloS one
Volume
11
Issue
4
Publish Date
2016
Start Page
e0152670
DOI
10.1371/journal.pone.0152670

Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship.

Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69-0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype ('A/A') fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD.

Authors
Dungan, JR; Qin, X; Horne, BD; Carlquist, JF; Singh, A; Hurdle, M; Grass, E; Haynes, C; Gregory, SG; Shah, SH; Hauser, ER; Kraus, WE
MLA Citation
Dungan, JR, Qin, X, Horne, BD, Carlquist, JF, Singh, A, Hurdle, M, Grass, E, Haynes, C, Gregory, SG, Shah, SH, Hauser, ER, and Kraus, WE. "Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship." PloS one 11.5 (January 2016): e0154856-.
PMID
27187494
Source
epmc
Published In
PloS one
Volume
11
Issue
5
Publish Date
2016
Start Page
e0154856
DOI
10.1371/journal.pone.0154856

Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long-chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490), we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER) stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1) These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10). Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2). Expression quantitative trait loci (eQTL) pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS) arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk.

Authors
Kraus, WE; Muoio, DM; Stevens, R; Craig, D; Bain, JR; Grass, E; Haynes, C; Kwee, L; Qin, X; Slentz, DH; Krupp, D; Muehlbauer, M; Hauser, ER; Gregory, SG; Newgard, CB; Shah, SH
MLA Citation
Kraus, WE, Muoio, DM, Stevens, R, Craig, D, Bain, JR, Grass, E, Haynes, C, Kwee, L, Qin, X, Slentz, DH, Krupp, D, Muehlbauer, M, Hauser, ER, Gregory, SG, Newgard, CB, and Shah, SH. "Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis." PLoS Genetics 11.11 (November 5, 2015): e1005553-.
Website
http://hdl.handle.net/10161/10957
PMID
26540294
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
11
Publish Date
2015
Start Page
e1005553
DOI
10.1371/journal.pgen.1005553

Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.

Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala.FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every 3 months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1 , Sa 1-P/So 1-P ratio, and Sa 1-P/mL in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities.High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.

Authors
Riley, RT; Torres, O; Matute, J; Gregory, SG; Ashley-Koch, AE; Showker, JL; Mitchell, T; Voss, KA; Maddox, JR; Gelineau-van Waes, JB
MLA Citation
Riley, RT, Torres, O, Matute, J, Gregory, SG, Ashley-Koch, AE, Showker, JL, Mitchell, T, Voss, KA, Maddox, JR, and Gelineau-van Waes, JB. "Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala." Molecular nutrition & food research 59.11 (November 2015): 2209-2224.
PMID
26264677
Source
epmc
Published In
Molecular Nutrition & Food Research
Volume
59
Issue
11
Publish Date
2015
Start Page
2209
End Page
2224
DOI
10.1002/mnfr.201500499

Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients.

The relationship between traffic-related air pollution (TRAP) and risk factors for cardiovascular disease needs to be better understood in order to address the adverse impact of air pollution on human health.We examined associations between roadway proximity and traffic exposure zones, as markers of TRAP exposure, and metabolic biomarkers for cardiovascular disease risk in a cohort of patients undergoing cardiac catheterization.We performed a cross-sectional study of 2,124 individuals residing in North Carolina (USA). Roadway proximity was assessed via distance to primary and secondary roadways, and we used residence in traffic exposure zones (TEZs) as a proxy for TRAP. Two categories of metabolic outcomes were studied: measures associated with glucose control, and measures associated with lipid metabolism. Statistical models were adjusted for race, sex, smoking, body mass index, and socioeconomic status (SES).An interquartile-range (990 m) decrease in distance to roadways was associated with higher fasting plasma glucose (β = 2.17 mg/dL; 95% CI: -0.24, 4.59), and the association appeared to be limited to women (β = 5.16 mg/dL; 95% CI: 1.48, 8.84 compared with β = 0.14 mg/dL; 95% CI: -3.04, 3.33 in men). Residence in TEZ 5 (high-speed traffic) and TEZ 6 (stop-and-go traffic), the two traffic zones assumed to have the highest levels of TRAP, was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 8.36; 95% CI: -0.15, 16.9 and β = 5.98; 95% CI: -3.96, 15.9, for TEZ 5 and 6, respectively).Proxy measures of TRAP exposure were associated with intermediate metabolic traits associated with cardiovascular disease, including fasting plasma glucose and possibly HDL-C.

Authors
Ward-Caviness, CK; Kraus, WE; Blach, C; Haynes, CS; Dowdy, E; Miranda, ML; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Mukerjee, S; Stallings, C; Smith, LA; Gregory, SG; Shah, SH; Hauser, ER; Neas, LM
MLA Citation
Ward-Caviness, CK, Kraus, WE, Blach, C, Haynes, CS, Dowdy, E, Miranda, ML, Devlin, RB, Diaz-Sanchez, D, Cascio, WE, Mukerjee, S, Stallings, C, Smith, LA, Gregory, SG, Shah, SH, Hauser, ER, and Neas, LM. "Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients." Environmental health perspectives 123.10 (October 2015): 1007-1014.
PMID
25807578
Source
epmc
Published In
Environmental health perspectives
Volume
123
Issue
10
Publish Date
2015
Start Page
1007
End Page
1014
DOI
10.1289/ehp.1306980

Epigenetic profiling identifies novel genes for ascending aortic aneurysm formation with bicuspid aortic valves.

  Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.  We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.  Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves.  Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.  Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test.    Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4).  The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients.  Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range:  -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections  Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms.  The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders.  These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.

Authors
Shah, AA; Gregory, SG; Krupp, D; Feng, S; Dorogi, A; Haynes, C; Grass, E; Lin, SS; Hauser, ER; Kraus, WE; Shah, SH; Hughes, GC
MLA Citation
Shah, AA, Gregory, SG, Krupp, D, Feng, S, Dorogi, A, Haynes, C, Grass, E, Lin, SS, Hauser, ER, Kraus, WE, Shah, SH, and Hughes, GC. "Epigenetic profiling identifies novel genes for ascending aortic aneurysm formation with bicuspid aortic valves." The heart surgery forum 18.4 (August 30, 2015): E134-E139.
PMID
26334848
Source
epmc
Published In
The heart surgery forum
Volume
18
Issue
4
Publish Date
2015
Start Page
E134
End Page
E139
DOI
10.1532/hsf.1247

Pregnancy continuation and organizational religious activity following prenatal diagnosis of a lethal fetal defect are associated with improved psychological outcome.

The aim of the article is to examine the psychological impact, specifically symptoms of grief, post-traumatic stress and depression, in women and men who either terminated or continued a pregnancy following prenatal diagnosis of a lethal fetal defect.This project investigated a diagnostically homogeneous group composed of 158 women and 109 men who lost a pregnancy to anencephaly, a lethal neural tube defect. Participants completed the Perinatal Grief Scale, Impact of Event Scale - Revised and Beck Depression Inventory-II, which measure symptoms of grief, post-traumatic stress and depression, respectively. Demographics, religiosity and pregnancy choices were also collected. Gender-specific analysis of variance was performed for instrument total scores and subscales.Women who terminated reported significantly more despair (p = 0.02), avoidance (p = 0.008) and depression (p = 0.04) than women who continued the pregnancy. Organizational religious activity was associated with a reduction in grief (Perinatal Grief Scale subscales) in both women (p = 0.02, p = 0.04 and p = 0.03) and men (p = 0.047).There appears to be a psychological benefit to women to continue the pregnancy following a lethal fetal diagnosis. Following a lethal fetal diagnosis, the risks and benefits, including psychological effects, of termination and continuation of pregnancy should be discussed in detail with an effort to be as nondirective as possible.

Authors
Cope, H; Garrett, ME; Gregory, S; Ashley-Koch, A
MLA Citation
Cope, H, Garrett, ME, Gregory, S, and Ashley-Koch, A. "Pregnancy continuation and organizational religious activity following prenatal diagnosis of a lethal fetal defect are associated with improved psychological outcome." Prenatal diagnosis 35.8 (August 2015): 761-768.
PMID
25872901
Source
epmc
Published In
Prenatal Diagnosis
Volume
35
Issue
8
Publish Date
2015
Start Page
761
End Page
768
DOI
10.1002/pd.4603

Comparison of GC-MS and GC×GC-MS in the analysis of human serum samples for biomarker discovery.

We compared the performance of gas chromatography time-of-flight mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) for metabolite biomarker discovery. Metabolite extracts from 109 human serum samples were analyzed on both platforms with a pooled serum sample analyzed after every 9 biological samples for the purpose of quality control (QC). The experimental data derived from the pooled QC samples showed that the GC×GC-MS platform detected about three times as many peaks as the GC-MS platform at a signal-to-noise ratio SNR ≥ 50, and three times the number of metabolites were identified by mass spectrum matching with a spectral similarity score Rsim ≥ 600. Twenty-three metabolites had statistically significant abundance changes between the patient samples and the control samples in the GC-MS data set while 34 metabolites in the GC×GC-MS data set showed statistically significant differences. Among these two groups of metabolite biomarkers, nine metabolites were detected in both the GC-MS and GC×GC-MS data sets with the same direction and similar magnitude of abundance changes between the control and patient sample groups. Manual verification indicated that the difference in the number of the biomarkers discovered using these two platforms was mainly due to the limited resolution of chromatographic peaks by the GC-MS platform, which can result in severe peak overlap making subsequent spectrum deconvolution for metabolite identification and quantification difficult.

Authors
Winnike, JH; Wei, X; Knagge, KJ; Colman, SD; Gregory, SG; Zhang, X
MLA Citation
Winnike, JH, Wei, X, Knagge, KJ, Colman, SD, Gregory, SG, and Zhang, X. "Comparison of GC-MS and GC×GC-MS in the analysis of human serum samples for biomarker discovery." Journal of proteome research 14.4 (April 2015): 1810-1817.
PMID
25735966
Source
epmc
Published In
Journal of Proteome Research
Volume
14
Issue
4
Publish Date
2015
Start Page
1810
End Page
1817
DOI
10.1021/pr5011923

TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone.

The Meckel syndrome (MKS) complex functions at the transition zone, located between the basal body and axoneme, to regulate the localization of ciliary membrane proteins. We investigated the role of Tmem231, a two-pass transmembrane protein, in MKS complex formation and function. Consistent with a role in transition zone function, mutation of mouse Tmem231 disrupts the localization of proteins including Arl13b and Inpp5e to cilia, resulting in phenotypes characteristic of MKS such as polydactyly and kidney cysts. Tmem231 and B9d1 are essential for each other and other complex components such as Mks1 to localize to the transition zone. As in mouse, the Caenorhabditis elegans orthologue of Tmem231 localizes to and controls transition zone formation and function, suggesting an evolutionarily conserved role for Tmem231. We identified TMEM231 mutations in orofaciodigital syndrome type 3 (OFD3) and MKS patients that compromise transition zone function. Thus, Tmem231 is critical for organizing the MKS complex and controlling ciliary composition, defects in which cause OFD3 and MKS.

Authors
Roberson, EC; Dowdle, WE; Ozanturk, A; Garcia-Gonzalo, FR; Li, C; Halbritter, J; Elkhartoufi, N; Porath, JD; Cope, H; Ashley-Koch, A; Gregory, S; Thomas, S; Sayer, JA; Saunier, S; Otto, EA; Katsanis, N; Davis, EE; Attié-Bitach, T; Hildebrandt, F; Leroux, MR; Reiter, JF
MLA Citation
Roberson, EC, Dowdle, WE, Ozanturk, A, Garcia-Gonzalo, FR, Li, C, Halbritter, J, Elkhartoufi, N, Porath, JD, Cope, H, Ashley-Koch, A, Gregory, S, Thomas, S, Sayer, JA, Saunier, S, Otto, EA, Katsanis, N, Davis, EE, Attié-Bitach, T, Hildebrandt, F, Leroux, MR, and Reiter, JF. "TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone." The Journal of cell biology 209.1 (April 2015): 129-142.
PMID
25869670
Source
epmc
Published In
The Journal of Cell Biology
Volume
209
Issue
1
Publish Date
2015
Start Page
129
End Page
142
DOI
10.1083/jcb.201411087

Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.

Expression quantitative trait loci (eQTL) play an important role in the regulation of gene expression. Gene expression levels and eQTLs are expected to vary from tissue to tissue, and therefore multi-tissue analyses are necessary to fully understand complex genetic conditions in humans. Dura mater tissue likely interacts with cranial bone growth and thus may play a role in the etiology of Chiari Type I Malformation (CMI) and related conditions, but it is often inaccessible and its gene expression has not been well studied. A genetic basis to CMI has been established; however, the specific genetic risk factors are not well characterized.We present an assessment of eQTLs for whole blood and dura mater tissue from individuals with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways related to marrow and bone dysfunction, as potential candidates in the development of CMI.Despite strong overall heterogeneity in expression levels between blood and dura, the majority of cis-eQTLs are shared by both tissues. The power to detect shared eQTLs was improved by using an integrative statistical approach. The identified tissue-specific and shared eQTLs provide new insight into the genetic basis for CMI and related conditions.

Authors
Lock, EF; Soldano, KL; Garrett, ME; Cope, H; Markunas, CA; Fuchs, H; Grant, G; Dunson, DB; Gregory, SG; Ashley-Koch, AE
MLA Citation
Lock, EF, Soldano, KL, Garrett, ME, Cope, H, Markunas, CA, Fuchs, H, Grant, G, Dunson, DB, Gregory, SG, and Ashley-Koch, AE. "Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation." BMC genomics 16 (January 22, 2015): 11-.
Website
http://hdl.handle.net/10161/15599
PMID
25609184
Source
epmc
Published In
BMC Genomics
Volume
16
Publish Date
2015
Start Page
11
DOI
10.1186/s12864-014-1211-8

Genetic variants associated with vein graft stenosis after coronary artery bypass grafting

© 2015 Forum Multimedia Publishing, LLC. Background: Vein graft stenosis after coronary artery bypass grafting (CABG) is common. Identifying genes associated with vein graft stenosis after CABG could reveal novel mechanisms of disease and discriminate patients at risk for graft failure. We hypothesized that genome-wide association would identify these genes. Methods: We performed a genome-wide association study on a subset of patients presenting for cardiac catheterization for concern of ischemic heart disease, who also underwent CABG and subsequent coronary angiography after CABG for clinical indications (n = 521). Cases were defined as individuals with ≥50% stenosis in any vein graft on any cardiac catheterization, and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization. Multivariable logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) and vein graft stenosis. Results: Sixty-nine percent of patients had vein graft failure after CABG. Seven SNPs were significantly associated with vein graft stenosis, including intronic SNPs in the genes PALLD (Rs6854137, P = 3.77 × 10 -6 ), ARID1B (Rs184074, P = 5.97 × 10 -6 ), and TMEM123 (Rs11225247, P = 8.25 × 10 -6 ); and intergenic SNPs near the genes ABCA13 (Rs10232860, P = 4.54 × 10 -6 ), RMI2 (Rs9921338, P = 6.15 × 10 -6 ), PRM2 (Rs7198849, P = 7.27 × 10 -6 ), and TNFSF4 (Rs17346536, P = 9.33 × 10-6). Conclusions: We have identified novel genetic variants that may predispose to risk of vein graft failure after CABG, many within biologically plausible pathways. These polymorphisms merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.

Authors
Shah, AA; Haynes, C; Craig, DM; Sebek, J; Grass, E; Abramson, K; Hauser, ER; Gregory, SG; Kraus, WE; Smith, PK; Shah, SH
MLA Citation
Shah, AA, Haynes, C, Craig, DM, Sebek, J, Grass, E, Abramson, K, Hauser, ER, Gregory, SG, Kraus, WE, Smith, PK, and Shah, SH. "Genetic variants associated with vein graft stenosis after coronary artery bypass grafting." Heart Surgery Forum 18.1 (January 1, 2015): E1-E5.
Source
scopus
Published In
The heart surgery forum
Volume
18
Issue
1
Publish Date
2015
Start Page
E1
End Page
E5
DOI
10.1532/HSF98.2015489

Human health implications from co-exposure to aflatoxins and fumonisins in maize-based foods in Latin America: Guatemala as a case study

Authors
Torres, O; Matute, J; Gelineau-van Waes, J; Maddox, JR; Gregory, SG; Ashley-Koch, AE; Showker, JL; Voss, KA; Riley, RT
MLA Citation
Torres, O, Matute, J, Gelineau-van Waes, J, Maddox, JR, Gregory, SG, Ashley-Koch, AE, Showker, JL, Voss, KA, and Riley, RT. "Human health implications from co-exposure to aflatoxins and fumonisins in maize-based foods in Latin America: Guatemala as a case study." World Mycotoxin Journal 8.2 (January 2015): 143-159.
Source
crossref
Published In
World Mycotoxin Journal
Volume
8
Issue
2
Publish Date
2015
Start Page
143
End Page
159
DOI
10.3920/WMJ2014.1736

A blood spot method for detecting fumonisin-induced changes in putative sphingolipid biomarkers in LM/Bc mice and humans.

Fumonisins (FB) are mycotoxins found in maize. They are hypothesised risk factors for neural tube defects (NTDs) in humans living where maize is a dietary staple. In LM/Bc mice, FB1-treatment of pregnant dams induces NTDs and results in increased levels of sphingoid base 1-phosphates in blood and tissues. The increased level of sphingoid base 1-phosphates in blood is a putative biomarker for FB1 inhibition of ceramide synthase in humans. Collection of blood spots on paper from finger sticks is a relatively non-invasive way to obtain blood for biomarker analysis. The objective of this study was to develop and validate in an animal model, and ultimately in humans, a method to estimate the volume of blood collected as blood spots on absorbent paper so as to allow quantification of the molar concentration of sphingoid base 1-phosphates in blood. To accomplish this objective, blood was collected from unexposed male LM/Bc and FB1-exposed pregnant LM/Bc mice and humans and applied to two types of absorbent paper. The sphingoid base 1-phosphates, absorbance at 270 nm (A270), and total protein content (Bradford) were determined in the acetonitrile:water 5% formic acid extracts from the dried blood spots. The results show that in both mouse and human the A270, total protein, and blood volume were closely correlated and the volume of blood spotted was accurately estimated using only the A270 of the extracts. In mouse blood spots, as in tissues and embryos, the FB1-induced changes in sphingolipids were correlated with urinary FB1. The half-life of FB1 in the urine was short (<24 h) and the elevation in sphingoid base 1-phosphates in blood was also short, although more persistent than the urinary FB1.

Authors
Riley, RT; Showker, JL; Lee, CM; Zipperer, CE; Mitchell, TR; Voss, KA; Zitomer, NC; Torres, O; Matute, J; Gregory, SG; Ashley-Koch, AE; Maddox, JR; Gardner, N; Gelineau-Van Waes, JB
MLA Citation
Riley, RT, Showker, JL, Lee, CM, Zipperer, CE, Mitchell, TR, Voss, KA, Zitomer, NC, Torres, O, Matute, J, Gregory, SG, Ashley-Koch, AE, Maddox, JR, Gardner, N, and Gelineau-Van Waes, JB. "A blood spot method for detecting fumonisin-induced changes in putative sphingolipid biomarkers in LM/Bc mice and humans." Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment 32.6 (January 2015): 934-949.
PMID
25833119
Source
epmc
Published In
Food Additives & Contaminants: Part A - Chemistry, Analysis, Control, Exposure & Risk Assessment
Volume
32
Issue
6
Publish Date
2015
Start Page
934
End Page
949
DOI
10.1080/19440049.2015.1027746

Using circulating tumor cells to inform on prostate cancer biology and clinical utility.

Substantial advances in the molecular biology of prostate cancer have led to the approval of multiple new systemic agents to treat men with metastatic castration-resistant prostate cancer (mCRPC). These treatments encompass androgen receptor directed therapies, immunotherapies, bone targeting radiopharmaceuticals and cytotoxic chemotherapies. There is, however, great heterogeneity in the degree of patient benefit with these agents, thus fueling the need to develop predictive biomarkers that are able to rationally guide therapy. Circulating tumor cells (CTCs) have the potential to provide an assessment of tumor-specific biomarkers through a non-invasive, repeatable "liquid biopsy" of a patient's cancer at a given point in time. CTCs have been extensively studied in men with mCRPC, where CTC enumeration using the Cellsearch® method has been validated and FDA approved to be used in conjunction with other clinical parameters as a prognostic biomarker in metastatic prostate cancer. In addition to enumeration, more sophisticated molecular profiling of CTCs is now feasible and may provide more clinical utility as it may reflect tumor evolution within an individual particularly under the pressure of systemic therapies. Here, we review technologies used to detect and characterize CTCs, and the potential biological and clinical utility of CTC molecular profiling in men with metastatic prostate cancer.

Authors
Li, J; Gregory, SG; Garcia-Blanco, MA; Armstrong, AJ
MLA Citation
Li, J, Gregory, SG, Garcia-Blanco, MA, and Armstrong, AJ. "Using circulating tumor cells to inform on prostate cancer biology and clinical utility." Critical reviews in clinical laboratory sciences 52.4 (January 2015): 191-210. (Review)
PMID
26079252
Source
epmc
Published In
Critical Reviews in Clinical Laboratory Sciences (Informa)
Volume
52
Issue
4
Publish Date
2015
Start Page
191
End Page
210
DOI
10.3109/10408363.2015.1023430

Missing genetic risk in neural tube defects: can exome sequencing yield an insight?

Neural tube defects (NTD) have a strong genetic component, with up to 70% of variance in human prevalence determined by heritable factors. Although the identification of causal DNA variants by sequencing candidate genes from functionally relevant pathways and model organisms has provided some success, alternative approaches are demanded.Next generation sequencing platforms are facilitating the production of massive amounts of sequencing data, primarily from the protein coding regions of the genome, at a faster rate and cheaper cost than has previously been possible. These platforms are permitting the identification of variants (de novo, rare, and common) that are drivers of NYTD etiology, and the cost of the approach allows for the screening of increased numbers of affected and unaffected individuals from NTD families and in simplex cases.The next generation sequencing platforms represent a powerful tool in the armory of the genetics researcher to identify the causal genetic basis of NTDs.

Authors
Krupp, DR; Soldano, KL; Garrett, ME; Cope, H; Ashley-Koch, AE; Gregory, SG
MLA Citation
Krupp, DR, Soldano, KL, Garrett, ME, Cope, H, Ashley-Koch, AE, and Gregory, SG. "Missing genetic risk in neural tube defects: can exome sequencing yield an insight?." Birth defects research. Part A, Clinical and molecular teratology 100.8 (August 2014): 642-646.
PMID
25044326
Source
epmc
Published In
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume
100
Issue
8
Publish Date
2014
Start Page
642
End Page
646
DOI
10.1002/bdra.23276

Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics.

Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar herniation, it is hypothesized that this heterogeneous disorder is due to multiple genetic and environmental factors. The purpose of the present study was to gain a better understanding of what factors contribute to this heterogeneity by using an unsupervised statistical approach to define disease subtypes within a case-only pediatric population.A collection of forty-four pediatric CMI patients were ascertained to identify disease subtypes using whole genome expression profiles generated from patient blood and dura mater tissue samples, and radiological data consisting of posterior fossa (PF) morphometrics. Sparse k-means clustering and an extension to accommodate multiple data sources were used to cluster patients into more homogeneous groups using biological and radiological data both individually and collectively.All clustering analyses resulted in the significant identification of patient classes, with the pure biological classes derived from patient blood and dura mater samples demonstrating the strongest evidence. Those patient classes were further characterized by identifying enriched biological pathways, as well as correlated cranial base morphological and clinical traits.Our results implicate several strong biological candidates warranting further investigation from the dura expression analysis and also identified a blood gene expression profile corresponding to a global down-regulation in protein synthesis.

Authors
Markunas, CA; Lock, E; Soldano, K; Cope, H; Ding, C-KC; Enterline, DS; Grant, G; Fuchs, H; Ashley-Koch, AE; Gregory, SG
MLA Citation
Markunas, CA, Lock, E, Soldano, K, Cope, H, Ding, C-KC, Enterline, DS, Grant, G, Fuchs, H, Ashley-Koch, AE, and Gregory, SG. "Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics." BMC medical genomics 7 (June 25, 2014): 39-.
PMID
24962150
Source
epmc
Published In
BMC Medical Genomics
Volume
7
Publish Date
2014
Start Page
39
DOI
10.1186/1755-8794-7-39

Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs' endothelial corneal dystrophy.

We investigated whether mitochondrial DNA (mtDNA) variants affect the susceptibility of Fuchs endothelial corneal dystrophy (FECD).Ten mtDNA variants defining European haplogroups were genotyped in a discovery dataset consisting of 530 cases and 498 controls of European descent from the Duke FECD cohort. Association tests for mtDNA markers and haplogroups were performed using logistic regression models with adjustment of age and sex. Subset analyses included controlling for additional effects of either the TCF4 SNP rs613872 or cigarette smoking. Our replication dataset was derived from the genome-wide association study (GWAS) of the FECD Genetics Consortium, where genotypes for three of 10 mtDNA markers were available. Replication analyses were performed to compare non-Duke cases to all GWAS controls (GWAS1, N = 3200), and to non-Duke controls (GWAS2, N = 3043).The variant A10398G was significantly associated with FECD (odds ratio [OR] = 0.72; 95% confidence interval [CI] = [0.53, 0.98]; P = 0.034), and remains significant after adjusting for smoking status (min P = 0.012). This variant was replicated in GWAS1 (P = 0.019) and GWAS2 (P = 0.036). Haplogroup I was significantly associated with FECD (OR = 0.46; 95% CI = [0.22, 0.97]; P = 0.041) and remains significant after adjusting for the effect of smoking (min P = 0.008) or rs613872 (P = 0.034).The 10398G allele and Haplogroup I appear to confer significant protective effects for FECD. The effect of A10398G and Haplogroup I to FECD is likely independent of the known TCF4 variant. More data are needed to decipher the interaction between smoking and mtDNA haplogroups.

Authors
Li, Y-J; Minear, MA; Qin, X; Rimmler, J; Hauser, MA; Allingham, RR; Igo, RP; Lass, JH; Iyengar, SK; Klintworth, GK; Afshari, NA; Gregory, SG; FECD Genetics Consortium,
MLA Citation
Li, Y-J, Minear, MA, Qin, X, Rimmler, J, Hauser, MA, Allingham, RR, Igo, RP, Lass, JH, Iyengar, SK, Klintworth, GK, Afshari, NA, Gregory, SG, and FECD Genetics Consortium, . "Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs' endothelial corneal dystrophy." Investigative ophthalmology & visual science 55.7 (June 10, 2014): 4577-4584.
PMID
24917144
Source
epmc
Published In
Investigative Ophthalmology and Visual Science
Volume
55
Issue
7
Publish Date
2014
Start Page
4577
End Page
4584
DOI
10.1167/iovs.13-13517

Urinary fumonisin B1 and estimated fumonisin intake in women from high- and low-exposure communities in Guatemala.

Fumonisin (FB) intake can be high when maize is a dietary staple. We determined (i) urinary FB (UFB) in women consuming maize in high- and low-exposure communities in Guatemala, (ii) the FB levels in maize, (iii) the relationship between UFB and FB intake, and (iv) the relative excretion of UFB1 , UFB2 , and UFB3 .Urine and maize were analyzed for FB for 1 year in three departments. Maize consumption was estimated by an interview questionnaire. Fumonisin B1 , B2 , and B3 (FB1 , FB2 and FB3 ), were detected in 100% of maize samples. FB1 in maize and urine was significantly higher in Jutiapa compared to Chimaltenango or Escuintla. The FB intake paralleled UFB1 in a dose-dependent manner but UFB1 was present in much higher levels than UFB2 or UFB3 compared to maize.In Jutiapa, agroecological conditions favored FB production. UFB1 mirrored the estimated FB intake. UFB1 > 0.1 ng/mL resulted in a dose-dependent increase in the risk of exceeding FB intake of 2 μg/kg b.w./day compared to women with no detectable UFB1 . More than 50% exceeded 2 μg/kg b.w./day when UFB1 was >0.5 ng/mL. UFB2 and UFB3 were rarely detected confirming that FB1 is either absorbed better or preferentially excreted in urine.

Authors
Torres, O; Matute, J; Gelineau-van Waes, J; Maddox, JR; Gregory, SG; Ashley-Koch, AE; Showker, JL; Zitomer, NC; Voss, KA; Riley, RT
MLA Citation
Torres, O, Matute, J, Gelineau-van Waes, J, Maddox, JR, Gregory, SG, Ashley-Koch, AE, Showker, JL, Zitomer, NC, Voss, KA, and Riley, RT. "Urinary fumonisin B1 and estimated fumonisin intake in women from high- and low-exposure communities in Guatemala." Molecular nutrition & food research 58.5 (May 2014): 973-983.
PMID
24375966
Source
epmc
Published In
Molecular Nutrition & Food Research
Volume
58
Issue
5
Publish Date
2014
Start Page
973
End Page
983
DOI
10.1002/mnfr.201300481

Association of autism with induced or augmented childbirth.

Authors
Miranda, ML; Anthopolos, R; Gregory, SG
MLA Citation
Miranda, ML, Anthopolos, R, and Gregory, SG. "Association of autism with induced or augmented childbirth." Am J Obstet Gynecol 210.5 (May 2014): 492-493. (Letter)
PMID
24380745
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
210
Issue
5
Publish Date
2014
Start Page
492
End Page
493
DOI
10.1016/j.ajog.2013.12.038

OMICS PROFILING HIGHLIGHTS ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION AND UBIQUITIN PROTEASOME PATHWAYS IN INSULIN RESISTANCE AND GLYCEMIC CONTROL

Authors
McGarrah, R; Craig, DM; Haynes, C; Hauser, E; Newgard, CB; Gregory, SG; Kraus, W; Shah, S
MLA Citation
McGarrah, R, Craig, DM, Haynes, C, Hauser, E, Newgard, CB, Gregory, SG, Kraus, W, and Shah, S. "OMICS PROFILING HIGHLIGHTS ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION AND UBIQUITIN PROTEASOME PATHWAYS IN INSULIN RESISTANCE AND GLYCEMIC CONTROL." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 63.12 (April 1, 2014): A1600-A1600.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
63
Issue
12
Publish Date
2014
Start Page
A1600
End Page
A1600

Genetic predisposition of behavioral response.

Authors
Gregory, SG
MLA Citation
Gregory, SG. "Genetic predisposition of behavioral response." Proceedings of the National Academy of Sciences of the United States of America 111.5 (February 2014): 1672-1673.
PMID
24449895
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
111
Issue
5
Publish Date
2014
Start Page
1672
End Page
1673
DOI
10.1073/pnas.1323421111

Induction or augmentation of labor and autism--reply.

Authors
Miranda, ML; Anthopolos, R; Gregory, SG
MLA Citation
Miranda, ML, Anthopolos, R, and Gregory, SG. "Induction or augmentation of labor and autism--reply." JAMA pediatrics 168.2 (February 2014): 191-192. (Letter)
PMID
24492875
Source
epmc
Published In
JAMA Pediatrics
Volume
168
Issue
2
Publish Date
2014
Start Page
191
End Page
192
DOI
10.1001/jamapediatrics.2013.4792

Association of autism with induced or augmented childbirth

Authors
Miranda, ML; Anthopolos, R; Gregory, SG
MLA Citation
Miranda, ML, Anthopolos, R, and Gregory, SG. "Association of autism with induced or augmented childbirth." American Journal of Obstetrics and Gynecology 210.5 (January 1, 2014): 492-493. (Letter)
Source
scopus
Published In
American Journal of Obstetrics & Gynecology
Volume
210
Issue
5
Publish Date
2014
Start Page
492
End Page
493
DOI
10.1016/j.ajog.2013.12.038

The epigenetics of Autism-Running beyond the bases

© 2014 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. Previous studies have established that there is a strong genetic component to the development of ASD, but these genetic risks do not account for all of the heritability of the disorder. This raises the prospect that alternative, epigenetic mechanisms may play a role in ASD development. Epigenetic mechanisms facilitate temporal and spatial regulation of gene expression, but are independent of changes to the underlying DNA sequence. Because epigenetic profi les are labile, they represent an intriguing mechanism whereby environmental infl uences, which are not severe enough to alter the DNA sequence of a cell, may alter gene expression and cellular response and contribute to ASD. In this chapter, we discuss the role of DNA methylation and histone modifi cations in the development of ASD.

Authors
Gregory, SG
MLA Citation
Gregory, SG. "The epigenetics of Autism-Running beyond the bases." Frontiers in Autism Research: New Horizons for Diagnosis and Treatment. January 1, 2014. 303-333.
Source
scopus
Publish Date
2014
Start Page
303
End Page
333
DOI
10.1142/9789814602167_0013

Genetic evaluation and application of posterior cranial fossa traits as endophenotypes for Chiari type I malformation.

Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the base of the skull. Although cerebellar tonsillar herniation (CTH) is hypothesized to result from an underdeveloped posterior cranial fossa (PF), patients are frequently diagnosed by the extent of CTH without cranial morphometric assessment. We recently completed the largest CMI whole genome qualitative linkage screen to date. Despite an initial lack of statistical evidence, stratified analyses using clinical criteria to reduce heterogeneity resulted in a striking increase in evidence for linkage. The present study focused on the use of cranial base morphometrics to further dissect this heterogeneity and increase power to identify disease genes. We characterized the genetic contribution for a series of PF traits and evaluated the use of heritable, disease-relevant PF traits in ordered subset analysis (OSA). Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 × 10(-3) ) and 22 (LOD = 3.45, p = 6 × 10(-5) ) containing several candidates warranting further investigation. This study underscores the genetic heterogeneity of CMI and the utility of PF traits in CMI genetic studies.

Authors
Markunas, CA; Enterline, DS; Dunlap, K; Soldano, K; Cope, H; Stajich, J; Grant, G; Fuchs, H; Gregory, SG; Ashley-Koch, AE
MLA Citation
Markunas, CA, Enterline, DS, Dunlap, K, Soldano, K, Cope, H, Stajich, J, Grant, G, Fuchs, H, Gregory, SG, and Ashley-Koch, AE. "Genetic evaluation and application of posterior cranial fossa traits as endophenotypes for Chiari type I malformation." Ann Hum Genet 78.1 (January 2014): 1-12.
PMID
24359474
Source
pubmed
Published In
Annals of Human Genetics
Volume
78
Issue
1
Publish Date
2014
Start Page
1
End Page
12
DOI
10.1111/ahg.12041

Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990–1998) and Education Research (1997–2007) Databases

Authors
Gregory, SG; Anthopolos, R; Osgood, CE; Grotegut, CA; Miranda, ML
MLA Citation
Gregory, SG, Anthopolos, R, Osgood, CE, Grotegut, CA, and Miranda, ML. "Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990–1998) and Education Research (1997–2007) Databases." Obstetrical & Gynecological Survey 69.1 (January 2014): 7-9.
Source
crossref
Published In
Obstetrical and Gynecological Survey
Volume
69
Issue
1
Publish Date
2014
Start Page
7
End Page
9
DOI
10.1097/01.ogx.0000442814.50107.fa

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmedor stochastic nature of hypomethylation, identifyingthesechanges is important in understanding vascular disease,asmaintenance ofacells' epigenetic profile is essential for maintaining cellularphenotype. Global hypomethylation of proliferating aorticSMCsandconcomitant decrease ofDNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by 'genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2'-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P 5 0.017, OR 5 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex disease. © The Author 2013.

Authors
Connelly, JJ; Cherepanova, OA; Doss, JF; Karaoli, T; Lillard, TS; Markunas, CA; Nelson, S; Wang, T; Ellis, PD; Langford, CF; Haynes, C; Seo, DM; Goldschmidt-Clermont, PJ; Shah, SH; Kraus, WE; Hauser, ER; Gregory, SG
MLA Citation
Connelly, JJ, Cherepanova, OA, Doss, JF, Karaoli, T, Lillard, TS, Markunas, CA, Nelson, S, Wang, T, Ellis, PD, Langford, CF, Haynes, C, Seo, DM, Goldschmidt-Clermont, PJ, Shah, SH, Kraus, WE, Hauser, ER, and Gregory, SG. "Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis." Human Molecular Genetics 22.25 (December 1, 2013): 5107-5120.
PMID
23912340
Source
scopus
Published In
Human Molecular Genetics
Volume
22
Issue
25
Publish Date
2013
Start Page
5107
End Page
5120
DOI
10.1093/hmg/ddt365

Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort.

We performed a gene-smoking interaction analysis using families from an early-onset coronary artery disease cohort (GENECARD). This analysis was focused on validating and expanding results from previous studies implicating single nucleotide polymorphisms (SNPs) on chromosome 3 in smoking-mediated coronary artery disease. We analyzed 430 SNPs on chromosome 3 and identified 16 SNPs that showed a gene-smoking interaction at P < 0.05 using association in the presence of linkage--ordered subset analysis, a method that uses permutations of the data to empirically estimate the strength of the association signal. Seven of the 16 SNPs were in the Rho-GTPase pathway indicating a 1.87-fold enrichment for this pathway. A meta-analysis of gene-smoking interactions in three independent studies revealed that rs9289231 in KALRN had a Fisher's combined P value of 0.0017 for the interaction with smoking. In a gene-based meta-analysis KALRN had a P value of 0.026. Finally, a pathway-based analysis of the association results using WebGestalt revealed several enriched pathways including the regulation of the actin cytoskeleton pathway as defined by the Kyoto Encyclopedia of Genes and Genomes.

Authors
Ward-Caviness, C; Haynes, C; Blach, C; Dowdy, E; Gregory, SG; Shah, SH; Horne, BD; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, C, Haynes, C, Blach, C, Dowdy, E, Gregory, SG, Shah, SH, Horne, BD, Kraus, WE, and Hauser, ER. "Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort." Hum Genet 132.12 (December 2013): 1371-1382.
PMID
23907653
Source
pubmed
Published In
Human Genetics
Volume
132
Issue
12
Publish Date
2013
Start Page
1371
End Page
1382
DOI
10.1007/s00439-013-1339-7

Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control

Authors
Shah, SH; Kwee, L; Stitziel, N; Hauser, ER; Haynes, C; Kathiresan, S; Gregory, SG; Kraus, WE
MLA Citation
Shah, SH, Kwee, L, Stitziel, N, Hauser, ER, Haynes, C, Kathiresan, S, Gregory, SG, and Kraus, WE. "Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype.

Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using 3109 Caucasian samples in 745 families, we evaluated association in the overall dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS genes were tested for genetic association with NTD subtypes, both for main effects as well as for the presence of interactions with the MTHFR C677T polymorphism. Nominal main effect associations were found with all subtypes, across all three NOS genes, and interactions were observed between SNPs in all three NOS genes and MTHFR C677T. Unlike the previous report, the most significant associations in our dataset were with cranial subtypes and the AG genotype of rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous findings by implicating a role for all three NOS genes, independently and through interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes.

Authors
Soldano, KL; Garrett, ME; Cope, HL; Rusnak, JM; Ellis, NJ; Dunlap, KL; Speer, MC; Gregory, SG; Ashley-Koch, AE
MLA Citation
Soldano, KL, Garrett, ME, Cope, HL, Rusnak, JM, Ellis, NJ, Dunlap, KL, Speer, MC, Gregory, SG, and Ashley-Koch, AE. "Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype." Birth Defects Res B Dev Reprod Toxicol 98.5 (October 2013): 365-373.
PMID
24323870
Source
pubmed
Published In
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Volume
98
Issue
5
Publish Date
2013
Start Page
365
End Page
373
DOI
10.1002/bdrb.21079

Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) databases.

IMPORTANCE: One in 88 children in the United States is diagnosed as having autism spectrum disorder. Significant interest centers on understanding the environmental factors that may contribute to autism risk. OBJECTIVE: To examine whether induced (stimulating uterine contractions prior to the onset of spontaneous labor) and/or augmented (increasing the strength, duration, or frequency of uterine contractions with spontaneous onset of labor) births are associated with increased odds of autism. DESIGN, SETTING, AND PARTICIPANTS: We performed an epidemiological analysis using multivariable logistic regression modeling involving the North Carolina Detailed Birth Record and Education Research databases. The study featured 625,042 live births linked with school records, including more than 5500 children with a documented exceptionality designation for autism. EXPOSURES: Induced or augmented births. MAIN OUTCOMES AND MEASURES: Autism as assessed by exceptionality designations in child educational records. RESULTS: Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children. CONCLUSIONS AND RELEVANCE: Our work suggests that induction/augmentation during childbirth is associated with increased odds of autism diagnosis in childhood. While these results are interesting, further investigation is needed to differentiate among potential explanations of the association including underlying pregnancy conditions requiring the eventual need to induce/augment, the events of labor and delivery associated with induction/augmentation, and the specific treatments and dosing used to induce/augment labor (e.g., exogenous oxytocin and prostaglandins).

Authors
Gregory, SG; Anthopolos, R; Osgood, CE; Grotegut, CA; Miranda, ML
MLA Citation
Gregory, SG, Anthopolos, R, Osgood, CE, Grotegut, CA, and Miranda, ML. "Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) databases." JAMA Pediatr 167.10 (October 2013): 959-966.
PMID
23938610
Source
pubmed
Published In
JAMA Pediatrics
Volume
167
Issue
10
Publish Date
2013
Start Page
959
End Page
966
DOI
10.1001/jamapediatrics.2013.2904

Interactions between Social/behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China

Authors
Zeng, Y; Cheng, L; Zhao, L; Tan, Q; Feng, Q; Chen, H; Shen, K; Li, J; Zhang, F; Cao, H; Gregory, SG; Yang, Z; Gu, J; Tao, W; Tian, X-L; Hauser, ER
MLA Citation
Zeng, Y, Cheng, L, Zhao, L, Tan, Q, Feng, Q, Chen, H, Shen, K, Li, J, Zhang, F, Cao, H, Gregory, SG, Yang, Z, Gu, J, Tao, W, Tian, X-L, and Hauser, ER. "Interactions between Social/behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China." BMC GERIATRICS 13 (September 9, 2013).
Website
http://hdl.handle.net/10161/15374
PMID
24016068
Source
wos-lite
Published In
BMC Geriatrics
Volume
13
Publish Date
2013
DOI
10.1186/1471-2318-13-91

Association of Gene Expression Signatures with Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality in CATHGEN

Authors
Kraus, WE; Feng, S; Hauser, ER; Gregory, SG; Haynes, C; Dowdy, ZE; Craig, DM; Shah, SH
MLA Citation
Kraus, WE, Feng, S, Hauser, ER, Gregory, SG, Haynes, C, Dowdy, ZE, Craig, DM, and Shah, SH. "Association of Gene Expression Signatures with Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality in CATHGEN." March 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
127
Issue
12
Publish Date
2013

Genetics of the Chiari i and II malformationsGenetics of the Chiari i and II malformations

© 2013 Springer Science+Business Media New York. All rights reserved. Chiari malformations are considered to have a multifactorial etiology, likely influenced by environmental and genetic factors. This chapter will detail the evidence that supports a genetic contribution to the disorder, including discussions of twin studies, familial aggregation, co-occurrence with known genetic syndromes, and previous genetic studies. While no susceptibility genes have been identified to date, gene identification efforts are continuing. It is expected that researchers will have a more complete understanding of the specific genes and biological pathways that contribute to disease development in the coming years. The future benefits from genetic research of Chiari I and II may include the development of genetic t ests that result in more accurate and faster diagnoses as well as new targeted treatment options for patients.

Authors
Markunas, CA; Ashley-Koch, AE; Gregory, SG; Markunas, CA; Ashley-Koch, AE; Gregory, SG
MLA Citation
Markunas, CA, Ashley-Koch, AE, Gregory, SG, Markunas, CA, Ashley-Koch, AE, and Gregory, SG. "Genetics of the Chiari i and II malformationsGenetics of the Chiari i and II malformations (PublishedPublished)." The Chiari Malformations. March 1, 2013. 93-101.
Source
scopus
Volume
9781461463696
Publish Date
2013
Start Page
93
End Page
101
DOI
10.1007/978-1-4614-6369-6_7

Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative splicing of interleukin 7 receptor (IL7R) exon 6.

Interleukin 7 receptor, IL7R, is expressed exclusively on cells of the lymphoid lineage, and its expression is crucial for the development and maintenance of T cells. Alternative splicing of IL7R exon 6 results in membrane-bound (exon 6 included) and soluble (exon 6 skipped) IL7R isoforms. Interestingly, the inclusion of exon 6 is affected by a single-nucleotide polymorphism associated with the risk of developing multiple sclerosis. Given the potential association of exon 6 inclusion with multiple sclerosis, we investigated the cis-acting elements and trans-acting factors that regulate exon 6 splicing. We identified multiple exonic and intronic cis-acting elements that impact inclusion of exon 6. Moreover, we utilized RNA affinity chromatography followed by mass spectrometry to identify trans-acting protein factors that bind exon 6 and regulate its splicing. These experiments identified cleavage and polyadenylation specificity factor 1 (CPSF1) among protein-binding candidates. A consensus polyadenylation signal AAUAAA is present in intron 6 of IL7R directly downstream from the 5' splice site. Mutations to this site and CPSF1 knockdown both resulted in an increase in exon 6 inclusion. We found no evidence that this site is used to produce cleaved and polyadenylated mRNAs, suggesting that CPSF1 interaction with intronic IL7R pre-mRNA interferes with spliceosome binding to the exon 6 5' splice site. Our results suggest that competing mRNA splicing and polyadenylation regulate exon 6 inclusion and consequently determine the ratios of soluble to membrane-bound IL7R. This may be relevant for both T cell ontogeny and function and development of multiple sclerosis.

Authors
Evsyukova, I; Bradrick, SS; Gregory, SG; Garcia-Blanco, MA
MLA Citation
Evsyukova, I, Bradrick, SS, Gregory, SG, and Garcia-Blanco, MA. "Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative splicing of interleukin 7 receptor (IL7R) exon 6." RNA 19.1 (January 2013): 103-115.
PMID
23151878
Source
pubmed
Published In
RNA (New York, N.Y.)
Volume
19
Issue
1
Publish Date
2013
Start Page
103
End Page
115
DOI
10.1261/rna.035410.112

Genetic screen of African Americans with Fuchs endothelial corneal dystrophy.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disorder that has been primarily studied in patients of European or Asian ancestry. Given the sparse literature on African Americans with FECD, we sought to characterize the genetic variation in three known FECD candidate genes in African American patients with FECD. METHODS: Over an 8-year period, we enrolled 47 African American probands with FECD. All participants were clinically examined with slit-lamp biomicroscopy, and when corneal tissue specimens were available, histopathologic confirmation of the clinical diagnosis was obtained. The coding regions of known FECD susceptibility genes collagen, type VIII, alpha 2 (COL8A2); solute carrier family 4, sodium borate transporter, member 11 (SLC4A11); and zinc finger E-box binding homeobox 1 (ZEB1 [also known as TCF8]) were Sanger sequenced in the 47 probands using DNA isolated from blood samples. RESULTS: Twenty-two coding variants were detected across the COL8A2, SLC4A11, and ZEB1 genes; six were nonsynonymous variants. Three novel coding variants were detected: a synonymous variant each in COL8A2 and SLC4A11 and one nonsynonymous variant in ZEB1 (p.P559S), which is predicted to be benign and tolerated, thus making its physiologic consequence uncertain. CONCLUSIONS: Variation in the COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of our African American cases and as such does not appear to significantly contribute to the genetic risk of FECD in African Americans. This observation is on par with findings from previous sequencing studies involving European or Asian ancestry patients with FECD.

Authors
Minear, MA; Li, Y-J; Rimmler, J; Balajonda, E; Watson, S; Allingham, RR; Hauser, MA; Klintworth, GK; Afshari, NA; Gregory, SG
MLA Citation
Minear, MA, Li, Y-J, Rimmler, J, Balajonda, E, Watson, S, Allingham, RR, Hauser, MA, Klintworth, GK, Afshari, NA, and Gregory, SG. "Genetic screen of African Americans with Fuchs endothelial corneal dystrophy. (Published online)" Mol Vis 19 (2013): 2508-2516.
PMID
24348007
Source
pubmed
Published In
Molecular vision
Volume
19
Publish Date
2013
Start Page
2508
End Page
2516

Outcome and life satisfaction of adults with myelomeningocele

Background: Myelomeningocele (MMC) commonly causes impairments in body structure and functions as well as cognitive disabilities that can have an adverse effect on adult life. Improved medical care has resulted in increased numbers of individuals with MMC surviving to adulthood, however little is known about the impact of MMC on the lives of adults age 25 years or older. Objective: To gain a better understanding of outcomes in education, employment, relationships, reproduction and life satisfaction of adults with MMC. Methods: A primarily quantitative multiple-choice questionnaire designed to capture outcomes in education, employment, relationships and reproduction, along with a previously validated life satisfaction checklist (LiSat-11), was completed by adults with MMC. Relationships between demographic variables, outcomes and life satisfaction were determined using cross tabulation analysis, logistic regression and linear regression. Results: Ninety adults with MMC, age 25-85 years (median age 32), reported a diverse range of outcomes in education, employment, relationships and reproduction. The most consistent variable associated with difficulty attaining adult milestones was hydrocephalus, the presence of which reduced the likelihood of living independently (p ≤ 0.001), having a partner (p = 0.003) and reproducing (p ≤ 0.001), but did not contribute to reduced life satisfaction. Conclusions: Adults with MMC, especially those without hydrocephalus, can obtain gainful employment, live independently, form partner relationships and have children, and these achievements contribute to life satisfaction. While MMC does not affect overall reported life satisfaction for adults, attention should be paid to specific domains with less reported satisfaction. © 2013 Elsevier Inc. All rights reserved.

Authors
Cope, H; McMahon, K; Heise, E; Eubanks, S; Garrett, M; Gregory, S; Ashley-Koch, A
MLA Citation
Cope, H, McMahon, K, Heise, E, Eubanks, S, Garrett, M, Gregory, S, and Ashley-Koch, A. "Outcome and life satisfaction of adults with myelomeningocele." Disability and Health Journal (2013).
PMID
23769483
Source
scival
Published In
Disability and Health Journal
Publish Date
2013
DOI
10.1016/j.dhjo.2012.12.003

Stratified whole genome linkage analysis of Chiari type I malformation implicates known Klippel-Feil syndrome genes as putative disease candidates.

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.

Authors
Markunas, CA; Soldano, K; Dunlap, K; Cope, H; Asiimwe, E; Stajich, J; Enterline, D; Grant, G; Fuchs, H; Gregory, SG; Ashley-Koch, AE
MLA Citation
Markunas, CA, Soldano, K, Dunlap, K, Cope, H, Asiimwe, E, Stajich, J, Enterline, D, Grant, G, Fuchs, H, Gregory, SG, and Ashley-Koch, AE. "Stratified whole genome linkage analysis of Chiari type I malformation implicates known Klippel-Feil syndrome genes as putative disease candidates. (Published online)" PLoS One 8.4 (2013): e61521-.
PMID
23620759
Source
pubmed
Published In
PloS one
Volume
8
Issue
4
Publish Date
2013
Start Page
e61521
DOI
10.1371/journal.pone.0061521

Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.

Given the importance of cardiovascular disease (CVD) to public health and the demonstrated heritability of both disease status and its related risk factors, identifying the genetic variation underlying these susceptibilities is a critical step in understanding the pathogenesis of CVD and informing prevention and treatment strategies. Although one can look for genetic variation underlying susceptibility to CVD per se, it can be difficult to define the disease phenotype for such a qualitative analysis and CVD itself represents a convergence of diverse etiologic pathways. Alternatively, one can study the genetics of intermediate traits that are known risk factors for CVD, which can be measured quantitatively. Using the latter strategy, we have measured 21 cardiovascular-related biomarkers in an extended multigenerational pedigree, the CARRIAGE family (Carolinas Region Interaction of Aging, Genes, and Environment). These biomarkers belong to inflammatory and immune, connective tissue, lipid, and hemostasis pathways. Of these, 18 met our quality control standards. Using the pedigree and biomarker data, we have estimated the broad sense heritability (H2) of each biomarker (ranging from 0.09-0.56). A genome-wide panel of 6,015 SNPs was used subsequently to map these biomarkers as quantitative traits. Four showed noteworthy evidence for linkage in multipoint analysis (LOD score ≥ 2.6): paraoxonase (chromosome 8p11, 21), the chemokine RANTES (22q13.33), matrix metalloproteinase 3 (MMP3, 17p13.3), and granulocyte colony stimulating factor (GCSF, 8q22.1). Identifying the causal variation underlying each linkage score will help to unravel the genetic architecture of these quantitative traits and, by extension, the genetic architecture of cardiovascular risk.

Authors
Nolan, D; Kraus, WE; Hauser, E; Li, Y-J; Thompson, DK; Johnson, J; Chen, H-C; Nelson, S; Haynes, C; Gregory, SG; Kraus, VB; Shah, SH
MLA Citation
Nolan, D, Kraus, WE, Hauser, E, Li, Y-J, Thompson, DK, Johnson, J, Chen, H-C, Nelson, S, Haynes, C, Gregory, SG, Kraus, VB, and Shah, SH. "Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family. (Published online)" PLoS One 8.8 (2013): e71779-.
Website
http://hdl.handle.net/10161/10873
PMID
23936524
Source
pubmed
Published In
PloS one
Volume
8
Issue
8
Publish Date
2013
Start Page
e71779
DOI
10.1371/journal.pone.0071779

Integration of Whole Genome Methylation with Metabolomics Identifies Novel Cardiovascular Disease Genes

Authors
Shah, SH; Feng, S; Grass, E; Haynes, C; Chryst-Ladd, M; Craig, D; Hauser, ER; Newgard, CB; Kraus, WE; Gregory, SG
MLA Citation
Shah, SH, Feng, S, Grass, E, Haynes, C, Chryst-Ladd, M, Craig, D, Hauser, ER, Newgard, CB, Kraus, WE, and Gregory, SG. "Integration of Whole Genome Methylation with Metabolomics Identifies Novel Cardiovascular Disease Genes." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Genetic Variants in the Bone Morphogenic Protein (BMP) Family of Genes Interact with Mobile Source Air Pollution to Increase Risk of Peripheral Arterial Disease

Authors
Ward-Caviness, C; Neas, L; Haynes, C; Blach, C; Burns, E; LaRocque-Abramson, K; Dowdy, E; Casco, W; Devlin, R; Diaz-Sanchez, D; Kraus, WE; Shah, SH; Gregory, SG; Miranda, ML; Hauser, ER
MLA Citation
Ward-Caviness, C, Neas, L, Haynes, C, Blach, C, Burns, E, LaRocque-Abramson, K, Dowdy, E, Casco, W, Devlin, R, Diaz-Sanchez, D, Kraus, WE, Shah, SH, Gregory, SG, Miranda, ML, and Hauser, ER. "Genetic Variants in the Bone Morphogenic Protein (BMP) Family of Genes Interact with Mobile Source Air Pollution to Increase Risk of Peripheral Arterial Disease." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Transcriptome profiling of genes involved in neural tube closure during human embryonic development using long serial analysis of gene expression (long-SAGE).

BACKGROUND: Neural tube defects (NTDs) are common human birth defects with a complex etiology. To develop a comprehensive knowledge of the genes expressed during normal neurulation, we established transcriptomes from human neural tube fragments during and after neurulation using long Serial Analysis of Gene Expression (long-SAGE). METHODS: Rostral and caudal neural tubes were dissected from normal human embryos aged between 26 and 32 days of gestation. Tissues from the same region and Carnegie stage were pooled (n ≥ 4) and total RNA extracted to construct four long-SAGE libraries. Tags were mapped using the UniGene Homo sapiens 17 bp tag-to-gene best mapping set. Differentially expressed genes were identified by chi-square or Fisher's exact test, and validation was performed for a subset of those transcripts using in situ hybridization. In silico analyses were performed with BinGO and EXPANDER. RESULTS: We observed most genes to be similarly regulated in rostral and caudal regions, but expression profiles differed during and after closure. In silico analysis found similar enrichments in both regions for biologic process terms, transcription factor binding and miRNA target motifs. Twelve genes potentially expressing alternate isoforms by region or developmental stage, and the microRNAs miR-339-5p, miR-141/200a, miR-23ab, and miR-129/129-5p are among several potential candidates identified here for future research. CONCLUSIONS: Time appears to influence gene expression in the developing central nervous system more than location. These data provide a novel complement to traditional strategies of identifying genes associated with human NTDs and offer unique insight into the genes associated with normal human neurulation.

Authors
Krupp, DR; Xu, P-T; Thomas, S; Dellinger, A; Etchevers, HC; Vekemans, M; Gilbert, JR; Speer, MC; Ashley-Koch, AE; Gregory, SG; National Birth Defects Prevention Study,
MLA Citation
Krupp, DR, Xu, P-T, Thomas, S, Dellinger, A, Etchevers, HC, Vekemans, M, Gilbert, JR, Speer, MC, Ashley-Koch, AE, Gregory, SG, and National Birth Defects Prevention Study, . "Transcriptome profiling of genes involved in neural tube closure during human embryonic development using long serial analysis of gene expression (long-SAGE)." Birth Defects Res A Clin Mol Teratol 94.9 (September 2012): 683-692.
PMID
22806986
Source
pubmed
Published In
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume
94
Issue
9
Publish Date
2012
Start Page
683
End Page
692
DOI
10.1002/bdra.23040

The kinetics of urinary fumonisin B1 excretion in humans consuming maize-based diets.

SCOPE: Fumonisins (FB) are mycotoxins found in maize. The purpose of this study was to (i) determine the relationship between FB(1) , FB(2) , and FB(3) intake and urinary excretion in humans, (ii) validate a method to isolate urinary FB on C(18) -SPE cartridges for international shipment, and (iii) test the method using samples from Guatemala. METHODS AND RESULTS: Volunteers (n = 10) consumed 206 grams/day of tortillas and biscuits prepared from masa flour and a product containing maize flour. Volunteers estimated their daily urine output and samples were analyzed for FB(1) , FB(2) , and FB(3) and hydrolyzed FB(1) . Only FB(1) was detected in urine suggesting lower absorption of FB(2) and FB(3) . Excretion was highly variable peaking soon after consumption began and decreasing rapidly after consumption stopped. Within 5 days after consumption ended, FB(1) was not detected in urine. In a study with eight volunteers, the average total urinary FB(1) was 0.5% of the intake. FB(1) was detected in 61% (107/177) of the samples collected in Guatemala. CONCLUSION: The results support the use of urinary FB(1) to assess ongoing exposure in population-based studies. However, relating the FB(1) concentration in urine to dietary intake of FB by individual subjects will be complicated due to interindividual variability and the rapidity of clearance.

Authors
Riley, RT; Torres, O; Showker, JL; Zitomer, NC; Matute, J; Voss, KA; Gelineau-van Waes, J; Maddox, JR; Gregory, SG; Ashley-Koch, AE
MLA Citation
Riley, RT, Torres, O, Showker, JL, Zitomer, NC, Matute, J, Voss, KA, Gelineau-van Waes, J, Maddox, JR, Gregory, SG, and Ashley-Koch, AE. "The kinetics of urinary fumonisin B1 excretion in humans consuming maize-based diets." Mol Nutr Food Res 56.9 (September 2012): 1445-1455.
PMID
22815244
Source
pubmed
Published In
Molecular Nutrition & Food Research
Volume
56
Issue
9
Publish Date
2012
Start Page
1445
End Page
1455
DOI
10.1002/mnfr.201200166

Clinical, radiological, and genetic similarities between patients with Chiari Type I and Type 0 malformations.

OBJECT: Although Chiari Type I (CM-I) and Type 0 (CM-0) malformations have been previously characterized clinically and radiologically, there have been no studies focusing on the possible genetic link between these disorders. The goal of this study was to identify families in whom CM-0 and CM-I co-occurred and to further assess the similarities between these disorders. METHODS: Families were ascertained through a proband with CM-I. Detailed family histories were obtained to identify first-degree relatives diagnosed with CM-0. Several criteria were used to exclude individuals with acquired forms of CM-I and/or syringomyelia. Individuals were excluded with syndromic, traumatic, infectious, or tumor-related syringomyelia, as well as CM-I due to a supratentorial mass, hydrocephalus, history of cervical or cranial surgery unrelated to CM-I, or development of symptoms following placement of a lumbar shunt. Medical records and MR images were used to characterize CM-I and CM-0 individuals clinically and radiologically. RESULTS: Five families were identified in which the CM-I proband had a first-degree relative with CM-0. Further assessment of affected individuals showed similar clinical and radiological features between CM-0 and CM-I individuals, although CM-I patients in general had more severe symptoms and skull base abnormalities than their CM-0 relatives. Overall, both groups showed improvement in symptoms and/or syrinx size following craniocervical decompression surgery. CONCLUSIONS: There is accumulating evidence suggesting that CM-0 and CM-I may be caused by a common underlying developmental mechanism. The data in this study are consistent with this hypothesis, showing similar clinical and radiological features between CM-0 and CM-I individuals, as well as the occurrence of both disorders within families. Familial clustering of CM-0 and CM-I suggests that these disorders may share an underlying genetic basis, although additional epigenetic and/or environmental factors are likely to play an important role in the development of CM-0 versus CM-I.

Authors
Markunas, CA; Tubbs, RS; Moftakhar, R; Ashley-Koch, AE; Gregory, SG; Oakes, WJ; Speer, MC; Iskandar, BJ
MLA Citation
Markunas, CA, Tubbs, RS, Moftakhar, R, Ashley-Koch, AE, Gregory, SG, Oakes, WJ, Speer, MC, and Iskandar, BJ. "Clinical, radiological, and genetic similarities between patients with Chiari Type I and Type 0 malformations." J Neurosurg Pediatr 9.4 (April 2012): 372-378.
PMID
22462700
Source
pubmed
Published In
Journal of neurosurgery. Pediatrics
Volume
9
Issue
4
Publish Date
2012
Start Page
372
End Page
378
DOI
10.3171/2011.12.PEDS11113

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5.

BACKGROUND: Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas). RESULTS: We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003. CONCLUSION: Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.

Authors
Nolan, DK; Sutton, B; Haynes, C; Johnson, J; Sebek, J; Dowdy, E; Crosslin, D; Crossman, D; Sketch, MH; Granger, CB; Seo, D; Goldschmidt-Clermont, P; Kraus, WE; Gregory, SG; Hauser, ER; Shah, SH
MLA Citation
Nolan, DK, Sutton, B, Haynes, C, Johnson, J, Sebek, J, Dowdy, E, Crosslin, D, Crossman, D, Sketch, MH, Granger, CB, Seo, D, Goldschmidt-Clermont, P, Kraus, WE, Gregory, SG, Hauser, ER, and Shah, SH. "Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5. (Published online)" BMC Genet 13 (February 27, 2012): 12-.
PMID
22369142
Source
pubmed
Published In
BMC Genetics
Volume
13
Publish Date
2012
Start Page
12
DOI
10.1186/1471-2156-13-12

Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma.

Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly complement current surgical therapy. Using multiple high-resolution genomic screening methods, we identified a single locus, adherens junctional associated protein 1 (AJAP1) on chromosome 1p36 that is lost or epigenetically silenced in many glioblastomas. We found AJAP1 expression absent or reduced in 86% and 100% of primary glioblastoma tumors and cell lines, respectively, and the loss of expression correlates with AJAP1 methylation. Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in glioblastoma cell lines. This work shows the significant loss of expression of AJAP1 in glioblastoma and provides evidence of its role in the highly migratory characteristic of these tumors.

Authors
Lin, N; Di, C; Bortoff, K; Fu, J; Truszkowski, P; Killela, P; Duncan, C; McLendon, R; Bigner, D; Gregory, S; Adamson, DC
MLA Citation
Lin, N, Di, C, Bortoff, K, Fu, J, Truszkowski, P, Killela, P, Duncan, C, McLendon, R, Bigner, D, Gregory, S, and Adamson, DC. "Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma." Mol Cancer Res 10.2 (February 2012): 208-217.
PMID
22241217
Source
pubmed
Published In
Molecular cancer research : MCR
Volume
10
Issue
2
Publish Date
2012
Start Page
208
End Page
217
DOI
10.1158/1541-7786.MCR-10-0109

Genome-Wide Association Identifies Genetic Variants Associated With Vein Graft Stenosis After Coronary Artery Bypass Grafting

Authors
Shah, AA; Craig, DM; Haynes, C; Sebek, JK; Grass, E; Abramson, K; Smith, PK; Hauser, ER; Gregory, SG; Kraus, WE; Shah, SH
MLA Citation
Shah, AA, Craig, DM, Haynes, C, Sebek, JK, Grass, E, Abramson, K, Smith, PK, Hauser, ER, Gregory, SG, Kraus, WE, and Shah, SH. "Genome-Wide Association Identifies Genetic Variants Associated With Vein Graft Stenosis After Coronary Artery Bypass Grafting." November 22, 2011.
Source
wos-lite
Published In
Circulation
Volume
124
Issue
21
Publish Date
2011

Genomic Rearrangements in Autism: The Contribution of Copy Number Loss and Gain to the Etiology of Autism Spectrum Disorders.

Authors
Gregory, SG
MLA Citation
Gregory, SG. "Genomic Rearrangements in Autism: The Contribution of Copy Number Loss and Gain to the Etiology of Autism Spectrum Disorders." October 2011. S17-S17.
Source
wos-lite
Volume
52
Publish Date
2011
Start Page
S17
End Page
S17

A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.

The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates β(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated β(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of β-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which β-adrenergic catecholamines, acting through both Gs-PKA and β-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, β-arrestin-1 (ARRB1), activated via β(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.

Authors
Hara, MR; Kovacs, JJ; Whalen, EJ; Rajagopal, S; Strachan, RT; Grant, W; Towers, AJ; Williams, B; Lam, CM; Xiao, K; Shenoy, SK; Gregory, SG; Ahn, S; Duckett, DR; Lefkowitz, RJ
MLA Citation
Hara, MR, Kovacs, JJ, Whalen, EJ, Rajagopal, S, Strachan, RT, Grant, W, Towers, AJ, Williams, B, Lam, CM, Xiao, K, Shenoy, SK, Gregory, SG, Ahn, S, Duckett, DR, and Lefkowitz, RJ. "A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. (Published online)" Nature 477.7364 (August 21, 2011): 349-353.
PMID
21857681
Source
pubmed
Published In
Nature
Volume
477
Issue
7364
Publish Date
2011
Start Page
349
End Page
353
DOI
10.1038/nature10368

Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease.

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n = 205) and the CATHGEN cardiovascular study (n = 1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n = 879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p = 2 × 10(-6) and 5 × 10(-6), respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.

Authors
Minear, MA; Crosslin, DR; Sutton, BS; Connelly, JJ; Nelson, SC; Gadson-Watson, S; Wang, T; Seo, D; Vance, JM; Sketch, MH; Haynes, C; Goldschmidt-Clermont, PJ; Shah, SH; Kraus, WE; Hauser, ER; Gregory, SG
MLA Citation
Minear, MA, Crosslin, DR, Sutton, BS, Connelly, JJ, Nelson, SC, Gadson-Watson, S, Wang, T, Seo, D, Vance, JM, Sketch, MH, Haynes, C, Goldschmidt-Clermont, PJ, Shah, SH, Kraus, WE, Hauser, ER, and Gregory, SG. "Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease." Hum Genet 129.6 (June 2011): 641-654.
PMID
21298289
Source
pubmed
Published In
Human Genetics
Volume
129
Issue
6
Publish Date
2011
Start Page
641
End Page
654
DOI
10.1007/s00439-011-0959-z

Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is a common, late-onset disorder of the corneal endothelium. Although progress has been made in understanding the genetic basis of FECD by studying large families in which the phenotype is transmitted in an autosomal dominant fashion, a recently reported genome-wide association study identified common alleles at a locus on chromosome 18 near TCF4 which confer susceptibility to FECD. Here, we report the findings of our independent validation study for TCF4 using the largest FECD dataset to date (450 FECD cases and 340 normal controls). Logistic regression with sex as a covariate was performed for three genetic models: dominant (DOM), additive (ADD), and recessive (REC). We found significant association with rs613872, the target marker reported by Baratz et al.(2010), for all three genetic models (DOM: P = 9.33×10(-35); ADD: P = 7.48×10(-30); REC: P = 5.27×10(-6)). To strengthen the association study, we also conducted a genome-wide linkage scan on 64 multiplex families, composed primarily of affected sibling pairs (ASPs), using both parametric and non-parametric two-point and multipoint analyses. The most significant linkage region localizes to chromosome 18 from 69.94cM to 85.29cM, with a peak multipoint HLOD = 2.5 at rs1145315 (75.58cM) under the DOM model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents evidence to support the role of the intronic TCF4 single nucleotide polymorphism rs613872 in late-onset FECD through both association and linkage studies.

Authors
Li, Y-J; Minear, MA; Rimmler, J; Zhao, B; Balajonda, E; Hauser, MA; Allingham, RR; Eghrari, AO; Riazuddin, SA; Katsanis, N; Gottsch, JD; Gregory, SG; Klintworth, GK; Afshari, NA
MLA Citation
Li, Y-J, Minear, MA, Rimmler, J, Zhao, B, Balajonda, E, Hauser, MA, Allingham, RR, Eghrari, AO, Riazuddin, SA, Katsanis, N, Gottsch, JD, Gregory, SG, Klintworth, GK, and Afshari, NA. "Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. (Published online)" PLoS One 6.4 (April 20, 2011): e18044-.
PMID
21533127
Source
pubmed
Published In
PloS one
Volume
6
Issue
4
Publish Date
2011
Start Page
e18044
DOI
10.1371/journal.pone.0018044

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/circgenetics.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circ Cardiovasc Genet 4.2 (April 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Authors
Sun, AY; Koontz, JI; Shah, SH; Piccini, JP; Nilsson, KR; Craig, D; Haynes, C; Gregory, SG; Hranitzky, PM; Pitt, GS
MLA Citation
Sun, AY, Koontz, JI, Shah, SH, Piccini, JP, Nilsson, KR, Craig, D, Haynes, C, Gregory, SG, Hranitzky, PM, and Pitt, GS. "The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction." Circulation. Cardiovascular genetics 4.2 (April 15, 2011): 163-168.
PMID
21498565
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
2
Publish Date
2011
Start Page
163
End Page
168
DOI
10.1161/CIRCGENETICS.110.958652

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sust