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A Genotype-Dependent Intermediate ECG Phenotype in Patients With Persistent Lone Atrial Fibrillation Genotype ECG-Phenotype Correlation in Atrial Fibrillation

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Author

Summary, in English

Background-Atrial fibrillation (AF) is heterogeneous at the clinical and molecular levels. Association studies have reported that common single-nucleotide polymorphisms in KCNE1 and SCN5A may predispose to AF In this study, we tested the hypothesis that specific AF-associated genotypes confer variation on the appearance of AF assessed by analysis of fibrillatory rate of the atria. Methods and Results-Twenty-six nonrelated patients (21 males, mean age 55 +/- 12 years) with persistent lone AF (median AF duration 5 weeks) not taking class I or III antiarrhythmic drugs were studied. Fibrillatory rate was obtained by spatiotemporal QRST cancellation and time-frequency analysis of the index surface ECG. Genotypes at the AF-associated loci in KCNE1 (S38G) and SCN5A (H558R) were determined by direct DNA sequencing. The atrial fibrillatory rate was 418 +/- 50 fibrillations per minute (range, 336 to 521) in the study cohort. Carriers of the 38 GG KCNE1 genotype (n=13) had significantly lower fibrillatory rates (392 +/- 36 versus 443 +/- 49 fibrillations per minute, P=0.006) compared to those with GS or SS genotype (n=13). Six patients (23%) with fibrillatory rates >450 fibrillations per minute, all had either the GS or SS genotype (chi(2) P=0.008). In contrast, both the heterozygeous and homozygeous SCN5A H558R polymorphism had no effect on fibrillatory rate. There were no significant associations between fibrillatory rate and clinical (age, gender, AF duration, drug treatment) or echocardiographic (left atrial diameter, left ventricular ejection fraction) variables. In multivariable regression analysis, the KCNE1 S38G genotype (SS/GS coded 0, GG coded 1) was the only independent predictor of fibrillatory rate (beta = -0.437, P=0.006) with a SE of the estimate of 44 fibrillations per minute. Conclusions-This study suggests that atrial fibrillatory rate obtained from the surface ECG is at least in part determined by KCNE1 (S38G) genotype, implying that this variant exerts functional effects on atrial electrophysiology. This intermediate ECG phenotype may be useful for elaborating genetic influences on AF mechanisms and identifying subsets of patients for variability in AF susceptibility or response to therapies. (Circ Arrhythmia Electrophysiol. 2009;2:24-28.)

Publishing year

2009

Language

English

Pages

24-28

Publication/Series

Circulation: Arrhythmia and Electrophysiology

Volume

2

Issue

1

Document type

Conference paper

Publisher

Lippincott Williams & Wilkins

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • atrial fibrillation
  • genetics
  • electrocardiography
  • electrophysiology

Conference name

29th Annual Scientific Session of the Heart-Rhythm-Society

Conference date

2008-05-15 - 2008-05-17

Status

Published

Research group

  • Signal Processing

ISBN/ISSN/Other

  • ISSN: 1941-3084
  • ISSN: 1941-3149