This Article Full Text Full Text (PDF) All Versions of this Article: 2/1/24    most recent CIRCEP.108.799098v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Husser, D. Articles by Bollmann, A. Search for Related Content PubMed Articles by Husser, D. Articles by Bollmann, A. Related Collections Electrophysiology Clinical genetics Electrocardiology Arrhythmias, clinical electrophysiology, drugs

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

Genotype ECG-Phenotype Correlation in Atrial Fibrillation

From the Department of Electrophysiology (D.H., A.B.), Heart Center, Leipzig University, Germany; and Division of Clinical Pharmacology (D.H., D.M.R., D.D., A.B.), Vanderbilt University, Nashville, Tenn; and Department of Electrical and Information Technology (M.S., L.S.), Lund University, Sweden.

Correspondence to Daniela Husser, MD, Department of Electrophysiology, Heart Center, Leipzig University, Strümpellstr. 39, 04289 Leipzig, Germany. E-mail dani11{at}gmx.net

Received June 13, 2008; accepted December 17, 2008.

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 38GG 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 (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 (β=–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.

Key Words: electrocardiography • electrophysiology • genetics • atrial fibrillation

Parts of this study were presented at the Annual Scientific Sessions of the American Heart Association 2007 and at the Annual Scientific Sessions of the Heart Rhythm Society 2008.