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A genotype dependent intermediate ECG phenotype in patients with persistent lone atrial fibrillation

Husser, D.; Stridh, Martin LU ; Darbar, D.; Roden, D. and Sörnmo, Leif LU (2009) In Circulation: Arrhythmia and Electrophysiology 2(1). p.24-28
Abstract
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... (More)
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 (χ2 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
electrocardiography, electrophysiology, atrial fibrillation, genetics
in
Circulation: Arrhythmia and Electrophysiology
volume
2
issue
1
pages
24 - 28
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:70349308417
ISSN
1941-3084
DOI
10.1161/​CIRCEP.108.799098
language
English
LU publication?
yes
id
4ff0553f-99ad-4490-903d-99a34bce04b3 (old id 1758949)
date added to LUP
2011-01-04 16:22:51
date last changed
2017-08-13 04:34:03
@article{4ff0553f-99ad-4490-903d-99a34bce04b3,
  abstract     = {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.<br/><br>
<br/><br>
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 &gt;450 fibrillations per minute, all had either the GS or SS genotype (χ2 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.<br/><br>
<br/><br>
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.},
  author       = {Husser, D. and Stridh, Martin and Darbar, D. and Roden, D. and Sörnmo, Leif},
  issn         = {1941-3084},
  keyword      = {electrocardiography,electrophysiology,atrial fibrillation,genetics},
  language     = {eng},
  number       = {1},
  pages        = {24--28},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Circulation: Arrhythmia and Electrophysiology},
  title        = {A genotype dependent intermediate ECG phenotype in patients with persistent lone atrial fibrillation},
  url          = {http://dx.doi.org/10.1161/​CIRCEP.108.799098},
  volume       = {2},
  year         = {2009},
}