Torsades de pointes complicating atrioventricular block: evidence for a genetic predisposition.
BACKGROUND
The prevalence of genetic risk factors has not been systematically evaluated in the setting of complete atriventricular (AV) block complicated by long QT syndrome (LQTS).


OBJECTIVE
This study was performed to determine to what extent acquired LQTS in the context of AV block has a genetic substrate.


METHODS
Among 420 recipients of pacemakers implanted over a 3-year period, we identified retrospectively 29 patients with complete AV block and a QT interval >600 ms in duration. A second study group included 22 randomly selected patients who had AV block and a QT interval <600 ms. Normal controls were 100 consecutive individuals without medical history. Genetic studies screening for HERG, KCNQ1 KCNE1, KCNE2, and SCN5A mutations were performed.


RESULTS
We identified four mutations on genes encoding potassium channels in five patients with AV block and acquired LQTS. These mutations were not found among patients with AV block and a QT interval <600 ms in duration or in healthy volunteers. Functional expression of three HERG mutations (R328C, R696C, and R1047L) had a dominant negative effect on wild-type I(Kr). One KCNE2 mutation (R77W) identified in a patient treated with flecainide did not alter I(Kr).


CONCLUSIONS
This study showed that complete AV block complicated by LQTS was associated with HERG mutations in 17% of cases. Further studies are needed to identify factors, genetic or environmental, which may be implicated in bradycardia-related abnormalities of ventricular repolarization.
Chevalier
Philippe
P
Hôpital Cardiologique, Hospices Civils de Lyon, Lyon, France. philippe.chevalier@chu-lyon.fr
Bellocq
Chloé
C
Millat
Gilles
G
Piqueras
Eric
E
Potet
Franck
F
Schott
Jean-Jacques
JJ
Baró
Isabelle
I
Lemarec
Hervé
H
Barhanin
Jacques
J
Rousson
Robert
R
Rodriguez-Lafrasse
Claire
C
D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006327:Heart Block / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D012189:Retrospective Studies; D016171:Torsades de Pointes / Q000209:etiology / Q000235:genetics*
D015221:Potassium Channels