Key result
The b1AR Arg389Arg genotype was associated with a significantly higher rate of successful flecainide-induced cardioversion (55.5%, OR 3.30) compared to other variants in patients with atrial fibrillation.
Why the study?
Does beta1-adrenoceptor polymorphism predict the success of flecainide-induced cardioversion in patients with atrial fibrillation?
Observational (n=145)
Single-blind
Does beta1-adrenoceptor polymorphism predict the success of flecainide-induced cardioversion in patients with atrial fibrillation?
Odds Ratio: 3.3 (95% CI 1.34–8.13)
Absolute Event Rate: 55.5% vs 29.5%
p-value: p=0.003
The beta1-adrenoceptor Arg389Arg genotype is associated with increased flecainide potency for cardioversion and higher heart rates during atrial fibrillation.
Should not yet guide genotype-based flecainide use in AF; hypothesis-generating for prospective validation of Arg389Arg effects.
BACKGROUND: Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta(1)-adrenoceptor (beta(1)AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different beta(1)AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation. METHODOLOGY/PRINCIPAL FINDINGS: In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual beta(1)AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with beta(1)AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34-8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10-0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110+/-2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8+/-2.4 bpm) and Gly389Gly (96.9+/-5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; p<0.001). CONCLUSIONS: The beta(1)AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation.
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Nia et al. (2010) conducted an observational in Atrial Fibrillation (n=145). b1AR Arg389Arg genotype vs. Arg389Gly and Gly389Gly genotypes was evaluated on Success of flecainide-induced cardioversion (OR 3.30, 95% CI 1.34-8.13, p=0.003). The b1AR Arg389Arg genotype was associated with a significantly higher rate of successful flecainide-induced cardioversion (55.5%, OR 3.30) compared to other variants in patients with atrial fibrillation.
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