Abstract
BackgroundAntiarrhythmic action of flecainide is based on sodium channel blockade. Beta1-adrenoceptor (β1AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different β1AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation.Methodology/Principal FindingsIn 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual β1AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with β1AR 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).ConclusionsThe β1AR 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.
Highlights
Flecainide is used for cardioversion in patients with recent onset atrial fibrillation (AF)
The b1AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation
In the present study we aimed to determine whether the two SNPs position 389 (P389) and position 49 (P49) of b1AR are relevant in predicting AF, antiarrhythmic drug therapy and flecainide-induced cardioversion in patients with recent onset AF
Summary
Flecainide is used for cardioversion in patients with recent onset atrial fibrillation (AF). It has been successfully implemented for outof-hospital use as a pill-in-the-pocket approach in patients without structural heart disease [1,2]. In patients with organic heart disease our group recently reported that a single dosage of flecainide is not harmful, but less efficient than in healthy subjects [3]. The antiarrhythmic effect of flecainide is based on Na+ current (INa) inhibition [4]. Antiarrhythmic action of flecainide is based on sodium channel blockade. The aim of the present study was to evaluate the impact of different b1AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation
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