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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.

Background: Flecainide is used as a pill-in-the-pocket treatment for pharmacological cardioversion in patients without structural heart disease and atrial fibrillation (AF). In patients with structural heart disease and elevated cardiovascular risk, flecainide is believed to be harmful. Therefore, data about safety and effectiveness of single-dose flecainide for cardioversion in patients at elevated cardiovascular risk are lacking., Objectives: One-hundred and six consecutive patients with recent onset AF and known structural heart disease and/or elevated PROCAM-score did receive oral flecainide 300 mg for cardioversion., Methods: The effectiveness, safety and influencing factors of flecainide for cardioversion in high-risk patients were prospectively assessed., Results: In 43 of 106 patients (40.6%), sinus rhythm could be restored within 192.4 +/- 10.7 min by flecainide. The PROCAM-score was 41.5 +/- 0.56 in patients with successful cardioversion compared to 45.7 +/- 0.74 in patients without successful cardioversion (P < 0.001). ACE-inhibitor co-medication was associated with a significantly lower rate of conversion by flecainide (HR 2.3, 95% CI, 1.12-4.26, P < 0.01). In 58 of 63 patients in whom cardioversion by flecainide was not effective, electrical cardioversion was performed which was successful in 47 patients. Life-threatening arrhythmias did not occur in any patient. The most common side effect was sinus-bradycardia and transient sinus arrest (2-4 s) immediately after conversion., Conclusions: When monitored properly, flecainide is safe and useful for cardioversion in patients at elevated cardiovascular risk.

Background: Antiarrhythmic 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 Findings: In 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 flecainideinduced 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; ρ = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; ρ = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; ρ = 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; ρ = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110±2.7 bpm; ρ = 0.03 vs. other variants) compared to Arg389Gly (104.86±2.4 bpm) and Gly389Gly (96.9±65.8 bpm) carriers. The Arg389Gly- Ser49Gly genotype was more common in patients with a trial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; ρ ,0.001). Conclusions: The 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. [ABSTRACT FROM AUTHOR]