Impact of serum flecainide level on control of atrial fibrillation in a case treated with cardiac resynchronization therapy

Abstract

A 72-year-old male patient with dilated cardiomyopathy was treated with oral flecainide (100 mg/day) for persistent atrial fibrillation (AF) that could not be converted to sinus rhythm by electrical cardioversion. Initiation of flecainide treatment provided sinus rhythm without prolongation of QRS and QTc, bradycardia and first-degree atrioventricular block at a serum flecainide level of 438 ng/mL. Then, he received cardiac resynchronization therapy (CRT). Dose reduction to 50 mg/day because of stabilization of heart rate after CRT produced AF at a serum flecainide level of 270 ng/mL. Electrical cardioversion did not restore the AF to a sinus or pacing rhythm. Dose escalation of flecainide (to 100 mg/day) restored the pacing rhythm at a serum flecainide level of 401 ng/mL. This case suggests that in the Japanese population, serum flecainide level should be maintained at >300 ng/mL to control AF even after effective CRT.

SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients

“…We previously reported that the serum flecainide concentration should be maintained at ≥300 ng/mL to control the paroxysms of supraventricular tachyarrhythmias [21][22][23]. The recommended serum flecainide concentration in Hap B carriers, however, is likely to be ≥200 ng/mL because the cumulative efficacy rate at around 200 ng/mL was similar to that at 300 ng/mL in the HapA homozygotes (Fig.…”

“…Tachyarrhythmias were well controlled in 63.0% of the HapB carriers and 51.6% of the HapA homozygotes; this difference was not significant (P = 0.18; Table 2). The influence of the SCN5A promoter haplotype on the anti-arrhythmic efficacy of flecainide was compared between the patients with serum flecainide concentrations <300 ng/mL and ≥300 ng/mL according to the previous reports [21][22][23]. The HapB carriers achieved clinically relevant flecainide efficacy more frequently (68.8%) when the serum flecainide concentrations were <300 ng/mL, compared with the HapA homozygotes (42.9%; P = 0.022; Table 2).…”

“…The lower limit of the recommended therapeutic range for serum flecainide concentration, which remains somewhat controversial, varies from 200 to 400 ng/mL for suppression of ventricular arrhythmia [16,18,20]. We previously reported that the serum flecainide concentration was recommended to maintain ≥300 ng/mL in patients with supraventricular tachyarrhythmias [21][22][23]. However, according to a previous 5 report, some patients showed sufficient effectiveness of flecainide at concentrations <300 ng/mL [21].…”