BACKGROUND: Conventional therapy with beta-blockers is incompletely effective in 
preventing arrhythmic events in patients with catecholaminergic polymorphic 
ventricular tachycardia (CPVT). We have previously discovered that flecainide in 
addition to conventional drug therapy prevents ventricular arrhythmias in 
patients with genotype-positive CPVT.
OBJECTIVE: To study the efficacy of flecainide in patients with 
genotype-negative CPVT.
METHODS: We studied the efficacy of flecainide for reducing ventricular 
arrhythmias during exercise testing and preventing arrhythmia events during 
long-term follow-up.
RESULTS: Twelve patients with genotype-negative CPVT were treated with 
flecainide. Conventional therapy failed to control ventricular arrhythmias in 
all patients. Flecainide was initiated because of significant ventricular 
arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline 
exercise test before flecainide, 6 patients had ventricular tachycardia and 5 
patients had bigeminal or frequent ventricular premature beats. Flecainide 
reduced ventricular arrhythmias at the exercise test in 8 patients compared to 
conventional therapy, similar to that in patients with genotype-positive CPVT in 
our previous report. Notably, flecainide completely prevented ventricular 
arrhythmias in 7 patients. Flecainide was continued in all patients except for 
one who had ventricular tachycardia at the exercise test on flecainide. During a 
follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted 
cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide 
was not discontinued owing to side effects in any of the patients.
CONCLUSIONS: Flecainide was effective in patients with genotype-negative CPVT, 
suggesting that spontaneous Ca(2+) release from ryanodine channels plays a role 
in arrhythmia susceptibility, similar to that in patients with genotype-positive 
CPVT.