Accelerated supraventricular rates suppressed ventricular arrhythmias in CPVT mouse models (VA score 0.6 vs 1.7; P<0.05) and in 33% of CPVT patients during exercise testing.
Observational (n=18)
Absolute Event Rate: 0.6% vs 1.7%
p-value: p=<0.05
RATIONALE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA). OBJECTIVE: To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. METHODS AND RESULTS: Using CPVT mouse models (Casq2(-/-) and RyR2(R4496C/+) mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia in 86% of Casq2(-/-) mice (6/7) and significantly reduced the VA score (atropine: 0.6±0.2 versus vehicle: 1.7±0.3; P85% of their maximum-predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In 6 CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise. CONCLUSIONS: Accelerated supraventricular rates suppress VAs in 2 CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced ventricular tachycardia in treatment-refractory CPVT patients.
Faggioni et al. (Tue,) conducted a observational in Catecholaminergic polymorphic ventricular tachycardia (CPVT) (n=18). Accelerated supraventricular rates (atropine, atrial overdrive pacing, or exercise) vs. Vehicle or baseline heart rate was evaluated on Ventricular arrhythmia (VA) score in Casq2(-/-) mice (p=<0.05). Accelerated supraventricular rates suppressed ventricular arrhythmias in CPVT mouse models (VA score 0.6 vs 1.7; P<0.05) and in 33% of CPVT patients during exercise testing.