Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations.
Calcium channel antagonism in RyR2 defects.


BACKGROUND
Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations.


RESULTS
Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study.


CONCLUSIONS
This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.
Swan
Heikki
H
Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. heikki.swan@helsinki.fi
Laitinen
Päivi
P
Kontula
Kimmo
K
Toivonen
Lauri
L
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002395:Catecholamines / Q000502:physiology; D005080:Exercise Test; D006801:Humans; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D009154:Mutation; D015203:Reproducibility of Results; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000517:prevention & control*; D014700:Verapamil / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D002395:Catecholamines; D019837:Ryanodine Receptor Calcium Release Channel; D008278:Magnesium Sulfate; D014700:Verapamil