High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.
OBJECTIVE
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening.


RESULTS
Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up.


CONCLUSIONS
Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.
Haugaa
Kristina Hermann
KH
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo 0027, Norway. kristina.haugaa@rr-research.no
Leren
Ida Skrinde
IS
Berge
Knut Erik
KE
Bathen
Jørn
J
Loennechen
Jan Pål
JP
Anfinsen
Ole-Gunnar
OG
Früh
Andreas
A
Edvardsen
Thor
T
Kongsgård
Erik
E
Leren
Trond P
TP
Amlie
Jan P
JP
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000235:genetics*; D002648:Child; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D015444:Exercise; D005080:Exercise Test; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D019837:Ryanodine Receptor Calcium Release Channel