High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

Abstract

AIM:

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.

METHODS AND 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.

CONCLUSION:

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.

• Authors: Kristina Hermann Haugaa, Ida Skrinde Leren, Knut Erik Berge, Jørn Bathen, Jan Pål Loennechen, Ole-Gunnar Anfinsen, Andreas Früh, Thor Edvardsen, Erik Kongsgård, Trond P Leren, Jan P Amlie
• Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 12 Issue 3 Pg. 417-23 (Mar 2010) ISSN: 1532-2092 [Electronic] England
• PMID: 20106799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Catecholamines
• Ryanodine Receptor Calcium Release Channel

Topics

• Adolescent
• Adrenergic beta-Antagonists (therapeutic use)
• Adult
• Aged
• Catecholamines (genetics)
• Child
• Defibrillators, Implantable
• Electrocardiography
• Exercise
• Exercise Test
• Family Health
• Female
• Genetic Testing
• Heart Rate
• Humans
• Male
• Middle Aged
• Point Mutation
• Prevalence
• Ryanodine Receptor Calcium Release Channel (genetics)
• Tachycardia, Ventricular (drug therapy, epidemiology, genetics)
• Young Adult