Exercise testing in asymptomatic gene carriers exposes a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy

J Am Coll Cardiol. 2013 Nov 5;62(19):1772-9. doi: 10.1016/j.jacc.2013.04.084. Epub 2013 Jun 27.


Objectives: The aim of this study was to determine if exercise testing could expose a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene carriers.

Background: Management of asymptomatic ARVC gene carriers is challenging because of variable penetrance of disease and the recognition that sudden cardiac death may be the first clinical manifestation.

Methods: Exercise-induced abnormalities during exercise treadmill testing (ETT) were initially compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls. In phase 2 of the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia or cardiac arrest were evaluated to determine if ETT abnormalities in asymptomatic gene carriers were common to patients with a malignant electrical form of the disease.

Results: Depolarization abnormalities during ETT were found to develop more frequently in asymptomatic gene carriers compared with healthy controls: epsilon waves appeared in 4 of 28 (14%) compared with 0 of 30 (0%) (p = 0.048), premature ventricular contractions in 17 of 30 (57%) compared with 3 of 30 (10%) (p = 0.0003), and new QRS terminal activation duration ≥ 55 ms in 7 of 22 (32%) compared with 2 of 29 (7%) (p = 0.03). Superior axis premature ventricular contractions occurred only in gene carriers. In the second phase of the study, the frequency of these abnormalities was found to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), superior axis premature ventricular contractions in 21 of 25 (84%), and new terminal activation duration ≥ 55 ms in 8 of 12 (67%).

Conclusions: Exercise testing exposes a latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia. ETT may be useful in guiding treatment decisions, exercise prescription, and prioritizing medical surveillance in asymptomatic ARVC gene carriers.

Keywords: ARVC; ECG; ETT; PKP2; PVC; RBBB; T-wave inversion; TAD; TFC; TWI; arrhythmia; arrhythmogenic right ventricular cardiomyopathy; electrocardiographic; exercise; exercise treadmill test; genetics; plakophilin-2; premature ventricular contraction; right bundle branch block; task force criteria; terminal activation duration.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arrhythmogenic Right Ventricular Dysplasia / diagnosis*
  • Arrhythmogenic Right Ventricular Dysplasia / genetics
  • Arrhythmogenic Right Ventricular Dysplasia / physiopathology
  • Diagnosis, Differential
  • Electrocardiography*
  • Exercise Test / methods*
  • Female
  • Genetic Predisposition to Disease*
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Plakophilins / genetics
  • Young Adult


  • Plakophilins