Evaluation of age at symptom onset, proband status, and sex as predictors of disease severity in pediatric catecholaminergic polymorphic ventricular tachycardia

Heart Rhythm. 2021 Nov;18(11):1825-1832. doi: 10.1016/j.hrthm.2021.07.061. Epub 2021 Jul 29.

Abstract

Background: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist.

Objective: The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events.

Methods: A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups.

Results: A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on β-blocker or flecainide alone vs 10% (5/48) in patients on β-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001).

Conclusion: Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.

Keywords: Catecholaminergic polymorphic ventricular tachycardia; Inherited arrhythmia; Pediatrics; Risk predictors; Ryanodine receptor.

Publication types

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

MeSH terms

  • Adolescent
  • Age of Onset
  • Canada / epidemiology
  • Child
  • Female
  • Humans
  • Male
  • Risk Factors
  • Severity of Illness Index
  • Sex Factors
  • Tachycardia, Ventricular / epidemiology*
  • Tachycardia, Ventricular / therapy
  • United States / epidemiology

Supplementary concepts

  • Polymorphic catecholergic ventricular tachycardia