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.

Amsterdam University Medical Center Amsterdam Netherlands; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart

BC Children's Hospital Vancouver Canada

Children's Hospital Los Angeles Los Angeles California

Children's Hospital of Wisconsin Milwaukee Wisconsin

Cleveland Clinic Cleveland Ohio

Division of Cardiology University of British Columbia Vancouver Canada

European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart; Hospital Sant Joan de Déu Barcelona Spain

Hong Kong Children's Hospital Hong Kong SAR China

Indiana University School of Medicine Indianapolis Indiana

Motol University Hospital Prague Czech Republic

Nationwide Children's Hospital Columbus Ohio

Nemours Children's Clinic Orlando Florida

Oregon Health Science University Portland Oregon

Rady Children's Hospital San Diego California

Sibley Heart Center Children's Healthcare of Atlanta Atlanta Georgia

University Alabama Birmingham Birmingham Alabama

University of Alberta Edmonton Canada

University of Gottingen Gottingen Germany

University of Iowa Stead Family Children's Hospital Iowa City Iowa

University of Louisville Louisville Kentucky

University of Michigan Ann Arbor Michigan

University of Utah Salt Lake City Utah

Vanderbilt University Medical Center Nashville Tennessee

Virginia Commonwealth University Richmond Virginia

References provided by Crossref.org

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia