An Evaluation of Age at Symptom-Onset, Proband Status and Sex as Predictors of Disease Severity in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia
Abstract
BACKGROUND: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death and a risk stratification tool does not exist. OBJECTIVE: To determine whether proband status, age of 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 of 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 females and 65 males, and 106 probands and 27 relatives. Localization of RYR2 variants to hotspots differed based on proband status and age of 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 (IQR:3-11) after time of symptom-onset. Proband status, rather than age of symptom-onset or sex, was an independent predictor of time to first cardiac event (p=0.008, HR=4.4).
The 5-, 10- and 15- year event-free survival rate for probands were 77%, 56%, 46% and for relatives were 96%, 91%, 86%, respectively. Event-risk after diagnosis was 48% (n=32/67) in patients on β-blocker or flecainide alone versus 10% (n=5/48) on β-blocker plus flecainide and/or left cardiac sympathetic denervation (p<0.001).
CONCLUSION: Proband status, but not age of 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.