Prognostic relevance of baseline exercise stress test in RYR2-related CPVT

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AIMS: Exercise stress test (EST) represents the gold standard for diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). We aimed to determine the relevance of exercise induced VT for the occurrence of LAE at follow-up. METHODS AND RESULTS: In RYR2-related CPVT patients who underwent a baseline EST, we assessed the incidence and severity of ventricular arrhythmias (VA). Data were analysed using logistic regression models and Cox proportional hazards models. The primary outcome was the occurrence of life-threatening arrhythmic event (LAE; composite of sudden cardiac death, aborted cardiac arrest, or hemodynamically non-tolerated VT) at follow-up. In 102 RYR2-related CPVT patients (65 females; median age 16 years, IQR: 11-36 years), exercise-induced VT (bidirectional in 64% of cases) was elicited in 56% patients. VT could not be induced in pre-school children. Lower basal heart rate, early onset VA (within the first step of EST) and heart rate at the first minute of recovery were associated with exercise-induced VT. Cox analyses showed that early onset VA (HR 6.0, 95% CI: 1.3-27.9, P = 0.022) and exercise-induced VT (HR 6.6, 95% CI: 1.5-29.1, P = 0.012) at baseline EST were significantly associated with the occurrence of LAE at follow-up, and remained associated even after correction for symptoms. CONCLUSION: Early onset VA and exercise-induced VT at baseline EST was associated with LAE at follow-up, allowing to identify a sub-set of patients at higher risk already at diagnosis.

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