PO-04-139 THE CLINICAL COURSE OF GENOTYPE-POSITIVE PHENOTYPE-NEGATIVE PATIENTS WITH RYR2-MEDIATED CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but potentially lethal inherited cardiac arrhythmia, mostly associated with RYR2 variants. Data on phenotype-negative patients with a RYR2 variant, a growing population due to cascade screening, are lacking. We aimed to assess the clinical course of phenotype-negative patients with a RYR2 variant. All patients from the International CPVT Registry with a (likely) pathogenic RYR2 variant who were asymptomatic (defined as absence of syncope or sudden cardiac arrest [SCA]) were included if they had a negative phenotype (defined as absence of any ventricular ectopy) on baseline exercise stress test (EST) off anti-arrhythmic drugs. All ESTs during follow-up were assessed for the development of a phenotype, and data on arrhythmic events (defined as syncope, appropriate implantable cardioverter defibrillator (ICD) shock, SCA, and sudden cardiac death) during follow-up were collected. One-hundred-four patients were included (median age at first cardiologic examination 17.9 [IQR 10.4-39.2] years, 55 (52.9%) females, from 35 families with 30 different RYR2 variants). During a median follow-up duration of 6.1 [IQR 3.0-9.1] years, 449 ESTs of 79 patients were collected. When censoring at the last EST, 50.2% (95% CI 38.7-62.9) of the patients developed a phenotype at 5 years follow-up (Figure), including 25 on beta-blocker therapy. During follow-up, the overall arrhythmic event-rate was 0.010 per person year. Four (3.8%) patients experienced a syncope, of whom one was untreated and three were treated with a β1-selective beta-blocker, including one with confirmed non-adherence. Two of 3 patients with ESTs during follow-up prior to syncope had developed a phenotype. One showed a phenotype immediately after the event. One patient who had become phenotype-positive experienced a recurrent event (appropriate ICD shock). One (1.0%) patient had a SCA while being phenotype-positive and non-adherent to beta-blocker and flecainide. Twenty-nine patients never received medical therapy and were event-free during a median follow-up duration of 3.9 [IQR: 0.2-9.7] years. Following the initial phenotype-negative screening, approximately half of the patients with a RYR2 variant developed a phenotype during 5 years of follow-up. The event rate was low and only two patients had a near-fatal arrhythmic event, both after developing a phenotype. This information could guide management of phenotype-negative patients with CPVT.