PO-03-156 SPECTRUM AND PREVALENCE OF RYR2-OPATHIES DURING LIFE AND AFTER SUDDEN DEATH

Disease-causative variants in the RYR2-encoded ryanodine receptor (RyR2)/calcium release channel (CRC) result a spectrum of clinical phenotypes, most notably catecholaminergic polymorphic ventricular tachycardia (CPVT) and CRC deficiency syndrome (CRCDS). In addition, ultra-rare RYR2 genetic are observed small number unexplained sudden cardiac arrest (SCA) death (SCD) cases. To determine phenotypes living deceased patients with referred to quaternary heart rhythm program functional effects these on RyR2/CRC. Retrospective review all evaluated clinically Mayo Clinic Windland Smith Rice Genetic Heart Rhythm between July 2000 June 2022 decedents for molecular autopsy was used identify those ≥1 variant RYR2. Basic demographic data were then extracted from electronic record patients/decedents classified as either (i) CPVT1 (ii) CRCDS, (iii) idiopathic fibrillation (IVF), (iv) arrhythmogenic right cardiomyopathy (ARVC), or (v) dismissed normal. Among 4,782 evaluated, 192 qualifying identified 251 (5.2%; 53% female; age 23 +/- 16 years) patients. Of these, 51(20.3%) had history prior 72 (28.7%) arrhythmic syncope. Clinically, 196 (78.1%), 5 (2%) SCA survivors default diagnosis IVF, 2 (1.2%) 3 diagnosed ARVC, remaining 11 (4.4%) no phenotype concerning family history. 292 decedents, 34 distinct victims (11.6%; 41.2% mean at 16.6 +/-8.9 years). whom circumstances known, 63% exertional. Collectively, this suggests that majority RyR2-opathies arises secondary RyR2-mediated CPVT. However, given diagnostic ambiguity associated identification an survivor/youthful SCD decedent, better screening tools needed evaluate possibility CRCDS.