One Heart, Two Problems: Cardiomyopathy and CPVT Secondary to RYR2 Mutation

Abstract

<h3>Introduction</h3> RYR2 mutations are known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disorder with risk for life threatening atrial (AT) and ventricular (VT) arrhythmias. Individuals with RYR2 mutation less commonly exhibit arrhythmogenic right ventricular cardiomyopathy (ARVC). We report the first case of a pediatric patient with RYR2 mutation, manifesting with CPVT, ARVC, and severe dysfunction requiring heart transplant (HTx). <h3>Case Report</h3> A 4.5 year old male with developmental delay presented after multiple syncopal episodes both at rest and with activity. A Holter showed AT, and he was started on a beta adrenergic antagonist with decreased frequency of syncopal episodes. He then developed sinus bradycardia with marked sinus pauses, prompting dual chamber pacemaker placement at age 6 years. He later exhibited bidirectional VT and whole exome sequencing identified a de novo, likely pathogenic variant in RYR2. He was medically managed until 16 years of age when he had syncope with exercise and was found to have both frequent AT and moderately depressed ventricular function with an ejection fraction of 45%. Given recurrent syncope with exercise, he underwent uncomplicated sympathectomy and optimization of his medical antiarrhythmic management. Over the next few months, he developed progressive heart failure symptoms and was admitted with worsening biventricular dysfunction and tachyarrhythmias. During his admission, he had a cardiac arrest with initial monitoring demonstrating VT, and was placed on extracorporeal membrane oxygenation support. He was transitioned to a durable left ventricular assist device (VAD), and was eventually listed for HTx. His VAD course was complicated by RV dysfunction needing PDE5 inhibitor; his arrhythmia burden was managed on flecainide, sotalol, and nadolol. After 80 days of VAD support, he underwent HTx. Pathology of his explanted heart revealed biventricular fibrofatty myocardial replacement consistent with ARVC with prominent LV involvement. <h3>Summary</h3> This case highlights an expanded spectrum of RYR2 mutation related disease which may include prominent atrial arrhythmias, ARVC, and developmental delay. Patients with CPVT and RYR2 mutation warrant close monitoring for ventricular dysfunction, especially if there is a significant arrhythmia burden.