Abstract 4142141: The Genetic and Phenotypic Determinants of Life-Threatening Arrhythmias in Pediatric Bileaflet Mitral Valve Prolapse Arrhythmia Syndrome

Background: Bileaflet mitral valve prolapse (BMVP) is a rare disease in the pediatric population. It may be a proarrhythmic substrate, particularly when present with mitral annular disjunction (MAD). There is less known about the genetic etiology and phenotypic spectrum of patients diagnosed with BMVP in childhood. Objective: To determine the genetic and phenotypic factors that influence arrhythmia development and cardiac arrest in pediatric patients with BMVP. Methods: We established a cohort of pediatric probands with at least one clinical encounter at Duke University Hospitals. Patients were categorized by underlying cardiac condition leading to groups of idiopathic BMVP, aortopathies, cardiac channelopathies/cardiomyopathies, and congenital heart disease (CHD). We grouped patients by presence of MAD. Primary outcome was ventricular arrhythmias. Secondary outcomes were cardiac arrest, pacemaker or implantable cardioverter defibrillator (ICD) placement, and secondary cardiac surgery. Rates of arrhythmia and secondary outcomes were compared using Fisher’s exact test. Freedom from event curves were generated to track first arrhythmia episodes and age at diagnosis and compared using a log-rank test. Results: 54 pediatric patients were included with 30 (55.6%) female and an average age at diagnosis of 8.2 years. Patients with concurrent CHD had earlier BMVP diagnosis compared to those with idiopathic BMVP and cardiac channelopathies/cardiomyopathies (p < 0.05). Yield of gene panel testing was 71.88% LP/P overall, 56.25% in isolated BMVP, and 12.5% in MAD. Among the pathogenic variants found in MAD, 60% were aortopathy genes, 20% cardiomyopathy/channelopathy genes, and 20% in sudden unexpected death in epilepsy genes. The most common arrhythmia was ventricular tachycardia found in 52% of arrhythmia episodes, followed by supraventricular tachycardia (19%), and ventricular fibrillation (15%) which only was seen in MAD. The rate of arrhythmia in MAD was higher (55%) compared to 14% in patients with isolated BMVP (p < 0.001), and rates of breakthrough arrhythmia were similar between groups. Patients with MAD had a rate of 27.27% for pacemaker or ICD placement compared to 2.33% in patients with isolated BMVP (p < 0.05). Conclusions: BMVP is likely a common phenotype with a variety of genetic and phenotypic subtypes. Presence of MAD increases risk of arrhythmia and need for a pacemaker or ICD in patients with BMVP independent of the underlying cardiac condition.