Ce-452775-1 predictors for sudden cardiac death and sustained ventricular arrhythmias among high-risk patients with arrhythmogenic mitral valve prolapse syndrome

Although mitral valve prolapse (MVP) is a benign entity overall, there is a small subset of patients with MVP, particularly bileaflet MVP, who may experience life-threatening ventricular arrhythmias (VAs) secondary to arrhythmogenic MVP syndrome. Studies characterizing this group have been limited by small sample sizes and single center design. To assemble a worldwide case series examining the clinical phenotype of arrhythmogenic MVP syndrome including clinical, imaging, and treatment characteristics and predictors of sudden cardiac death (SCD). We retrospectively identified subjects with MVP and VAs across 17 international centers. We stratified our subjects into two groups: 1) MVP-SCD group with sudden cardiac death, sustained ventricular tachycardia (VT), or ventricular fibrillation (VF); and 2) the MVP-PVC group with significant (symptomatic, >5% burden, bigeminy, pleomorphic, requiring therapy) premature ventricular complexes (PVCs) only. Deidentified data was abstracted locally and combined into a central registry for analysis. A total of 217 subjects with arrhythmogenic MVP syndrome were included; 148 (68%) had history of SCD or VT/VF (MVP-SCD group) and 69 (32%) had history of significant PVCs (MVP-PVC group). Phenotypically, subjects in both groups were similar (average age of 44 years, 66% female, 72% with bileaflet MVP, 58% with mitral annular disjunction, 56% with inferolateral T-wave inversions, and 44% with delayed enhancement on cardiac magnetic resonance imaging). Syncope was more common in MVP-SCD subjects than in MVP-PVC subjects (47% vs. 22%, p=0.001) as were anterolateral T-wave inversions (22% vs 7%, p=0.011). Subjects in the MVP-SCD group were less likely to have been prescribed beta blockers (35.7% vs 51.5%, p=0.029) and were significantly less likely to have prior mitral valve surgery (5.5% vs 19.7%, p=0.002). When completed, an electrophysiology (EP) study was positive in 42/72 (58%). However, 15/45 (33.3%) of the MVP-SCD subjects had a negative EP study. In this large worldwide case series, subjects with arrhythmogenic MVP syndrome were young, female, and had bileaflet MVP with mitral annular disjunction. A history of syncope and anterolateral T-wave inversions were associated with SCD and sustained VT/VF. Prior beta blocker prescription and prior mitral valve surgery were less common in SCD and VT/VF patients than in PVC patients. A negative electrophysiology study had limited negative predictive value in high-risk patients.