Inheritance of Imaging Parameters of Arrhythmic Risk in Mitral Valve Prolapse: A Pedigree Study

BACKGROUND: A subset of patients with mitral valve prolapse (MVP), a highly heritable condition, experience sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, the inheritance of phenotypic imaging features of arrhythmic MVP remains unknown. METHODS: We recruited 23 MVP probands, including 9 with SCA/SCD and 14 with frequent/complex ventricular ectopy. Participants underwent interviews, 2-dimensional and speckle-tracking echocardiography, and 48-hour Holter/event monitoring. Each individual was categorized as having a normal mitral valve, MVP, or borderline MVP. We assessed mitral annular disjunction, curling, global longitudinal strain, segmental peak longitudinal strain, electrical/mechanical dispersion, and the postsystolic shortening index in family members and unrelated healthy controls. RESULTS: We enrolled 23 pedigrees (14 extended pedigrees, 4 trios, and 5 duos) with a total of 121 participants (mean age 45 years, 50% women). Multigenerational SCA/SCD occurred in 2 of 14 extended pedigrees (14%) with an SCA/SCD proband. Mitral annular disjunction was present in 2 generations among 3 families (13%) and absent in 3 of 9 (33%) SCA/SCD cases. Compared with nonarrhythmic cases, arrhythmic MVP cases had more bileaflet involvement, mitral annular disjunction, curling, and abnormal valvular-myocardial mechanics, as expressed by a higher mid-inferior/inferolateral postsystolic shortening index ( P <0.05). Among arrhythmic MVP cases, those with SCA had the highest mechanical dispersion ( P =0.04). Family members with normal valves had lower global longitudinal strain and greater mechanical dispersion compared with nonpedigree controls (both P <0.05). CONCLUSIONS: In the context of familial MVP, SCA/SCD is rarely observed in multiple generations and is not consistently linked to mitral annular disjunction. Instead, SCA may result from combination of abnormal valvular-myocardial mechanics and a substrate of increased mechanical/electrical dispersion. Family members with normal mitral valves also exhibit mildly abnormal global strain parameters, suggesting an underlying myopathy independent of MVP expression. Future studies are needed to determine whether SCA/SCD in MVP requires the concomitant presence of abnormal mechanics and a primary genetic myopathy.