Bahira Shahim

Mitral valve prolapse (MVP) is a heart valve disorder affecting 1 in 40 people in which the mitral valve protrudes into the atrium during cardiac contractions. Although overall benign, MVP is associated with mitral regurgitation, heart failure, and arrhythmias, accounting for 8% of sudden cardiac deaths in people &lt

40y. Recent work proposed that abnormal valve displacement during systole (mitral annulus disjunction, MAD) and cardiac fibrosis are key arrhythmic mechanisms. However, fundamental questions remain unexplored, including the co-evolution of MVP, MAD and fibrosis over time, the impact of mitral interventions on fibrosis and arrhythmia risk, and the optimal timing and type of interventions in the presence of MAD. We will address these issues by studying (aim 1) 50 MVP patients undergoing mitral valve surgery using repeated cardiac magnetic resonance imaging (CMR) and long-term implantable ECG, (aim 2) the impact of MAD on prognosis in 2000 surgical patients, (aim 3) the evolution of MAD, MVP and fibrosis over 20 years using unique CMR follow-up data in 136 Marfan patients with naturally high MVP and MAD prevalence (≈45%), and by studying (aim 4) extracted mitral valves in MVP patients with or without MAD using single cell RNA sequencing to examine whether acquired genetic abnormalities leading to tissue mosaicism underly disease progression. The results will shed new light on the mechanisms underlying adverse outcomes in MVP with important clinical implications.