LAUSR

BACKGROUND Cardiac fibrosis in mitral valve prolapse (MVP) is implicated in the development of sudden cardiac death (SCD), however, the pattern remains poorly characterized. OBJECTIVE This study aimed to systematically quantify left and right ventricular fibrosis in individuals with isolated MVP and SCD (iMVP-SCD), whereby other potential causes of death are excluded, compared to a control cohort. METHODS Individuals with iMVP-SCD were identified from the Victorian Institute of Forensic Medicine, Australia and matched for age, sex and body-mass index to control cases with non-cardiac death. Cardiac tissue sections were analyzed to determine collagen deposition in the left ventricular free wall (anterior, lateral and posterior portions), interventricular septum and right ventricle. Within the iMVP-SCD cases, the endocardial-epicardial distribution of fibrosis within the LV was specifically characterized. RESULTS There were 17 cases with iMVP-SCD matched 1:1 with 17 controls yielding 149 samples and 1,788 histological regions. The iMVP-SCD group had increased left ventricular (anterior, lateral and posterior; all p<0.001) and interventricular septum fibrosis (p<0.001), but similar amounts of right ventricular fibrosis (p=0.62) compared to controls. In iMVP-SCD, left ventricular fibrosis was significantly higher in the lateral and posterior wall compared to the anterior wall and interventricular septum (all p<0.001). Within the lateral and posterior wall, iMVP-SCD cases had a significant endocardial-to-epicardial gradient of cardiac fibrosis (p<0.01) similar to other known conditions which cause cardiac remodeling. CONCLUSION Our study indicates that non-uniform left ventricular remodeling with both localized and generalized left ventricular fibrosis is important in the pathogenesis of SCD in individuals with MVP.