Systematic quantification of histologic ventricular fibrosis in isolated mitral valve prolapse and sudden cardiac death.

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: The purpose of this study was 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 noncardiac 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-to-epicardial distribution of fibrosis within the left ventricle was specifically characterized. RESULTS: Seventeen cases with iMVP-SCD were matched 1:1 with 17 controls, yielding 149 samples and 1788 histologic regions. The iMVP-SCD group had increased left ventricular (anterior, lateral, and posterior; all P <.001) and interventricular septum fibrosis (P <.001), but similar amounts of right ventricular fibrosis (P = .62) compared to controls. In iMVP-SCD, left ventricular fibrosis was significantly higher in the lateral and posterior walls compared to the anterior wall and interventricular septum (all P <.001). Within the lateral and posterior walls, iMVP-SCD cases had a significant endocardial-to-epicardial gradient of cardiac fibrosis (P <.01) similar to other known conditions that cause cardiac remodeling. CONCLUSION: Our study indicates that nonuniform left ventricular remodeling with both localized and generalized left ventricular fibrosis is important in the pathogenesis of SCD in individuals with MVP.

Characteristic Histopathological Findings and Cardiac Arrest Rhythm in Isolated Mitral Valve Prolapse and Sudden Cardiac Death.

Background The association between mitral valve prolapse (MVP) and sudden death remains controversial. We aimed to describe histopathological changes in individuals with autopsy-determined isolated MVP (iMVP) and sudden death and document cardiac arrest rhythm. Methods and Results The Australian National Coronial Information System database was used to identify cases of iMVP between 2000 and 2018. Histopathological changes in iMVP and sudden death were compared with 2 control cohorts matched for age, sex, height, and weight (1 group with noncardiac death and 1 group with cardiac death). Data linkage with ambulance services provided cardiac arrest rhythm for iMVP cases. From 77 221 cardiovascular deaths in the National Coronial Information System database, there were 376 cases with MVP. Individual case review yielded 71 cases of iMVP. Mean age was 49±18 years, and 51% were women. Individuals with iMVP had higher cardiac mass (447 g versus 355 g; P<0.001) compared with noncardiac death, but similar cardiac mass (447 g versus 438 g; P=0.64) compared with cardiac death. Individuals with iMVP had larger mitral valve annulus compared with noncardiac death (121 versus 108 mm; P<0.001) and cardiac death (121 versus 110 mm; P=0.002), and more left ventricular fibrosis (79% versus 38%; P<0.001) compared with noncardiac death controls. In those with iMVP and witnessed cardiac arrest, 94% had ventricular fibrillation. Conclusions Individuals with iMVP and sudden death have increased cardiac mass, mitral annulus size, and left ventricular fibrosis compared with a matched cohort, with cardiac arrest caused by ventricular fibrillation. The histopathological changes in iMVP may provide the substrate necessary for development of malignant ventricular arrhythmias.