The Association Between Mitral Valve Prolapse With Ventricular Arrhythmias and Sudden Cardiac Death

Abstract

The mitral valve is one of four heart valves, and is situated between the left atrium and left ventricle. Its role is to facilitate the unidirectional flow of blood through the left atrium and ventricle by opening in diastole and closing in systole. Mitral valve prolapse (MVP) involves the atrial displacement of the mitral valve during ventricular systole. While MVP has been linked to the development of sudden cardiac death (SCD) through the development of malignant ventricular arrhythmias (VAs), this association remains controversial. This thesis examines the relationship between MVP, VAs and SCD.

Chapter 1 reviews the published literature surrounding MVP, VAs and SCD. A historical context and contemporary link between MVP and SCD are discussed. Various histopathological, cardiac imaging and electrophysiological findings in MVP and VAs or SCD are explored. The current pathophysiological understanding of SCD in MVP is highlighted, and provides a premise for subsequent chapters.

Chapter 2 systematically reviews all cases of MVP and SCD reported in the literature. The cases in the literature describe a predominantly young, female population with frequent premature ventricular complexes (PVCs) and prolapse involving both mitral valve leaflets. Cardiac arrest usually occurs as a result of ventricular fibrillation. Leaflet redundancy (defined as thickness greater than or equal to 5mm) is the only independent predictor of SCD.

Chapter 3 describes histopathological findings and cardiac arrest rhythm in individuals with isolated MVP (iMVP, whereby other potential causes of death are excluded) and SCD. Individuals with iMVP-SCD have increased cardiac mass, mitral annulus size and left ventricular fibrosis compared to a control group matched for age, sex, height and weight. In those with iMVP and witnessed cardiac arrest, ventricular fibrillation is the predominant cardiac arrest rhythm. These findings suggest that histopathological changes in MVP may provide the substrate necessary for the development of VAs leading to SCD.

Chapter 4 comprehensively and systematically quantifies left and right ventricular fibrosis in individuals with iMVP-SCD compared to a matched control group. Individuals with iMVP-SCD have more left ventricular and interventricular septum fibrosis but similar degree of right ventricular fibrosis compared to the control group. In those with iMVP-SCD, there is more fibrosis in the lateral and posterior walls of the left ventricle with an endocardial-epicardial gradient of fibrosis, which is similar to other conditions that cause cardiac remodelling. These findings indicate that non-uniform left ventricular remodelling with both localised and generalised fibrotic changes are important in the pathogenesis of SCD in MVP.

Chapter 5 compares the incidence of VAs detected with continuous cardiac rhythm monitoring in patients with MVP and controls, and examines whether certain factors predicted for the development of VAs within the MVP group. Over a 24-month follow-up period, those with MVP had a significantly higher overall incidence of VAs compared to control groups. Within the MVP group, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging was predictive for the development of VAs.

Chapter 6 evaluates the role of mitral regurgitation and mitral valve surgery with regards to VAs in patients with redundant leaflet MVP. In patients with redundant leaflet MVP, severity of mitral regurgitation does not affect PVC burden while mitral valve surgery does not reduce PVC burden in unselected patients with MVP. Based on the significant change in PVC burden in two patients, the role of mitral valve surgery in selected patients with MVP warrants further investigation.