Abstract

This study aims to define the clinical history and significance of mitral leaflet (ML) adaptation in ischemic mitral regurgitation (IMR). Mitral regurgitation (MR) (leaking of left heart valve) frequently complicates myocardial infarction (MI) (heart attack) and is associated with doubled mortality and morbidity. Unfortunately, its mechanism is incompletely understood and treatment options are often limited and ineffective. It has been widely accepted that IMR is purely "functional", because the ML appear grossly normal, but only tethered by left ventricular and annular dilatation, preventing adequate closure. Therefore, contemporary treatment of IMR focus mainly on annular and ventricular remodeling. However, the ML tissues are metabolically active capable of cell activation and matrix proteins production. Recent animal studies has suggested that the ML actively adapt to mechanical stretch by increasing its surface area and thickness, casting doubt on functional IMR being purely "functional". In clinical settings, our understanding of the natural history of ML adaptation is very limited. Its incidence, timing, clinical significance, and interactions with annulus and ventricular remodeling remain undefined. The clinical data has been lacking because imaging techniques were previously unable to assess leaflet surface area in vivo. Recent advance in real-time 3-dimensional echocardiography (RT3DE) has enabled us to assess mitral valve 3D geometry non-invasively, providing a new way to study ML adaptation in clinical settings. We hypothesize that ML adaptation does occur in IMR after MI, attempting to increase in size to compensate for the tethering caused by ventricular and annular dilatation. To test this hypothesis, we will prospectively study 2 groups of patients presenting with MI, one group complicated with IMR, one group without. We will follow them up with serial RT3DE from the acute phase of MI to the chronic phase for 1 year. The 3D geometry of ML, annulus and left ventricle will be analyzed using a novel software developed and validated collaboratively by the Chinese University of Hong Kong and the University of Hong Kong. We will (1) compare the prospective changes of ML geometry between the 2 groups, (2) define the long-term natural history of ML adaptation, (3) explore how it is related to pathogenesis of IMR, and (4) identify potential factor(s) that affect ML adaptation. We believe the results of this project will significantly increase our knowledge on mitral valve adaptation in IMR. Understanding and potentially influencing the adaptive mechanisms will contribute to new, much needed treatment for IMR, a common and often devastating disorder. Researcher ID (E-9217-2013) : http://www.researcherid.com/rid/E-9217-2013

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