Mitral valve disease—morphology and mechanisms

Abstract

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but—even in adult life—remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular–ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease.

Comparison of Deep Sedation With General Anesthesia in Patients Undergoing Percutaneous Mitral Valve Repair

“…Mitral valve regurgitation (MR) is one of the most common valvular diseases worldwide and leads to heart failure and other potentially severe complications 1. Since there is still a high rate of patients with an indication for mitral valve repair, who cannot receive surgical repair because of an increased perioperative risk,2 percutaneous edge‐to‐edge mitral valve reconstruction (PMVR) using the MitraClip system (Abbott Vascular) has become a safe and viable alternative to treat severe mitral regurgitation in these patients 3.…”

Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: a 4.8-year prospective cohort study

“…Recently, it is emerging that degenerative MVDs are the result of modified adult valve biology [4,5]. Particularly, Levine and colleagues have recently underlined that MVDs are the result of a 'living valve', which with advancing age shows active changes mediated both by valvular endothelial and interstitial cells and alterations in composition and turnover of elements of extracellular matrix [6]. Accordingly, in surgically excised human myxomatous tissues, an overexpression of transforming growth factor-β cytokine (TGF-β) pathway, an increased release of metalloproteinases (MMPs), and down-expression of related inhibitors (TIMPs), responsible for degeneration of collagen and elastin structures, have been observed [7][8][9][10][11][12][13][14][15].…”

The mechanisms, diagnosis and management of mitral regurgitation in mitral valve prolapse and hypertrophic cardiomyopathy

“…In hypertrophic cardiomyopathy (HCM), the leaflet elongation exceeds the needs of the reduced volume of the LV, further aggravating the left ventricular outflow tract (LVOT) obstruction and can predispose to systolic anterior motion (SAM) of the MV. 5,7 In MVP, the leaflets are long and exhibit structural fibroelastic abnormalities. 5,8 The surgical treatment has an important role in the natural history of the disease and it has been proven to be the only treatment that may efficiently prevent heart failure, improving symptoms and reducing mortality by 70%.…”

“…It has recently been demonstrated that it can react to the morphological changes that involve the LV and that it may also alter its structure irrespective of the state of the nearby structures. 5,6 However, concurrent with ventricular remodeling, mitral leaflets can become inadequately small (as seen in dilated cardiomyopathies) or suffer a process of elongation. In hypertrophic cardiomyopathy (HCM), the leaflet elongation exceeds the needs of the reduced volume of the LV, further aggravating the left ventricular outflow tract (LVOT) obstruction and can predispose to systolic anterior motion (SAM) of the MV.…”

“…1 MR may also arise due to a congenital or an acquired pathological state. 5 Until now, the mitral valve (MV) was considered a passive structure. It has recently been demonstrated that it can react to the morphological changes that involve the LV and that it may also alter its structure irrespective of the state of the nearby structures.…”