Myxomatous mitral valve disease bench to bedside: LDL-density-pressure regulates Lrp5

Abstract

The myxomatous mitral valve is the most common form of valvular heart disease. The pathologic presentation of myxomatous mitral valve disease varies between valve thickness, degree of leaflet prolapse and the presence or absence of flail leaflets. Recent molecular biology studies have confirmed that the myxomatous changes in mitral valve prolapse equals a cartilage phenotype, which is regulated by the Lrp5 receptor. Clinically, echocardiography defines the valve pathology to determine the surgical approach to valve repair or replacement. Furthermore, the timing of surgical valve repair is controversial and is the subject of a current multicenter trial. The results will resolve the timing of whether watchful waiting versus early surgical valve repair decreases morbidity and mortality of this disease process. This review will summarize the current understanding of the cellular and hemodynamic mechanisms of myxomatous mitral valve disease, which may have future implications in the targeted therapy of this disease process.

Keywords::

• LDL-density-pressure theory
• Lrp5 receptor
• mitral valve prolapse
• mitral valve regurgitation
• myxomatous mitral valve
• surgery
• valvular heart disease

Financial & competing interests disclosure

NM Rajamannan is the inventor on a patent for methods to slow progression of valvular heart disease. This patent is owned by the Mayo Clinic and the author does not receive any royalties from this patent. This work is supported by NIH grant funding: 5R01HL085591 and 3R01HL085591S1. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The European Society of Cardiology and American College of Cardiology/American Heart Association valvular guidelines suggest two different timing to surgical valve repair, based on the presence and absence of symptoms. However, the long-term safety, morbidity and mortality data still remain to be firmly established, in part due to the need for more stringent risk stratification using valve pathology, hemodynamics and clinical symptoms.

• A well-designed, adequately powered clinical surgical trial is ongoing to address these shortcomings and provide a more definitive assessment of the indications of timing to surgical valve repair.

• Experimental studies indicate the potential for traditional cardiovascular risk factors in the development of myxomatous mitral valve disease; future epidemiologic studies testing this hypothesis are necessary to further define this hypothesis and the potential for targeting this disease with cholesterol-lowering medications and antihypertensive therapy.

Notes