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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.

SUBMITTER: Rajamannan NM

PROVIDER: S-EPMC4048944 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Rajamannan Nalini M NM

Expert review of cardiovascular therapy 20140301 3

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 surgic ...[more]

PMID: 24575776

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Project description:BackgroundTranscatheter mitral valve repair is beneficial in patients with mitral regurgitation (MR), left ventricular dysfunction, and persistent symptoms despite maximally tolerated medical therapy.ObjectivesThe aim of this study was to evaluate the safety and feasibility of transcatheter mitral cerclage ventriculoplasty in patients with MR and either heart failure with reduced ejection fraction or preserved ejection fraction and in subjects with prior edge-to-edge repair but persistent or recurrent symptomatic MR.MethodsThe National Heart, Lung, and Blood Institute Division of Intramural Research Transcatheter Mitral Cerclage Ventriculoplasty Early Feasibility Study (NCT03929913) was an investigator-initiated prospective multicenter study. The primary endpoint was technical success measured at exit from the catheterization laboratory. Follow-up included heart failure quality-of-life assessments and serial imaging with echocardiography and cardiac computed tomography.ResultsNineteen subjects consented and underwent cerclage, 63% with heart failure with reduced ejection fraction and 37% with heart failure with preserved ejection fraction, with ischemic cardiomyopathy in 26% and nonischemic cardiomyopathy in 74%. There were no procedural deaths, strokes, or transient ischemic attacks or other major cardiovascular adverse events. The primary endpoint was met in 17 subjects. Cerclage induced sustained reductions in mitral regurgitant volume (-41%) and effective orifice area (-33%) after a median of 337 days. Cerclage resulted in improvements in 6-minute walking distance (+78 m) and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (+22 points) at 30 days that were maintained after a median of 265 days. New complete heart block developed in 6 of 17 subjects. Three deaths occurred on postprocedural days 79, 159, and 756, unrelated to cerclage.ConclusionsTranscatheter mitral cerclage ventriculoplasty resulted in significant and sustained improvements in mitral regurgitation and in heart failure quality-of-life assessments.

Project description:BackgroundMitral annular disjunction (MAD) consists of an altered spatial relation between the left atrial wall, the attachment of the mitral leaflets, and the top of the left ventricular (LV) free wall, manifested as a wide separation between the atrial wall-mitral valve junction and the top of the LV free wall. Originally described in association with myxomatous mitral valve disease, this abnormality was recently revisited by a surgical group that pointed its relevance for mitral valve reparability. The aims of this study were to investigate the echocardiographic prevalence of mitral annular disjunction in patients with myxomatous mitral valve disease, and to characterize the clinical profile and echocardiographic features of these patients.MethodsWe evaluated 38 patients with myxomatous mitral valve disease (mean age 57 ± 15 years; 18 females) and used standard transthoracic echocardiography for measuring the MAD. Mitral annular function, assessed by end-diastolic and end-systolic annular diameters, was compared between patients with and without MAD. We compared the incidence of arrhythmias in a subset of 21 patients studied with 24-hour Holter monitoring.ResultsMAD was present in 21 (55%) patients (mean length: 7.4 ± 8.7 mm), and was more common in women (61% vs 38% in men; p = 0.047). MAD patients more frequently presented chest pain (43% vs 12% in the absence of MAD; p = 0.07). Mitral annular function was significantly impaired in patients with MAD in whom the mitral annular diameter was paradoxically larger in systole than in diastole: the diastolic-to-systolic mitral annular diameter difference was -4,6 ± 4,7 mm in these patients vs 3,4 ± 1,1 mm in those without MAD (p < 0.001). The severity of MAD significantly correlated with the occurrence of non-sustained ventricular tachycardia (NSVT) on Holter monitoring: MAD›8.5 mm was a strong predictor for (NSVT), (area under ROC curve = 0.74 (95% CI, 0.5-0.9); sensitivity 67%, specificity 83%). There were no differences between groups regarding functional class, severity of mitral regurgitation, LV volumes, and LV systolic function.ConclusionsMAD is a common finding in myxomatous mitral valve disease patients, easily recognizable by transthoracic echocardiography. It is more prevalent in women and often associated with chest pain. MAD significantly disturbs mitral annular function and when severe predicts the occurrence of NSVT.

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

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

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