Mitral regurgitation: impaired systolic function, eccentric hypertrophy, and increased severity are linked to lower phosphocreatine/ATP ratios in humans.

Abstract

A number of phosphorus (31P) magnetic resonance spectroscopy (MRS) studies link alterations of high-energy phosphate metabolism in valvular disease and cardiomyopathy to the clinical severity of heart failure. However, correlations between MRS and indexes of ventricular dysfunction are inconclusive to date. We examined whether changes in 31P MRS are associated with the impaired contractility, which predisposes to chronic congestive heart failure in patients with mitral regurgitation. Thirteen normal control subjects and 22 patients with echocardiographically characterized chronic mitral regurgitation were studied by 31P MRS. The apical phosphocreatine-to-ATP ratio (PCr/ATP) was lower in severe disease (P<.02) and those on therapy (n=13, 1.29+/-0.29, P<.01) in contrast to control subjects (n=13, 1.61+/-0.3). Compared to those with mild mitral regurgitation, patients with more severe incompetence had lower mean myocardial PCr/ATP ratios (mild, n=6, 1.73 [0.17], P<.05 and P<.01; moderate, n=5, 1.49 [0.18], P<.05; and severe, n=1, 1.29 [0.32], P<.01). PCr/ATP in those referred for mitral valve replacement was lower (n=8, 1.17+/-0.23) although not significantly decreased compared with the ratio among subjects on medical therapy alone (n=5, 1.48+/-0.29). PCr/ATP correlated with the end-systolic diameter (r2=.7, P<.001), end-diastolic diameter (r2=.32, P<.05), left ventricular wall thickness (r2=.38, P<.01), left atrial dimension (r2=.36, P<.05), and derived measurements such as the percent fractional shortening (2=.5, P<.01), and left ventricular mass/body surface area (r2=.5, P<.001) but not with wall stress. These results demonstrate that abnormalities of PCr/ATP in mitral regurgitation are related to disease severity as measured by dimensional indexes of left ventricular dilatation. They suggest that impaired high-energy phosphate metabolism is a marker of hypertrophy and heart failure.