Cardiac Energetics in Severe Mitral Regurgitation; Relationship with Eccentric Hypertrophy, Stroke Volume and Effects of Valve Repair

Abstract

Understanding changes in ATP metabolism may lead to improved risk stratification in severe primary mitral regurgitation (MR). Here we seek to compare the energetic phenotype of volume-overload pathological hypertrophy with athletic hypertrophy and with the normal heart under catecholamine stress. 19 severe-MR patients underwent cardiac magnetic resonance and 31P-spectroscopy for energetics including PCr/ATP, the pseudo-first-order forward rate constant of the creatine kinase reaction (kf) and CK flux (kf×[PCr]). When compared with 20 healthy controls, severe-MR was associated with lower PCr/ATP (1.58±0.32 vs 2.08±0.28, p<0.001). This related to severity of regurgitation (r-0.59, p<0.001) but not to LVEF (r-0.20, p=0.23) or LV systolic strain (p=0.18). When compared to 17 athletes with similarly increased end-diastolic volume (athletes 107±10 ml/m2 vs 114±22, p=0.29), severe-MR had greater total cardiac output (by 42%, p<0.001), and lower PCr/ATP (by 28%, p<0.001) and CK flux (by 41%, p=0.04). When compared to normal hearts during dobutamine stress at matched cardiac output levels, median kf (by 45%, p=0.08) and CK flux (by 53%, p=0.02) were lower in severe-MR. PCr/ATP increased (by 17%, p=0.04) following mitral valve repair (MVR) in a subset of patients (n=14, median 7 months). 7 patients during MVR and 6 patients without volume loading donated LV biopsy, revealing that creatine was not lower in severe-MR. Even with normal LVEF, severe-MR is associated with reduced PCr/ATP, CK kf and CK flux. PCr/ATP reduction resolved with MVR. Thus, targeting CK capacity and/or flux may be a therapeutic strategy to prevent/treat systolic failure in MR. Graphical Abstract