Cardiac energetics in severe mitral regurgitation: relationship with eccentric hypertrophy, stroke volume, and effects of valve repair

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.

Nineteen severe-MR patients underwent cardiac magnetic resonance and ³¹P-spectroscopy for energetics, including phosphocreatine to adenosine triphosphate ratio (PCr/ATP), the pseudo-first-order forward rate constant of the creatine kinase reaction (k_f) and CK flux (k_f × [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 is related to the 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 k_f (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). Seven patients during MVR and six 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 k_f, 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.