Metabolic manipulation in dilated cardiomyopathy: Assessing the role of trimetazidine.

Objective: To study the role of metabolic modulator (trimetazidine: TMZ) in dilated cardiomyopathy (DCM). Optimizing altered substrate metabolism in heart failure (HF) with metabolic modulators allows more efficacious energy production from glucose than from free fatty acids.

Methods: 100 patients of DCM (47.7 years, NYHA class 2.17, LVEF 27.3%) were randomized to TMZ (20mg tid, n=50) vs conventional therapy (n=50). Functional status, BNP and various echocardiographic parameters were assessed at 3-6 months.

Results: At 3 months, TMZ group had significantly improved NYHA class (2.25 vs 1.85), 6min walk test (349.7 vs 402m), LVD-36 score (25.5 vs 21) and BNP (744.7 vs 248.3pg/ml), all p 0.001. Significant improvement was also seen in LV end-systolic (LVESV, 87.1±27.5 vs 78.5±24.9ml/m2, p 0.001), LV end-diastolic volumes (LVEDV, 117.6±29.3 vs 110.9±27.4ml/m2, p 0.001), LVEF (27 vs 30.9%, p 0.001) and LV wall stress (90.2±18.9 vs 71.1±13.2dyn/cm2, p 0.0001). The % change in LVESV, LVEDV, LVEF and LV wall stress was -9.5%, -5.4%, +8.4% and -21.8%. Other echo parameters also improved after 3 months of TMZ (E/A ratio 1.9 vs 1.2, p=0.001, E/A VTI 2.7 vs 1.6, p=0.001, myocardial performance index, MPI 0.8 vs 0.7, p=0.0001), Tissue Doppler parameters (E/E' septal (19.7 vs 12.5, p=0.001) and E/E' lateral (13.3 vs 9.4, p=0.0001)). Patients in control group had no change in NYHA class, LVD-36 scores, LV volumes or LVEF at 3 months although BNP and LV wall stress reduced to a slight extent. Patients on TMZ had further improvement in NYHA class, walk test, BNP levels and echocardiographic parameters at 6 months.

Conclusions: Metabolic modulators (TMZ) may help in improving LV function in DCM. In this study, benefit was noted by 3 months with further improvement at 6 months.