Hybrid cardiac rehabilitation at anaerobic threshold reduces myocardial fibrosis and improves outcomes in HFrEF post-MI: a multicenter RCT

Methods In a multicenter randomized controlled trial, 116 patients with HFrEF post-MI were assigned 1:1 to either a control group (n=58) receiving guideline-directed medical therapy and lifestyle counseling, or an intervention group (n=58) receiving an additional 90-day hybrid CR program. The intervention consisted of individualized exercise training based on AT intensity (determined by cardiopulmonary exercise testing), combining supervised aerobic training and resistance exercises both in-hospital and at home. Assessments were performed at baseline, 45 days, 90 days, and 6 months, including:Echocardiography (LVEF),Cardiac magnetic resonance (CMR; extracellular volume fraction, ECV),Peak oxygen uptake (VO2peak),6-minute walk distance (6MWD),Handgrip strength,Depression (PHQ-9),Health-related quality of life (SF-12),And incidence of heart failure (HF) hospitalization. Results At 90 days, compared with controls, the intervention group showed:Significant improvement in LVEF (from 43.8±5.3% to 47.0±6.4%; ΔLVEF: +3.4±4.1% vs. −0.6±7.1% in controls; p<0.01),Reduction in myocardial fibrosis, with lower ECV in the interventricular septum (ΔECV: −2.8±6.0 vs. +1.6±4.8) and infarct zone (ΔECV: −5.6±5.2 vs. +1.2±8.5; p<0.05),Enhanced exercise capacity: VO2peak increased from 22.6±5.1 to 24.2±5.5 ml/kg/min (ΔVO2peak: +1.6±3.8 vs. −0.1±3.2 ml/kg/min; p<0.05), and 6MWD improved by 69.9±53.5 m vs. 18.4±56.1 m (p<0.01),Improved physical function: Increased handgrip strength (left +3.2±5.0 kg, right +3.5±6.3 kg vs. left +1.1±8.0 kg, right +0.5±4.4 kg in controls; p<0.05),Better mental health and quality of life: Greater reduction in depressive symptoms (ΔPHQ-9: −1.7±2.9 vs. −0.4±2.3) and larger improvement in SF-12 score (ΔSF-12: +12.5±22.8 vs. +5.5±18.5; p<0.05).At 6-month follow-up, no patients in the intervention group were hospitalized for HF, compared to 6 cases (10.3%) in the control group (p<0.05). No deaths occurred in either group. Conclusions In this multicenter RCT, a 90-day hybrid cardiac rehabilitation program delivered at anaerobic threshold intensity significantly improved cardiac function, reduced myocardial fibrosis, enhanced exercise capacity and mental wellbeing, and prevented heart failure readmissions in patients with HFrEF post-MI. These findings provide high-level evidence supporting the role of intensity-guided, remote-supported CR as a cornerstone of secondary prevention after MI.