Early Cardiac Rehabilitation After Acute Heart Failure Hospitalization and Its Long-Term Benefits in the Presence of Cardiac Fibrosis: A Prospective Cohort Study

Aim To evaluate whether initiation of cardiac rehabilitation (CR) within 6 weeks improves long-term outcomes of patients with acute heart failure (HF). Methods Patients with acute HF who participated in an HF disease management program from January 2019 to July 2022 were prospectively enrolled. Eligible patients were divided into two groups: early CR (and continued home-based CR during the follow-up period) and non-CR. The primary outcome was all-cause mortality. Secondary outcomes were rehospitalisation for recurrent HF and changes in 12-item Kansas City Cardiomyopathy Questionnaire scores from baseline to 6 months and 1 year. A post-hoc analysis stratified by lysyl oxidase-like 2 (LOXL2) levels assessed CR benefits for patients with cardiac fibrosis. Results Of 162 patients, 34 received early CR. The non-CR group was older (median age: 58.5 vs. 53.0 years, p=0.022) and had higher N-terminal pro-B-type natriuretic peptide levels (4552.5 vs. 1275.0 pg/mL, p=0.002). Propensity score matching yielded 33 patients per group. Over 2.85 years, the early CR group had lower all-cause mortality (0 vs. 87.16 events per 1000 patient-years, rate difference: −0.087 [95% confidence interval {CI}: −0.143 to −0.031], p=0.002). Patients with LOXL2 >200 pg/mL benefited the most (0 vs. 172.3 events per 1000 patient-years, rate difference: −0.172 [95% CI: −0.299 to −0.046], p=0.008). Conclusion Early post-discharge exercise-based CR was associated with reduced all-cause mortality in patients with acute HF. Patients with more severe cardiac fibrosis, indicated by higher LOXL2 levels, derived greater benefits from the CR program. Large-scale trials are needed to validate these findings. Trial registration The study protocol was registered at ClinicalTrials.gov (identifier: NCT03782337 ). Lay summary Early exercise after discharge for patients with acute heart failure is feasible, and early cardiac rehabilitation with nearly 3 years of follow-up is associated with a reduction in all-cause mortality without significant risks. Furthermore, for patients with severe cardiac fibrosis, cardiac rehabilitation can result in an even greater reduction in all-cause mortality. Based on our findings, cardiac rehabilitation and exercise recommendations should be initiated early after discharge in patients with acute heart failure, particularly those with cardiac fibrosis.