Lysyl Oxidase-like 2-Guided Benefits of Early Cardiac Rehabilitation in Acute Heart Failure: A Prospective Cohort Study in Taiwan

<b>Background/Objectives:</b> The objectives of this study were to determine whether the early initiation of cardiac rehabilitation (CR) within 6 weeks of discharge improves long-term outcomes in patients hospitalized for acute heart failure (HF) and to evaluate whether baseline lysyl oxidase-like 2 (LOXL2) levels affect the response to CR. <b>Methods:</b> We prospectively enrolled patients with acute HF who completed a structured Heart Failure Disease Management Program between January 2019 and July 2022. Participants were categorized into an early-CR group (initiating supervised CR within 6 weeks post-discharge and continuing a home-based program) or a non-CR group. The primary outcome was all-cause mortality. The secondary outcomes included HF rehospitalization and changes in scores on the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at 6 and 12 months. A post hoc analysis was conducted to stratify patients by baseline LOXL2 levels in order to assess differential CR effects in relation to the severity of cardiac fibrosis. <b>Results:</b> Out of 162 patients, 34 participated in early CR. After 1:1 propensity score matching, each group contained 33 patients. Over a median follow-up of 2.85 years, the early-CR group experienced lower all-cause mortality (0 vs. 87.2 events per 1000 patient-years; rate difference: -0.087). A subgroup analysis revealed the greatest benefit among patients with LOXL2 levels > 200 pg/mL (0 vs. 172.3 events per 1000 patient-years; rate difference: -0.172). <b>Conclusions:</b> Early post-discharge CR was associated with improved survival in patients with acute HF. The survival benefit was more pronounced in patients with an elevated level of LOXL2, suggesting its potential role as a biomarker for fibrosis-guided CR strategies. Health systems seeking scalability may consider embedding exercise-based and biomarker-guided CR programs within clinical networks early on to improve access while advancing patient-centered care. Further randomized trials are warranted to confirm these findings.