Effect of physical exercise-based cardiac rehabilitation on frail patients with heart failure: focus on endothelial dysfunction

This narrative review examines the interplay between frailty, heart failure (HF), and endothelial dysfunction, with a specific focus on the role of exercise-based cardiac rehabilitation (CR) in older and frail adults. Frailty and HF frequently coexist and share pathophysiological mechanisms - including chronic inflammation, oxidative stress, and impaired nitric oxide (NO) signaling - that exacerbate endothelial dysfunction and contribute to reduced functional capacity and poor prognosis. We synthesize current evidence linking endothelial impairment to both frailty and HF progression, and we evaluate findings from clinical trials investigating exercise-centered CR, hybrid CR, and cardiac telerehabilitation in this population. Across studies, CR consistently improves physical performance, exercise tolerance, and quality of life, with several trials reporting measurable enhancements in endothelial function, such as improved flow-mediated dilation or increased mobilization of endothelial progenitor cells. Benefits appear strongest when programs are multidomain and individualized to the frailty phenotype, integrating aerobic, resistance, balance, and mobility training. However, heterogeneity in study designs, limited enrollment of frail older adults, and the frequent designation of endothelial outcomes as secondary endpoints constrain the ability to draw firm mechanistic conclusions. Overall, available evidence indicates that CR is a feasible and effective therapeutic strategy to counteract vascular dysfunction, reduce frailty severity, and potentially disrupt the negative cycle that accelerates HF progression in older patients. Future studies should prioritize frail populations, adopt standardized endothelial assessments as primary outcomes, and evaluate long-term clinical impact. Tailored CR models, including hybrid and telerehabilitation programs, are likely essential to improve access, adherence, and vascular outcomes in this vulnerable group.