Strategies for exercise rehabilitation and potential mechanisms to ameliorate exercise intolerance in stable heart failure: Cardiopulmonary and skeletal muscle function

Heart failure (HF) is a systemic disorder characterized by exercise intolerance, a core prognostic marker that arises from coordinated dysfunction of the cardiac, pulmonary and skeletal muscle systems.This review illustrates the vicious cycle of the cardiopulmonary-skeletal muscle axis: the impaired cardiac reserve acts as the initiating factor to induce pulmonary congestion and muscle hypoperfusion. Deteriorated pulmonary function serves as an amplifier to aggravate cardiac load and peripheral oxygen delivery defects. Pathological skeletal muscle remodeling, as a feedback regulator, disrupts cardiopulmonary homeostasis via unbalanced myokine secretion, mitochondrial damage and impaired oxygen extraction. Exercise rehabilitation (ER), a Class I A intervention for stable HF, interrupts this cycle through multi-organ adaptive remodeling. (1) Cardiac adaptations include promoting physiological myocardial remodeling, reducing interstitial fibrosis, and enhancing angiogenesis. (2) Pulmonary adaptations cover optimizing diaphragmatic structure, alleviating inflammation, and improving pulmonary hemodynamics. (3) Skeletal muscle adaptations involve regulating muscle protein metabolism, enhancing mitochondrial oxidative capacity, and optimizing endothelial function. The ER also modulates myokines (myostatin, irisin etc.) to mediate inter-organ crosstalk and synergistic protection. Clinically, combined aerobic, resistance training and inspiratory muscle training optimally improves exercise tolerance in New York Heart Association Functional Classification I-III (NYHA I-III) patients. For NYHA IV patients unable to perform active training, enhanced external counterpulsation offers a passive hemodynamic alternative. This review establishes the cardiopulmonary-skeletal muscle axis and highlights its clinical value: synchronous assessment and multi-organ intervention break single-organ limitation, better alleviating exercise intolerance. It provides mechanistic evidence and stratified exercise strategies to support standardized ER implementation in HF.