Cardiopulmonary Exercise Testing-based High-intensity Interval Training For Improving Heart Failure With Preserved Ejection Fraction

Cardiovascular-Kidney-Metabolic (CKM) Syndrome is a continuous clinical disease spectrum integrating cardiovascular, renal, and metabolic disorders. Heart failure with preserved ejection fraction (HFpEF) is considered Stage 4 of CKM syndrome, characterized primarily by impairment of cardiac structure and function. Numerous studies have confirmed that exercise intervention is effective in improving metabolic profiles and inflammatory status in Stages 0-3 of CKM syndrome (e.g., obesity, metabolic syndrome, hypertension, and diabetes), and significantly improves clinical outcomes. However, for Stage 4 CKM syndrome, especially in patients with HFpEF, conventional exercise prescription faces significant challenges in balancing safety and efficacy. Moreover, traditional "one-size-fits-all" exercise rehabilitation strategies have failed to significantly improve clinical outcomes due to the lack of individualized precision approaches.

To address this gap, this study proposes to adopt a multicenter, randomized, controlled design, enrolling patients with HFpEF at Stage 4 of CKM syndrome and randomly assigning them to either a personalized high-intensity interval training (HIIT) intervention group or a standard care control group. The \*\*primary endpoint\*\* of this study is the change in peak oxygen consumption (peak VO₂) from baseline after 24 weeks of intervention. In addition, a series of \*\*secondary endpoints\*\* have been established for comprehensive evaluation, including inflammatory biomarkers, cardiac structure and function, quality of life, and composite clinical events. These endpoints aim to comprehensively assess the intervention effects from the perspectives of cardiopulmonary function, metabolism and inflammation, quality of life, and clinical outcomes, as well as to explore the underlying mechanisms.

This study is expected to validate the beneficial effects of personalized exercise on peak VO₂ and various secondary endpoints in patients with Stage 4 CKM syndrome. It will not only provide high-level evidence-based support for exercise therapy in HFpEF but also deepen the understanding of the role of exercise intervention in the full-course management of CKM syndrome, offering key scientific support for the development of precision prevention and treatment strategies across all stages.