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

Overview

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.

Interventions

• Behavioral High-intensity interval training
  Subjects in the intervention group will receive a personalized high-intensity interval training (HIIT) protocol based on cardiopulmonary exercise testing (CPET) and will undergo a 24-week HIIT intervention, four times per week.The exercise protocol consisted of a 5-minute warm-up at 30-40 watts, followed by 8 cycles of high-intensity exercise performed at 80-90% of peak VO₂ for 30 seconds, each interspersed with a 60-second active recovery period of low-intensity exercise at 50-60% of peak VO₂ ,

Primary outcome measures

• Peak VO2 [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]

Secondary outcome measures (12)

• Blood specimen [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Blood specimen [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Blood specimen [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Blood specimen [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Blood specimen [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Kansas City Cardiomyopathy Questionnaire (KCCQ) [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• The New York Heart Association (NYHA) Functional Classification [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Montreal Cognitive Assessment (MoCA) [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Hospital Anxiety and Depression Scale (HADS) [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• International Physical Activity Questionnaire (IPAQ) [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]
• Peak O₂ pulse [Time frame: Baseline（week 0），Mid-term（week 12），End of study（week 24 ）]

Eligibility criteria

Inclusion criteria

• Men and women aged 35-70 years;
• Physical inactivity / sedentary lifestyle defined as:

Sedentary behavior: average daily sitting time > 6 hours over the past 6 months; AND/OR Insufficient physical activity: average weekly moderate-intensity physical activity < 150 minutes or vigorous-intensity physical activity < 75 minutes as assessed by the International Physical Activity Questionnaire (IPAQ);

• Patients with HFpEF at Stage 4 of CKM syndrome who have been clinically stable within the past month (New York Heart Association \[NYHA\] functional class II-III);
• Willingness to improve health status through appropriate exercise.

Exclusion criteria

• Presence of contraindications to cardiopulmonary exercise testing (CPET);
• Positive findings on the exercise electrocardiogram (ECG) during CPET;
• Diagnosis of psychiatric disorders;
• Presence of movement disorders or lower extremity exercise-related injuries within the past 6 months;
• Women who are pregnant, breastfeeding, or planning to become pregnant in the near future;
• Other conditions deemed unsuitable for participation in this study by the investigators;
• Refusal to sign the informed consent form.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 12 centers

• Beijing Chao-Yang Hospital, Capital Medical University — Beijing
• Beijing Hospital — Beijing
• Beijing Xiaotangshan Hospital — Beijing
• Beijing Zhongguancun Hospital — Beijing
• Community Health Station of the Party School of the Central Committee of C.P.C — Beijing
• Jimenli Community Health Service Center — Beijing
• Peking University First Hospital — Beijing
• Peking University People's Hospital — Beijing
• … and 4 more centers

Identifiers

NCT: NCT07693049 · CPHIT-2 · BRWEP2024W014090204 · 2025ZD0546100 · TY2025008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗