This study aims to investigate the efficacy and safety of exercise rehabilitation in patients with cardiorenal syndrome (CRS).

Building on previous research demonstrating that exercise rehabilitation can effectively improve cardiac function and cardiopulmonary endurance in patients with chronic heart failure, this study will further explore its role in the context of CRS, a condition where such effects remain understudied. CRS patients typically exhibit reduced cardiopulmonary endurance, with significantly lower peak oxygen uptake (VO₂ peak) and 6-minute walk test (6MWT) distance compared to non-CRS patients.

Adults aged 18-75 with chronic heart failure with reduced ejection fraction (HFrEF) complicated by chronic renal insufficiency will be enrolled and randomly assigned to two groups: 1. Basic treatment group: 30 patients receive only basic drug treatment for 6 months. 2. Exercise rehabilitation group: 30 patients receive basic drug treatment combined with home-based exercise rehabilitation for 6 months (with personalized exercise prescriptions formulated based on cardiopulmonary exercise test results or 6MWT for those unable to complete the former). The study will explore the efficacy and safety of exercise rehabilitation in the prevention and management of CRS by comparing changes in target biomarkers, renal function indicators, cardiac function indicators, cardiopulmonary exercise test results, Minnesota Living with Heart Failure Questionnaire scores, and the incidence of adverse events before and after treatment between the two groups.

The participants will:

Complete cardiopulmonary exercise tests or 6MWT before treatment initiation. Receive basic drug treatment; those in the exercise rehabilitation group will additionally perform home-based exercise rehabilitation according to the exercise prescription.

Attend regular follow-up visits within 6 months. Undergo assessments of related indicators (biomarkers, renal function, cardiac function, etc.) before and after treatment.

This study is designed to evaluate the efficacy and safety of home-based exercise rehabilitation as an adjuvant intervention for patients with Cardiorenal Syndrome (CRS) complicated by Chronic Heart Failure with Reduced Ejection Fraction (HFrEF). Building on prior evidence that exercise rehabilitation improves cardiac function and cardiopulmonary endurance in patients with uncomplicated chronic heart failure, this study addresses a critical gap: the lack of data on how such interventions perform in CRS, a condition characterized by bidirectional cardiorenal impairment that often exacerbates both cardiac and renal dysfunction.

CRS patients with HFrEF typically exhibit reduced cardiopulmonary reserve, as evidenced by lower peak oxygen uptake (VO₂ peak) and 6-minute walk test (6MWT) distance compared to non-CRS patients. This impairment is driven by intertwined pathophysiological mechanisms, including neurohormonal activation, systemic inflammation, and reduced renal clearance of cardiotoxic metabolites-factors that may be modulated by structured exercise. The home-based exercise approach is selected for its clinical relevance: it aligns with long-term patient adherence (avoiding barriers to clinic-based training, such as transportation or scheduling) and allows for personalized intensity adjustments, a key safety consideration in patients with dual organ dysfunction.

Exercise prescriptions for the intervention group are tailored using a two-step assessment protocol to ensure safety and individualization:

1. Cardiopulmonary Exercise Test (CPET): For patients able to complete CPET (per exercise risk assessment), the anaerobic threshold (AT) is identified via gas exchange analysis (using a metabolic cart). Exercise intensity is set at 60-70% of the heart rate corresponding to AT (HR-AT)-a range validated to improve cardiopulmonary endurance without inducing excessive cardiac or renal stress in HFrEF patients.
2. 6MWT Alternative: For patients unable to complete CPET (e.g., due to severe dyspnea or fatigue), exercise intensity is derived from 6MWT results. The target walking speed is set at 70-80% of the average speed achieved during the 6MWT, with duration adjusted to match energy expenditure levels equivalent to the CPET-derived protocol.

The 6-month exercise program focuses on aerobic training (e.g., brisk walking, stationary cycling) with progressive adjustments: initial sessions are 20-30 minutes, 3 times weekly, with 5-10 minute increments in duration (up to 45 minutes) and 5-10% increments in intensity every 2 weeks, based on patient-reported tolerance (assessed via the Borg Rating of Perceived Exertion scale, 0-10) and monthly follow-up monitoring.

To mitigate intervention-related risks, all participants undergo monthly remote or in-clinic follow-up:

• Vital Sign Checks: Resting heart rate, blood pressure, and body weight (to monitor fluid retention, a marker of renal or cardiac decompensation) are recorded at each visit.
• Adverse Event Tracking: Any cardiac (e.g., angina, arrhythmia), renal (e.g., acute kidney injury), or musculoskeletal events are documented using standardized clinical definitions, with protocol adjustments (e.g., temporary exercise pause, intensity reduction) implemented as needed.

This design ensures that the intervention is both mechanistically targeted to CRS pathophysiology and practically feasible for long-term patient engagement, while prioritizing safety in a vulnerable patient population.

Inclusion Criteria:

• Patients with chronically stable HFrEF complicated by kidney dysfunction (eGFR < 90 mL/min/1.73m²)
• NYHA class II-III
• Low risk in exercise risk assessment
• Aged 18-75 years

Exclusion Criteria:

• Uncontrolled hypertension
• Severe arrhythmias (including frequent ventricular premature contractions, ventricular tachycardia, rapid atrial fibrillation, sick sinus syndrome, and second-degree or higher atrioventricular block)
• Obstructive hypertrophic cardiomyopathy
• Moderate to severe stenotic valvular heart disease
• Deep vein thrombosis or pulmonary embolism
• History of syncope
• Severe anemia
• Abnormal thyroid function
• Severe pulmonary diseases
• Mental illnesses
• Osteoarticular or muscular diseases that impede rehabilitation training