An interventional study of Exercise-Based Cardiac Rehabilitation and Guideline-Directed Medical Therapy in HF - Heart Failure, HFpEF - Heart Failure With Preserved Ejection Fraction and Readmission Rates, sponsored by Fundación para la Investigación del Hospital Clínico de Valencia. Not yet recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-27.
Sponsored by Fundación para la Investigación del Hospital Clínico de Valencia · Not applicable, Interventional, and Treatment
Heart failure with preserved ejection fraction (HFpEF) is a common condition among older adults. It is associated with frequent hospitalizations, impaired functional capacity, reduced quality of life, and high healthcare utilization. Despite recent advances in pharmacological therapy, many patients continue to experience recurrent clinical deterioration and functional decline. Exercise-based cardiac rehabilitation has demonstrated benefits in improving physical performance and quality of life. Still, its effect on long-term clinical outcomes in patients with high-risk HFpEF has not been established.
The EMPOWER-HFpEF study is a multicenter, randomized, controlled trial designed to evaluate whether an early, individualized, multimodal exercise-based cardiac rehabilitation program improves clinical outcomes compared with usual care in patients with HFpEF. Eligible participants will be randomly assigned in a 1:1 ratio to receive either usual care alone or usual care plus a structured 12-month exercise-based cardiac rehabilitation program. The intervention includes an initial 6-month supervised phase, followed by a 6-month hybrid phase combining supervised sessions with structured home- or community-based exercise to promote long-term adherence and maintenance of physical activity.
The primary objective is to determine whether this rehabilitation strategy reduces adverse clinical outcomes, including all-cause mortality, heart failure hospitalizations, all-cause hospitalizations, and outpatient heart failure decompensation, while improving functional capacity and health-related quality of life over 12 months. The results of this study will provide evidence on the effectiveness of a long-term multimodal exercise-based cardiac rehabilitation program as part of the comprehensive management of patients with HFpEF.
Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all heart failure cases and is associated with a high burden of recurrent hospitalizations, impaired functional capacity, and reduced health-related quality of life. Despite advances in guideline-directed medical therapy, many patients continue to experience recurrent clinical events and progressive functional decline. Exercise-based cardiac rehabilitation has demonstrated consistent benefits on exercise capacity and quality of life in patients with heart failure; however, robust evidence regarding its impact on long-term clinical outcomes in patients with HFpEF remains limited, particularly in high-risk populations.
EMPOWER-HFpEF is a multicenter, prospective, randomized, controlled clinical trial designed to evaluate the effectiveness of an early, individualized, multimodal exercise-based cardiac rehabilitation program in patients with high-risk HFpEF. Eligible participants will be randomly assigned in a 1:1 ratio to receive either guideline-directed medical therapy alone or guideline-directed medical therapy plus a structured exercise-based cardiac rehabilitation program. The intervention will be delivered over 12 months and consists of an initial 6-month supervised phase, followed by a 6-month hybrid phase that combines supervised and home-based exercise, with the to promote long-term adherence and maintenance of physical activity.
Participants will be followed for 12 months. The study is designed to determine whether this rehabilitation strategy improves clinically relevant outcomes while preserving functional status and health-related quality of life. The results are expected to provide evidence to support the integration of long-term exercise-based cardiac rehabilitation into the routine management of patients with HFpEF.
Exclusion Criteria:
Participants receive guideline-directed medical therapy, regular follow-up in the heart failure clinic, lifestyle education, and individualized recommendations for home-based physical activity, in accordance with current clinical practice.
Other: Guideline-Directed Medical Therapy
Participants receive guideline-directed medical therapy plus a structured 12-month exercise-based cardiac rehabilitation program consisting of a 6-month supervised phase followed by a 6-month hybrid supervised and home-based phase.
Behavioral: Exercise-Based Cardiac Rehabilitation · Other: Guideline-Directed Medical Therapy
A structured, individualised, multimodal exercise-based cardiac rehabilitation program delivered over 12 months. The intervention includes aerobic exercise, resistance training, inspiratory muscle training, and lifestyle counselling. It consists of an initial 6-month supervised phase, followed by a 6-month hybrid phase that combines supervised and home-based exercise to promote long-term adherence and maintenance of physical activity.
Participants receive guideline-directed medical therapy according to current heart failure guidelines, regular follow-up in the heart failure clinic, lifestyle education, and individualized recommendations to maintain regular physical activity as part of routine clinical care.
Hierarchical composite clinical outcome (win ratio)
Comparison between treatment groups using a hierarchical composite endpoint analyzed according to the win ratio method. The hierarchical endpoint includes, in order of priority, all-cause mortality, heart failure hospitalization, all-cause hospitalization, outpatient heart failure decompensation without hospitalization, days alive and out of hospital, change in physical function assessed by the Short Physical Performance Battery (SPPB; total score range 0-12, with higher scores indicating better physical function), and change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS; score range 0-100, with higher scores indicating better health status).
Time frame: 12 months
All-Cause Mortality
Occurrence of death from any cause.
Time frame: 12 months
Heart Failure Hospitalization or Outpatient Heart Failure Decompensation
Occurrence of hospitalization for worsening heart failure or outpatient heart failure decompensation not requiring hospitalization.
Time frame: 12 months
All-Cause Hospitalization
Occurrence of hospitalization for any cause.
Time frame: 12 months
Health-Related Quality of Life
Change from baseline in health-related quality of life assessed using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS). Scores range from 0 to 100, with higher scores indicating better health status.
Time frame: Baseline and 12 months
Physical Function
Change from baseline in physical function assessed using the Short Physical Performance Battery (SPPB). The SPPB total score ranges from 0 to 12 points, with higher scores indicating better lower extremity physical performance and functional status.
Time frame: Baseline and 12 months
Peak Oxygen Uptake
Change from baseline in peak oxygen uptake (peak VO₂), measured by symptom-limited cardiopulmonary exercise testing and expressed as mL/kg/min, in a predefined subgroup of approximately 80 participants.
Time frame: Baseline and 12 months
Left Ventricular Diastolic Function
Change from baseline in left ventricular filling pressure, assessed by transthoracic echocardiography using the average E/e' ratio, calculated from septal and lateral mitral annular early diastolic velocities. Unit of Measure: Average E/e' ratio (unitless)
Time frame: Baseline and 12 months
Right Ventricular Systolic Function
Change from baseline in right ventricular systolic function, assessed by transthoracic echocardiography using tricuspid annular plane systolic excursion (TAPSE). Unit of Measure: millimetres (mm)
Time frame: Baseline and 12 months
Left Ventricular End-Diastolic Volume Index
Change from baseline in left ventricular end-diastolic volume index (LVEDVi) measured by transthoracic echocardiography using the biplane Simpson method and indexed to body surface area. Unit of Measure: millilitres per square meter (mL/m²)
Time frame: Baseline and 12 months
Estimated Pulmonary Artery Systolic Pressure
Change from baseline in estimated pulmonary artery systolic pressure (PASP) assessed by transthoracic echocardiography using the peak tricuspid regurgitation velocity and estimated right atrial pressure. Unit of Measure: millimetres of mercury (mmHg)
Time frame: Baseline and 12 months
Heart Failure Biomarker: N-terminal Pro-B-type Natriuretic Peptide
Change from baseline in circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. Unit of Measure: pg/mL
Time frame: Baseline and 12 months
Heart Failure Biomarker: Carbohydrate Antigen 125
Change from baseline in circulating carbohydrate antigen 125 (CA125) concentration. Unit of Measure: U/mL
Time frame: Baseline and 12 months
Plan to share: Yes — De-identified individual participant data relevant to the published study findings will be considered for sharing following an appropriate request, subject to applicable institutional policies and ethical and legal requirements.
Supporting information: Study protocol, Sap
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Fundación para la Investigación del Hospital Clínico de Valencia