Exercise-Based Cardiac Rehabilitation for Patients With Heart Failure With Preserved Ejection Fraction (EMPOWER-HFpEF) (EMPOWER-HFpEF)

Effects of a Supervised Exercise Training Program on Clinical Outcomes, Functional Capacity, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction (EMPOWER-HFpEF)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Exercise Training; HFpEF - Heart Failure With Preserved Ejection Fraction; HF - Heart Failure; Readmission Rates; Cardiac Rehab
• Intervention / Treatment: Other: Guideline-Directed Medical Therapy; Behavioral: Exercise-Based Cardiac Rehabilitation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patricia Fernández Saiz, PhD; Phone Number: 96 162 89 18; Email: patricia.fernandez@incliva.es

Study Locations

• Spain
  • Valencia, Spain, 46010
    • INCLIVA
    • Contact: Patricia Fernández, PhD; Phone Number: 96 162 89 18; Email: patricia.fernandez@incliva.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older.
• Diagnosis of heart failure with preserved ejection fraction (HFpEF) according to current clinical guidelines, defined by: a) signs and/or symptoms of heart failure; b) left ventricular ejection fraction ≥50%; c) elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) (≥220 pg/mL); and, d) objective evidence of structural and/or functional cardiac abnormalities consistent with HFpEF.
• High-risk clinical profile, defined by at least one of the following: a) hospitalization for acute or worsening heart failure within the previous 120 days; b) outpatient worsening heart failure within the previous 120 days requiring emergency department evaluation or intensification of oral or intravenous diuretic therapy in a specialized heart failure clinic; c) recent diagnosis of symptomatic HFpEF (≤120 days) with New York Heart Association (NYHA) functional class II-III; or d) stable symptomatic HFpEF (NYHA class II-III) with at least two of the following comorbidities: hypertension, diabetes mellitus, obesity (body mass index ≥30 kg/m²), chronic kidney disease, dyslipidemia, obstructive sleep apnea, or stable coronary artery disease, together with elevated NT-proBNP (≥220 pg/mL in patients in sinus rhythm or ≥600 pg/mL in patients with atrial fibrillation).
• Clinically stable at the time of enrollment, with no requirement for intravenous therapy or major changes in heart failure treatment during the previous 2 weeks.
• Considered by the investigator to be able to participate in a structured exercise-based cardiac rehabilitation program safely.
• Able and willing to provide written informed consent before any study-specific procedures.

Exclusion Criteria:

• Inability to safely participate in a structured exercise-based cardiac rehabilitation program because of severe neurological or musculoskeletal disorders, significant cognitive impairment, or severe psychiatric illness that, in the opinion of the investigator, would interfere with study participation.
• Clinically unstable heart failure at the time of enrollment, defined by the need for intravenous therapy, recent major changes in heart failure treatment, or ongoing heart failure decompensation.
• Severe valvular heart disease considered to be the primary cause of the patient's symptoms.
• Acute coronary syndrome, unstable angina, or coronary revascularization within the previous 2 weeks.
• Uncontrolled hypertension, defined as resting systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg, or resting heart rate ≥110 beats/min despite guideline-directed medical therapy.
• Severe primary pulmonary disease predominantly limiting functional capacity, including significant pulmonary hypertension, chronic thromboembolic pulmonary disease, or severe chronic obstructive pulmonary disease.
• Primary cardiomyopathy or known infiltrative heart disease.
• Severe non-cardiac comorbidity associated with an estimated life expectancy of less than 1 year, in the opinion of the investigator.
• Inability to provide written informed consent or to comply with study procedures and follow-up requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Guideline-Directed Medical Therapy; 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 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.
Experimental: Exercise-Based Cardiac Rehabilitation; 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.	Other: Guideline-Directed Medical Therapy; 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.; Behavioral: Exercise-Based Cardiac Rehabilitation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Mortality	Occurrence of death from any cause.	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.	12 months
All-Cause Hospitalization	Occurrence of hospitalization for any cause.	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.	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.	Baseline and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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)	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)	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)	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	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	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
• Collaborators: Generalitat Valenciana

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: July 17, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Quality of Life; Cardiac Rehabilitation; Heart Failure with Preserved Ejection Fraction; Readmission
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: EMPOWER-HFpEF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: De-identified individual participant data and supporting documents will be considered for sharing following publication of the primary study results, for a period to be determined in accordance with institutional policies and applicable regulations.
• IPD Sharing Access Criteria: Access to de-identified individual participant data and supporting documentation will be considered upon reasonable request. Requests will be reviewed on a case-by-case basis by the study investigators in accordance with institutional policies, ethical requirements, and applicable legal and regulatory frameworks. Access may require a data sharing agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No