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

N/ANot Yet RecruitingNCT07727096

Fundación para la Investigación del Hospital Clínico de Valencia390 enrolled

Overview

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.

Interventions

Exercise-Based Cardiac RehabilitationBEHAVIORAL

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.

Guideline-Directed Medical TherapyOTHER

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts