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.
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.
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.
Parallel
Exercise-Based Cardiac Rehabilitation
BehavioralA 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 Therapy
Other interventionParticipants 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).
All-Cause Mortality
Occurrence of death from any cause.
Heart Failure Hospitalization or Outpatient Heart Failure Decompensation
Occurrence of hospitalization for worsening heart failure or outpatient heart failure decompensation not requiring hospitalization.
All-Cause Hospitalization
Occurrence of hospitalization for any cause.
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.
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.
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)
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)
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)
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Fundación para la Investigación del Hospital Clínico de Valencia
Lead sponsor
Generalitat Valenciana
Collaborator
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