eHealth Lifestyle Intervention To Enhance Outcomes in HFpEF (ELITE-HFpEF)

Randomized Trial Of A Digital Lifestyle Education Strategy In Patients With Heart Failure And Overweight Or Obesity: The ELITE-HFpEF Study

The goal of this clinical trial is to learn if a digital lifestyle education program improves exercise capacity in adults who have heart failure with preserved ejection fraction (HFpEF) and overweight or obesity. HFpEF is a type of heart failure in which the heart muscle is stiff and does not relax well, even though its pumping strength looks normal. The main questions it aims to answer are:

• Does the program improve how much oxygen participants can use during exercise, a measure of fitness, after 6 months?
• Does the program improve participants' quality of life and help them lose weight?

Researchers will compare a group that uses the digital program plus usual care to a group that receives usual care alone. This will show whether the program adds a benefit.

Participants will:

• Be placed by chance into one of the two groups
• Use a study website with short videos on exercise, healthy eating, and managing stress (program group), with new content every week for 6 months
• Have exercise tests, an ultrasound scan of the heart, blood tests, and complete a quality-of-life questionnaire at the start and after 6 months

Both groups will keep taking their usual heart failure medicines.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Obesity & Overweight; Heart Failure and Preserved Ejection Fraction
• Intervention / Treatment: Behavioral: Digital lifestyle education program; Other: Usual Care

Detailed Description

Background and rationale. Obesity is a central driver of heart failure with preserved ejection fraction (HFpEF), not merely a comorbidity. Visceral adipose tissue behaves as an active endocrine organ, releasing proinflammatory cytokines (TNF-alpha, IL-1, IL-6) that promote systemic inflammation, endothelial dysfunction, and adverse cardiac remodeling, contributing to ventricular stiffness and diastolic dysfunction. Pharmacological options with proven benefit in this phenotype, such as GLP-1 receptor agonists and dual GLP-1/GIP analogs, are not currently reimbursed by the Spanish National Health System, which limits their use. Structured lifestyle programs improve exercise capacity in HFpEF but are resource intensive and difficult to scale. A web-based digital intervention may offer a sustainable and accessible alternative to support exercise capacity, weight management, and quality of life in patients with HFpEF and overweight or obesity.

Study design. This is a single-center, randomized, open-label, parallel-group trial with 1:1 allocation and a 6-month follow-up, conducted at Hospital Universitario Reina Sofía (Córdoba, Spain). Eligible participants are recruited from outpatient cardiology clinics. Because the intervention is behavioral and delivered through a web platform, blinding of participants and treating clinicians is not feasible; however, core outcome measures are objective (cardiopulmonary exercise testing) or analyzed by assessors unaware of group assignment where feasible.

Randomization and allocation concealment. The allocation sequence is generated by computer using simple randomization and prepared centrally by an independent investigator. Assignments are concealed in sequentially numbered, opaque, sealed envelopes opened consecutively only after eligibility is confirmed, which keeps recruiting staff unaware of the upcoming assignment and minimizes selection bias.

Intervention delivery. Participants allocated to the intervention group receive access to a study-specific web platform with structured healthy-lifestyle content delivered as short educational videos (5 to 10 minutes) grouped into thematic modules. Modules unlock progressively every week across the 6-month follow-up and cover three domains: adapted physical exercise (guided routines of progressive intensity focused on aerobic activity and functional muscle strengthening), healthy eating (Mediterranean diet principles, menu planning, and portion control), and psychoemotional support (motivation techniques, stress management, and adherence to habit change). The control group receives the usual recommendations provided during routine consultation. Both groups receive guideline-directed therapy for HFpEF, including SGLT2 inhibitors and GLP-1 receptor agonists as indicated.

Procedures and biospecimens. Most assessments (venous blood sampling, echocardiography, and cardiopulmonary exercise testing) are part of routine clinical care for patients with heart failure and are performed at baseline and at 6 months. For inflammatory profiling, additional samples are collected and stored at -80 degrees Celsius for later batched analysis, including high-sensitivity CRP, IL-6, and a 92-biomarker inflammation panel (Olink Target 96 Inflammation). Body composition is assessed by bioelectrical impedance analysis.

Statistical analysis. The trial is analyzed under a treatment-policy estimand, estimating the effect of the assigned intervention regardless of adherence, partial exposure, or intercurrent events such as medication changes or loss to follow-up. The sample size is based on a previous exercise-training trial in HFpEF (Ex-DHF pilot): assuming a between-group difference in the change in peak oxygen uptake of 3 mL/kg/min (standard deviation 3 mL/kg/min), 90% power, and a two-sided alpha of 0.05, 46 participants (23 per arm) are required; 52 will be enrolled to allow for about 10% loss to follow-up. Continuous variables are summarized as mean with standard deviation or median with interquartile range according to distribution and compared with the Student t test or the Wilcoxon test. Categorical variables are summarized as counts and percentages and compared with the chi-square or Fisher exact test. The primary analysis uses analysis of covariance (ANCOVA) for the change in peak oxygen uptake at 6 months, adjusted for the baseline value; continuous secondary endpoints are analyzed analogously. Time-to-event clinical endpoints are analyzed with Cox proportional-hazards models, reporting adjusted hazard ratios with 95% confidence intervals. Analyses are performed in R, with two-sided statistical significance set at p < 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rafael Gonzalez-Manzanares, MD, PhD; Phone Number: +34 957 010 438; Email: rafael.gonzalez@imibic.org
• Study Contact Backup: Name: José Carlos Garrido Gracia; Phone Number: +34 677 906 567; Email: josecarlos.garrido@imibic.org

Study Locations

• Spain
  • Córdoba
    • Córdoba, Córdoba, Spain, 14004
      • IMIBIC
      • Contact: José C Garrido Gracia; Phone Number: +34 677 906 567; Email: josecarlos.garrido@imibic.org
      • Principal Investigator: Manuel Cabello Terrón, MD
      • Principal Investigator: José López Aguilera, MD PhD
      • Principal Investigator: Rafael González Manzanares MD PhD
      • Sub-Investigator: Ángela Heredia Torres, MD
      • Sub-Investigator: Ana Fernández Ruiz, MD PhD
      • Sub-Investigator: Juan C Castillo Domínguez, MD PhD
      • Sub-Investigator: Soledad Ojeda Pineda, MD PhD
      • Sub-Investigator: Dolores Mesa, MD PhD
      • Sub-Investigator: Rafaela Luque López, RN
      • Sub-Investigator: Juan M García Medina, RN

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age over 18 years
• Body mass index (BMI) over 27 kg/m²
• Symptoms consistent with heart failure
• Left ventricular ejection fraction (LVEF) of 50% or higher
• Elevated NT-proBNP according to the European Society of Cardiology age-adjusted rule-in thresholds: 125 pg/mL or higher if under 50 years, 250 pg/mL or higher if 50 to 75 years, and 500 pg/mL or higher if 75 years or older
• Echocardiographic abnormalities: left ventricular hypertrophy, left atrial enlargement, or diastolic dysfunction

Exclusion Criteria:

• Body mass index (BMI) over 40 kg/m²
• Life expectancy of less than 1 year
• Chronic kidney disease on renal replacement therapy
• Moderate or greater valvular heart disease
• Inability to exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Digital lifestyle intervention; Access to the study web platform with weekly lifestyle education modules, plus guideline-directed HFpEF therapy.	Behavioral: Digital lifestyle education program; Access to a study-specific web platform delivering structured healthy-lifestyle content as short videos (5 to 10 minutes) in thematic modules that unlock weekly over 6 months, covering adapted physical exercise, Mediterranean-diet-based healthy eating, and psychoemotional support.
Active Comparator: Usual care; Standard lifestyle recommendations given during routine consultation, plus guideline-directed HFpEF therapy.	Other: Usual Care; Standard lifestyle recommendations provided during routine cardiology consultation, without access to the study web platform. Both groups continue guideline-directed medical therapy for HFpEF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak oxygen uptake (VO2max)	Change from baseline in peak oxygen uptake (VO2max, mL/kg/min) measured by cardiopulmonary exercise testing (cardiopulmonary exercise testing, CPET). Higher values indicate greater functional capacity.	Baseline and 6 months
Change in peak oxygen uptake (VO2max)	Change from baseline in peak oxygen uptake (VO2max, mL/kg/min) measured by cardiopulmonary exercise testing (cardiopulmonary exercise testing, CPET). Higher values indicate greater functional capacity. The between-group difference in change is analyzed by ANCOVA adjusted for the baseline value.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score	Change from baseline in the KCCQ overall summary score, a patient-reported measure of heart failure-related health status. Scores range from 0 to 100; higher scores indicate better health status and quality of life.	Baseline and 6 months
Percent change in body weight	Percent change from baseline in body weight (kilograms) at 6 months.	Baseline and 6 months
Worsening heart failure	Number of participants with a worsening heart failure event, defined as hospitalization for decompensated heart failure or an outpatient or day-hospital visit requiring intravenous diuretic therapy.	6 months
All-cause mortality	Number of participants who die from any cause during follow-up.	6 months
Change in fat mass	Change from baseline in fat mass (kilograms) measured by bioelectrical impedance analysis. Unit of Measure: kilograms	Baseline and 6 months
Change in high-sensitivity C-reactive protein (hs-CRP)	Change from baseline in circulating C-reactive protein (hs-CRP). Unit: mg/L	Baseline and 6 months
Change in interleukin-6 (IL-6)	Change from baseline in circulating C-reactive protein interleukin-6 (IL-6). Unit: pg/mL	Baseline and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VE/VCO2 slope	Change from baseline in the minute ventilation to carbon dioxide production (VE/VCO2) slope on cardiopulmonary exercise testing. Unit of Measure: ratio.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Collaborators: Sociedad Andaluza de Cardiología
• Investigators: Principal Investigator: Manuel Cabello Terrón, MD, H. Universitario Reina Sofía de Córdoba; Principal Investigator: José López Aguilera, MD PhD, H. Universitario Reina Sofía de Córdoba / IMIBIC; Principal Investigator: Rafael Gonzalez-Manzanares, MD PhD, H. Universitario Reina Sofía de Córdoba / IMIBIC / CIBERCV / CNIC

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: quality of life; obesity; overweight; telemedicine; mHealth; eHealth; digital health; lifestyle intervention; Mediterranean diet; cardiac rehabilitation; cardiopulmonary exercise testing; HFpEF; web-based intervention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Nutrition Disorders; Heart Diseases; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Heart Failure; Overweight; Obesity; Heart Failure, Diastolic
• Other Study ID Numbers: ELITE-HFpEF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A decision on sharing individual participant data has not yet been made. Any data sharing will comply with EU Regulation 2016/679 (GDPR) and Spanish Organic Law 3/2018, the terms of the participant informed consent, and approval by the reference Research Ethics Committee. If a sharing plan is established, this record will be updated.

Drug and device information, study documents

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