eHealth Lifestyle Intervention To Enhance Outcomes in HFpEF

Overview

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.

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.