Effects of a Multicomponent Training Program on Cardiac Function, Skeletal Muscle Metabolism, Functional Capacity, and Quality of Life in Patients With HFpEF: SENSORFIT-4HEART Study (SENSORFIT-4HEA)

SENSORFIT-4HEART: Smart Exercise preScriptiOn and Remote Monitoring FITness Platform for HEART Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with increasing incidence and poor prognosis, accounting for up to 50% of heart failure cases. It is strongly associated with aging, cardiovascular risk factors (hypertension, diabetes, obesity), and is more prevalent in women than men. Patients with HFpEF frequently present with dyspnea, debilitating fatigue, poor quality of life, frequent hospitalizations, and high mortality rates. This study aims to evaluate the effects of a structured exercise program on cardiac function, skeletal muscle metabolism, functional capacity, and quality of life in patients with HFpEF, and to explore whether these benefits are mediated by circulating exerkines.

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure With Preserved Ejection Fraction (HFPEF)
• Intervention / Treatment: Behavioral: Supervised training

Detailed Description

Standard pharmacological treatments have shown limited prognostic benefit, highlighting the need for non-pharmacological strategies. Exercise training may represent an effective therapeutic tool, with potential to improve cardiac remodeling, skeletal muscle bioenergetics, exercise tolerance, and quality of life. Importantly, exerkines-molecules secreted by skeletal muscle and other organs in response to exercise-may mediate systemic beneficial effects by modulating metabolic, immuno-inflammatory, and growth pathways.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Navarre
    • Pamplona, Navarre, Spain, 31010
      • Universidad Pública de Navarra (UPNA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients diagnosed with heart failure with preserved ejection fraction according to 2021 ESC guidelines for Heart Failure.
• Left ventricular ejection fraction (LVEF) >40%, and/or evidence of structural and/or functional cardiac abnormality (diastolic dysfunction, elevated filling pressures, BMI>30 kg/m2)
• Elevated natriuretic peptides (BNP ≥35 pg/mL or NT-proBNP ≥125 pg/mL)
• Stable symptomatic heart failure patients (New York Heart Association functional class II-III/IV) during the last month

Exclusion Criteria:

• Participation in cardiac rehabilitation within the past 12 months.
• Contraindications to physical exercise training.
• Alternative diagnoses that could explain symptoms of HF (dyspnea, fatigue), in the judgment of the cardiologist.
• Significant pulmonary disease, including primary pulmonary hypertension.
• Severe chronic lung disease, including COPD requiring home oxygen, chronic nebulizer therapy, long-term oral steroids, or hospitalization for decompensated pulmonary disease within the past 12 months.
• Hemoglobin <10 g/dL.
• Body mass index (BMI) >40 kg/m².
• Inability to perform a valid baseline cardiopulmonary exercise test
• Inability to comprehend study information or complete questionnaires (e.g., psychiatric disorder, dementia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supervised exercise program; Participants assigned to this arm will receive supervised multicomponent exercise program delivered twice per week, combining resistance training (RT) with aerobic training within the same session. The RT session duration will increase progressively from 10 to 20 min at 40-70 % of one repetition maximum (1-RM) twice weekly. RT include progressively three series × 10-15 repetitions of leg press, knee extensors, chest press, and horizontal rowing.	Behavioral: Supervised training; Supervised training
No Intervention: Usual care; Patients allocated to this arm will receive the usual care plus explicit recommendations for home-based aerobic and strength training (Vivifrail program).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen consumption	Changes in peak oxygen consumption between and within groups at 12-week Unit of measure of peak oxygen consumption: mL/kg/min. Maximal functional capacity will be evaluated using incremental and symptom-limited cardiopulmonary exercise testing on a bicycle ergometer, beginning with a workload of 25 W and increasing gradually in a ramp protocol at 25-W increments every 3 minute. We define maximal functional capacity as when the patient stops pedalling because of symptoms and the respiratory exchange ratio (RER) was >1. Gas exchange data and cardiopulmonary variables were averages of values taken every 10 seconds. Peak oxygen consumption (PeakVO2) was defined as the highest value of VO2 during the last 20 seconds of exercise.	Baseline and 12-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lean mass (kg)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Changes in blood pressure	Systolic and diastolic blood pressure of participants in fasting condition will be analyzed by electronic tensiometer and reported in mmHg.	Baseline and 12-week
Changes in Heart rate	Heart rate of participants in fasting condition will be analyzed by electronic tensiometer and reported in pulses/min.	Baseline and 12-week
Changes in muscle strength	Grip strength of participants will be measured using a manual dynamometer and reported in kg. Pectoral press, bilateral leg-press, knee extension, and back press) will be measured using a eGYM machines and reported in kg	Baseline and 12-week
Changes in quality of life	We will use the EuroQol five-dimension five-level questionnaire (EQ-5D-5L) to assess health-related quality of life. The EQ-5D-5L includes five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on a 5-point scale ranging from 1 (no problems) to 5 (extreme problems). The responses are combined into an index value ranging from -0.594 to 1, where higher scores indicate a better health-related quality of life.	Baseline and 12-week
Physical activity and sedentary behaviour (in minutes)	Physical activity level objectively measured using Actigraph Accelerometry. This will be worn on the waist and will passively record physical activity and sedentary behavior.	Baseline and 12-week
Pittsburgh Sleep Quality Index	A 19-item self-report questionnaire that assesses subjective sleep quality and disturbances over the past month will be evaluated by Pittsburgh Sleep Quality Index. The global score ranges from 0 to 21, with higher scores indicating poorer sleep quality.	Baseline and 12-week
Epidemiological Studies-Depression Scale questionnaire	Depression levels will be assessed using the Center for Epidemiological Studies-Depression Scale (CES-D) questionnaire, which is validated and widely employed in cardiometabolic patients. The CES-D consists of 20 items, each rated on a 4-point Likert scale ranging from 0 (rarely or none of the time) to 3 (most or all of the time), assessing the frequency of depressive symptoms during the past week. The total score ranges from 0 to 60, with higher scores indicating greater depressive symptomatology.	Baseline and 12-week
Cognitive Function	Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), a validated screening tool that evaluates multiple cognitive domains, including executive function, memory, attention, language, and visuospatial abilities. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance.	Baseline and 12-week
Adherence to the Mediterranean Diet	Adherence to the Mediterranean dietary pattern will be assessed using the Mediterranean Diet Adherence Screener (MEDAS), a validated 14-item questionnaire designed to evaluate compliance with key components of the Mediterranean diet. Each item is scored 0 or 1, depending on whether the dietary criterion is met, yielding a total score ranging from 0 to 14, where higher scores indicate greater adherence to the Mediterranean diet.	Baseline and 12-week
Psychological Distress	The Kessler Psychological Distress Scale (K10) will be used to assess nonspecific psychological distress, including symptoms of anxiety and depression, experienced over the past four weeks. The K10 consists of 10 items, each rated on a 5-point Likert scale ranging from 1 (none of the time) to 5 (all of the time), resulting in a total score between 10 and 50. Higher scores indicate greater psychological distress.	Baseline and 12-week
Haematology	Erythrocyte count (×10⁶ cells/µL), haematocrit (%), haemoglobin (g/dL), platelet count (×10³ cells/µL), leukocyte count (×10³ cells/µL), and erythrocyte mean corpuscular volume (fL) will be quantified using a Coulter haematology analyzer (Brand, City, Country).	Baseline and 12-week
Concentrations of circulating cytokines, adipokines, myokines, and bone metabolism biomarkers.	Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IFN-γ, TNF-α, IL-1ra, and TNF sRII-α), adipokines (adiponectin, adipsin, resistin, PAI-1 active, insulin, and leptin), and myokines (irisin) will be quantified using Luminex xMAP technology. In addition, biomarkers related to bone metabolism (ACTH, DKK-1, FGF-23, osteocalcin, osteopontin [OPN], osteoprotegerin, PTH, and sclerostin [SOST]) will be measured with the same platform. Each analyte will be reported separately as an independent outcome, with concentrations expressed in pg/mL or ng/mL, as appropriate for the specific biomarker.	Baseline and 12-week
Resting energy expenditure	Resting energy expenditure is measured in the fasting and fed state by indirect calorimetry	Baseline and 12-week
N-terminal pro-B-type natriuretic peptide (NT-proBNP)	N-terminal pro-B-type natriuretic peptide (NT-proBNP) will be quantified by standardized immunoassay (e.g., electrochemiluminescence immunoassay, ECLIA) following manufacturer's instructions	Baseline and 12-week
Lean mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Appendicular lean mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Fat mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Fat mass (kg)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Visceral adipose tissue (kg)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Lean mass/fat mass ratio	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Fat free mass	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week
Whole bone mineral density (g/cm2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	Baseline and 12-week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipidomic	Lipidomic will be expressed and analyzed in plasma and serum according to their intensity measured in arbitrary units (UA), which carries a direct relation with its concentration in blood. Performed in a randomly selected sub-sample of approximately 30% of study participants	Baseline and 12-week
Mitochondrial leak respiration	Mitochondrial O2 flux is measured by high-resolution respirometry in muscle mass tissue. Performed in a randomly selected sub-sample of approximately 30% of study participants	Baseline and 12-week
Proteome profile	Assessment of changes in proteins profile following intervention in blood. Performed in a randomly selected sub-sample of approximately 30% of study participants. Each outcome will be reported separately, with concentrations expressed in pg/mL or ng/mL, as appropriate for the specific analyte.	Baseline and 12-week

Collaborators and Investigators

• Sponsor: Universidad Pública de Navarra
• Collaborators: Complejo Hospitalario de Navarra; NavarraBiomed Biomedical Research Center; Centro de Investigación Médica Aplicada (CIMA); Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Actual): February 1, 2025
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: September 23, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Quality of life; Cardiac function; Exerkines; PeakVO2; Skeletal muscle bioenergetics
• Additional Relevant MeSH Terms: Behavior; Motor Activity
• Other Study ID Numbers: PI_2023/146 (Other Identifier: Fundación Miguel Servet)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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