Effects of a Supervised Training Program on Functional Capacity in Patients With HFpEF and Chronotropic Incompetence

NCT05649787 | Completed DMC

• 1 other identifier: Training-HR
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective study, blinded for the evaluator, randomized (1:1:1:1) to receive standard management alone or combined with a program of training (aerobic alone or combined with strength exercises) that will be carried out in a single centre. After randomization, patients will be clinically evaluated. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 12 weeks. Patients with heart failure with preserved ejection fraction, functional class NYHA II-III, and chronotropic incompetence criteria will be enrolled. A sample size estimation \[alfa: 0.05, power: 80%, a 15% loss rate, and at least a delta change of mean peakVO2: +2,4 mL/kg/min (SD±2)\] of 80 patients (20 per arm) would be necessary to test our hypothesis.

Conditions

Heart Failure With Preserved Ejection Fraction; Chronotropic Incompetence

Keywords

Heart Failure with Preserved Ejection Fraction; Chronotropic incompetence; Functional capacity

Outcome Measures

Primary Outcomes (1)

• Peak oxygen consumption

  Maximal functional capacity will be evaluated using incremental and symptom-limited cardiopulmonary exercise testing on a bicycle ergometer, beginning with a workload of 10 W and increasing gradually in a ramp protocol at 10-W increments every 1 minute. We define maximal functional capacity as when the patient stops pedalling because of symptoms and the respiratory exchange ratio (RER) was \>1. During exercise, patients will be monitored with 12-lead electrocardiogram and blood pressure measurements every 2 minutes. 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. Primary outcome: changes in peak oxygen consumption between and within groups at 12-week Unit of measure of peak oxygen consumption: mL/kg/min

  Peak oxygen consumption will be evaluated at first visit and after 3 months. We will evaluate peak oxygen consumption change from baseline.

Secondary Outcomes (2)

• Chronotropic response

  Chronotropic index will be evaluated at first visit and after 3 months. We will evaluate chronotropic index change from baseline.

• Kansas City Cardiomyopathy Questionnaire Scales

  The Kansas City Cardiomyopathy Questionnaire will be evaluated at first visit and after 3 months. We will evaluate the Kansas City Cardiomyopathy Questionnaire change from baseline.

Study Arms (4)

Usual care

NO INTERVENTION

Patients allocated to this arm will receive the usual care plus explicit recommendations for home-based aerobic and strength training.

Supervised aerobic training

ACTIVE COMPARATOR

Patients allocated to this arm will receive the usual care plus supervised aerobic training

Behavioral: Supervised aerobic training

Supervised aerobic plus low to moderate-intensity strenght training

ACTIVE COMPARATOR

Patients allocated to this arm will receive the usual care plus supervised aerobic and low to moderate-intensity strength training

Behavioral: Supervised aerobic training; Behavioral: Supervised aerobic plus low to moderate-intensity strength training

Supervised aerobic plus moderate to high-intensity strenght training

ACTIVE COMPARATOR

Patients allocated to this arm will receive the usual care plus supervised aerobic and moderate to high-intensity strength training.

Behavioral: Supervised aerobic training; Behavioral: Supervised aerobic plus moderate to high-intensity strength training

Interventions

Supervised aerobic training BEHAVIORAL

Supervised moderate to high-intensity interval aerobic training

Supervised aerobic plus low to moderate-intensity strenght training; Supervised aerobic plus moderate to high-intensity strenght training; Supervised aerobic training

Supervised aerobic plus low to moderate-intensity strength training BEHAVIORAL

Supervised moderate to high-intensity interval aerobic training plus low to moderate-intensity strength training

Supervised aerobic plus low to moderate-intensity strenght training

Supervised aerobic plus moderate to high-intensity strength training BEHAVIORAL

Supervised moderate to high-intensity interval aerobic training plus moderate to high-intensity strength training

Supervised aerobic plus moderate to high-intensity strenght training

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with heart failure with preserved ejection fraction according to 2021 ESC guidelines for Heart Failure.
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) \>125 pg/mL in the last month
• Stable symptomatic heart failure patients (New York Heart Association functional class II-III/IV) during the last month
• Age ≥ 60 years old.
• Blunted heart rate (HR) response during a maximal cardiopulmonary exercise testing (CPET), defined as a chronotropic index \<0.62 if previous treatment with Beta-blockers or chronotropic index \<0.80 in patients without beta-blockers. Chronotropic index= \[HRpeak exercise - HRrest\] / \[220 - age - HRrest\]

You may not qualify if:

• Inability to perform a valid baseline cardiopulmonary exercise test
• Cardiac pacemaker
• Significant primary moderate-to-severe valve disease
• Effort angina or signs of ischemia during CPET
• Primary cardiomyopathies
• Cardiac transplantation
• Any other comorbidity with a life expectancy of less than one year

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (1)

INCLIVA

Valencia, 46010, Spain

Location

Related Publications (2)

• Palau P, de Amo I, Nunez G, Flor C, de la Espriella R, Garcia-Conejo C, Berlanga-Tovar SE, Casana-Granell J, Calatayud J, Dominguez E, Sanchis-Gomar F, Meyer M, Sanchis J, Nunez J, Lopez L. Effect of exercise training in patients with chronotropic incompetence and heart failure with preserved ejection fraction: the TRAINING-HR randomized clinical trial. Eur J Prev Cardiol. 2026 Feb 3;33(2):265-275. doi: 10.1093/eurjpc/zwaf269. Erratum In: Eur J Prev Cardiol. 2025 Dec 30:zwaf781. doi: 10.1093/eurjpc/zwaf781.

  PMID: 40294211 DERIVED

• Palau P, Nunez J, Dominguez E, de la Espriella R, Nunez G, Flor C, de Amo I, Casana J, Calatayud J, Ortega L, Marin P, Sanchis J, Sanchis-Gomar F, Lopez L. Effect of exercise training in patients with chronotropic incompetence and heart failure with preserved ejection fraction: Training-HR study protocol. Curr Probl Cardiol. 2024 Dec;49(12):102839. doi: 10.1016/j.cpcardiol.2024.102839. Epub 2024 Sep 4.

  PMID: 39242065 DERIVED

Study Officials

• Patricia Palau, MD, PhD

  Instituto de Investigacion Sanitaria INCLIVA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Blinded only for the evaluator of primary and secondary endpoints
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective study, blinded for the evaluator, randomized (1:1:1:1) to receive standard management alone or combined with a program of training (aerobic alone or combined with strength exercises) that will be carried out in a single centre.

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 14, 2022
• Study Start: January 18, 2023
• Primary Completion: November 18, 2024
• Study Completion: December 31, 2024
• Last Updated: February 27, 2025

Record last verified: 2025-02

Locations

ES (1)