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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— Training-HR  

Official title:

Effects of a Supervised Training Program on Functional Capacity in Patients With Heart Failure and Preserved Ejection Function and Chronotropic Incompetence

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05649787
• Other study ID #: 2022/103
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: December 2023
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: Marta Peiró, PhD
• Phone: +0034 961973536
• Email: mpeiro[@]incliva.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent clinical entity that predominantly affects women >60 years old, whose incidence has increased in the last decade and has a complex and multifactorial pathophysiology. Chronotropic incompetence (CrI) has emerged as a crucial mechanism, particularly in patients older than 60 years, and is associated with more significant functional impairment. Supervised training programs in patients with heart failure and reduced ejection fraction and CrI have improved functional capacity and chronotropic response. However, we do not have evidence about the effects of a supervised training program on patients with HFpEF and CrI. This work aims to evaluate the effect of a supervised exercise program for 12 weeks in patients with HFpEF and CrI on peak oxygen consumption (peakVO2) and chronotropic response. 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 HFpEF, functional class NYHA II-III, and CrI 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• 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]

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronotropic Incompetence
• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

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

Locations

Country	Name	City	State
Spain	INCLIVA	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Chronotropic response	Heart rate (HR) response during the maximal cardiopulmonary exercise testing will be evaluated following the chronotropic index (CIx) formula. The chronotropic index is evaluated by the following formula, including heart rate at peak effort, heart rate at rest and age. Chronotropic index: (peak heart rate-rest heart rate)/ [220-age-rest heart rate)].; Secondary outcome: changes in chronotropic response in between and within groups at 12-week Heart rate unit: beats per minute Age unit: years The chronotropic index has no units of measure.	Chronotropic index will be evaluated at first visit and after 3 months. We will evaluate chronotropic index change from baseline.
Secondary	Kansas City Cardiomyopathy Questionnaire Scales	The Kansas City Cardiomyopathy Questionnaire includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life, and self-efficacy (the patient's understanding of how to manage their heart failure). All Kansas City Cardiomyopathy Questionnaire domains are scaled from 0 to 100, where scores represent health status as follows: 0 to 24, very poor to poor; 25 to 49, poor to fair; 50 to 74, fair to good; and 75 to 100, good to excellent.; A change of 5 points is considered to be a small but clinically important change, whereas changes of 10 and 20 points are considered moderate-to-large and large-to-very-large clinical changes.	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.