Exercise Training Following Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

NCT02413151 | Completed Results DMC

• 1 other identifier: PTDC/DES/120249/2010
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiac resynchronization therapy(CRT) is recommended to reduce mortality and morbidity in chronic heart failure(CHF) patients New York Heart Association(NYHA) class III-IV who are symptomatic despite optimal medical therapy, with a reduced left ventricular(LV) ejection fraction(LVEF) and prolonged complex QRS. CRT improves the prognosis however, despite the improvement, all major trials have demonstrated that one third of the patients are non-responders to CRT. Three months after the CRT implant, the responders have a significant increase in endothelial function(EntF), a decrease in the LV end-systolic volume, and increase in LVEF, 6 minute walk test(6MWT), improvements in NYHA class and quality of life. It is currently unknown if adding an exercise training(ExT) program following CRT provides better clinical outcomes than CRT alone. Prior studies on CRT and ExT have been preliminary in nature, but suggest small improvements in functional capacity(FC). The correction of endothelial dysfunction is associated with a significant improvement in exercise capacity evidenced by a 26%increase in peak oxygen uptake. These findings are important because CHF patients with the greatest sympathetic activation and the most reduced EntF have the poorest prognosis. Our experience with coronary artery disease patients, and most recently data in patients with CHF show that an ExT program that combines aerobic exercise(AE) and resistance exercise training are more effective than an AE program alone, and the aerobic interval training showed better improvements than continuous endurance training. It is unknown how CHF with more severe functional limitations responds to ExT and, more important, the explanation of the physiological mechanism that can explain the improvements as a consequence of ExT. This lack of scientific information is urgent since this is the group of patients that normally is targeted for CRT. The investigators propose to use a stratified randomized longitudinal study to determine the additional effects of a 6 month ExT in addition to CRT in NYHA stage III-IV HF patients. The aims of the study are:1-to determine whether a long-term ExT program follow the CRT provides better clinical outcomes than CRT alone and 2-To identify the mechanisms of the hypothesize improvement. The results of this project will represent an important contribution by understanding the role of ExT after CRT NYHA stage III-IV heart failure(HF) patients, an understudied population with poor clinical outcome. Understanding the potential mechanisms associated with clinical improvement and outcome is essential for the rehabilitative process to develop new innovative therapies in this high risk population. The investigators will use state-of-art methods including an integrated assessment autonomic nervous system(ANS) and arterial function using 123I-MIBG scintigraphy.

Conditions

Cardiac Resynchronization Therapy; Chronic Heart Failure

Keywords

Exercise training; Cardiac resynchronization therapy; Autonomic nervous system modulation; Chronic Heart failure

Outcome Measures

Primary Outcomes (3)

• Changes in a Composite Measure of Clinical Status - New York Heart Association Functional Class

  The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina. I - Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc. II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest. IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

  6 months after CRT implantation

• Changes in Cardiac Function - Left Ventricular Ejection Fraction

  6 months after CRT implantation

• Changes in Exercise Testing Variables - Maximum Rate of Oxygen Consumption (VO2peak)

  6 months after CRT implantation

Secondary Outcomes (9)

• Changes in Exercise Testing Variables - Heart Rate Recovery at 1st Minute (HRR1)

  6 months after CRT implantation

• Changes in Inflammatory Markers - Plasmatic Tumor Necrotic Factor Alpha (TNF-alpha)

  6 months after CRT implantation

• Changes in Inflammatory Markers - Plasmatic Brain Natriuretic Peptide (BNP)

  6 months after CRT implantation

• Changes in a Composite Measure of Quality of Life - HeartQoL T Score

  6 months after CRT implantation

• Changes in Exercise Testing Variables - Duration of Cardiopulmonary Testing (CPETduration)

  6 months after CRT implantation

Study Arms (2)

Exercise Training Program

EXPERIMENTAL

The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods.

Behavioral: Exercise training program; Device: Cardiac resynchronization therapy (CRT)

Control

ACTIVE COMPARATOR

Regular lifestyle

Device: Cardiac resynchronization therapy (CRT)

Interventions

Exercise training program BEHAVIORAL

The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of peak HR. Each interval, including the last one, is separate by 3 minutes active pauses, walking at 60% to 70% of HRpeak. Total aerobic exercise time at this moment will be 28 minutes and will be maintain to the end of ExT intervention period.

Exercise Training Program

Cardiac resynchronization therapy (CRT) DEVICE

Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.

Control; Exercise Training Program

Eligibility Criteria

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

You may qualify if:

• Patients with chronic heart failure (CHF), classified in NYHA functional class III or IV;
• Receiving optimal medical therapy for CHF (including an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and a beta-blocker unless a contraindication is evident) with a stable condition for more than 1 month (no hospitalization for HF, no change in medication, and no change in NYHA functional class);
• Left ventricular ejection fraction (LVEF) \< 35%;
• QRS duration ≥ 120 ms.

You may not qualify if:

• If they are younger than 18 years or are unable to sign informed consent;
• Patients who had been treated with an intravenous inotropic agent within the 30 days prior to implantation (these medications affect endothelial function after they are discontinued);
• Unstable angina pectoris;
• Orthopedic or neurological limitations to exercise.

Sponsors & Collaborators

• University of Lisbon: lead

Study Sites (1)

Santa Marta Hospital

Lisbon, Portugal

Location

Related Publications (33)

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  PMID: 31123810 DERIVED

• Abreu A, Oliveira M, Silva Cunha P, Santa Clara H, Portugal G, Goncalves Rodrigues I, Santos V, Morais L, Selas M, Soares R, Branco L, Ferreira R, Mota Carmo M; BETTER-HF investigators. Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients? Rev Port Cardiol. 2017 Oct;36(10):687-694. doi: 10.1016/j.repc.2017.02.016. Epub 2017 Oct 12. English, Portuguese.

  PMID: 29031455 DERIVED

• Abreu A, Oliveira M, Silva Cunha P, Santa Clara H, Santos V, Portugal G, Rio P, Soares R, Moura Branco L, Alves M, Papoila AL, Ferreira R, Mota Carmo M; BETTER-HF investigators. Predictors of response to cardiac resynchronization therapy: A prospective cohort study. Rev Port Cardiol. 2017 Jun;36(6):417-425. doi: 10.1016/j.repc.2016.10.010. Epub 2017 May 27. English, Portuguese.

  PMID: 28554585 DERIVED

MeSH Terms

Interventions

Cardiac Resynchronization Therapy

Intervention Hierarchy (Ancestors)

Cardiac Pacing, Artificial; Electric Stimulation Therapy; Therapeutics

Results Point of Contact

• Title: Maria Helena Santa-Clara Pombo Rodrigues
• Organization: University of Lisbon

santaclara@fmh.ulisboa.pt

00351917377277

Study Officials

• Maria Helena Santa-Clara Pombo Rodrigues, PhD

  University of Lisbon

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 9, 2015
• Study Start: January 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: May 14, 2019
• Results First Posted: April 17, 2019

Record last verified: 2019-05

Locations

PT (1)