Rehabilitation in Patients With Congenital Heart Disease (CARE-GUCH)

Cardiac Rehabilitation in Patients With Complex Congenital Heart Disease: Improvement of Exercise Intolerance

Exercise intolerance is a major burden for patients with complex congenital heart disease (CHD), significantly affecting their quality of life. Cardiopulmonary exercise testing provides a reliable tool both for assessing exercise capacity of CHD patients and for risk stratification and is becoming part of the routine clinical assessment of these patients. Exercise has an effect on the muscular, metabolic and circulatory systems. While exercise training has been widely studied in chronic heart failure, its efficacy in adults with CHD remain unknown. The investigators hypothesize that structured exercise training will improve exercise intolerance, in particular peak VO2. The aim of this multicenter, randomized study is to evaluate the impact of structured exercise training on exercise intolerance in patients with complex CHD.

Study Overview

• Status: Terminated
• Conditions: Heart Defects, Congenital
• Intervention / Treatment: Behavioral: Structured exercise training

Detailed Description

This is a randomized, prospective, multicenter, interventional study.

After study patients have given written consent they will be randomized either in the interventional group with a rehabilitation program or in the control group without rehabilitation program. Patients who are randomized in the control group are allowed to perform the rehabilitation program 12 months after randomisation. Patients in the interventional group will perform structured exercise training on 3 weekdays during a 12-weeks period. Training will be performed by ergometer and low-impact gymnastic and relaxation training.

All study participants have the following investigations at the beginning of the study and after 12 weeks:

• Cardiopulmonary exercise testing with spirometry
• 6-minute walk test
• Blood work: BNP, Creatinine, Sodium, Potassium, Urat, Cholesterol (HDL-L and LDL-L)
• Validated Heart failure questionnaires (SF-36 and Minnesota Living with heart failure questionnaire, German version for Basel, Zürich and Bern) All tests will be repeated as clinically indicated in a follow-up visit 12 months after baseline

Primary outcome is:

Comparison of peak VO2 at the end of rehabilitation between both groups.

Secondary outcomes are:

• Comparison of 6-min walk test, VE/VCO2 slope, anaerobic threshold and heart rate and blood pressure response after rehabilitation between both groups
• Changes of 6-min walk test, peak VO2, VE/VCO2 slope, anaerobic threshold and heart rate and blood pressure response at the end and 12 months after rehabilitation.
• Changes of quality-of-life assessed by validated heart failure questionnaire at the end and 12 months after rehabilitation and comparison between both groups.
• Changes of levels of brain-natriuretic peptide at the end and 12 months after rehabilitation.
• Adverse events during rehabilitation including new onset of arrhythmia, admission due to worsening heart failure or death.

The calculated sample size to reach a power of 0.80 is 83 patients in each arm. Patients with complex CHD and exercise intolerance are at increased risk for premature death and severe cardiac complications including arrhythmia needing treatment, heart failure and circulatory failure, pulmonary hemorrhage, pulmonary embolism and endocarditis. Hence, the likelihood of major adverse cardiac events during the study phase is considerably high. However, there is no evidence of functional worsening by low-level exercise. Smaller studies with patients with congenital heart disease and/or pulmonary hypertension did not report safety issues. Although sudden cardiac death is one of the leading modes of death in this population, it is extremely rare that sudden death occurs during exercise. Cardiac patients who are at specific risk for exercise-induced arrhythmia are not included into the study (i.e. patients with hypertrophic obstructive cardiomyopathy).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain
    • Virgen Macarena University Hospital
• Switzerland
  • Basel, Switzerland, 4052
    • University Hospital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Zurich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with complex CHD including cyanotic heart disease, subaortic right ventricle physiology, single ventricle physiology, Ebstein anomaly with ≥ moderate tricuspid regurgitation and patients with Tetralogy of Fallot (including those with pulmonary atresia of Fallot type or double-outlet right ventricle of Fallot type) and either residual free pulmonary regurgitation or left- or right ventricular systolic dysfunction (demonstrated by echocardiography or cardiac MRI).
2. Peak VO2 < 85% of predicted (standardized for age, gender, weight and height) obtained by cardiopulmonary exercise testing
3. Sedentary lifestyle (< 30 minutes of regular exercise per week)

Exclusion Criteria:

1. Patients with dyspnea New York Heart Association (NYHA) class IV.
2. Severe left ventricular outflow tract obstruction.
3. Unstable angina or recent myocardial infarction (<12 months).
4. Uncontrolled ventricular arrhythmia.
5. Recent intervention (<12 months)
6. Life expectancy <12 months
7. No consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Structured Exercise training; 12 weeks ambulatory low level exercise training	Behavioral: Structured exercise training; 12 weeks low level ambulatory structured exercise training
No Intervention: Control group; No structured exercise training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peak VO2	Comparison between both groups	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minute walk test	between both groups and within groups	12 weeks
VE/VCO2	Comparison between groups and within groups	12 weeks
heart rate response	Difference between peak heart rate and resting heart rate Comparison between groups and within groups	12 weeks
QoL	Comparison between groups and within groups Minnesota Heart failure Score and SF 36	12 weeks
BNP	Comparison between groups and within groups	12 weeks
Adverse events	cardiac related adverse events including cardiac death	12 weeks
peak VO2	Comparison between groups and within groups	12 months
VE/VCO2	Comparison between groups and within groups	12 months
Heart rate response	Comparison between groups and within groups	12 months
6 minute walk test	Comparison between groups and within groups	12 months
QoL	Comparison between groups and within groups	12 months
BNP	Comparison between groups and within groups	12 months
Cardiac adverse events	Comparison between groups and within groups	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 1, 2011
• First Posted (Estimate): November 2, 2011

Study Record Updates

• Last Update Posted (Actual): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Heart Defects, congenital
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Heart Defects, Congenital
• Other Study ID Numbers: CARE-GUCH