Exercise MRI to Evaluate Cardiorespiratory Fitness in Children With Heart Disease

Exercise cardiac MRI's are the non-invasive gold standard for assessing biventricular function during exercise. While exercise MRI has not been previously studied in pediatric HTRs, it has been effectively utilized in children with single ventricle congenital heart disease. The purpose of this study is to fully understand the cardiac adaptations induced by exercise training.

Primary objective: Evaluate the association between exercise MRI cardiac and skeletal muscle measures and cardiorespiratory fitness in pediatric acquired (HTRx) and CHD participants.

Hypothesis: Cardiac adaptations to exercise and skeletal muscle functioning will be positively associated with measured CRF in CHD patients and those post-transplant.

Secondary objective: Evaluate changes in exercise MRI measures of cardiac and skeletal muscle function following a 12-week high-intensity interval training (HIIT) exercise protocol in children with acquired and congenital heart disease.

Hypothesis: a 12-week HIIT intervention will result in improvements in cardiac and skeletal muscle responses to exercise.

This will be a single-center, prospective observational study.

Participants will include 10-18 year old pediatric heart transplant recipients (HTR) and congenital heart disease (CHD) patients followed at the Stollery Children's Hospital.

Participants will undergo cardiopulmonary exercise testing (CPET) using a cycle ergometer and standardized protocols. On a separate day (within 2 weeks of the testing), participants will return and undergo a standard cardiac MRI to assess resting ventricular structure and function. They will then complete an exercise cardiac MRI assessment using an MRI-compatible stepping ergometer.

Participants and their parent will also be asked to complete questionnaires to determine their feelings towards exercise and physical activity.

As this will be a single-center study. The analysis will be largely exploratory and the sample size will be determined based on the available patient population. Based on a review of potentially eligible participants at our center, the investigators anticipate recruiting 10 participants post-HTR and 10 CHD participants to evaluate the primary objective. As the secondary objective (changes in cardiac and skeletal muscle MRI measures) requires repeated assessments and involvement in the MedBIKE™ HIIT trial, recruitment to address this objective may be lessened; the investigators thus anticipate recruiting ~6 participants post-transplant and 6 participants with CHD. The statistical analysis will be carried out in collaboration with the Women and Children's Health Research Institute (WCHRI) biostatistics team (accounted for in budget). Differences in MRI and CPET measures among participants, and changes in the measures (Objective 2) will be evaluated by independent t-tests or Mann-Whitney tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Pearson correlations will be used to evaluate associations between VO2peak (and other CPET measures of CRF) and measures of cardiac function and output and peripheral muscle oxygen extraction.

Inclusion criteria

• 10 - 18 year olds followed at the Stollery Children's Hospital
• Heart transplant recipients ≥6 months post-transplant
• Have a moderate-complex congenital heart disease diagnosis

Exclusion criteria

• Non-English speaking
• Exercise restricted by the patient's clinical cardiologist
• Clinical antibody- or cellular-mediated rejection within 3-months of the assessment or during the study period (for HTRs)
• Previous involvement in a CR or exercise intervention program
• Previous exercise stress test demonstrating sustained arrhythmias, ST segment elevation or depression greater than 3mm, an inappropriate rise in blood pressure (BP) (<20 mmHg) or a systolic BP >200 mmHg, or symptoms of chest pain or syncope
• Resting arterial saturation <85% or oxygen requirements
• Moderate ventricular systolic dysfunction (or worse) at the most recent echocardiogram
• History of chest pain on exertion; unrepaired/unpalliated CHD
• Arrhythmias in the last year (including supraventricular tachycardia, ventricular tachycardia, atrioventricular block or history of (Mobitz II or worse))
• New York Heart Association class II or worse symptoms
• Active medical inter-current illness limiting ability to participate
• Cognitive impairment limiting the communication needed for the exercise MRI
• Research MRI contraindications (e.g. any type of pacemaker), or any orthopedic limitation preventing exercise testing
• Extracardiac or congenital abnormality limiting the participant's functional ability to exercise
• Pregnant