The Impact of Exercise-Induced Cardiac Remodeling on Myocardial Efficiency

Study Overview
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Brief Summary
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This research study is being conducted to find out how heart function and energy use differ among healthy endurance athletes, individuals who do not exercise regularly, and patients with hypertrophic cardiomyopathy. The research study involves taking part in a cardiopulmonary exercise test (CPET), two positron emission tomography (PET) scans, an echocardiogram, and blood draws. The study will consist of a total of three visits scheduled over a maximum of two weeks. By determining how heart function and energy use differ between our three groups of healthy endurance athletes, individuals who do not exercise regularly, and patients with hypertrophic cardiomyopathy, the investigators hope to have this work translate into a novel clinical tool for differentiating pathologic changes of the heart from physiological changes in heart. This is otherwise known as gray-zone left ventricular hypertrophy, or enlargement of the left ventricle.

Detailed Description
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The investigators anticipate that by defining the myocardial metabolic profiles of exercise-induced left ventricular hypertrophy (EI-LVH) and hypertrophic cardiomyopathy (HCM), we will determine if these differ sufficiently to distinguish these two forms of LVH. Because HCM causes sudden death with physical activity, it is critically important to determine the etiology of undifferentiated gray zone LVH in the athlete presenting for medical evaluation, and existing mechanisms of assessing myocardial structure and function are not universally adequate. The investigators anticipate that the work may translate into a novel clinical tool for differentiating pathology from physiology in gray-zone LVH. The complementary mechanistic goal of this study is to combine comprehensive evaluations of myocardial functional parameters and metabolism to better understand the link between function and metabolism and, ultimately, the biological mechanisms of EI-LVH and LVH due to HCM. There are three specific aims to the research study. The first specific aim is to define the relationships between changes in myocardial metabolic efficiency (MME) and changes in myocardial mechanics that accompany EI-LVH. The second is to establish and compare myocardial metabolic profiles of EI-LVH and HCM. The third is to analyze a subset of the endurance athlete subjects to determine the impact of aerobic exercise training on MME over a 90-day period. The study will employ a mixed study design. The study is a cross-sectional design but will analyze a subset of endurance athletes longitudinally with repeated measures after 90 days from the first three study visits. For the cross sectional design, the first study visit will be at Massachusetts General Hospital and will involve a cardiopulmonary exercise test (CPET) on an upright bicycle, with blood sampling before the CPET at rest, and after exercise. Study visits two and three will follow the same protocol. Both study visits two and three will occur at Brigham and Women's Hospital and will involve an echocardiogram and a positron emission tomography (PET) scan. Both visits will include blood sampling at rest, and then either the resting PET scan or a PET scan after acute exercise provocation on a supine bicycle. Study visits two and three will occur on two sequential mornings.

Official Title
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The Impact of Exercise-Induced Cardiac Remodeling on Myocardial Efficiency: A Multimodality Structural, Functional, and Metabolic Evaluation.

Conditions
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Cardiomyopathy, Hypertrophic

Intervention / Treatment
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* Other: PET Scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Endurance Athletes: Age ≥ 18-60 Official participation in a collegiate varsity rowing team OR participation in competitive endurance athletics (defined as >= 10 hours of exercise training per week with the majority dedicated to endurance activities (i.e. cycling, rowing, running). Inclusion Criteria for Healthy Volunteers: Age ≥ 18-60 0-5 hours of exercise per week without anticipated changes in exercise habits over study period Able to exercise on an upright bicycle ergometer Exclusion Criteria for Endurance Athletes and Healthy Volunteers: Known medical disease (including but not limited to known cardiac or pulmonary disease, diabetes or contraindications to exercise testing such as uncontrolled cardiac arrhythmia, excessive blood pressure of more than 200/100 mmHg at rest, active exacerbation of congestive heart failure or reactive airways disease). Pregnancy Inclusion Criteria for HCM Patients: Established HCM diagnosis as per above (20 subjects) Age ≥ 18-50 No anticipated changes to baseline exercise program (if any) over the study period Able to exercise on an upright bicycle ergometer Exclusion Criteria for HCM Patients: Obstructive LVOT gradient > 30 mmHg, at rest or with provocation. Reduced LVEF < 53%. NYHA class III or IV heart failure symptoms. History of sudden cardiac death or hemodynamically significant ventricular tachycardia. History of unexplained syncope. Having a Class I or IIa AHA/ACC indication for ICD placement without an ICD Known medical disease (including but not limited to known cardiac or pulmonary disease other than HCM, diabetes, or contraindications to exercise testing such as uncontrolled cardiac arrhythmia, excessive blood pressure of more than 200/100 mmHg at rest, active exacerbation of congestive heart failure or reactive airways disease). Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Volunteers/Control<br>Age and body surface area (BSA) matched volunteers who are sedentary or normally active. Normally active is defined as less than 5 hours of exercise per week. Healthy volunteer subjects must be able to exercise on an upright bicycle ergometer and be between the ages of 18-50. | Other: PET Scan<br>* PET scan using a tracer that is under a physician sponsored IND.<br>|
| Hypertrophic Cardiomyopathy/HCM<br>HCM subjects are patients that are age and BSA-matched with the athletes who then have an established clinical diagnosis of HCM without left ventricular (LV) outflow tract obstruction. There can be no anticipated changes to baseline exercise program (if any) over the study period. HCM subjects must be able to exercise on an upright bicycle ergometer and be between the ages of 18-50. | Other: PET Scan<br>* PET scan using a tracer that is under a physician sponsored IND.<br>|
| Endurance Athletes<br>Official participation in a collegiate athletic varsity rowing team OR participation in competitive endurance athletics. Competitive endurance athletics is defined as greater than or equal to 10 hours of exercise training per week with the majority dedicated to endurance activities such as cycling, rowing, or running. Endurance athlete subjects must be able to exercise on an upright bicycle ergometer and be between the ages of 18-50. | Other: PET Scan<br>* PET scan using a tracer that is under a physician sponsored IND.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Metabolic Efficiency | The ratio of myocardial oxygen consumption to myocardial work. | up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Blood Flow Reserve using PET | Difference in blood flow at rest and with exercise. | up to 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiomyopathy, Hypertrophic, Athletes, Endurance, Healthy Volunteers