Effect of Exercise Training on Left Ventricular Function in Patients Post Myocardial Infarction

Study Overview
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Brief Summary
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Patients who have suffered a heart attack are at risk of developing worsening heart function and heart failure. Exercise training has a beneficial effect on heart function and prevents heart failure. The aim of the current study is to investigate the effect of exercise training on heart function in patients who have suffered a heart attack.

Detailed Description
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Patients who have suffered a myocardial infarction are at significant risk for developing heart failure and progressive left ventricular dysfunction One of the proposed mechanisms responsible for this observation is reduction in myocardial beta-adrenergic receptor density due to elevated cell membrane protein G - protein coupled receptor kinase -2 (GRK2). It is known that exercise training preserves heart function in patients who have suffered a myocardial infarction. The mechanism for this is not clear. The purpose of this study is to examine the effect of exercise training on myocardial function and GRK2 levels in patients who have suffered a myocardial infarction, with the hypothesis that exercise training in this population reduces GRK2 levels and preserves or improves myocardial function.

Official Title
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Effect of Exercise Training on Left Ventricular Function in Patients Post Myocardial Infarction: The EXercise Interval Training - V Study

Conditions
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Myocardial Infarction, Heart Failure, Coronary Artery Disease

Intervention / Treatment
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* Other: Secondary prevention and cardiac rehabilitation clinic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myocardial infarction Complete revascularization: no residual major epicardial coronary artery coronary stenosis ≥ 70%; no residual left main coronary stenosis ≥ 40%. Stage A-C heart failure, New York Heart Association class I-III. Stable dose of medications during the 4 weeks prior to enrolment. Able to perform a maximal cardiopulmonary stress test. Capacity and willingness to provide sign informed consent. Exclusion Criteria: Pregnant Coronary artery bypass surgery: patients post coronary artery bypass graft exhibit wall motion abnormalities that may interfere with speckle tracking analysis. Incomplete revascularization with major epicardial coronary artery (left anterior descending, circumflex, or right coronary) stenosis ≥ 70%. Myocardial necrosis in the absence of significant flow limiting coronary artery stenosis or thrombosis, with the exception of documented STEMI and successful thrombolytic therapy resulting on no significant residual epicardial coronary artery stenosis. Significant valvular disease that is greater than moderate in severity History of non-ischemic cardiomyopathy (dilated, restrictive, infiltrative cardiomyopathy, hypertrophic, LV non compaction, or Takotsubo cardiomyopathy) Significant resting ECG abnormalities that preclude accurate speckle tracking. Paced rhythm. left bundle branch block Atrial arrhythmias (ex. persistent/permanent atrial fibrillation, atrial flutter). Frequent ventricular ectopics Significant ventricular arrhythmias (non-sustained ventricular tachycardia or syncope). New York Heart Association class IIIb - IV symptoms. Severe LV systolic dysfunction (Ejection fraction ≤ 30%) Active decompensated heart failure with orthopnea or paroxysmal nocturnal dyspnea. Uncontrolled resting arterial hypertension > 180/110 mmHg. More than moderate systemic disease Chronic inflammation or infection. Any contraindication to exercise training or any condition limiting ability to partake in adequate exercise stress testing or training (peripheral artery disease, articular, neurologic, or psychiatric pathology)

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise training<br>Secondary prevention and cardiac rehabilitation clinic of the Montreal Heart Institute. Subjects will undergo twice weekly exercise training with high intensity interval training for a period of 12 weeks. | Other: Secondary prevention and cardiac rehabilitation clinic<br>* Secondary prevention and cardiac rehabilitation clinic of the Montreal Heart Institute. Subjects will undergo twice weekly exercise training with high intensity interval training for a period of 12 weeks.<br>|
| No Intervention: control<br>Individuals in this group are offered current ACC/AHA recommendations on physical activity in patients post-myocardial infarction. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lymphocyte GRK2 mRNA level | change in lymphocyte GRK2 mRNA levels | at baseline and following 12 weeks exercise training intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular systolic function | change in left ventricular systolic function | at baseline and following 12 weeks exercise training intervention | 
| Left ventricular dimensions | Change in left ventricular dimensions | at baseline and following 12 weeks exercise training intervention | 
| Plasma epinephrine | change in plasma epinephrine | at baseline and following 12 weeks exercise training intervention | 
| heart rate variability | change change in autonomic tone | at baseline and following 12 weeks exercise training intervention | 
| exercise capacity (VO2max) | Change before and after exercise training | at baseline and following 12 weeks exercise training intervention | 
| ambulatory blood pressure | Change in awake and 24h blood pressure | at baseline and following 12 weeks exercise training intervention | 
| Plasma brain natriuretic peptide | change in plasma brain naturietic peptide | at baseline and following 12 weeks exercise training intervention | 
| Maximal cardiac output and stroke volume using electrical bioimpedance | change in maximal cardiac output and stroke volume | at baseline and following 12 weeks exercise training intervention | 
| lymphocyte GRK2 protein levels | change in lymphocyte GRK2 protein levels | at baseline and following 12 weeks exercise training intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise training, High intensity interval training, left ventricular systolic function, G-protein related kinase 2, heart failure, myocardial infarction, coronary artery disease, beta adrenergic receptor