Blood Flow Reserve: Effects After Training With Heavy Inspiratory Exercises

Study Overview
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Brief Summary
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The goal of this single-site, parallel-group, double-blind, sham-controlled randomized control trial is to examine the effect of high-intensity inspiratory muscle strength training (IMST) on coronary blood flow assessed using positron emission tomography coronary perfusion imaging in patients with coronary artery disease (CAD). The main question it aims to answer are: • if high-intensity IMST will improve coronary blood flow in patients with CAD, which could be assessed using positron emission tomography coronary perfusion imaging. Participants will be asked to complete the 8-week high-intensity or low-intensity IMST. Researchers will compare high and low-intensity IMST groups to see if coronary blood flow increases after IMST.

Detailed Description
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Coronary artery disease (CAD) is a leading cause of morbidity and mortality. With the aging population, increasing number of patients with CAD has frailty and immobility. The health benefits of traditional aerobic exercise have been well-established; however, alternative exercise programs, such as inspiratory muscle training (IMST), may provide greater merits. IMST is a form of exercise that engages the diaphragm and accessory respiratory muscles to repeatedly inhale against resistance, which can be achieved in less time and widely applicable even for immobile or frail patients compared to conventional aerobic exercise. Since barriers to conventional exercise training include immobility, lack of time, and access to facilities, IMST may be a beneficial exercise form that can overcome those factors. A previous study has shown that high-intensity IMT can lower blood pressure and improved vascular endothelial function. Improvements in endothelial function of coronary arteries could improve coronary blood flow, leading to the improvement of anginal symptoms as well as quality of life. IMST might offer a widely applicable, feasible, time-efficient form of training for CAD patients. Our study will examine the preliminary efficacy of IMST on coronary blood flow in patients with CAD.

Official Title
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The Efficacy of Inspiratory Muscle Strength Training on Coronary Blood Flow in Patients With Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: High-intensity IMST
* Device: Low-intensity IMST


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: ≥18 years of age; Patients referred to PET at the University of Ottawa Heart Institute; able to perform a respiratory exercise testing; and, Patients with clinical stability, including no change in medications for the past one month. Exclusion criteria: unstable angina or established diagnosis of severe valvular heart disease, hypertrophic obstructive cardiomyopathy, chronic obstructive pulmonary disease; unable to follow training/breathing instructions; unable to return for follow-up visit; presence of any major non-cardiac problem that would adversely affect survival during the study in the opinion of the investigator; or, unable to provide informed consent.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-intensity IMST<br>Participants who will be trained with high-intensity IMST | Device: High-intensity IMST<br>* Participants will use the POWERbreathe KHP2 inspiratory muscle training device. All participants will be assigned to perform 30 inspiratory maneuvers (5 sets of 6, 1-minute rest between sets), 6 days per week, for 6 weeks. Participants will be trained at 55% PIMAX during week 1, 65% PIMAX during week 2, and 75% PIMAX during weeks 3 to 6.<br>|
| Sham Comparator: Low-intensity IMST<br>Participants who will be trained with low-intensity IMST | Device: Low-intensity IMST<br>* Participants will use the POWERbreathe KHP2 inspiratory muscle training device. All participants will be assigned to perform 30 inspiratory maneuvers (5 sets of 6, 1-minute rest between sets), 6 days per week, for 6 weeks. Participants will be trained at 15% PIMAX for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global myocardial flow reserve | Change in global myocardial flow reserve on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Global stress myocardial blood flow | Change in global stress myocardial blood flow on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global rest myocardial blood flow | Change in global rest myocardial blood flow on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Maximum myocardial flow reserve | Change in maximum myocardial flow reserve on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Maximum myocardial blood flow at rest and stress | Change in maximum myocardial blood flow at rest and stress on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Global coronary vascular resistance at stress and rest | Change in global coronary vascular resistance at stress and rest on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Maximum coronary vascular resistance at stress and rest | Change in maximum coronary vascular resistance at stress and rest on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Mean segmental (17-segment model) myocardial flow reserve | Change in mean segmental (17-segment model) myocardial flow reserve on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Mean segmental (17-segment model) myocardial blood flow at stress and rest | Change in mean segmental (17-segment model) myocardial blood flow at stress and rest on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Maximal segmental (17-segment model) myocardial blood flow at stress and rest | Change in maximal segmental (17-segment model) myocardial blood flow at stress and rest on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| Summed stress score, summed rest score, and summed difference score | Change in summed stress score, summed rest score, and summed difference score on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| % left ventricular ischemia | Change in % left ventricular ischemia on positron emission tomography coronary perfusion imaging before and after IMST | Through study completion, an average of 8 weeks | 
| General quality of life | Change in general Quality of life assessed using the EQ5D-5L | Through study completion, an average of 8 weeks | 
| Angina symptom | Change in angina symptom assessed using the Seattle angina Questionnaire | Through study completion, an average of 8 weeks | 
| Adherence of IMST program | The proportion of participants adhering to prescribed IMST sessions | Through study completion, an average of 8 weeks | 
| Respiratory Muscle Strength | Respiratory Muscle Strength assessed by % change in maximal inspiratory pressure | Through study completion, an average of 8 weeks | 
| Resting blood pressure | Resting blood pressure measured in a seated position after a 5-minute rest period using an automated blood pressure monitor. | Through study completion, an average of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inspiratory muscle strength training, coronary artery disease, positron emission tomography, myocardial blood flow