High-intensity Inspiratory Muscle Training as a Pre-cardiac Rehabilitation in Heart Disease

Study Overview
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Brief Summary
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Background/aim: Endothelial function is closely associated with coronary artery health among individuals being treated for heart disease. An impairment in endothelial function promotes arterial stiffening that directly contributes to elevated systolic blood pressure as a result of increased vascular resistance. Inspiratory muscle training is simply a form of training consisting of repeated inspirations against resistance. Inspiratory muscle training has also been applied to patients with chronic disease or as an additional therapy for cardiac rehabilitation and it has proven to be safe in these groups. Few studies in the literature examined the effects of high-intensity inspiratory muscle training in this population, however, these studies did not examine the direct effects of inspiratory muscle training on vascular function. To the best of our knowledge, the effects of inspiratory muscle training in patients with heart disease on endothelial function and arterial stiffness prior to starting cardiac rehabilitation have not been investigated. This study aims to investigate and interpret whether high-intensity inspiratory muscle training, beyond the usual care of heart disease, improves endothelial function and arterial stiffness. Methods: The study was designed as a randomized controlled trial. Patients will be allocated for inspiratory muscle training (IMT) with 60% of maximum inspiratory pressure (MIP) or sham inspiratory muscle training (Sham-control), for 4 weeks. In both groups, before and after 4-week training, cardiovascular functions will be measured and compared.

Detailed Description
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Background: Cardiovascular diseases (CVD) remain a leading cause of morbidity and mortality in both men and women in developed and developing societies (Joseph et al., 2017). Some degree of pulmonary dysfunction is highly likely in patients with heart disease compared to those without(Calles et al., 2016; Cahalin and Arena, 2015). This can affect pulmonary function, and gas exchange, as well as decrease maximum inspiratory and expiratory pressures (MIP and MEP, respectively)(Dos Santos et al., 2019; Haeffener et al., 2008; Roncada et al., 2015; Cahalin and Arena, 2015). Inspiratory muscle training has been shown to be an effective form of training that enhances lung function. It consists of repetitive breath cycles where one inspires against resistance placed by a device and expires against no resistance. Studies that have applied this form of training in patients with heart disease have found significant improvements in MIP-MEP, tidal volume, vital capacity, and 6-minute walking distance. Few studies have examined the effects of high-intensity (between 50-80% of MIP) inspiratory muscle training in patients with heart disease (Dos Santos et al., 2019; Dos Santos et al., 2021; Laoutaris et al., 2007; Miozzo et al., 2018; Sadek et al., 2022). This level of training has been associated with greater improvements in the aferomentioned outcomes of interest, however, no study has explored the effects of high-intensity inspiratory muscle training in patients with heart disease on measures of cardiovascular function. Aim: This study aims to investigate and interpret whether high-intensity inspiratory muscle training, beyond the usual care, improves endothelial function and arterial stiffness on cardiovascular function in patients with heart disease. Methods: The study was designed as a randomized controlled trial. After coronary artery bypass graft surgery, patients will be invited to the study. The demographic and clinical characteristics of the patients will be recorded after consent is obtained from the volunteer patients who meet the inclusion criteria. Subsequently, patients will be randomly divided into two groups for inspiratory muscle training (IMT) with 60% maximum inspiratory pressure (MIP) or sham inspiratory muscle training (Sham-control), for 4 weeks. In both groups, before and after 4-week training, resting blood pressure (systolic/diastolic), resting heart rate, endothelial function, arterial stiffness, functional exercise capacity, the severity of dyspnea, and inspiratory muscle functions will be measured.

Official Title
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Effects of High-intensity Inspiratory Muscle Training as a Pre-cardiac Rehabilitation Intervention on Cardiovascular Functions in Patients With Heart Disease

Conditions
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Coronary Artery Bypass Graft, CABG

Intervention / Treatment
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* Device: IMT
* Device: Sham-IMT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >18 years old Be able to walk independently. Had coronary artery bypass graft (CABG) surgery, history of percutaneous coronary interventions, heart failure, and/or myocardial infarction. Sufficient English language comprehension and cognitive ability to understand the study protocol, give informed consent and follow instructions. Exclusion Criteria: Being a current smoker (or tobacco). Having a diagnosed chronic disease such as inflammatory bowel disease/irritable bowel syndrome, cerebrovascular diseases, COPD, chronic kidney disease requiring dialysis, neurological disorders, or diseases that may affect motor/cognitive function [multiple sclerosis, Parkinson's disease, polio, Alzheimer's disease, dementia, or other brain diseases of ageing]) Getting a score below 24 on the Standardized Mini Mental Test Using antipsychotic medications commonly used to treat schizophrenia or schizoaffective disorders (i.e., haloperidol) Having had any other previous cardiothoracic operation except CABG (e.g. Pneumonectomy, lobectomy, etc.) Having a history of unstable-angina Having had pneumonia in the last 3 months

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Patients who will perform inspiratory muscle training (IMT) with %60 of MIP intensity | Device: IMT<br>* The IMT protocol will consist of high-intensity daily training - 2 sets of 30 breaths with a 1-minute rest between sets, twice a day for 4 weeks using an IMT Threshold device (Threshold IMT Philips® Respironics, Inc). The intensity of the training will be set to 60% of each patient's maximal inspiratory pressure.<br>|
| Sham Comparator: Sham Group<br>Patients who will perform Sham-IMT | Device: Sham-IMT<br>* The sham IMT protocol will consist of high-intensity daily training - 2 sets of 30 breaths with a 1-minute rest between sets, twice a day for 4 weeks using an IMT Threshold device (Threshold IMT Philips® Respironics, Inc) without intensity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inspiratory muscle function | maximal inspiratory pressure (MIP) is the highest pressure measured during inspiration will be used. | 4 weeks | 
| endothelial function | flow-mediated dilation (FMD) ultrasound measurements of brachial artery flow-mediated dilatation will be performed. | 4 weeks | 
| arterial stiffness | arterial stiffness will be assessed by measuring pulse wave velocity. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional exercise capacity | maximal distance in 6 minute walk test will be used. | 4 weeks | 
| dyspnea | The modified Medical Research Council (mMRC) Dyspnea Scale, which have 5 points (0 to 4) will be used. High scores presented worsen dyspnea. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery bypass graft, inspiratory muscle training, endothelial function, arterial stiffness, CABG