Effectiveness of Inspiratory Muscle Training for People With Ischemic Heart Disease Revascularized by Percutaneous Transluminal Coronary Angioplasty.

Myocardial ischemia According to the Spanish Heart Foundation, myocardial ischemia (MI) is the disease caused by atherosclerosis of the coronary arteries, responsible for providing blood to the heart muscle. Coronary atherosclerosis is a slow process of collagen formation and accumulation of lipids (fats) and inflammatory cells (lymphocytes) that causes narrowing of the lumen of the coronary arteries. This process begins in the first decades of life, but does not present symptoms until the stenosis of the coronary artery becomes so severe that it causes an imbalance between the supply of oxygen to the myocardium and its metabolic needs3. In this case, myocardial ischemia occurs, which may be chronic, known as chronic coronary syndrome or stable angina pectoris, or sudden occlusion due to thrombosis of the artery, which causes a lack of oxygenation of the myocardium that gives rise to coronary syndrome. Acute also called unstable angina and acute myocardial infarction. MI reduces force production, causes arrhythmias, and causes muscle damage, leading to acute ischemic contractile failure of the heart. Patients with chronic ischemic heart disease have lower evaluations of their social life and their coping with daily routine.

The consequence of the processes described above is that people who suffer from MI decrease their tolerance to exercise, functionality and performance in activities of daily living, which leads them to sedentary behaviors, worsening their quality of life. Furthermore, a vicious circle of inactivity and clinical and functional deterioration is established that produces a general worsening of physical condition and atrophy of peripheral and respiratory muscles. All of these circumstances lead to a decrease in functional capacity and therefore to a worse prognosis of the disease.

Regarding the risk factors that lead to the development of MI, there is a combination of socioeconomic, metabolic, behavioral and environmental risk factors. Among them are advanced age, high blood pressure, an unhealthy diet, high cholesterol, diabetes, obesity, smoking, a sedentary lifestyle, stress, family history and harmful consumption of toxins, among others. Most of these factors are modifiable and it is one of the fundamental pillars of their treatment to get affected people to change their lifestyle. The incidence is higher in men since women benefit from a hormonal protective effect during their fertile life. This circumstance disappears with menopause, which equalizes the cases in both sexes from 45-50 years of age.

Epidemiology It is estimated that in 2020 there were 244.1 million people living with MI worldwide. Of them, 141 million were men and 103.1 million were women. The regions of North Africa, the Middle East, Central Asia, South Asia and Eastern Europe had the highest prevalence rates. The global mortality rate was 112.37 per 100,000, this being also higher in the regions with the highest prevalence.

MI affects approximately 126 million people worldwide, representing 1.72% of the world's population. It is the main cause of death, with 9 million deaths annually. The incidence begins to increase in the fourth decade of life and is higher in men than in women. In developed countries, about a third of all deaths in people over 35 years of age are attributed to this disease. In the United States, it is estimated that almost half of men and approximately one-third of women will experience some symptoms of MI during their lifetime. In the European Union, cardiovascular diseases account for 40% of all deaths. Furthermore, the economic costs associated with MI are significant. The treatment of cardiovascular diseases constitutes 54% of total health expenditure, and contributes approximately a quarter of productivity losses.

Coronary heart disease is closely related to aging. Therefore, despite the decrease in its incidence observed in recent decades, all indicators suggest that its incidence will increase in the years to come. Coronary syndromes are expected to increase between 69% and 119% by 2049, mainly due to the growth of the population of patients over 75 years of age. For the group of patients between 25 and 75 years of age, the incidence is projected to remain stable in the coming decades.

Treatment

It usually consists of thrombolysis (revascularization of the artery or arteries whose flow is compromised) and can be done in two ways:

* By open surgery performing a bridge between two vessels that redirects blood to the affected myocardium. * By performing a percutaneous transluminal coronary angioplasty (PTCA). This option is less invasive and uses a balloon at the tip of a thin tube, called a catheter, to widen the artery. A small spring is usually placed to keep the artery open.

Secondary prevention Once the first cardiovascular event has occurred, it is important to prevent it from happening again. This is called secondary prevention. In this regard, the non-pharmacological strategy with the most evidence at present to reduce mortality, cardiovascular disability, improve the quality of life of patients and prevent further cardiovascular events is cardiac rehabilitation programs (CRP). Moreover, their cost-effectiveness is well known. These include smoking cessation, control of other cardiovascular risk factors, health education, psychological therapy, and a multimodal exercise program (cardiovascular and strength training). Usually 2-3 training sessions are performed weekly for 8-10 weeks.

Inspiratory muscle training Specific inspiratory muscle training (IMT) consists of applying higher than usual workloads to the muscles responsible for generating the necessary negative pressure inside the thorax for air to enter the lungs. This overload induces adaptations that produce an increase in the strength of this musculature. It is widely used as part of the treatment of people with chronic respiratory diseases and people with heart failure (HF). It is a very safe intervention that reduces dyspnea and improves functional capacity and quality of life in these patients.

Overload is achieved by breathing in through specific devices containing a valve whose threshold can be regulated. In order to decide the pressure at which each individual will train, his or her Maximum Inspiratory Pressure (MIP) must be measured beforehand. Training protocols at high loads, between 50% and 80% of the MIP, are those that obtain the best results according to the available evidence for patients with HF and for patients revascularized with grafting by open surgery. Therefore, the intervention will be performed with loads of 70% of the MIP value, completing 3 sets of 10 repetitions, 4 days a week, with 3 minutes rest between sets, during the 8 weeks of the CRP.

Hypothesis and Objectives

Justification In view of the perspective presented above and the available literature, it is pertinent to conduct a low-risk randomized clinical trial evaluating the effectiveness of the addition of IMT to a CRP of people with IC with PTCA. A recently published review9 concludes that the quality of the evidence for inspiratory muscle training for the improvement of maximal oxygen consumption and expiratory muscle strength in this population is very low. However, it should be taken into account that most of the clinical trials carried out to date have been performed on patients who underwent open surgery, so that the literature is scarce in percutaneously operated patients. In this sense, the results of our study will be specifically focused on percutaneously revascularized patients, thereby increasing knowledge of the effects of this intervention in the subgroup of patients with IHD and PTCA on these and other variables. Although CRP have been shown to be effective there is limited evidence on the addition of an IMT in patients with IHD. Clinical practice guidelines do not routinely recommend IMT due to this lack of evidence, so we aim to shed light on its effectiveness.

Hypotheses The addition of inspiratory muscle training to a cardiac rehabilitation program for people with percutaneously revascularized ischemic heart disease will lead to better results in terms of functional capacity and muscle strength, in addition to social support, anxiety, depression, coping with the disease, sexual dysfunction, quality of life, quality of sleep, eating habits and body composition, after 16 sessions of intervention compared to the control group.

H2.- It is expected that a large proportion of the participants will present anxiety and depression, poor coping with the disease and poor control of cardiovascular risk factors.

H3.- There will be greater effects of the intervention on the variables in the subgroup of women, due to their greater degree of commitment to the intervention program.

Objectives

I. General objective

\- To analyze the effectiveness of the addition of inspiratory muscle training to a cardiac rehabilitation program in people with percutaneously revascularized ischemic heart disease after 16 sessions of intervention, based on functional capacity, in addition to muscle strength, social support, anxiety, depression, coping with the disease, sexual dysfunction, quality of life, sleep quality, eating habits and body composition.

II. Secondary objectives

* To know the biopsychosocial profile of this population based on functional capacity, in addition to muscular strength, social support, anxiety, depression, coping with the disease, sexual dysfunction, quality of life, quality of sleep, eating habits and body composition. * To analyze gender differences through subgroup analysis. Methodology

The present clinical trial has been previously approved by the Provincial Research Ethics Committee of Malaga with Code SICEIA-2024-001869 in its session number 9, held on 09/26/2024.

The characteristics of the proposed clinical trial are reported in accordance with the SPIRIT standards (Standard Protocol Items: Recommendations for Interventional Trials).

Study design Randomized, controlled (parallel), triple-blind, low-risk clinical trial.

Study Setting The study will be carried out at the Cardiac Rehabilitation Unit (CRU) of the Hospital Universitario Virgen de la Victoria de Málaga (HUVV).

Study Subjects Persons with Myocardial Ischemia (MI) referred to the CRU of the HUVV who have undergone PTCA.

Inclusion criteria: i) people with MI with PTCA; ii) both sexes; iii) over 18 years of age; iv) under 80 years of age; v) absence of cognitive deficit and/or physical limitations that would prevent them from performing physical exercise or completing the questionnaires necessary for participation in the study.

Exclusion criteria: i) Disease or condition that contraindicates exercise such as severe hypertrophic obstructive cardiomyopathy, severe aortic stenosis and/or dissecting aortic aneurysm; ii) Patients who refuse treatment or do not sign the informed consent.

Sampling, Sample Size and Randomization Consecutive sampling will be carried out with patients attending the HUVV CRU and meeting the criteria described above.

The sample size was calculated to detect differences between groups in our main variable, functional capacity measured by maximal oxygen consumption. According to the meta-analysis by Fabero-Garrido et al , people with ischemic heart disease who have undergone an inspiratory muscle training program have a mean difference of 2.18 ml O2/kg/min with respect to the control group and we want to find a deviation of 1 MET (3.5 ml O2/kg/min). The calculations were carried out with the statistical software G\*Power 3.1, considering in all cases a confidence level of 95% and a power of 80%.

In view of the above, a sample size of 33 subjects per group (66 in total) was established. In addition, to minimize the impact of possible dropouts, the total sample was increased by 10% to 72 patients, which will lead to the final inclusion of 36 patients in each group.

Randomization of partici

• The Charlson Comorbidity Index [Срок оценки: Between recruitment and the start of intervention]
• Sleep Quality [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Level of physical activity [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• The left ventricular ejection fraction (LVEF) [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Maximal Inspiratory Pressure (MIP) [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.MIP will be reassessed midway through the program to readjust the training load.]
• Maximal Expiratory Pressure (MEP) [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Quality of life [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Anxiety and Depression [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Functional Social Support [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Erectile Dysfunction [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Dyspnea [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]
• Body Composition by Bioimpedance [Срок оценки: First measurement between recruitment and the beginning of the intervention, second measurement between the end of the intervention and 2 weeks after the intervention.]