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 forproviding blood to the heart muscle. Coronary atherosclerosis is a slow process ofcollagen formation and accumulation of lipids (fats) and inflammatory cells (lymphocytes)that causes narrowing of the lumen of the coronary arteries. This process begins in thefirst decades of life, but does not present symptoms until the stenosis of the coronaryartery becomes so severe that it causes an imbalance between the supply of oxygen to themyocardium and its metabolic needs3. In this case, myocardial ischemia occurs, which maybe chronic, known as chronic coronary syndrome or stable angina pectoris, or suddenocclusion due to thrombosis of the artery, which causes a lack of oxygenation of themyocardium that gives rise to coronary syndrome. Acute also called unstable angina andacute myocardial infarction. MI reduces force production, causes arrhythmias, and causesmuscle damage, leading to acute ischemic contractile failure of the heart. Patients withchronic ischemic heart disease have lower evaluations of their social life and theircoping with daily routine.The consequence of the processes described above is that people who suffer from MIdecrease their tolerance to exercise, functionality and performance in activities ofdaily living, which leads them to sedentary behaviors, worsening their quality of life.Furthermore, a vicious circle of inactivity and clinical and functional deterioration isestablished that produces a general worsening of physical condition and atrophy ofperipheral and respiratory muscles. All of these circumstances lead to a decrease infunctional 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 ofsocioeconomic, metabolic, behavioral and environmental risk factors. Among them areadvanced age, high blood pressure, an unhealthy diet, high cholesterol, diabetes,obesity, smoking, a sedentary lifestyle, stress, family history and harmful consumptionof toxins, among others. Most of these factors are modifiable and it is one of thefundamental 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 effectduring their fertile life. This circumstance disappears with menopause, which equalizesthe 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 MIworldwide. Of them, 141 million were men and 103.1 million were women. The regions ofNorth Africa, the Middle East, Central Asia, South Asia and Eastern Europe had thehighest prevalence rates. The global mortality rate was 112.37 per 100,000, this beingalso higher in the regions with the highest prevalence.MI affects approximately 126 million people worldwide, representing 1.72% of the world'spopulation. It is the main cause of death, with 9 million deaths annually. The incidencebegins to increase in the fourth decade of life and is higher in men than in women. Indeveloped countries, about a third of all deaths in people over 35 years of age areattributed to this disease. In the United States, it is estimated that almost half of menand approximately one‐third of women will experience some symptoms of MI during theirlifetime. In the European Union, cardiovascular diseases account for 40% of all deaths.Furthermore, the economic costs associated with MI are significant. The treatment ofcardiovascular diseases constitutes 54% of total health expenditure, and contributesapproximately a quarter of productivity losses.Coronary heart disease is closely related to aging. Therefore, despite the decrease inits incidence observed in recent decades, all indicators suggest that its incidence willincrease 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 ofage. For the group of patients between 25 and 75 years of age, the incidence is projectedto remain stable in the coming decades.TreatmentIt usually consists of thrombolysis (revascularization of the artery or arteries whoseflow is compromised) and can be done in two ways: ‐ By open surgery performing a bridge between two vessels that redirects blood to theaffected myocardium. ‐ By performing a percutaneous transluminal coronary angioplasty (PTCA). This optionis less invasive and uses a balloon at the tip of a thin tube, called a catheter, towiden 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 toprevent it from happening again. This is called secondary prevention. In this regard, thenon‐pharmacological strategy with the most evidence at present to reduce mortality,cardiovascular disability, improve the quality of life of patients and prevent furthercardiovascular events is cardiac rehabilitation programs (CRP). Moreover, theircost‐effectiveness is well known. These include smoking cessation, control of othercardiovascular risk factors, health education, psychological therapy, and a multimodalexercise program (cardiovascular and strength training). Usually 2‐3 training sessionsare performed weekly for 8‐10 weeks.Inspiratory muscle training Specific inspiratory muscle training (IMT) consists ofapplying higher than usual workloads to the muscles responsible for generating thenecessary negative pressure inside the thorax for air to enter the lungs. This overloadinduces adaptations that produce an increase in the strength of this musculature. It iswidely used as part of the treatment of people with chronic respiratory diseases andpeople with heart failure (HF). It is a very safe intervention that reduces dyspnea andimproves functional capacity and quality of life in these patients.Overload is achieved by breathing in through specific devices containing a valve whosethreshold can be regulated. In order to decide the pressure at which each individual willtrain, 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 obtainthe best results according to the available evidence for patients with HF and forpatients revascularized with grafting by open surgery. Therefore, the intervention willbe performed with loads of 70% of the MIP value, completing 3 sets of 10 repetitions, 4days a week, with 3 minutes rest between sets, during the 8 weeks of the CRP.Hypothesis and ObjectivesJustification In view of the perspective presented above and the available literature, itis pertinent to conduct a low‐risk randomized clinical trial evaluating the effectivenessof the addition of IMT to a CRP of people with IC with PTCA. A recently published review9concludes that the quality of the evidence for inspiratory muscle training for theimprovement of maximal oxygen consumption and expiratory muscle strength in thispopulation is very low. However, it should be taken into account that most of theclinical trials carried out to date have been performed on patients who underwent opensurgery, so that the literature is scarce in percutaneously operated patients. In thissense, the results of our study will be specifically focused on percutaneouslyrevascularized patients, thereby increasing knowledge of the effects of this interventionin the subgroup of patients with IHD and PTCA on these and other variables. Although CRPhave been shown to be effective there is limited evidence on the addition of an IMT inpatients with IHD. Clinical practice guidelines do not routinely recommend IMT due tothis lack of evidence, so we aim to shed light on its effectiveness.Hypotheses The addition of inspiratory muscle training to a cardiac rehabilitationprogram for people with percutaneously revascularized ischemic heart disease will lead tobetter results in terms of functional capacity and muscle strength, in addition to socialsupport, anxiety, depression, coping with the disease, sexual dysfunction, quality oflife, quality of sleep, eating habits and body composition, after 16 sessions ofintervention compared to the control group.H2.‐ It is expected that a large proportion of the participants will present anxiety anddepression, 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 subgroupof women, due to their greater degree of commitment to the intervention program.ObjectivesI. General objective ‐ To analyze the effectiveness of the addition of inspiratory muscle training to acardiac rehabilitation program in people with percutaneously revascularized ischemicheart disease after 16 sessions of intervention, based on functional capacity, inaddition to muscle strength, social support, anxiety, depression, coping with thedisease, sexual dysfunction, quality of life, sleep quality, eating habits and bodycomposition.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 withthe disease, sexual dysfunction, quality of life, quality of sleep, eating habitsand body composition. ‐ To analyze gender differences through subgroup analysis. MethodologyThe present clinical trial has been previously approved by the Provincial Research EthicsCommittee of Malaga with Code SICEIA‐2024‐001869 in its session number 9, held on09/26/2024.The characteristics of the proposed clinical trial are reported in accordance with theSPIRIT 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) ofthe Hospital Universitario Virgen de la Victoria de Málaga (HUVV).Study Subjects Persons with Myocardial Ischemia (MI) referred to the CRU of the HUVV whohave undergone PTCA.Inclusion criteria: i) people with MI with PTCA; ii) both sexes; iii) over 18 years ofage; iv) under 80 years of age; v) absence of cognitive deficit and/or physicallimitations that would prevent them from performing physical exercise or completing thequestionnaires necessary for participation in the study.Exclusion criteria: i) Disease or condition that contraindicates exercise such as severehypertrophic obstructive cardiomyopathy, severe aortic stenosis and/or dissecting aorticaneurysm; ii) Patients who refuse treatment or do not sign the informed consent.Sampling, Sample Size and Randomization Consecutive sampling will be carried out withpatients 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 themeta‐analysis by Fabero‐Garrido et al , people with ischemic heart disease who haveundergone an inspiratory muscle training program have a mean difference of 2.18 mlO2/kg/min with respect to the control group and we want to find a deviation of 1 MET (3.5ml O2/kg/min). The calculations were carried out with the statistical software G*Power3.1, 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) wasestablished. In addition, to minimize the impact of possible dropouts, the total samplewas increased by 10% to 72 patients, which will lead to the final inclusion of 36patients in each group.Randomization of participants will be performed through a computer program that generatesa sequence of random numbers.Cardiac Rehabilitation Program.The usual CRP will be carried out and supervised by the usual multidisciplinary team ofthe HUVV. It is composed of a cardiologist, a rehabilitation physician, aphysiotherapist, a nurse and a psychologist. Prior to inclusion in the study, eachparticipant will undergo a simple ergometry test to determine their maximum heart rate(MHR), observe their behavior at maximum effort and rule out conditions thatcontraindicate exercise. The study subjects will attend the cardiac rehabilitation roomof the hospital 3 days a week. Two of these days will be dedicated to physical exercisesessions and the third to health education and a group psychological therapy session.The health education session will deal with a different topic each week (basic knowledgeof their pathology, proper medication, safe physical exercise, sexual dysfunction,healthy eating and control of cardiovascular risk factors).On the other hand, those subjects suffering from erectile dysfunction will be offered thepossibility of being seen in the urology office. The rehabilitation physician willperform a nutritional assessment by bioimpedanciometry and a morphological assessment ofthe quadriceps and another of abdominal fat, both by ultrasound. Participants with poorlycontrolled diabetes and/or morbid obesity will see the endocrinologist of the cardiacrehabilitation team.The training sessions will last approximately 75 minutes. The structure will be asfollows: ‐ Reception of patients, taking of constants (blood pressure, heart rate and glycemiain case of diabetic patients) and placement of telemetry. ‐ Warm up ‐ Strength Exercise: It will consist of different exercises with dumbbells and elasticbands involving various joints. We will work at 50% of 1 repetition maximum (1RM)measured indirectly with the method of 20 repetitions maximum (20RM). Three sets of10 repetitions of the following exercises will be completed: elbow flexion, shoulderabduction and knee extension. The rest interval between sets will be 30 seconds. ‐ Cardiovascular Exercise: It will be performed on a treadmill or stationary bicycle.It will have a duration of 30 minutes. The first month the patient will be trainedat 70% of the heart rate resulting from applying the Karvonen formula and the secondmonth at 80%. The modality may be continuous or intervallic depending on thepatient's tolerance. ‐ Relaxation and return to calm: patients will remain seated in chairs for 5 minutesduring which a guided relaxation audio will be played. ‐ Checking of constants and farewell.Patients will be weighed every week to monitor their evolution and rule out possibleadverse effects of the training. The program will be extended for 8 weeks untilcompleting 16 concurrent training sessions. At the end of the program, ergometry, bloodanalysis and the rest of the tests will be repeated.MaskingNone of the participants will know to which group they belong since they will all begiven the same EEMI device. For the control group a load of 5 cmH2O will be set. Thiswork intensity is below that necessary to achieve adaptations in the inspiratory musclesand will therefore function as a placebo.The evaluators will also not know to which group the study subjects belong since theywill not participate in the assignment or intervention process.The analysis will be done independently since the data will be delivered coded.Statistical analysisMeasures of central tendency and dispersion will be used for numerical variables, as wellas relative frequencies for categorical variables to assess comparability between groups.All relevant variables will be examined for this purpose.Exploratory data analysis will be performed to identify and address outliers that mayaffect the results. Appropriate corrections will be applied to mitigate their influence.To contrast the differences between the control and experimental groups, the Student'st‐test for independent samples or the nonparametric Mann‐Whitney test will be usedaccording to the normality of the data, measured with the Kolmogorov‐Smirnov test. Forpre‐ and post‐intervention comparisons, Student's t test for paired samples will be usedin case of normality or the Wilcoxon test, otherwise. In the case of qualitativevariables, chi‐square test will be used.In addition to the aforementioned statistical analyses, possible complex and nonlinearrelationships between variables will be explored by means of regression models ormultivariate analyses, such as multiple regression or principal component analysis.The analyses will be performed with the IBM SPSS v.24 statistical program. Anticipatedrisks and contingency plansAnticipated risk Contingency plan:Non‐compliance of participants with the IMT Submission of paper log of compliance in theform of a diaryIncorrect performance of the IMT technique Weekly reinforcement session at HUVVDoubts about the performance of the IMT by the participants The physiotherapistsupervising the CRP physical exercise will always be available during the sessions toclarify any doubts.Prospective It would be interesting to study in future clinical trials the specifictraining of the expiratory musculature (EMT) in these patients, both in isolation andconcurrently with inspiratory training. There are studies that have shown benefits inpostural stability and walking speed due to the strengthening of the central musculatureof the body.It would also be interesting to measure the medium‐ and long‐term effects of EMT, as sofar existing studies have not done so.Justification of available resources The University of Cadiz, through its Library, willprovide the bibliographic resources necessary for the development of this researchproject, such as access to the main publishers and indexed scientific journals.The HUVV will provide the facilities and materials used by the CRP for this study.The interviews and some of the pre‐ and post‐intervention measurements will be carriedout in the cardiac rehabilitation office of the HUVV. Its dimensions are 7m2 and it hasthe following materials: ‐ JAMARTm approved hydraulic dynamometer. ‐ Hogan Health Industries hand‐held dynamometer, MicroFet 2 model. ‐ Measuring tape. ‐ Bioimpedance meter, Akern brand, Nutrilab model. ‐ MicroRPM® digital portable manometer.Physical training, health education sessions, group psychology therapies and somemeasurements will be carried out in the cardiac rehabilitation room of the HUVV. It hasan area of 80m2. and has the following equipment: ‐ 2 treadmills. ‐ 6 exercise bikes. ‐ Dumbbells. ‐ Elastic bands. ‐ Telemetry systems for patients. ‐ Computer with the necessary software to monitor electrocardiograms and heart rates(Mortaraâ system). ‐ Monitors where to observe the electrography in real time. ‐ Chairs for taking constants and for health education and relaxation sessions. ‐ Loudspeaker and playback system for relaxation audios. ‐ Blood pressure monitors, stethoscopes and glucometers to monitor patients' vitalsigns. ‐ Defibrillator and stretcher in case of adverse effects. ‐ 43" flat screen for health education sessions.Ergometry tests will be performed by a cardiologist and a specialized nurse from thecardiology service of the HUVV in its exercise physiology laboratory. The laboratory isequipped with the following elements: ‐ Treadmill ‐ Sphygmomanometer, glucometer and phonendoscope. ‐ Computer with the appropriate software to perform the incremental exercise protocol. ‐ Defibrillator. ‐ StretcherThis project is supported theoretically and technically by the TIC‐256 Intelligent SocialKnowledge Based Systems (IntellSOK) research group and the Pain Observatory of theUniversity of Cadiz. Both entities have extensive experience in the development ofresearch studies and have the technical resources and knowledge necessary for the properimplementation of the proposed project.Ethical and/or biosafety implications of the proposed research. The present project willfollow the ethical principles established for medical research on human subjectsaccording to the Declaration of Helsinki.The present clinical trial has been previously approved by El Comité de Ética eInvestigación con medicamentos (CEIm) Provincial de Málaga (Spain), withcommunication/application code: SICEIA‐2024‐001869.Since data from real subjects will be used, it is essential to guarantee theirconfidentiality, privacy and data protection. To this end, the participation of thesubjects will be voluntary, and it is an indispensable requirement to sign the informedconsent form for participation in the study. Participants will be able to withdraw fromthe study whenever they wish to do so. To safeguard the identity of the subjects, theirnames and surnames will be coded in the database.This is a low‐intervention clinical trial, since IMT is a very safe intervention, as itis routinely performed in other populations of chronic cardiac and respiratory patientswithout any relevant adverse effects having been reported.In addition, patients will be scrupulously stratified according to their cardiovascularrisk and the cardiac rehabilitation team at the HUVV has extensive experience in trainingthis type of patient and its professionals are in constant training.The damages incurred by the participants will be covered by the individual or collectiveself‐insurance that the researcher in question has already contracted for the usualpractice of his or her profession.To publish the results of the project in international peer‐reviewed journals and presentthe results at congresses worldwide, the Consolidated Standards of Reporting Trials(CONSORT) statement will be followed. In addition, as part of the knowledge translationstrategy, we will disseminate the results on institutional websites and social media,contact news organizations and identify partner institutions interested in the results.