The effect of inspiratory muscle training on dysfunctional breathing and functional ability in patients with chronic heart failure. A study protocol for a randomized controlled trial

Objective of the proposal trial

The aim of the study is to investigate the effect of IMT on dysfunctional breathing, diaphragmatic thickness and functional ability. Secondary objective is to investigate the effect of IMT on maximal inspiratory pressure (MIP), dyspnea, and quality of life in patients with CHF.

Study design

This single-center, randomized controlled, single-blinded clinical trial is designed to investigate the effectiveness of IMT on breathing pattern, diaphragmatic thickness and functional ability in patients with CHF. The study protocol adheres to the guidelines outlined in the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) statement.¹⁵ A completed SPIRIT checklist has been uploaded to an approved open repository. Ethical approval has been granted by the Ethics Committee of the University of West Attica (approval number: 51604/04-06-2025), and the trial is registered with the Clinical Trial Registry (registration number: NCT07104357).

This study includes a four-week intervention period. A total of 22 outpatients with CHF will be randomly assigned to two groups with a 1:1 ratio. The intervention group will be trained with IMT in conjunction with DB and the control group will receive only DB. There will be two measurements of the outcomes (0 and 4 weeks). The flow diagram of the study protocol is presented in Figure 1.

Figure 1. Flow chart of the study in accordance with the SPIRIT statement.

IMT: inspiratory muscle training; DB: diaphragmatic breathing.

Study setting

All assessments will be conducted individually at the Laboratory of Advanced Physiotherapy in the Physiotherapy Department of the University of West Attica (UNIWA) in Athens, which will coordinate the study. All measurements will take place in the same laboratory. All participants will receive five treatment sessions for four weeks. Specifically, the first two sessions at every week will be conducted in the Laboratory, and the remaining three sessions will be home-based.

Recruitment procedures

Participant recruitment will take place in the outpatient care unit of the Cardiological Clinic at “Evangelismos General Hospital” in Athens. The hospital’s research committee has approved the study protocol (76/21–03-25). Patients will enter the study according to the inclusion and exclusion criteria. Eligible participants who agree to take part in the study will be provided with detailed information about the benefits and the risks of the study. All participants will read and sign the consent form. They will be informed about (a) the study’s objectives and methods, (b) their voluntary participation, with the right to decide whether to take part, (c) their right to withdraw from the study at any time, even after signing the consent form, and (d) assurance that their decision to participate will not impact the research services provided.

Inclusion and exclusion criteria

Eligible participants will be adults aged ≥18 years with a clinical diagnosis of heart failure within the previous three to twelve months. Participants must be current outpatients in a stable optimal medical regimen for at least 3 months, able to perform IMT and breathing exercises. If they are clinically stable, without hospital admission in the previous 3 months and without participation in any other training program in the previous 6 months, they will qualify to participate in the study.¹⁶ The exclusion criteria from the study are unstable angina or recent acute myocardial infarction, uncontrolled hypertension, valve disease, and peripheral arterial disease and a 6MWT assessment of less than 300 meters.¹⁷ Patients with previous pulmonary disease (forced vital capacity <80% of predicted and/or forced expiratory volume in 1 seċ < 70% of predicted),¹⁸ history of exercise-induced asthma, and smokers will be also excluded.

Randomization, allocation concealment, and blinding

The randomization will be carried out by the secretary of the Cardiological Clinic at ‘Evangelismos General Hospital’ using sequentially numbered, opaque, sealed envelopes to achieve allocation concealment. The secretary will open the sealed envelopes and independently allocate the participants to groups in a 1:1 ratio sequentially. The main researcher will be the only person aware of the participants’ randomization. All research colleagues will be blinded to group allocations.

Sample size

The calculation of the appropriate sample size to examine differences between groups, was based on the effect size of 0.48 in the study of Padula and colleagues.¹⁹ More specifically, with an effect size of 0.48, power of 0.80, and α = 0.05, the minimum sample size was found to be 16 participants, corresponding to 8 patients allocated in the experimental group and 8 in the control group. Taking approximate a 20% drop rate and a 7% missing rate into account²⁰ the final sample size was set to 11 per group. Thus, a total of 22 patients for the intervention and the control group will be recruited in this study.

Initial assessments

A cardiologist of the outpatient clinic of ‘Evangelismos Hospital’ will examine the cardiac function of the out-patients and provide the diagnosis of heart failure. A physiotherapist will measure the MIP for each out-patient and administer the questionnaires in a random order.

Interventions

All participants will attend a two-hour session to be informed about their disease and its consequences on their breathing pattern, functional ability and quality of life by the main researcher.

IMT and DB will be provided by two separate physiotherapists (one for IMT and another one for DB) at the laboratory of Advanced Physiotherapy at the Physiotherapy Department, UNIWA, Athens. Brief descriptions of the interventions planned for each group are provided below ( Table 1).

Experimental group: Participants (n = 11) will perform 20 sessions of respiratory muscle strengthening (20 minutes at 30–60% of MIP), using the Threshold Inspiratory Muscle Training device, and DB with pursed-lips exhalation for breathing retraining (calm breathing up to tidal volume-TV for 10 minutes). The specific training will take place five (5) days a week, once a day, for four (4) weeks, with a total duration of approximately 30 minutes.¹⁹ During IMT, the initial inspiratory load will be set at 30% of the patient’s maximal static MIP. Training loads will be adjusted weekly to ensure a 10% increase in MIP for each patient, reaching a final load of 60% MIP at the fourth week.¹⁴ Patients will complete three sets of 15 repetitions in every session. During DB, patients will be asked to inhale slowly (TV) through the nose, directing the airflow towards the diaphragm, allowing the upper abdomen to rise. Exhalation will be performed slowly through pursed lips, while engaging the abdominal muscles to push the air out. Patients will be instructed to maintain a breathing rate of 12–16 breaths per minute.

Control group: Participants will receive breathing retraining as described above for the intervention group.

Any departure from the administration of treatment sessions (such as missing more than one appointment) or any exacerbation of cardiac symptoms, which requires hospitalization, will lead to exclusion.

Outcome measures

Outcomes will be assessed by independent research colleagues. The evaluations will take place at two points: prior to treatment (week 0), and post-treatment (week 4). Primary outcomes are the dysfunctional breathing (Hi-Lo Test), the diaphragm thickness (diaphragmatic ultrasonography), and the functional capacity (6MWT). Secondary outcomes such as MIP, dyspnea (MRC), and quality of life (SF-12 v2) will be also assessed.

Primary outcome measures

Dysfunctional breathing will be assessed with the Hi-Lo breathing test.²¹ A physiotherapist will place one hand on the participant’s chest and the other on their abdomen while calm breathing up to TV. The test is considered positive if the upper chest breathing pattern is observed as dominant.²² Patients with functional breathing patterns exhibit noticeable abdominal expansion without visible superior migration of the thoracic cage.²³

Diaphragmatic thickness will be evaluated with a diaphragmatic ultrasonography which is a reliable and non-invasive technique for evaluating diaphragm thickness, an indicator of hypertrophy or atrophy.²⁴ The assessment will take place in the supine position that provides greater reproducibility and less variability.²⁵ Measurements will be recorded in millimeters (mm), with normal diaphragm thickness typically ranging from 1 to 5 mm. Anatomical aspects will be assessed using an ultrasound device, E-CUBE 8LE (Seoul, Republic of Korea).

Functional capacity will be assessed with the 6-Minute Walk Test (6MWT), a simple and effective tool by measuring the maximum distance a person can walk in six minutes.²⁶ This test is particularly suitable for individuals with CHF, as it poses a low risk of acute cardiac events for evaluating functional capacity.²⁷ The 6MWT requires a flat, hard walking path measuring 30 meters in length, with markers placed every 3 meters and two cones to indicate the turning points. Additional equipment includes a stopwatch and a lap counter. The patient’s heart rate, blood pressure, and oxygen saturation will be recorded before and after the test.²⁶ Since the 6MWT evaluates functional capacity and performance can be influenced by various factors, it is essential to conduct the test following a consistent and standardized protocol to ensure reliable results.

Secondary outcome measures

Maximal inspiratory pressure (MIP) will assess the inspiratory muscle strength. The measurement is taken at the mouth while the individual performs a maximal inhalation starting from residual volume, holding it for at least one second.²⁸ Based on the force-length relationship, MIP increases as the diaphragm’s resting length increases that is, when the diaphragm is positioned higher or the lung volume is lower.²⁸ MIP is a reliable and reproducible measure that does not depend on the patient’s respiratory flow. In patients with heart failure, a MIP below 70% of the predicted value is indicative of inspiratory muscle weakness.

Functional dyspnea will be assessed with the Medical Research Council (MRC) Dyspnea scale, a simple grading system to evaluate the functional disability due to dyspnea.²⁹ Patients self-report their level of disability by selecting one of five grades (0–4) that best describes their experience. In the present study, the Greek version of the MRC Scale will be used to assess the sensation of breathlessness.

Quality of life will be evaluated with the Short Form Survey (SF-12v2), a questionnaire with 12-items, that measures quality of life in terms of physical and mental health.³⁰ It is a shorter version of the SF-36 and is commonly used in clinical trials with a short-self reported simple format indicating no special knowledge to complete it. The Greek version of the SF-12v2 will be used to assess quality of life.

Anticipated dates of trial commencement and completion

The study will start in October 2025 and is scheduled to be completed in November 2026.

Data collection

The researcher colleagues will collect data (0, 4 weeks), send them to the secretariat of the Cardiological Clinic, which will forward it to the statistician. Throughout the study, the supervisor Professor of the main researcher (PostDoc candidate at the Physiotherapy dept of the University of West Attica-UNIWA) will oversee the data collection process.

Data management

Evaluation data will be retrieved from a predefined spreadsheet containing baseline characteristics. The primary researcher and the supervisor will ensure that a secure database will be used to record and maintain the data in a SPSS file. The paper copies used for the evaluation, the signed informed consent and any other paper documents related to the study will be securely maintained within the study setting. Following the completion of the study, the spreadsheets will be forwarded to the statistician for the analysis.

Statistical analysis

IBM Statistical Package for Social Sciences software (version 29.0, SPSS, Chicago, Illinois) will be used for the analyses. Descriptive statistics will be employed to elucidate the distributional characteristics of the dataset. The reliability of repeated measures for the study variables will be determined through the Intraclass Correlation Coefficient (ICC). A 2 × 2 repeated measures ANOVA with Bonferroni adjustment will be conducted for the interaction effect between intervention (experimental and control group) and time (0 and 4 weeks) for every dependent variable separately. Eta-squared (η²) will be used for the expression of the total variance explained by the respective interaction effects. The evaluation of the homogeneity of variance will be conducted by Levene’s test. The predetermined level of statistical significance is set at p < 0.05.

Monitoring

Data monitoring

A data monitoring committee of members from the UNIWA Physiotherapy Department will periodically review the accumulating data, determining if the trial should be modified or discontinued.

Harms

The procedures of the study (assessments and intervention) will be conducted by experienced physiotherapists. A clinical staff member will oversee the entire procedure, and any adverse events will be promptly reported to the UNIWA committee throughout the trial.

Auditing

An evaluation of the study will be conducted on the 2^nd week. IMT intensity adjustments will be performed every week. Should any alteration or deviation from the protocol be observed, it will be recorded and addressed accordingly.

Ethics and dissemination

Research ethics approval

The Ethics Committee of UNIWA approved the present study under protocol no. 51604/04-06-2025. The ethics approval was obtained on 4th June 2025 from the University of West Attica. The study fully adheres to the Helsinki Declaration’s “Ethical Principles of Medical Research Involving Human Subjects.” Any protocol modifications will be promptly disclosed to the Ethics Committee. The trial is registered at the Clinical trials.gov database with identification number NCT07104357.

Protocol amendments

The study has already been modified and accepted in accordance with the suggestions from the UNIWA Ethics Committee. No further modifications are permitted.

Consent

Study participants will receive a translated version of the study protocol. Prior to participation, all individuals involved in the study will be fully informed, and written consent will be obtained from each participant.

Confidentiality

At the time of randomization, every participant will get a code number that will secure blinding and confidentiality of the participants. A confidentiality statement will be included in the consent form and will be signed accordingly. Participants’ confidentiality will be maintained throughout the study. No personal information will be disclosed.

Access to data

The primary researcher, the supervisor and the statistician will have access to the data.

Ancillary and post-trial care

The entire procedure and the study protocol will be overseen by professionals and the physiotherapy dept. of the UNIWA committee. After the trial, participants will be monitored for approximately four weeks to address any potential harms or issues that will arise, and they will be able to contact the main researcher.

Study status

The study will start on September 2025.

Study dissemination

This work will be presented in International Conference Proceedings and published in an indexed journal.