Comparative Effects of Different Inspiratory Muscle Training Modalities in Patients With Heart Failure.

NCT07688863 | Enrolling By Invitation

• 1 other identifier: 17B2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effects of three different modalities of inspiratory muscle training (IMT) in patients diagnosed with chronic heart failure who exhibit reduced or mid-range left ventricular ejection fraction (LVEF \< 50%). Patients will be recruited from cardiac rehabilitation programs and must be clinically stable before entering the protocol. The study has a total duration of 8 weeks and is divided into two distinct phases. During the first 2 weeks, participants will undergo a familiarization phase to learn the proper breathing techniques with the devices and to complete baseline resting and functional clinical evaluations. The following 6 weeks will comprise the effective training phase, consisting of 3 weekly sessions of high-intensity inspiratory training. Participants will be randomly assigned to one of three parallel groups:

• Group 1 (Pressure-Threshold IMT): Participants will train using a mechanical pressure-threshold device at an initial high-intensity load of 60% of their baseline maximal inspiratory pressure (MIP).
• Group 2 (Electronic Flow-Resistive IMT): Participants will train at a high-intensity load of 60% of their baseline MIP utilizing the PowerBreathe KH2 electronic device, which provides a dynamic, flow-dependent automated resistance.
• Group 3 (Control / Sham IMT): Participants will perform the same breathing protocol but using a mechanical device set at a low, non-training intensity of 15% of their baseline MIP. For all three groups, training volume is standardized to 5 sets of 8 repetitions (40 inspiratory efforts per session). To ensure progressive overload, training intensity will be increased by 10% of the initial baseline MIP value every 2 weeks. The main outcomes to be evaluated before and immediately after the 8-week period include maximal inspiratory muscle strength, structural changes in respiratory muscles (diaphragmatic and parasternal intercostal thickening fraction measured via ultrasound), cardiac autonomic balance (heart rate variability), and health-related quality of life. Additionally, dynamic responses such as respiratory and locomotor muscle oxygenation (measured continuously via Near-Infrared Spectroscopy \[NIRS\] during a respiratory metabolic reflex provocation test) and overall cardiopulmonary exercise capacity (measured via an incremental cycle ergometer test) will be analyzed. This study aims to determine which training modality provides the most effective physiological adaptations to optimize rehabilitation in this population.

Conditions

Heart Failure; Muscle Weakness; Inspiratory Muscle Weakness; Heart Failure and Mildly Reduced Ejection Fraction; Heart Failure and Reduced Ejection Fraction

Keywords

inspiratory muscle training; Heart Failure; Quality of Life; Maximal Inspiratory Pressure; Metaboreflex; Near-Infrared Spectroscopy; Cardiopulmonary Exercise Testing; Diaphragmatic Ultrasound

Outcome Measures

Primary Outcomes (3)

• Change in Maximal Inspiratory Pressure (MIP)

  Maximal Inspiratory Pressure (MIP) will be assessed from residual volume using a calibrated digital manometer according to standardized international guidelines. The highest value obtained from at least three reproducible maneuvers (varying less than 10%) will be recorded to quantify changes in volitional inspiratory muscle strength

  Baseline (Week 0) and post-intervention (Week 9).

• Change in Peak Oxygen Consumption (VO2 peak)

  Peak oxygen consumption will be evaluated during a incremental symptom-limited cardiopulmonary exercise test (CPET) on a cycle ergometer using a breath-by-breath metabolic cart to assess changes in aerobic capacity.

  Baseline (Week 0) and post-intervention (Week 9).

• Change in Health-Related Quality of Life via Minnesota Living with Heart Failure Questionnaire (MLHFQ)

  Changes in disease-specific health-related quality of life will be assessed using the unabbreviated Minnesota Living with Heart Failure Questionnaire (MLHFQ). The total score ranges from 0 to 105, where a higher score indicates a worse health-related quality of life and greater symptom limitation.

  Baseline (Week 0) and post-intervention (Week 9).

Secondary Outcomes (4)

• Change in Ventilatory Efficiency (VE/VCO2 slope)

  Baseline (Week 0) and post-intervention (Week 9).

• Change in Multi-Muscle Tissue Oxygen Saturation Kinetics (SmO2)

  Baseline (Week 0) and post-intervention (Week 9).

• Change in Diaphragmatic and Parasternal Intercostal Ultrasound Parameters

  Baseline (Week 0) and post-intervention (Week 9).

• Change in Inspiratory Muscle Endurance Time

  Baseline (Week 0) and post-intervention (Week 9).

Study Arms (3)

Mechanical Pressure- Threshold 60% IMT

EXPERIMENTAL

High-intensity inspiratory muscle training utilizing a mechanical pressure-threshold device. The training protocol consists of 3 supervised sessions per week for 6 weeks (18 sessions total), with a standardized volume of 5 sets of 8 repetitions per session. The training load is established based on the patient's initial baseline Maximal Inspiratory Pressure (MIP). To ensure progressive overload, intensity is specifically structured as follows: 60% of baseline MIP during weeks 1-2, progressing to 70% during weeks 3-4, and reaching 80% during weeks 5-6.

Device: Mechanical Pressure-Threshold IMT Device

Electronic Flow-Resistive 60% IMT

EXPERIMENTAL

High-intensity inspiratory muscle training utilizing the PowerBreathe KH2 electronic flow-resistive device, which delivers automated, dynamic resistance throughout the breath. The protocol consists of 3 supervised sessions per week for 6 weeks (18 sessions total), with a standardized volume of 5 sets of 8 repetitions per session. The training load is calibrated based on the initial baseline Maximal Inspiratory Pressure (MIP), using a progressive overload scheme: 60% of baseline MIP during weeks 1-2, advancing to 70% during weeks 3-4, and reaching 80% during weeks 5-6.

Device: PowerBreathe KH2 Electronic IMT Device

Sham Control IMT

SHAM COMPARATOR

Low-intensity inspiratory muscle training serving as a sham control, utilizing a mechanical pressure-threshold device set to a sub-therapeutic load. To simulate the active treatment arms, the protocol consists of 3 supervised sessions per week for 6 weeks (18 sessions total), with the exact same standardized volume of 5 sets of 8 repetitions per session. The training load is based on the initial baseline Maximal Inspiratory Pressure (MIP) but kept intentionally low to avoid true physiological conditioning: 15% of baseline MIP during 6 weeks

Device: Sub-therapeutic Mechanical IMT Device (Sham)

Interventions

Mechanical Pressure-Threshold IMT Device DEVICE

A mechanical threshold loading device used to deliver high-intensity inspiratory muscle training. Resistance is load-dependent, requiring the participant to generate sufficient negative pressure to open the valve.

Mechanical Pressure- Threshold 60% IMT

PowerBreathe KH2 Electronic IMT Device DEVICE

An electronic flow-resistive device that delivers automated, dynamic, and electronically controlled resistance throughout the entire inspiratory phase to optimize muscle loading.

Electronic Flow-Resistive 60% IMT

Sub-therapeutic Mechanical IMT Device (Sham) DEVICE

The same mechanical threshold loading device model, but configured with a sub-therapeutic, low-resistance load to serve as a physiological control without training effect

Sham Control IMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented clinical diagnosis of chronic Heart Failure with Reduced Ejection Fraction (HFrEF) according to the European Society of Cardiology (ESC) guidelines.
• Left Ventricular Ejection Fraction (LVEF) less than or equal to 40% documented by echocardiography within the last 12 months.
• Clinically stable condition for at least 3 months prior to enrollment, with no hospitalizations or major changes in optimized medical therapy.
• New York Heart Association (NYHA) functional class I to IV.
• Evidence of inspiratory muscle weakness, defined as a baseline Maximal Inspiratory Pressure (MIP) \< 70% of the predicted value for age and sex.
• Age greater than or equal to 18 years.
• Patient must be capable of understanding the protocol instructions and must provide signed written informed consent.

You may not qualify if:

• Presence of primary severe pulmonary or respiratory diseases (e.g., Chronic Obstructive Pulmonary Disease \[COPD\] GOLD stage III or IV, active asthma, severe pulmonary hypertension, or restrictive lung disease).
• Recent myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within the last 6 months.
• Severe uncorrected valvular heart disease or complex, uncontrolled ventricular arrhythmias.
• Orthopedic, neurological, or musculoskeletal limitations that prevent the safe execution of an incremental cardiopulmonary exercise test on a cycle ergometer or the performance of the isometric handgrip protocol.
• Cognitive impairment or psychological conditions that limit the ability to follow instructions, maintain correct diaphragmatic breathing technique, or properly seal the training device mouthpiece.
• Current participation in another structured physical rehabilitation or formal sports training program that could confound the systemic results of the intervention.
• Any acute infectious, inflammatory, or medical condition that, in the investigator's opinion, poses a safety risk during high-intensity training.

Sponsors & Collaborators

• Universidad Nacional Andres Bello: lead

Study Sites (1)

Universidad Andrés Bello, Campus Viña del Mar

Viña del Mar, Valparaiso, 2520000, Chile

Location

Related Publications (10)

• Zacarias Rondinel T, Bocchi L, Cipriano Junior G, Chiappa GRDS, Martins GS, Mateus SRM, Cahalin LP, Cipriano GFB. Diaphragm thickness and mobility elicited by two different modalities of inspiratory muscle loading in heart failure participants: A randomized crossover study. PLoS One. 2024 May 24;19(5):e0302735. doi: 10.1371/journal.pone.0302735. eCollection 2024.

  PMID: 38787839 BACKGROUND

• Kabbadj K, Taiek N, El Hjouji W, El Karrouti O, El Hangouche AJ. Cardiopulmonary Exercise Testing: Methodology, Interpretation, and Role in Exercise Prescription for Cardiac Rehabilitation. US Cardiol. 2024 Dec 20;18:e22. doi: 10.15420/usc.2024.37. eCollection 2024.

  PMID: 39872828 BACKGROUND

• Bilbao A, Escobar A, Garcia-Perez L, Navarro G, Quiros R. The Minnesota living with heart failure questionnaire: comparison of different factor structures. Health Qual Life Outcomes. 2016 Feb 17;14:23. doi: 10.1186/s12955-016-0425-7.

  PMID: 26887590 BACKGROUND

• Tuesta M, Alvarez C, Pedemonte O, Araneda OF, Manriquez-Villarroel P, Berthelon P, Reyes A. Average and Interindividual Effects to a Comprehensive Cardiovascular Rehabilitation Program. Int J Environ Res Public Health. 2022 Dec 24;20(1):261. doi: 10.3390/ijerph20010261.

  PMID: 36612584 BACKGROUND

• Bosnak-Guclu M, Arikan H, Savci S, Inal-Ince D, Tulumen E, Aytemir K, Tokgozoglu L. Effects of inspiratory muscle training in patients with heart failure. Respir Med. 2011 Nov;105(11):1671-81. doi: 10.1016/j.rmed.2011.05.001. Epub 2011 May 31.

  PMID: 21621993 BACKGROUND

• Juarez M, Castillo-Rodriguez C, Soliman D, Del Rio-Pertuz G, Nugent K. Cardiopulmonary Exercise Testing in Heart Failure. J Cardiovasc Dev Dis. 2024 Feb 20;11(3):70. doi: 10.3390/jcdd11030070.

  PMID: 38535093 BACKGROUND

• American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002 Aug 15;166(4):518-624. doi: 10.1164/rccm.166.4.518. No abstract available.

  PMID: 12186831 BACKGROUND

• Rittayamai N, Marinpong V, Chuaychoo B, Tscheikuna J, Brochard LJ. Ultrasound Evaluation of Parasternal Intercostal, Diaphragm Activity, and Their Ratio in Male Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2024 Apr 15;209(8):1016-1018. doi: 10.1164/rccm.202310-1769LE. No abstract available.

  PMID: 38319129 BACKGROUND

• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.

  PMID: 35363499 BACKGROUND

• Azambuja ACM, de Oliveira LZ, Sbruzzi G. Inspiratory Muscle Training in Patients With Heart Failure: What Is New? Systematic Review and Meta-Analysis. Phys Ther. 2020 Dec 7;100(12):2099-2109. doi: 10.1093/ptj/pzaa171.

  PMID: 32936904 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Heart Failure, Systolic; Muscle Weakness

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Gabriel I Garrido Cerda, PhD(c)

  university Andrés Bello

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: To minimize performance bias, the clinical staff supervising the daily training sessions (care providers) will remain completely blinded to group allocations, as devices and digital interfaces will be pre-configured and delivered using coded identifiers. Furthermore, the external investigator responsible for primary data acquisition and testing (cardiopulmonary exercise testing and diaphragmatic ultrasound) will remain strictly blinded to group assignments. Finally, the statistician conducting the analysis in R will handle all datasets using randomized codes, which will be broken only after processing all outcomes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator and Doctoral Candidate, PhD in Rehabilitation Sciences at Andres Bello University

Model Details: A randomized, parallel-group, single-blind clinical trial. Eligible participants will be randomly allocated in a 1:1:1 ratio into one of three parallel arms: Group 1 (High-Intensity Pressure-Threshold IMT), Group 2 (High-Intensity Electronic Flow-Resistive IMT using the PowerBreathe KH2), or Group 3 (Low-Intensity Sham Control IMT). All interventions will run concurrently over a total span of 8 weeks. This duration includes a 2-week baseline testing and technical familiarization period, followed by a 6-week progressive training protocol consisting of 18 effective sessions. Outcomes will be assessed by an external investigator blinded to group allocations (single-blind design). Statistical analysis will be executed using coded identifiers for each arm to maintain allocation concealment until the processing of all respiratory, metabolic, and tissue oxygenation variables is finalized in R.

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: July 7, 2026
• Study Start: June 17, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 7, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data and supporting documents will be available beginning 6 months after the primary publication of the trial results and will remain accessible for a period of 36 months.
• Access Criteria: Data will be shared exclusively with qualified academic researchers who submit a methodologically sound research proposal that aligns with the scope of this trial. To gain access, interested parties must submit their proposal and statistical analysis plan directly to the Principal Investigator via email. Requests are subject to formal approval by the investigator and require a signed formal Data Sharing Agreement to ensure compliance with participant confidentiality and ethical standards.

Locations

CL (1)