Comparative Effects of Different Inspiratory Muscle Training Modalities in Patients With Heart Failure. (IMT-HF-COMPARE)

Effects of Inspiratory Muscle Training on Maximal Inspiratory Pressure, Cardiopulmonary Capacity, and Quality of Life in Patients With Heart Failure

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure; Muscle Weakness; Inspiratory Muscle Weakness; Heart Failure and Reduced Ejection Fraction; Heart Failure and Mildly Reduced Ejection Fraction
• Intervention / Treatment: Device: Mechanical Pressure-Threshold IMT Device; Device: PowerBreathe KH2 Electronic IMT Device; Device: Sub-therapeutic Mechanical IMT Device (Sham)

Detailed Description

This clinical trial aims to explore the underlying physiological mechanisms and comparative systemic adaptations of mechanical pressure-threshold versus electronic flow-resistive inspiratory muscle training (IMT) in patients with Heart Failure with Reduced Ejection Fraction (HFrEF). Patients with HFrEF frequently exhibit respiratory muscle weakness, which triggers an early activation of the inspiratory muscle metaboreflex. This reflex increases sympathetic vasoconstrictor drive to active locomotor muscles, accelerating peripheral fatigue, exacerbating dyspnea, and limiting overall exercise tolerance.

To systematically address these mechanisms, the protocol is structured into a precise multi-stage timeline distributed over 8 consecutive weeks:

1. Methodological Familiarization and Baseline Testing (Weeks 1-2):

   To eliminate the confounding "learning effect" and ensure internal data validity, the first two weeks are exclusively dedicated to patient technical habituation. Participants will learn proper diaphragmatic breathing techniques, device interface seal (using flanged mouthpieces and nose clips), and device manipulation under submaximal loads. Concurrently, baseline clinical profiling will be conducted, including spirometry, maximal inspiratory pressure (MIP), resting cardiac autonomic balance through Heart Rate Variability (HRV), and central vascular stiffness via Pulse Wave Velocity (PWV).

2. High-Intensity Standardized Intervention (Weeks 3-8):

   The formal training phase lasts 6 weeks with a frequency of 3 supervised sessions per week, totaling 18 effective sessions. To preserve biomechanical quality and prevent disproportionate dyspnea or early neuromuscular fatigue in this clinical population, the training volume is strictly set to 5 sets of 8 repetitions (40 breathing efforts per session), separated by standardized resting intervals.

   The progression scheme utilizes a linear model based on the initial baseline MIP, preventing the logistical friction of constant maximum re-testing in fragile patients:

   • Weeks 3-4: 60% of baseline MIP (Groups 1 and 2) or 15% (Group 3).
   • Weeks 5-6: Progression to 70% of baseline MIP (Groups 1 and 2) or 15% (Group 3).
   • Weeks 7-8: Progression to 80% of baseline MIP (Groups 1 and 2) or 15% (Group 3).

3. Advanced Dynamic Evaluations:

   • Muscle Oxygenation and Metaboreflex Provocation (NIRS): Peripheral blood flow redistribution and tissue oxygen saturation kinetics (SmO2) will be tracked continuously via three percutaneous Near-Infrared Spectroscopy sensors (Moxy Monitor®) placed simultaneously on the right intercostal space (respiratory pump), vastus lateralis of the quadriceps (locomotor reference), and the dominant forearm flexor mass (non-locomotor control). The provocation protocol includes an inspiratory resistive load test at 60% MIP until task failure (inability to sustain target pressure for three consecutive breaths), followed immediately by an isometric Handgrip peripheral fatigue protocol (12 repetitions of 10-second maximal voluntary contractions with 30-second rests).
   • Cardiopulmonary Exercise Testing (CPET): Maximal oxygen consumption (VO2max) and ventilatory efficiency (VE/VCO2 slope) will be evaluated using a cycle ergometer under an incremental ramp protocol. Following the recommendations of Tuesta et al. (2023), the workload increase rate will be individually tailored based on the patient's NYHA functional class: 5 W/min for Class IV, 6-7 W/min for Class III, 8-9 W/min for Class II, and 9 W/min or more for Class I, targeting an optimal test duration between 8 and 12 minutes to peak exhaustion.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Valparaiso
    • Viña del Mar, Valparaiso, Chile, 2520000
      • Universidad Andrés Bello, Campus Viña del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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).
2. Recent myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within the last 6 months.
3. Severe uncorrected valvular heart disease or complex, uncontrolled ventricular arrhythmias.
4. 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.
5. Cognitive impairment or psychological conditions that limit the ability to follow instructions, maintain correct diaphragmatic breathing technique, or properly seal the training device mouthpiece.
6. Current participation in another structured physical rehabilitation or formal sports training program that could confound the systemic results of the intervention.
7. Any acute infectious, inflammatory, or medical condition that, in the investigator's opinion, poses a safety risk during high-intensity training.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mechanical Pressure- Threshold 60% IMT; 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; 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.
Experimental: Electronic Flow-Resistive 60% IMT; 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; An electronic flow-resistive device that delivers automated, dynamic, and electronically controlled resistance throughout the entire inspiratory phase to optimize muscle loading.
Sham Comparator: Sham Control IMT; 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); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ventilatory Efficiency (VE/VCO2 slope)	The VE/VCO2 slope will be calculated via linear regression from the initiation of exercise to the respiratory compensation point during the cardiopulmonary exercise test, reflecting changes in ventilatory efficiency and ventilation-perfusion matching.	Baseline (Week 0) and post-intervention (Week 9).
Change in Multi-Muscle Tissue Oxygen Saturation Kinetics (SmO2)	Multi-muscle tissue oxygen saturation (SmO2) kinetics will be continuously monitored via Near-Infrared Spectroscopy (NIRS) using three simultaneous Moxy sensors (intercostal space, vastus lateralis, and dominant forearm flexors). The assessment will follow a strict sequential protocol: first, patients will perform an inspiratory resistive load challenge at 60% MIP until task failure to induce respiratory muscle fatigue and trigger the metaboreflex; immediately following, they will execute a peripheral isometric handgrip protocol (12 repetitions of 10-second maximal voluntary contractions with 30-second rests) to evaluate the specific systemic vasoconstrictor impact and blood flow redistribution across respiratory, locomotor, and non-locomotor beds.	Baseline (Week 0) and post-intervention (Week 9).
Change in Diaphragmatic and Parasternal Intercostal Ultrasound Parameters	B-mode ultrasound will be used to evaluate respiratory muscle morphology. Diaphragmatic thickness will be measured at the zone of apposition at end-expiration and end-inspiration to calculate the thickening fraction. Concurrently, the thickness and thickening fraction of the parasternal intercostal muscles will be assessed in the second intercostal space during quiet and maximal breathing to quantify structural adaptations and accessory muscle recruitment changes.	Baseline (Week 0) and post-intervention (Week 9).
Change in Inspiratory Muscle Endurance Time	Inspiratory muscle endurance will be quantified as the total time (in seconds) sustained during the constant-load resistive breathing challenge at 60% of baseline MIP until task failure (defined as the inability to overcome the target pressure for three consecutive breaths).	Baseline (Week 0) and post-intervention (Week 9).

Collaborators and Investigators

• Sponsor: Universidad Nacional Andres Bello
• Investigators: Principal Investigator: Gabriel I Garrido Cerda, PhD(c), university Andrés Bello

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Quality of Life; inspiratory muscle training; Maximal Inspiratory Pressure; Near-Infrared Spectroscopy; Cardiopulmonary Exercise Testing; Metaboreflex; Diaphragmatic Ultrasound
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Cardiovascular Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Heart Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Failure; Muscle Weakness; Heart Failure, Systolic
• Other Study ID Numbers: 17B2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) including baseline characteristics, maximal inspiratory pressure (MIP) values, diaphragmatic and parasternal intercostal ultrasound measurements, and breath-by-breath metabolic cart parameters (VO2, VCO2, VE) will be shared. Relative tissue oxygenation kinetics (SmO2) from the intercostal, vastus lateralis, and forearm sensors during the resistive load and handgrip protocols will also be available. Data will be shared upon reasonable request after formal publication of the primary trial results.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No