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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.
• Устройство 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

Первичные конечные точки

• Change in Maximal Inspiratory Pressure (MIP) [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]
• Change in Peak Oxygen Consumption (VO2 peak) [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]
• Change in Health-Related Quality of Life via Minnesota Living with Heart Failure Questionnaire (MLHFQ) [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]

Вторичные конечные точки (4)

• Change in Ventilatory Efficiency (VE/VCO2 slope) [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]
• Change in Multi-Muscle Tissue Oxygen Saturation Kinetics (SmO2) [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]
• Change in Diaphragmatic and Parasternal Intercostal Ultrasound Parameters [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]
• Change in Inspiratory Muscle Endurance Time [Срок оценки: Baseline (Week 0) and post-intervention (Week 9).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Чили · 1 центр

• Universidad Andrés Bello, Campus Viña del Mar — Viña del Mar

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07688863 · 17B2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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