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

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.

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.

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.