Heart failure is frequently associated with inspiratory muscle weakness, which contributes to dyspnea, reduced exercise capacity, impaired quality of life, and adverse cardiovascular outcomes. Although inspiratory muscle training (IMT) is a recommended adjunct to cardiovascular rehabilitation, the optimal training modality remains uncertain, particularly among patients with reduced and preserved ejection fraction.

This randomized controlled trial will evaluate the efficacy of a novel inspiratory muscle training protocol using tapered flow resistive loading (TFRL) compared with conventional threshold loading (TL) and usual care. A total of 108 clinically stable patients with heart failure (NYHA class II-III) will be enrolled. Participants will be stratified according to heart failure phenotype (reduced or preserved ejection fraction) and allocated to one of three groups: TFRL, TL, or control. Both training interventions will be performed for 8 weeks in combination with supervised exercise-based cardiac rehabilitation.

Primary and secondary outcomes will include inspiratory muscle strength and endurance, exercise capacity, pulmonary function, dyspnea, skeletal muscle oxygenation, autonomic balance, arterial stiffness, and health-related quality of life. The study is powered to detect moderate between-group differences and interaction effects with 80% statistical power and a two-sided alpha level of 0.05. Changes over time and between groups will be analyzed using analysis of covariance (ANCOVA), adjusting for baseline inspiratory muscle strength.

The trial aims to determine whether TFRL provides superior clinical and physiological benefits compared with conventional inspiratory muscle training and whether treatment responses differ according to heart failure phenotype.

Heart failure (HF) is a complex clinical syndrome characterized by the inability of the cardiovascular system to deliver sufficient blood flow and oxygen to meet the metabolic demands of peripheral tissues. It affects more than 64 million people worldwide and remains one of the leading causes of hospitalization, disability, and mortality among adults. Despite advances in pharmacological and device-based therapies, many patients continue to experience symptoms such as dyspnea, fatigue, exercise intolerance, and impaired quality of life. These symptoms are major determinants of disease burden and frequently persist despite optimal medical management.

Although heart failure has traditionally been considered a disorder primarily involving cardiac dysfunction, increasing evidence indicates that peripheral and respiratory impairments substantially contribute to functional limitations. Among these, inspiratory muscle weakness has emerged as an important and potentially modifiable factor. Reduced inspiratory muscle strength is common in patients with both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and has been associated with reduced exercise capacity, increased dyspnea, impaired ventilatory efficiency, autonomic dysfunction, and poorer clinical outcomes.

The pathophysiological consequences of inspiratory muscle weakness extend beyond the respiratory system. During exercise, fatigued respiratory muscles activate the respiratory muscle metaboreflex through stimulation of group III and IV afferent fibers. This reflex increases sympathetic nervous system activity and promotes peripheral vasoconstriction, particularly in locomotor muscles. As a consequence, blood flow is redistributed from exercising skeletal muscles toward the respiratory muscles, accelerating peripheral fatigue and limiting exercise tolerance. This mechanism contributes to the reduced functional capacity commonly observed in patients with heart failure.

Several studies have demonstrated that inspiratory muscle training (IMT) can improve inspiratory muscle strength and endurance, reduce dyspnea, enhance exercise performance, improve ventilatory efficiency, and increase quality of life. Additional evidence suggests that IMT may positively influence autonomic regulation, muscle oxygenation, endothelial function, and cardiovascular health. Consequently, inspiratory muscle training has become an increasingly important adjunctive therapy within cardiovascular rehabilitation programs.

Despite these promising findings, important questions remain unanswered. First, the optimal inspiratory muscle training modality for patients with heart failure has not been established. Most previous studies have employed inspiratory pressure-threshold devices. These devices require patients to generate a predetermined inspiratory pressure before airflow occurs, resulting in resistance that may not be maintained uniformly throughout the inspiratory maneuver. Consequently, the amount of inspiratory work performed during each breath may be limited.

A newer inspiratory training modality, known as tapered flow resistive loading (TFRL), may overcome some of these limitations. Unlike conventional threshold devices, TFRL dynamically adjusts resistance according to inspiratory airflow, allowing a greater training load to be maintained throughout a larger portion of the inspiratory maneuver. This results in higher inspiratory work and a contraction pattern that more closely resembles the physiological principles underlying skeletal muscle resistance training. Previous investigations in other cardiopulmonary populations have suggested that flow-resistive loading may produce greater physiological adaptations than traditional threshold loading. However, to date, this hypothesis has not been adequately tested in patients with heart failure.

A second important knowledge gap concerns potential differences in training responses between patients with reduced and preserved ejection fraction. Although inspiratory muscle weakness has been documented in both phenotypes, the underlying mechanisms may differ. Patients with reduced ejection fraction frequently exhibit greater skeletal muscle catabolism and peripheral muscle dysfunction, which could influence their response to respiratory muscle training. Conversely, evidence regarding inspiratory muscle training in HFpEF remains scarce and inconclusive. Only a limited number of studies have evaluated inspiratory muscle training in this population, and the available results have not established the most effective training strategy.

The present randomized controlled trial was designed to address these knowledge gaps and provide clinically relevant evidence regarding inspiratory muscle training in heart failure. The study will investigate whether a novel TFRL-based inspiratory muscle training program provides superior physiological and clinical benefits compared with conventional threshold loading and usual care. Furthermore, the trial will determine whether treatment effects differ according to heart failure phenotype.

A total of 108 patients with clinically stable heart failure and inspiratory muscle weakness will be enrolled. Participants will be classified according to ejection fraction phenotype and allocated to one of three intervention groups using a minimization procedure designed to balance important prognostic factors. All participants will simultaneously participate in a supervised cardiovascular rehabilitation program consisting of aerobic and resistance exercise training performed according to contemporary cardiac rehabilitation recommendations.

The inspiratory muscle training interventions will be individually prescribed according to maximal inspiratory pressure and progressively adjusted throughout the intervention period. The experimental intervention will utilize a tapered flow resistive loading device designed to maintain inspiratory resistance across a broad range of lung volumes. The comparator intervention will use a conventional inspiratory threshold loading device, representing current clinical practice. A control group will receive standard cardiovascular rehabilitation without inspiratory muscle training.

The study will comprehensively evaluate the effects of the interventions on respiratory, cardiovascular, functional, and patient-reported outcomes. Particular emphasis will be placed on understanding the physiological mechanisms through which inspiratory muscle training may improve exercise performance. These mechanisms include changes in respiratory muscle function, ventilatory efficiency, muscle oxygenation, autonomic balance, arterial stiffness, and symptom burden.

This investigation is expected to generate novel evidence regarding the clinical utility of tapered flow resistive loading in heart failure and provide important information for optimizing inspiratory muscle training prescription. By comparing two distinct inspiratory training modalities and examining responses in both reduced and preserved ejection fraction phenotypes, the study seeks to advance the personalization of cardiovascular rehabilitation strategies.

The results may contribute to future clinical practice recommendations by identifying more effective respiratory rehabilitation approaches capable of improving exercise tolerance, reducing dyspnea, enhancing quality of life, and potentially improving long-term cardiovascular outcomes in individuals living with heart failure.

Inclusion Criteria:

• History of symptomatic heart failure (NYHA functional class I and III).
• Participants able to understand and respond to the instructions given in the study
• Participants with stable disease at the moment of inclusion in this study.
• Unaltered dose and type of medication up to three months before the start of the study

Exclusion Criteria:

• Participants unable to perform a valid baseline cardiopulmonary exercise test.
• Participants with unstable angina, acute myocardial infarction, and/or heart surgery within the past three months.
• Participants with other concomitant cardiac or neurological disease.
• Participants with difficulties in maintaining a proper mouth seal or unable to avoid air leakage during pulmonary function testing.
• Participants in other non-pharmacological study will be also excluded.
• Current smokers.
• Cardiac acute decompensation.