Adding Inspiratory Muscle Training to Optimize Cardiac Rehabilitation for Heart Failure

/Abstract: Exercise intolerance and exertional dyspnea are hallmarks of heart failure with reduced ejection fraction (HFrEF). HFrEF patients have impaired locomotor muscle blood flow that directly contributes to submaximal exercise intolerance (and thereby limiting activities of daily living). Patients with HFrEF also exhibit exaggerated inspiratory muscle oxygen cost of breathing – a candidate mechanism contributing to exertional dyspnea in HFrEF. American College of Cardiology/American Heart Association guidelines recommend cardiac rehabilitation (CR) for patients with HFrEF (Class I recommendation). A core component of CR is exercise training. However, exercise training has a minimal impact on locomotor muscle blood flow and exertional dyspnea during submaximal exercise in HFrEF. Inspiratory muscle dysfunction is highly prevalent in HFrEF. In this context, inspiratory muscle training (IMT) is a clinically relevant intervention that targets the inspiratory muscles. IMT improves inspiratory muscle function, exercise tolerance, and quality of life in HFrEF. Importantly, IMT combined with exercise training leads to greater improvements in exercise tolerance and exertional symptoms than exercise training alone in patients with HFrEF. Our scientific premise is that the addition of IMT to CR increases locomotor muscle oxygen delivery and reduces inspiratory muscle oxygen cost of breathing during exercise contributing to the improvements in exercise tolerance and exertional symptoms with IMT combined with CR in HFrEF patients. The Specific Aims that will be explored in this proposal include: 1) To test if IMT combined with CR improves locomotor muscle blood flow during exercise compared to CR alone in patients with HFrEF, and 2) To test if IMT combined with CR reduces the exaggerated inspiratory muscle oxygen cost of breathing and improves ventilatory function to a greater extent than CR alone in patients with HFrEF. Both Aims are framed with testable hypotheses and clearly associated with the experimental protocol and statistical analysis plan. Our integrative, highly collaborative research team has the intellectual and technical expertise, established infrastructure, and clearly demonstrate high feasibility in performing all facets of these studies to address and interpret the Aims we have proposed. Our proposal addresses an important problem by focusing on ideas that are a significant departure from current paradigms on physiologic adaptations to exercise training in HFrEF patients. Our preliminary data and review of the rigor of prior research supporting our Aims provide strong justification for our innovative experimental design and gold standard techniques to reveal the physiologic mechanisms contributing to the improved exercise tolerance and exertional symptomology with IMT combined with CR in HFrEF. Finally, we have aligned our scientific premise, aims, and associated hypotheses with the NHLBI Research Priorities and the current NIH review criteria that emphasizes significance, impact, and innovation for R01 applications. Project Number: 1R01HL176491-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Joshua Smith | Institution: MAYO CLINIC ROCHESTER, ROCHESTER, MN | Award Amount: $745,851 | Activity Code: R01 | Study Section: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL17649101A1