Clinical Trials

Inclusion Criteria:

• HFrEF Patients: (≥18 yrs) receiving guideline directed pharmacologic medical therapy for >6 weeks (those with contraindications to medical therapy will meet inclusion criteria), NYHA symptoms I-III, no hospitalizations in the >3 months, have a body mass index ≤45 kg/m², currently be non-smokers with <30 pack year history and be able to exercise (i.e. without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise). Although HF medications may influence multiple physiologic systems, we feel it is important, practical, and safe to study these patients under conditions of optimal care. Concurrent withdrawal of pharmacologic therapy would likely be associated with moderate decompensation in a high proportion of patients. Accordingly, the impact of our studies will be generalizable to HF patients receiving standard optimized pharmacologic therapy, consistent with the general community. All patients will be managed by their primary care physician or cardiologist with additional review by the study team prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe.

Exclusion Criteria:

• Sustained ventricular tachycardia and/or ventricular fibrillation within 21 days of visit 1; (2) second or third degree heart block; (3) body mass index >45 kg/m²; (4) current smokers and/or smoking history >30 pack years; (5) pregnant women (testing will be done by research team if requested); (6) glomerular filtration rate of <30 mL/min/1.73m² (initial screen via clinical record within the past 6 months and this will be assessed on Visit 1); (7) individuals who are not able to engage in exercise; (8) symptomatic peripheral artery disease; (9) asthmatic patients with a low symptom perception and suffer frequency, severe exacerbations or with an abnormally low perception of dyspnea; (10) ruptured eardrum or any other condition of the ear; (11) history of spontaneous pneumothorax or osteoporosis with a history of rib fractures; or (12) history of lung disease.

• For individuals agreeing to undergo dual energy x-ray absorptiometry (DEXA) scanning for measurement of body composition as part of their study visit, additional exclusion criteria apply: recently administered gastrointestinal contrast or radionuclides; severe degenerative changes or fracture deformity in measurement areas; or inability to attain correct position and/or remain motionless for the measurement period.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/28/2025. Questions regarding updates should be directed to the study team contact.