Intermittent Hypoxic-Hyperoxic Exposure in Patients with Heart Failure - A Pilot Study

Heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction causes substantial global burden with limited therapies, especially for HFpEF. This pilot study assessed safety and efficacy of a 10-week individualized intermittent hypoxia-hyperoxia exposure (IHHE) program, hypothesizing good tolerability and improvements in exercise capacity and quality of life (QoL).

In this prospective mechanistic feasibility study, HFpEF and HFrEF patients completed supervised seated IHHE sessions three times weekly for 10 weeks using a medical altitude breathing device (ReOxy, Ai Mediq S.A., Luxembourg). Blood pressure (BP) was monitored before and after sessions. Pre- and post-intervention assessments included echocardiography, cardiopulmonary exercise testing (CPET), 6-minutes walking test (6MWT), isokinetic muscle strength, body composition, biomarkers, patient-reported outcomes, and clinically indicated right heart catheterization (RHC).

Nine outpatients (5 HFpEF, 4 HFrEF; age 66.6±10.9 years, 22% female, BMI 27.9±5.4 kg/m2) completed the study. IHHE was safe and well tolerated (adherence 95%), with no adverse events. Across weeks 1-10, post-session reductions in systolic (β =-5.95 mmHg) and diastolic blood pressure (β=-3.74 mmHg), and heart rate (β=-5.18 bpm) were measured (all p< 0.001). A significant decrease of fat mass index 9.32±2.56 vs. 8.92±2.41 kg/m2 (P=0.031), and visceral fat area 127.6±30.6 vs. 121.9±29.7 cm2 (P=0.005), as well as an increase of body mineral content 3.14±0.57 vs. 3.21±0.55 kg (P=0.028), and tissue impedance (RB250: 4.02±0.50 vs. 4.12±0.56 kHz, P=0.041), were measured. There was a numeric improvement (not statistically significant) of peak VO2 1536 [1148; 2064] vs. 1828 [1476; 2175] mL/min (P=0.674, about +300 mL/min), 6MWT 499.66±71.65 vs. 521.12±62.59 m (P=0.260, about +22 m), and right leg peak torque flexion 74±21.77 vs. 81.68±22.67 Nm (P=0.109) and extension 119.89±36.31 vs. 122.69±38.77 Nm (P=0.641). RHC showed no adverse acute hemodynamic effects, while invasively measured left ventricular systolic pressure decreased during hypoxia (151 vs. 120 mmHg). No changes in QoL were observed (P≥0.384).

Ten-week IHHE was safe and feasible in HF patients and led to improved BP and body composition and showed trends toward better exercise capacity. Larger randomized trials are needed to confirm these results.