Background: Heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction represents a major global health and economic burden. Despite its high prevalence, effective therapies, particularly for HfpEF, remain limited. Patients frequently exhibit reduced exercise capacity and impaired skeletal muscle function. This pilot study evaluated the safety and efficacy of a 10-week intermittent hypoxia-hyperoxia exposure (IHHE) program with individualized, progressively adjusted intensity in patients with HFpEF and HFrEF.
We hypothesized that IHHE would be well tolerated and improve exercise capacity and quality of life (QoL).
Methods: This prospective, mechanistic feasibility study included HFpEF and HFrEF patients diagnosed according to ESC criteria. The intervention consisted of IHHE using a medical altitude breathing device (ReOxy, Ai Mediq S.A., Luxembourg), performed three times weekly for 10 weeks under the supervision of a cardiologist and a sport schientist. Patients inhaled alternating hypoxic and hyperoxic air through a face mask while seated. Blood pressure (BP) was recorded before and after each session. Baseline and post-intervention assessments included echocardiography, CPET, 6-minute walk test (6MWT), quadriceps endurance, body composition (bioelectrical impedance), blood biomarkers, and QoL (SF-36, HADS, EQ-5D). Two patients underwent right heart catheterization (RHC), as this was clinically indicated for unexplained dyspnea, during IHHE to assess possible acute hemodynamic effects.
Results: Nine outpatients (5 HFpEF, 4 HFrEF; age 63 [59–78] years, 22% female; BMI 27.9 ± 5.4 kg/m²) were enrolled and completed the study. IHHE was safe and well tolerated, with no adverse events. RHC showed no acute rise in pulmonary artery or wedge pressures and no deterioration in cardiac output was observed; left ventricular systolic pressure decreased during hypoxia. Over 10 weeks, systolic and diastolic BP declined (diastolic: 83.4 ± 7.4 vs. 74.1 ± 11.0 mmHg, P=0.017) without change in heart rate. NT-proBNP levels fell non-significantly (430 [36.9–509] vs. 306 [50.6–641] pg/mL, P=0.426). 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) decreased, while body mineral content increased significantly (3.14 ± 0.57 vs. 3.21 ± 0.55 kg, P=0.028). Tissue impedance rose (RB250: 4.02 ± 0.50 vs. 4.12 ± 0.56 kHz, P=0.041), suggesting reduced congestion.
Peak quadriceps torque increased non-significantly; fatigue resistance improved (%Sdec: 8.70 [7.30–10.20] vs. 9.40 [9.00–14.60], P=0.027). Anaerobic threshold (803 ± 241 vs. 954 ± 317 mL/min, P=0.054), peak VO₂ (+300 mL/min), and 6MWT distance (+22 m) showed numerical improvements. QoL remained unchanged. Among HFpEF patients, resting metabolic rate (1521 ± 221 vs. 1547 ± 218 kcal, P=0.043) and fatigue scores (56.8 ± 11.8 vs. 44.6 ± 12.6, P<0.0001) improved.
Conclusion: IHHE over 10 weeks was safe and feasible in HF patients, leading to improvements in BP and body composition and trends toward enhanced exercise capacity and QoL. These promising results warrant confirmation in a larger, multicenter randomized clinical trial.
