Safety and feasibility of hypoxia exposure in patients with prior myocardial infarction

Objective: In mice, normobaric hypoxia exposure corresponding to 8,000 m altitude after myocardial infarction reactivated cardiomyocyte proliferation and improved left ventricular ejection fraction (LVEF). Translating these findings to patients might be limited by hypoxia-induced pulmonary hypertension and myocardial ischemia. Design and method: We conducted a feasibility and safety study at the: envihab facility in 4 patients who had experienced myocardial infarction with fully revascularized LAD-stenosis as culprit lesion 37-104 months prior study entry. Their peak VO2 ranged from 32 - 43 ml/kg/min. The study comprised a two-days baseline, 19 days normobaric hypoxia, and two-days recovery. We gradually lowered atmospheric oxygen to 0.118 FIO2, which is equivalent to 4500 m, and maintained that level for 4.5 days. We obtained transthoracic echocardiography, magnetic resonance imaging, and determined Troponin I, NTproBNP at baseline, during 0.118 FIO2, and recovery. Results: Except for symptoms of acute mountain sickness, hypoxia was well tolerated as severe adverse reactions did not occur and pulmonary hypertension rapidly abated during recovery. During the last 10 days of hypoxia, peripheral oxygen saturation was continuously <90%. LVEF was 50.7±11.0 % (mean±SD) baseline, 57.6±11.2% at 0.118 FIO2, and 57.3±11.2% during recovery. Furthermore, echocardiographic LV global longitudinal strain was -15.28±5.4% at baseline and -17.28±7.56 % in recovery. Magnetic resonance imaging confirmed these findings. NTproBNP diminished (baseline: 203±209 pg/ml, 0.118 FIO2: 122±101/pg/ml, recovery: 85±66 pg/ml) and Troponin I concentrations remained in the reference range throughout the study. In the patient with the largest LVEF increase following hypoxia, an additional 12 weeks follow-up measurement showed stable improvements in LVEF (baseline: 36%, recovery: 48%, 12 weeks follow-up: 47%), left ventricular strain, NTproBNP, and exertional dyspnea. Conclusions: Our study provides evidence regarding safety and potential of hypoxia exposure after myocardial infarction and lays the foundation for future studies assessing hypoxia-influences on cardiac regeneration. However, our findings have to be interpreted with caution given the small sample size and the selected patient population.