Cardiac safety of prolonged hypoxia exposure in fully revascularized patients with prior myocardial infarction

Abstract

BACKGROUND Treatments improving cardiac regeneration could transform clinical management of ischemic cardiomyopathy. In mice with experimental myocardial infarction, prolonged normobaric hypoxia exposure corresponding to around 8,000 m altitude induced myocardial mitosis and improved left ventricular function. We determined whether a similar approach could be feasible and safe in patients. METHODS We included four highly selected men with myocardial infarction in their history (3x STEMI, 1x NSTEMI). Patients had coronary 1-vessel disease with a fully revascularized LAD stenosis as culprit lesion. The study, which was conducted at the :envihab facility, included a two-day baseline, 19 days normobaric hypoxia, and a two-day recovery period. Atmospheric oxygen was gradually lowered to 11.8% and maintained at that level for 4 days. We obtained transthoracic echocardiography, magnetic resonance imaging of the heart and the brain at baseline, during 11.8% oxygen, and recovery, and daily 12-lead ECG. RESULTS Except for symptoms of acute mountain sickness, which improved over time, hypoxia was well tolerated and severe adverse reactions did not occur. Echocardiography revealed hypoxia-induced pulmonary hypertension, which rapidly abated during recovery. Mean left ventricular ejection fraction was 50.7±11.0 % (mean±SD) at baseline, 57.6±11.2 % during hypoxia, and 57.3±11.2 following recovery (p=0.045). Cardiac magnetic resonance imaging confirmed the finding. In patients with elevated NTproBNP at baseline, the measurement was decreased during hypoxia and following recovery. Troponin I concentrations remained in the reference range throughout the study. CONCLUSIONS In a small number of fully revascularized, highly selected patients with prior myocardial infarction, prolonged exposure to substantial normobaric hypoxia was feasible and safe despite reversible increases in pulmonary artery pressure. In fact, left ventricular ejection fraction and NTproBNP were improved during and following hypoxia exposure. Our findings provide critical information for further studies assessing influences of hypoxia on cardiac regeneration in human beings.