Abstract 14278: 14 Days of Severe, Sustained Normobaric Hypoxic Enhances Left Ventricular Contractility in Patients After Myocardial Infarction

Studies in mice with experimental myocardial infarction revealed, that sustained severe normobaric hypoxia (FiO2=0.07) reactivates cardiomyocyte proliferation and improves left ventricular ejection fraction. Our study aimed to test safety and feasibility in humans and to assess whether hypoxia improves left ventricular contractility in selected patients with myocardial scars following myocardial infarction.Three males, who suffered myocardial infarction 49-126 months prior to study entry, whose capability for hypoxia acclimatization was validated previously and one healthy male control participated in this proof-of-concept study. After preacclimatization we induced severe hypoxia by adding nitrogen until alveolar oxygen partial pressure reached about 35 mmHg. Hypoxia was maintained for 14 consecutive days (FiO2=0.095) and nights (FiO2=0.105). We assessed ventricular function by echocardiographic-derived global longitudinal strain (LVGLS), serum NTproBNP, high-sensitive Troponin I levels, and marker of myocardial repair. Cardiac 18F-FDG-PET-MRI was done at baseline, end of hypoxia exposure, and at 30 days follow-up. LVGLS increased in prior viable myocardium, but also in areas adjacent to the myocardial scar (baseline: -12.57±2.4 %, end of hypoxia: -14.37±2.62% recovery day 3: -14.33±2.72%, 30 days follow-up: -15.2±3.11%, p=0.0182). NTproBNP tended to decrease (baseline: 189±134 pg/ml, end of hypoxia: 127±28 pg/ml, recovery day 3: 114±18 pg/ml, 30 days follow-up: 108±65 pg/ml). These parameters were not affected in the control. MRI-derived left ventricular enddiastolic volume remained unchanged, but end-systolic left ventricular volume decreased in patients (baseline: 108±49 ml, recovery day 3: 92±50 ml, 30 days follow-up: 101±47 ml, p=0.0068). Troponin I remained in the reference range in all participants. The patient with the most pronounced increase in LVGLS revealed a relevant increase in FDG-uptake at the follow-up, which was also observed in areas adjacent to the myocardial scar.Given the small sample size and the selection of patients, our results have to be interpreted with caution. However, the data indicate potentially beneficial hypoxia-mediated effects in selected patients with ischemic heart disease.