Hypoxia and Cardiac Function in Patients With Prior Myocardial Infarction

I n mice with experimental myocardial infarction, sustained normobaric hypoxia corresponding to 8000 m altitude improves myocardial regeneration and left ventricular (LV) function likely by reducing oxidative DNA damage.1 Hypoxia-induced pulmonary hypertension or myocardial ischemia could limit translation to patients.We tested the feasibility and safety of exposing highly selected patients with previous myocardial infarction to normobaric hypoxia corresponding to ≈4500 m altitude for 4.5 days.We evaluated hypoxia influences on LV function and DNA repair in peripheral blood mononuclear cells (PBMCs). 2 We recruited patients with previous myocardial infarction, fully revascularized LAD lesions, no angina pectoris, or cardiac decompensation in the past 12 months who were otherwise healthy, physically fit, and had previously tolerated >2000 m altitude.The local ethics committee approved the study.In the German Aerospace Center (DLR):envihab hypoxia module, we decreased the fraction of inspired oxygen (F I O 2 ) stepwise by adding nitrogen over 14 days, maintained 0.118 F I O 2 for 4.5 days (hypoxia), and returned normoxia (Figure [A]).We obtained transthoracic echocardiograms on the second acclimatization day and daily at 0.118 F I O 2 and during the first 2 recovery days at 0.209 F I O 2 to assess right ventricular anatomy, tricuspid annular plane systolic excursion, biplane LV ejection fraction, LV global longitudinal strain, and systolic pulmonary artery pressure.We acquired short-axis real-time cardiac magnetic resonance imaging at 33 ms temporal resolution during spontaneous breathing for 9.9 s per slice 3 at baseline, 0.118 F I O 2 , and early recovery.We obtained venous blood samples for cardiovascular biomarker and catecholamine measurements.We examined ex vivo DNA repair by exposing PBMCs isolated from all patients at baseline, during hypoxia, and during recovery to 1G X-Ray irradiation and assessed cells for DNA double-strand break repair while maintaining oxygen conditions ex vivo.Of 11 screened patients, we included 4 men (age, 54-63 years;body mass index, 21-25 kg/m 2 ; VO 2 max, 32-43 mL/kg per minute) 37 to 104 months following myocardial infarction (3× ST-segment-elevation myocardial infarction, 1× non-ST-segment-elevation myocardial infarction).We excluded 1 woman with thrombocytosis and another woman because of right ventricular involvement.Participants had isolated left anterior descending artery mid-segmental to ostial culprit lesions fully revascularized through interventions and myocardial scars.All received heart failure medications (Figure [C]).At 0.118 F I O 2 , all participants experienced acute mountain sickness symptoms without signs of cardiac decompensation (Lake Louise Acute Mountain Sickness Score: baseline, 3.25±1.5;hypoxia, 5.25±1.04;recovery, 0.75±0.96points).Hypoxia-induced pulmonary hypertension rapidly abated in recovery (Figure [C]).Arterial oxygen partial pressure decreased from 94±10 to 51±3 mm Hg.High-sensitivity troponin I was never elevated.Supine plasma norepinephrine was 2.24±0.09nmol/L at baseline, 5.33±1.55nmol/L during hypoxia, and 4.01±1.4nmol/L during recovery.