Unloading of the Left Ventricle with More Delayed Reperfusion May Reduce Reperfusion Injury
Presenter
Sara Hazaveh, M.D., Hackensack University Medical Center, Hackensack, NJ
Sara Hazaveh, M.D. and Faraz A Faraz, M.D., Hackensack University Medical Center, Hackensack, NJ
Keywords: Acute Coronary Syndromes (ACS) and Complex and High-risk Coronary Intervention (CHIP)
Background
Successful management of acute myocardial infarction (AMI) emphasizes early reperfusion therapy for decades. Further reduction in door-to-balloon (DTB) times has not improved post-AMI heart failure and mortality. Preclinical studies and the DTU-STEMI clinical trial (Door-To-Unload in ST-Segment-Elevation Myocardial Infarction Pilot Trial) have suggested that mechanically unloading the left ventricle (LV) prior to reperfusion for 30-minutes can reduce infarct size and myocardial injury in STEMI without cardiogenic shock by reducing reperfusion injury. Clinical Case Case A 49-year-old male with 30-pack-year smoking experienced typical AMI symptoms while driving at 10:00AM. Emergency medical services was activated and patient taken to outside community hospital arriving there at 11:38AM. Electrocardiogram en-route with anterolateral wall STEMI. STEMI code activated. Initial labs notable for lactate 2.5 and Troponin-T 460 ng/uL (normal <22ng/L). At 11:52AM he was emergently taken to cardiac catheterization laboratory where he was noted to be hypotensive on transfer to catheterization table, emergently intubated and norepinephrine and vasopressin started for hemodynamic support. Left heart catheterization (LHC) at approximately 12:00PM showed LVEDP (LV end diastolic pressure) of 38 and LVEF (LV ejection fraction) of <20% with occluded RCA and LAD. Impella CP placed for myocardial protection and LV unloading, patient emergently transferred to our tertiary care center for advanced therapies. He underwent successful stenting and reperfusion of occluded RCA at 16:17PM and of LAD at 16:52PM. Ischemia onset to unloading time 2.5 hours and unloading to reperfusion time of 5 hours, reperfusion established 7.5 hours after AMI. Post complete revascularization impella CP upgraded to axillary 5.5 due to mild hematuria and continued pressor requirements. After PCI LVEF 15% with severe left ventricular hypokinesis. One week later, echocardiogram with improved LVEF 35-40%. Conclusion New approaches for AMI management are needed as efforts to reduce total ischemic time have not reduced post-AMI complications. Preclinical models suggest mechanical LV unloading prior to reperfusion reduces reperfusion injury and infarct size. Possible explanations include reduction in endothelin-1 and thus calcium release or the development of microcirculatory collateral blood flow to the myocardium at risk. On a mechanistic level, LV unloading can maintain mitochondrial morphology, function, and cardiolipin levels in the infarcted zone compared to reperfusion alone. Cardiolipin is an integral part of the inner-mitochondrial membrane. Duration that mitochondria and associated signaling mechanisms can remain functional under anaerobic conditions hasn't been explored. Presented case had LV unloading with delayed perfusion more than what has been used in studies suggesting that mitochondrial mechanisms under anaerobic conditions may be functional for longer periods. Given the central role of mitochondria for anaerobic respiration during ischemia and reperfusion injury, more studies exploring mitochondrial integrity with unloading and delayed reperfusion are needed.