Abstract
The region of myocardium hypoperfused during ischemia, also known as the area at risk (AAR), has sought our attention since the earliest understandings of the wavefront of progressive myocardial infarction (MI) due to acute coronary syndromes (ACS).1 Edema took center stage as evidence accrued that cardiomyocytes take on water in the setting of ischemia and reperfusion2; this, in turn, led to the notion that the myocyte's survival was determined by whether sarcolemmal membrane resistance was exceeded.3 The development of nuclear scintigraphic techniques afforded demonstration of the perfusion deficit in vivo at the time of presentation. Comparison with histology in a number of autopsy hearts confirmed that in many patients, a large scintigraphic defect often was present despite a small area of irreversibly injured or infarcted myocardium; that is, there appeared to be myocardium at risk of irreversible injury but potentially salvageable.4 The authors presciently concluded that this group of patients had the “greatest promise for intervention.” Articles see p 210 and 228 Fast forward to the present era of rapid mechanical revascularization coupled with a host of pharmacological maneuvers to restore blood flow, and what do we find: reduced but still significant morbidity (≥3.4% patients per year develop heart failure after MI5), mortality (≈20% of men and women aged >40 years die in the first year after initial MI6), and cost of subsequent care (≈$32,000 per patient is spent in the first year after MI7). Although increased infarct size consistently portends worse outcomes,8,9 it would make sense to develop interventions that reduce ultimate infarct size while myocardium is still salvageable; this, in turn, requires reliable …
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