Insights into myocardial microstructure during infarct healing and remodeling: pathologists need not apply.

Healing of acute myocardial infarction (MI) and subsequent increase in left ventricular (LV) cavity size or LV remodeling1 is a complex process.2 LV remodeling depends largely on infarct size3 and transmurality which in turn is determined by the status of the epicardial infarct artery4 and the microvasculature.5 Within a larger, near-transmural or transmural infarction, there is myocyte loss, in part because of apoptosis, and cellular slippage6 that leads to reduced tensile strength within the infarct zone and subsequent infarct expansion.7 Infarct expansion and wall thinning in the infarct zone then leads to regional cavity dilatation and increased wall stress throughout the LV. Elevated wall stress in turn activates the renin-angiotensin system and other autocrineparacrine systems8 and cellular hypertrophy ensues.9 Cellular hypertrophy occurs primarily in noninfarcted regions adjacent to the infarcted segment and is eccentric due to the laying down of sarcomeres in series.10,11 Eccentric cellular hypertrophy in noninfarcted regions together with fibrosis12 contribute to mechanical dysfunction in adjacent noninfarcted regions that persists during remodeling.13 Remote noninfarcted regions are initially mildly dysfunctional in the first few days after large MI,14 but these recover over the next several weeks as global LV function improves.15 The sum total of these events is a deleterious increase in end-diastolic and -systolic cavity sizes. It is the latter that is the most important determinant of outcome after acute MI.16