Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage

Background —Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here we evaluated the time-course of edema reaction in ST-segment elevation MI (STEMI) patients by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large animal model. Methods —A total of 16 anterior STEMI patients successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR exams were performed: STEMI patients were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls only once. T2 relaxation time in the myocardium (T2-mapping) and the extent of edema on T2W-STIR (i.e. CMR-MaR) were evaluated at all time-points. In the experimental study, 20 pigs underwent 40-min-ischemia/reperfusion followed by serial CMR exams at 120-min and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography (MDCT) during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. Results —In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2W-STIR ("CMR-MaR") varied with the timing of the CMR exam. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 post-reperfusion, coinciding with the deferred edema wave, were similar to values measured by reference MDCT. Conclusions —Post-MI edema in patients follows a bimodal pattern, which affects CMR estimates of MaR. Dynamic changes in post-STEMI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between day 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.