Response by Fernández-Jiménez et al to Letters Regarding Article, “Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage”

Abstract

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 patients with ST-segment-elevation MI 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 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography 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 T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography. CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI 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 days 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.

Effect of Early Metoprolol During ST-Segment Elevation Myocardial Infarction on Left Ventricular Strain

“…Edema is a very dynamic process during the first week after myocardial infarction (24), and strain closely associates with its intensity and volume (20). Moreover, cardioprotective therapies may affect the extent and intensity of post-myocardial infarction edema (25).…”

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

“…Contrast-enhanced steady state free precession imaging provides superior image quality to T2-weighted imaging and has been validated against SPECT 103 and angiographic scores 104 . Still, there has been some debate regarding the validity of CMR based evaluation of MaR 105,106 and the most appropriate timing for it, considering the bimodal pattern of edema after myocardial infarction [107][108][109][110] . However, a recent study in pigs validated contrast-enhanced steady state free precession imaging and T2-weighted imaging against histopathology to measure MaR seven to ten days after LAD artery occlusion and found good agreement, confirming its applicability in this time frame 111 .…”

“…Furthermore, myocardial edema determined by CMR has also been argued to correlate better with the extent of myocardial infarction than with MaR 171 . Although these methods are validated and widely used to evaluate MaR, the above mentioned issues have questioned the appropriateness of their use to measure MaR in studies of cardioprotection 105,110,169,170 .…”

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction

“…This complex tissue-level heterogeneity makes CMR appealing for non-invasive characterisation of myocardial injury after myocardial infarction [3]. Previous studies have demonstrated the utility of undertaking CMR imaging 24-72 h after PPCI, and some as early as few hours after myocardial infarction (MI) [4][5][6]. These studies revealed imaging features most likely reflective of the underlying dynamic tissue-level changes [4,5].…”