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 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.This study was partially supported by a competitive grant from the Spanish Society of Cardiology (Proyectos de Investigacion Traslacional en Cardiologia de la Sociedad Espanola de Cardiologia 2015, for the project Caracterizacion tiSUlar miocaRdica con resonancia magnetica en pacientes tras inFarto agudo de mioCardio con elevacioN de ST sometidos a angloplastia Coronaria primaria. Estudio SURF-CNIC), by a competitive grant from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria- and the European Regional Development Fund (ERDF/FEDER) (PI10/02268 and PI13/01979), the Spanish Ministry of economy, industry, and competitiveness (MEIC) and ERDF/FEDER SAF2013-49663-EXP. Dr Fernandez-Jimenez holds a FICNIC fellowship from the Fundacio Jesus Serra, the Fundacion Interhospitalaria de Investigacion Cardiovascular, and the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), and Dr Aguero is a FP7-PEOPLE-2013-ITN-Cardionext fellow. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare, and is part of a bilateral research program between Hospital de Salamanca Cardiology Department and the CNIC. This research program is part of an institutional agreement between FIIS-Fundacion Jimenez Diaz and CNIC. The CNIC is supported by the MEIC and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).S