Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials

Abstract

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes.

Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model

“…Conversely, on the TTC stained heart slices obtained from animals belonging to the IGF-1 MSPs group there was little thinning in the infarcted area with presence of a mixture of infarcted and viable tissue. This heterogeneous tissue is represented as grey area on CMR images and thus construed as infarction since these voxels are above the threshold used to define abnormal myocardium 55 . Consequently, no significant differences between groups regarding the percentage of infarction were found, despite the differences in tissue characteristics that were evidenced macroscopically after TTC staining.…”

Role of Cardiac Magnetic Resonance to Improve Risk Prediction following Acute ST-elevation Myocardial Infarction

“…For visualization of acute IS, LGE images are acquired at least 10 min (typically 10-20 min) after bolus infection of the contrast agent [12]. In the very early phase following STEMI, reperfusion-related edema with an increase of the interstitial space causes overestimation of acute LGE-determined IS [54]. Accordingly, quantification of acute IS by LGE is recommended to be performed 3-7 days after infarction [54].…”

“…In the very early phase following STEMI, reperfusion-related edema with an increase of the interstitial space causes overestimation of acute LGE-determined IS [54]. Accordingly, quantification of acute IS by LGE is recommended to be performed 3-7 days after infarction [54]. Acute IS quantified in this time range was shown to be highly prognostic in STEMI patients [55][56][57].…”

“…A recent study specifically addressing this question disclosed that the higher risk of cardiovascular complications in anterior STEMI patients is explained by the larger IS of this subgroup without any further contribution of infarct location per se [65]. The crucial prognostic role of IS has recently also been emphasized by the consensus document of the Journal of the American College of Cardiology (JACC) Scientific Expert Panel in which IS by LGE has been recommended as primary CMR endpoint measure in experimental and clinical trials [54]. The concept of IS assessment has lately been expanded to the entire myocardium by evaluating the presence and prognostic impact of multiple myocardial scars in the clinical setting of STEMI.…”

“…Coronary occlusion in acute STEMI leads to time-dependent cell death starting from the subendocardium and proceeding towards subepicardial layers, a process called "wavefront phenomenon" [34]. The myocardial area supplied by the occluded artery is in jeopardy to become necrotic and is therefore referred to as myocardial area at risk (AAR) [54]. The goal of timely revascularization is to terminate the progression of the necrotic wavefront and thereby prevent as much AAR as possible from becoming irreversibly damaged.…”