Multimodality Cardiac Imaging Substudy of the DAPT-SHOCK-AMI Randomized Trial: Echocardiographic and Cardiac Magnetic Resonance Assessment of Cangrelor versus Crushed Ticagrelor in Cardiogenic Shock Complicating Acute Myocardial Infarction

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock (AMI-CS), the myocardium sustains a dual injury: ischemia of the culprit territory and global hypoperfusion from low cardiac output. Whether platelet inhibition at reperfusion affects the microcirculation, the infarct, the noninfarcted myocardium, and ventricular function, and over what time course, has not been examined with serial imaging. The prespecified multimodality imaging substudy of the randomized DAPT-SHOCK-AMI trial (intravenous cangrelor versus crushed oral ticagrelor) addressed this question. METHODS: Patients at prespecified imaging sites underwent serial echocardiography (208 enrolled; evaluable examinations in 175, 120, and 99 patients in the acute phase, at 1 month, and at 1 year) and cardiac magnetic resonance (CMR; 93 enrolled; 73, 68, and 63); 81 patients (40 and 41) underwent both modalities. Blinded core laboratories analyzed all studies. The primary imaging endpoint was microvascular obstruction (MVO) on acute CMR, evaluable in 60 patients; secondary endpoints were infarct size, native T1 of the global, infarcted, and remote myocardium, left ventricular (LV) ejection fraction (LVEF), global longitudinal strain (GLS), E/e', and left atrial volume, and their changes. Comparisons between the cangrelor and crushed ticagrelor arms used covariate-adjusted logistic or linear regression; the substudy was not separately powered. RESULTS: The odds of acute MVO were lower with cangrelor (adjusted odds ratio 0.27 [95% CI 0.08 to 0.98]; P=0.023). Infarct size did not differ between the arms. At 1 year, native T1 of the remote myocardium was lower with cangrelor (adjusted mean 1114 [95% CI 1057 to 1171] versus 1171 [1115 to 1228] ms; P=0.005). Over 1 year, LVEF increased more with cangrelor on echocardiography (37.9% versus 21.7% of the acute value; adjusted P=0.046) and CMR (15.8% versus 2.1%; P=0.027), with greater improvement in GLS, lower E/e', and less left atrial enlargement; no parameter differed between the arms at 1 month. CONCLUSIONS: In AMI-CS, serial multimodality imaging characterized microvascular, tissue-level, and functional injury over 1 year. Cangrelor was associated with less acute MVO, lower remote native T1, and more complete recovery of LV function than crushed ticagrelor, without a difference in infarct size; these hypothesis-generating findings suggest differences in the microcirculation and non-infarcted myocardial injury but do not establish a treatment mechanism.