Intravenous dexrazoxane for haemorrhagic myocardial infarction: the SHIELD-MI study.

BACKGROUND AND AIMS: Intramyocardial hemorrhage (IMH) after reperfused ST-elevation myocardial infarction (STEMI) is associated with adverse outcomes, yet no therapy specifically targets it. Dexrazoxane (DXZ) may mitigate iron-mediated injury from IMH. METHODS: SHIELD-MI was a single-center, non-randomized, placebo-controlled, sequential-cohort phase IIa study with participants and the cardiac MRI (CMR) core laboratory blinded to treatment. Twenty-five patients received intravenous DXZ 250 mg before primary PCI and at 4, 8, and 12 h thereafter. Twenty-five comparators, selected from 78 placebo-treated patients, were matched on total ischemic time, culprit territory, and pre-PCI occlusion status. Primary endpoints were left ventricular ejection fraction (LVEF) and IMH volume on CMR at 48-72 h, evaluating early ventricular function and hemorrhagic myocardial injury after reperfusion. RESULTS: In the matched analytic cohort (n=50), LVEF was higher in patients receiving DXZ (39.8±7.7% vs. 34.7±10.1%; P=0.048), permitting formal testing of IMH volume, which was lower with DXZ (2.0±3.4% LV vs. 6.3±6.0% LV; P=0.004). The prespecified fixed-sequence criterion was therefore met at both steps. Infarct size was lower with DXZ (29.1±13.1% LV vs. 43.8±18.6% LV; P=0.002). Hemorrhagic MI occurred in 6/25 (24%) versus 16/25 (64%) participants (P=0.010). No drug-related serious adverse events were observed. CONCLUSIONS: Peri-procedural intravenous DXZ was associated with lower IMH and infarct size and higher LVEF, without safety concerns. These exploratory findings identify IMH as a candidate therapeutic target warranting a randomized trial.