Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern: Imaging and histological tissue characterization

It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon. This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion. The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls. In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h. Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial

We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference –11.4; 95% confidence interval [CI] –18.6 to –4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference –11.1; 95% CI –21.5 to –0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

Very low risk ST-segment elevation myocardial infarction? It exists and may be easily identified

Early discharge protocols have been proposed for ST-segment elevation myocardial infarction (STEMI) low risk patients despite the existence of few but significant cardiovascular events during mid-term follow-up. We aimed to identify a subgroup of patients among those considered low-risk in which prognosis would be particularly good. We analyzed 30-day outcomes and long-term follow-up among 1.111 STEMI patients treated with reperfusion therapy. Multivariate analysis identified seven variables as predictors of 30-day outcomes: Femoral approach; age > 65; systolic dysfunction; postprocedural TIMI flow < 3; elevated creatinine level > 1.5 mg/dL; stenosis of left-main coronary artery; and two or higher Killip class (FASTEST). A total of 228 patients (20.5%), defined as very low-risk (VLR), had none of these variables on admission. VLR group of patients compared to non-VLR patients had lower in-hospital (0% vs. 5.9%; p < 0.001) and 30-day mortality (0% vs. 6.25%: p < 0.001). They also presented fewer in-hospital complications (6.6% vs. 39.7%; p < 0.001) and 30-day major adverse events (0.9% vs. 4.5%; p = 0.01). Significant mortality differences during a mean follow-up of 23.8 ± 19.4 months were also observed (2.2% vs. 15.2%; p < 0.001). The first VLR subject died 11 months after hospital discharge. No cardiovascular deaths were identified in this subgroup of patients during follow-up. About a fifth of STEMI patients have VLR and can be easily identified. They have an excellent prognosis suggesting that 24–48 h in-hospital stay could be a feasible alternative in these patients.