A multicentre, prospective, randomised controlled trial to assess the safety and effectiveness of cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction: the COOL AMI EU Pivotal Trial

Abstract

Background: Despite primary PCI (PPCI), STEMI can still result in large infarct size (IS).New technology with rapid intravascular cooling showed positive signal for reduction in IS in anterior STEMI.Aims: We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to primary PCI (PPCI) in conscious patients with anterior STelevation myocardial infarction (STEMI) without cardiac arrest.Methods: Hypothermia was induced using ZOLL ® Proteus™ Intravascular Cooling System.After randomization of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischemic delay in hypothermia group (232 vs 188 minutes; p <0.001).Results: There were no differences in angiographic features and PPCI result between the groups. Intravascular temperature at wire crossing was 33.3+0.9°C. Infarct size/left ventricular mass (IS/LV) by cardiac magnetic resonance (CMR) at day 4-6 was 21.3% in hypothermia group and 20.0% in control group (p=0.540). Major adverse cardiac events (MACE) at 30 days were non significantly increased in hypothermia group (8.6% vs 1.9%; p=0.117) while cardiogenic shock (10.3% vs 0%; p=0.028) and paroxysmal atrial fibrillation (43.1% vs 3.8%; p<0.001) were significantly more frequent in hypothermia group. 5 Conclusion: Intravascular ZOLL TM Proteus Cooling System reduced temperature to 33.3 o Cbefore PPCI in patients with anterior STEMI. Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in longer ischemic delay, did not reduce IS/LV mass and was associated with increased adverse events.

Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial

“…However, a recently published report concluded that out-of-hospital induced cooling, as an adjunct to primary percutaneous coronary intervention did not improve myocardial salvage as assessed with CMR in patients with STEMI [ 19 ]. Additionally, in the Cool-AMI study, a reduction of body core temperature to 33.3 °C before primary PCI in patients with anterior STEMI was associated with increased risk for adverse events [ 20 ]. Concomitant reduced fall in levels of CK-MB in the 48 h treatment arm compared with the 24-h arm in a sub-study of the TTH 48 trial further support the potential deleterious effects on the myocardium of TTM for comatose survivors of OHCA in patients with AMI [ 21 ].…”

Hypothermia for Cardioprotection in Patients with St-Elevation Myocardial Infarction: Do Not Give It the Cold Shoulder Yet!

“…Multiple randomized controlled trials have studied hypothermia for cardioprotection, and all were negative for the primary endpoint, either IS or IS/MaR [26][27][28][29][30][31][32]. A study-level meta-analysis of randomized trials investigating systemic hypothermia for cardioprotection in STEMI (Figure 1) did not show a decrease in IS compared to standard PCI (standardized mean difference of IS −0.17, 95% confidence interval −0.52 to 0.19).…”

“…It is obvious that cooling methods that intend to cool the entire body are by definition time-consuming. Even the strongest cooling devices cause a delay in treatment [32]. This delay (with longer ischemic time) is at the expense of the benefit achieved by hypothermia.…”

“…Third, systemic hypothermia causes side effects. Shivering occurred in all patients, necessitating the need for anti-shivering medication [26][27][28][29][30][31][32]. Furthermore, systemic hypothermia may provoke atrial arrhythmias [32].…”

New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction

“…Also, although not statistically significant (8.6% vs. 1.9%; p = 0.12), there was an excess of major adverse events-including atrial fibrillation, ventricular tachycardia/fibrillation, and stent thrombosis. Actually, the study was stopped prematurely due to a 44-min increase in total ischemic delay in the hypothermia group [70].…”