cooling in myocardial infarction

Conditions: ST-elevation Myocardial Infarction

Summary: the primary goal in the treatment of acute myocardial infarction is to reperfuse the ischemic myocardium to reduce infarct size. animal data and human data suggest that whole-body cooling to temperatures below 35°c before revascularisation can additionally reduce infarct size and therefore improves outcome in these patients. the purpose of the study is to determine if a combined cooling strategy started in the out-of-hospital arena is able to reduce infarct size in acute myocardial infarction.

background: contemporary therapy in patients with an on-going st-elevation myocardial infarction (stemi) is to reperfuse the ischemic myocardium as soon as possible to reduce infarct size and associated complications. a recent pilot-study showed a significant reduction in infarct size by the induction of pre-reperfusion hypothermia. objectives: to demonstrate a reduction in infarct size/myocardium at risk (measured by magnet resonance imaging) in patients with st-elevation myocardial infarction by strategic temperature management with the use of external cooling pads in the out-of-hospital setting and the continuation with cold saline and central venous catheter cooling in hospital. in a parallel translational study, the molecular effects of rapid and early cooling on inflammatory processes at the culprit lesion site will be defined. methodology: randomized, prospective, controlled trial number of subjects: 120 patients (60 per group) investigational medical device: emcools flex pad is an external cooling pad, that consists of multiple cooling cells filled with a patented cooling gel. emcools flex pad will be used in the out-of-hospital setting to initiate cooling. the philips rtx endovascular system™ is an endovascular thermal control system that circulates cooled saline through an indwelling central venous catheter in a closed-loop manner. it will be used in combination with 1-2 litres of intravenous cold saline to induce hypothermia below 35 degrees celsius. duration: one hour after successful revascularization the cooling procedure will be stopped, subjects will be covered with a blanket and are allowed to passively re-warm. clinical follow-up for 180 days. primary endpoint: myocardial infarct size (as a percentage of myocardium at risk) assessed by cardiac mri at 4±2 days. influence of target temperature management on coronary macrophages and monocytes as well as impact on plasma levels of immune cell chemotaxis and activation.

Eligibility criteria:
inclusion criteria: * age between 18 and 75 years * immediate transfer to cath-lab is possible * anterior or inferior st-segment myocardial infarction * st-segment elevation of \>0.2mv in 2 or more anatomically contiguous leads * duration of symptoms \<6 hours exclusion criteria: * participation in another study * patients presenting with cardiac arrest/cardiogenic shock * tympanic temperature \<35.0°c prior to enrolment * thrombolytic therapy * previous mi * previous pci or coronary artery bypass graft * severe heart failure at presentation (defined as a new york heart association (nyha) functional class iii or iv), or killip classes ii through iv * clinical signs of active infection * end-stage kidney disease or hepatic failure * recent stroke (within the past six months) * conditions that may be exacerbated by hypothermia, such as haematological dyscrasias, oral anticoagulant treatment with international normalized ratio \>1.5, severe pulmonary disease * pregnancy * women of childbearing potential * allergy to meperidine, buspirone, magnesium, or polyvinyl chloride * use of a monoamine oxidase inhibitor such as selegiline in the previous 14 days * absolute contraindications against mri (pm, icd, ferromagnetic implants)

Keywords: myocardial infarction myocardial reperfusion injury reperfusion injury anterior wall myocardial infarction inferior wall myocardial infarction pathologic processes myocardial ischemia