Cooling in 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.

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)