Strategic Target Temperature Management in Myocardial Infarction (STATIM)

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: 60 patients (30 per group) Inclusion criteria: - Age between 18 and 75 years - Expected time from first medical contact to revascularization <90 minutes - Anterior or inferior ST-Elevation myocardial infarction - Duration of symptoms <6 hours Main exclusion criteria: 1. - Patients presenting with cardiac arrest - Previous myocardial infarction in medical history - absolute contraindications against MRI (PM, ICD) 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 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 (4C using pressure cuff) 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 42 days. Influence of target temperature management on coronary macrophages and monocytes as well as impact on plasma levels of immune cell chemotaxis and activation.

Heart attack is one of the leading causes of death in western civilization. Many improvements in the care of patients with this medical problem have been developed in the past decades. The reason for a heart attack is the occlusion of a vessel (coronary artery) supplying the heart with blood. Without blood supply muscle cells of the heart cannot survive for more than minutes up to a few hours. The current therapy of choice is to implant small, expandable metal tubes (a so called stent) during a special X-ray examination as soon as possible. But even if blood supply is restored amongst others the immune system causes further damage to heart cells (so called reperfusion injury). Reducing the body temperature to levels below 35C (therapeutic hypothermia) has shown to reduce this reperfusion injury in animal models but only if the temperature has been reached before the x-ray examination.In our study we started reducing the body temperature of the patients even after arrival of the emergency medical service on scene to utilise the longest time period possible for this therapy. We reduced the body temperature by three steps. 1st Step: Application of ice packs on the surface of the patient. 2nd Step: Administration of cold infusions. 3rd Step: placement of a cooling catheter in a large vessel. With this strategy we were able to reduce the body temperature below 35C in more the 80% of the patients. Our main focus was how many heart muscle can be salvaged additionally to the current standard therapy. This was evaluated with cardiac magnetic resonance imaging.After evaluation of the study data we were not able to detect an additional effect of therapeutic hypothermia. When looking on other complications of a heart attack (e.g. heart failure, arrhythmias, death) we also not found a difference. When looking only on patients presenting early after symptom onset we were able to detect an improved salvage of heart tissue. This underlines the importance of symptom recognition and early emergency call when symptoms are compatible with a heart attack. In summary our study was not able to prove the concept of a smaller damage when body temperature was lowered during the performance of the standard therapy. Still, many question are unanswered, especially which temperature should be reached and how long this temperature should be kept. Therefore further research of this topic is required.