Mild systemic hypothermia during angioplasty therapy for ST-segment myocardial infarction is safe and well tolerated, but did not reduce infarct size. A subanalysis of patients suggested some benefit for anterior MI, but this will require further evaluation. ¡°I think that this study is an important first step in a clinical evaluation for systemic hypothermia. Animal models have shown that systemic hypothermia can reduce infarct size. The challenge has been in doing this in awake patients who are undergoing primary angioplasty therapy for acute infarction,¡± said William O¡¯Neill, MD, of William Beaumont Hospital in Royal Oak, Michigan.

Dr. O¡¯Neill and colleagues designed the COOL-MI trial to test the safety and efficacy of a cooling catheter (Reprieve Endovascular Temperature Therapy System, Radiant Medical Inc.) in primary angioplasty compared to primary angioplasty alone. The Reprieve system is a closed-loop exchange catheter. A 10 F sheath is inserted into the femoral vein, and the catheter is advanced into the inferior vena cava. Cooling occurs by convection using chilled saline. Patients in the trial presented to the hospital within six hours of symptom onset consistent with anterior ST-segment elevation or inferior ST-segment-elevation MI. They could be excluded if they had had an MI within the last month, cardiogenic shock or sensitivity to hypothermia.

The trial included 392 patients; 193 were randomized to the cooling catheter where researchers attempted to achieve a temperature of 33o C or three hours, followed by a warming period. Another 199 patients were in the control group. Time from symptom onset to hospital arrival was 238 minutes in the control group and 237 in the treatment group. Approximately 42% of the infarcts were anterior and approximately 58% were inferior. Door-to-balloon time was 92 minutes in the control group and 110 minutes in the treated group. Initially, TIMI-3 flow was present in 20% of both groups. Stents were used in a high proportion of both groups. Eighty percent of patients were taking GP IIb/IIIa inhibitors. Researchers measured the primary outcome of infarct size at 30 days, and a safety outcome of major adverse cardiovascular events.

Target temperature of 33o C was achieved in 72% of patients; 88% had a temperature of lower than 34o C. Time to minimum temperature was 75 minutes. ¡°One of the most important parts of the study was to find out if systemic hypothermia was tolerable in patients and, in fact, we found that it was¡±, Dr. O¡¯Neill said. Infarct size was 13.8% in the control group and 14.1% in the hypothermia group, an insignificant difference. However, in the group of patients who had an anterior MI and were cooled to less than 35o C at the time of reperfusion, the infarct size was 9.3% vs. 21.9% for those who were not cooled, a statistically significant difference. ¡°We think that there is some value in cooling anterior MI patients, in particular if we can reach a target temperature of less than 35o C before reperfusion¡±, Dr. O¡¯Neill said.

Severe adverse cardiovascular events were recorded in 3.9% of the control patients and 6.2% of the cooled patients. There were four deaths in the control group and six deaths in the cooled group. Vascular complications were quite similar between the two groups. ¡°Another concern was that hypothermia was arrhythmogenic, and, in fact, we found that this was not the case. Although there were a high number of events, they were not different between the two groups¡±, Dr. O¡¯Neill said. Secondary outcomes of change in ejection fraction and CKMB found no statistically significant differences. Dr. O¡¯Neill cautioned that understanding ¡°optimal¡± hypothermia is ¡°still in its infancy. It appears as though cooling patients less than 35o C will be required, and it appears as though trying to get these patients cooled in a quicker time frame will be required. All of these will be the subject of important clinical evaluations in the future, and we¡¯re committed to future clinical research to optimize this clinical therapy¡±.