Hypothermia at Primary PCI Fails to Limit MI Size, but Subgroup Success Intrigues: CHILL MI

October 31, 2013

SAN FRANCISCO, CA — Patients undergoing primary PCI for ST-elevation MI (STEMI) under conditions of induced hypothermia don't benefit with smaller infarcts, at least not in general, according to the negative primary result of the CHILL-MI trial.

But the study, presented here at TCT 2013 , suggested in post hoc analyses that the technique of rapidly cooling core body temperature by a few degrees throughout coronary stenting just might limit infarct size in patients with large anterior MIs who get to the cath lab within four hours of symptom onset.

In such early-presenting anterior-MI patients in CHILL-MI, a small subgroup of the trial's 120 patients randomized to primary PCI with or without induced hypothermia, the hypothermia group showed a one-third drop in infarct size at MRI conducted about four days later. The improvement by MRI reached significance, although just barely.

And that infarct-size improvement might have conferred a clinical benefit, although with such small numbers, it's merely tantalizing: the hypothermia group ultimately showed a significant decrease in heart-failure events by day 45, and all such events were among the 31 anterior-MI patients.

Dr David Erlinge

In formally presenting the study, principal investigator Dr David Erlinge (Skane University Hospital, Lund, Sweden) pointed to years of animal studies suggesting that hypothermia protects cardiomyocytes during ischemia and can limit infarct size but also that it has little effect after reperfusion has occurred. And several clinical trials retrospectively showed pronounced MI-limiting effects after PCI with hypothermia that reached core temperatures of 35°C or lower.

At a press conference on CHILL-MI, Dr Bernard Gersh (Mayo Clinic, Rochester, MN), who didn't participate in the study, said he thinks the results are good enough to recommend a larger, more definitive randomized trial of the technique.

"In a way this is the last frontier of reperfusion therapy. We know how to treat people, [but] we don't know how to modify reperfusion injury," Gersh said. Among the challenges is that by the time most patients present with their evolving STEMI, "it's probably too late to make a difference in terms of infarct size. We can open the artery, but we probably can't modify the reperfusion injury."

On the other hand, mortality is so low in patients who present very early after symptom onset—for example, within 20 minutes—Gersh said, it would be tough to show a clinical benefit from hypothermia.

In this study, patients were randomized within six hours of symptom onset; 61 underwent hypothermia induction before primary PCI (and 59 did not). As Erlinge described it, the process started with an infusion of pressurized saline solution at 4°C, 10 mL/kg for patients with anterior MI and 20 mL/kg for those with inferior MI, followed by endovascular insertion of a cooling catheter (Philips Healthcare).

Stenting was performed and reperfusion achieved at a mean core temperature of 34.7°C; 77% of patients in the hypothermia group achieved a core temperature of <35°C. The process continued with cooling for an hour after the procedure.

For the two groups, the time from symptoms to randomization averaged about 130 minutes; the time from randomization to opening of the infarct artery was 42 minutes in the hypothermia group and 33 minutes in controls.

Speaking with heartwire , Erlinge said although the endovascular cooling procedure added a mean of nine minutes to the time to achieving reperfusion, he doesn't think that was a clinically important delay.

In the exploratory analysis of the 82 patients who had presented within four hours of symptom onset, hypothermia was associated with a 21% decrease in infarct size by MRI (p=0.049). The decrease was nonsignificant (p=0.15) at 13% in the subset with inferior MIs but was a significant 33% (p=0.046) among those with anterior MIs.

There were no significant differences by treatment group in development of microvascular obstruction or in high-sensitivity troponin-T levels, CKMB levels, or natriuretic peptides.

Interviewed by heartwire , Dr Louis A Cannon (Michigan Heart & Vascular Specialists, Petoskey), who had sat on a panel that formally critiqued Erlinge's CHILL-MI presentation, agreed that the signal of an effect of induced hypothermia in anterior MIs suggests that the technique may limit infarction and translate into clinical benefit.

Taking a step further, he said it also suggests that hypothermia induction with primary stenting may turn out to be a treatment for only a select group of patients—for example, those presenting early with persisting coronary occlusion causing a significant anterior-wall MI and poor LV function.

CHILL-MI was funded by Philips. Erlinge discloses receiving honoraria for speaking from Philips and Zoll. Cannon discloses grant support from Abbott Vascular; consulting fees or honoraria from Abbott Vascular, Boston Scientific, Medtronic, and Covidien; and financial support from Cardiovascular Ingenuity.


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