By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine,
University of California,
San Francisco, Director,
Cardiac Catheterization Laboratory,
San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SOURCE: Nichol G, et al. Prospective, multicenter, randomized, controlled pilot trial of peritoneal hypothermia in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2015;8(3). pii: e001965. doi: 10.1161/CIRCINTERVENTIONS.114.001965. Epub 2015 Feb 19.
Systemic hypothermia as a means to protect against tissue damage is a strategy that has found its way into clinical practice guidelines in the post-cardiac arrest population, in which cooling has demonstrated a neuroprotective effect in multiple contemporary clinical trials. Countless animal models have suggested a similar profound myocardial protective effect in acute myocardial infarction (MI). This explains the surfeit of interest in hypothermia for ST elevation MI. External cooling is both slow and uncomfortable; thus, opening the door for other innovative methods for achieving this end.
The VELOCITY trial used a novel automated peritoneal lavage system to induce rapid hypothermia in ST-elevation MI patients undergoing primary percutaneous intervention. Fifty-four patients with STEMI presenting within 6 hours of symptom onset were randomized to control or to peritoneal cooling before and for 3 hours after cardiac catheterization. Infarct size was assessed by cardiac MRI between 3 and 5 days post-infarct. Safety, as assessed at 30 days, was a composite of death, reinfarction, ischemia-driven target vessel revascularization, major bleeding, sepsis, pneumonia, peritonitis, severe arrhythmia, or renal failure. Hypothermia was successfully achieved in more than 96% of patients, in most of them prior to first balloon inflation. Unsurprisingly, this was achieved at the expense of a small but significant increase in door-to-balloon times — median door-to-balloon times were 62 [51-81] minutes in the hypothermia group and 47 [37-55] minutes in the control group (P = 0.007). Infarct size was not reduced significantly in the peritoneal lavage group. On the contrary, the primary safety endpoint occurred in six of the hypothermia patients and in none of the controls. Of these six events, three were definite stent thrombosis. The authors also reported one case each of cardiac death, major bleeding, ventricular arrhythmia, and sepsis — all in the hypothermia group.
The authors concluded that, although hypothermia by the peritoneal lavage system was feasible and effective, it resulted in an increase in treatment times and safety events, without a measured benefit in infarct size.
Controlled hypothermia in STEMI patients has had a rather long and storied history. More than 10 years ago, the COOL-MI trial reported on a larger population (n = 392) of similar patients randomized to control treatment or to automated endovascular cooling via the femoral vein, in addition to primary PCI. In that trial, as in this one, hypothermia resulted in no significant difference in infarct size. In COOL-MI, however, the non-prespecified anterior MI group showed an apparent decrease in infarct size, keeping the dream of hypothermia in STEMI alive. Despite the addition of an invasive procedure in the setting of primary PCI and systemic anticoagulation, there was no price paid in terms of major adverse cardiac events. Similar results were found in the ICE-IT trial of the same era. More recently, the CHILL-MI trial (published in early 2014) used a different endovascular cooling system to achieve rapid and safe hypothermia in STEMI patients, but again, without demonstrating a decrease in infarct size for the entire cohort (the subset of early anterior infarctions again suggested a small benefit).
The addition of invasive whole-body cooling to a time-sensitive procedure such as primary PCI is challenging indeed, and the investigators are to be commended for their work. The search for interventions to reduce infarct size and improve outcomes in ST-segment-elevation MI has yielded multiple promising candidates. This includes interventions as varied as ischemic post-conditioning and remote ischemic conditioning, as well as simple measures such as pre-reperfusion beta blockade and adenosine infusion. Most of these are less cumbersome and time consuming than systemic hypothermia and do not carry the necessary penalty in terms of time to reperfusion. In the case of controlled peritoneal hypothermia, not only was the sought-after reduction in infarct size not realized, but there was a safety penalty as well. Although the investigators suggest the need for an additional larger-scale, appropriately powered trial, I cannot help but wonder whether we should close the book on systemic hypothermia in acute MI.