VELOCITY Published: Peritoneal Cooling Does Not Decrease Infarct Size in STEMI

Controlled peritoneal hypothermia can be established rapidly in STEMI patients undergoing primary PCI though at the expense of longer door-to-balloon times, according to pilot study published online February 19, 2015, ahead of print in Circulation: Cardiovascular Interventions. Infarct size is unaffected, however, and patients who undergo cooling have a higher risk of postprocedural adverse events including stent thrombosis.

Results from the VELOCITY study were previously presented in September 2014 at the Transcatheter Cardiovascular Therapeutics symposium in Washington, DC.

“These findings have implications not only for the peritoneal approach to hypothermia but also raise general questions about the utility of systemic hypothermia to reduce infarct size,” write Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), and colleagues.

The researchers randomized 54 STEMI patients (median age 57 years; 85.2% male) at 7 centers in the United States and Canada to emergent PCI with (n = 28) or without (n = 26) hypothermia induced by the Velomedix Automated Peritoneal Lavage System (Velomedix; Menlo Park, CA) between January 2013 and January 2014. Baseline characteristics were similar between the 2 groups, and 46.3% of all infarcts were anterior.

Hypothermia—defined as core temperature at or below 34.9°C—was successfully achieved in 96.3% of patients, with a median temperature of 34.7°C at first balloon inflation. PCI was performed in all but 1 patient in each treatment group, with half also receiving aspiration thrombectomy. Angiographic success and ST-segment resolution rates were similar between the arms.

Median door-to-balloon time was shorter in the control vs hypothermia group (47 vs 62 minutes; P = .007), but the median symptom onset-to-balloon time only trended lower for controls (167.0 vs 172.5 minutes; P = .17). Median temperatures remained lower in the hypothermia group than in the controls 3 and 6 hours after hospital arrival but evened out by 12 hours.

At 30-day follow-up, no patients in the control group had a primary composite safety endpoint event (death, reinfarction, ischemia-driven TLR, major bleeding, sepsis, pneumonia, peritonitis, severe arrhythmias, or renal failure), compared with 6 (21.4%) of the patients who underwent hypothermia (P = .01). Events in the latter group included 3 cases of ischemia-driven TVR and 1 case each of cardiac death, reinfarction, major bleeding, ventricular tachycardia or fibrillation, and sepsis. Four patients (14.3%) experienced MACE (cardiac death, reinfarction, or ischemia-driven TVR), and 3 (11.0%)—all in the hypothermia arm—developed definite stent thrombosis.

Among the 46 PCI patients who underwent MRI 3 to 5 days postprocedure (median 4 days), the median myocardial infarct size was similar in the control vs hypothermia group (16.1% vs 17.2% of LV mass; P = .54). There were also no differences in myocardial salvage, microvascular obstruction, or LV volumes or function between the groups. These measures all remained similar at 30 days.

Time Is of the Essence

Given the high rate of successful hypothermia and the inability of the treatment to reduce infarct size, Dr. Stone and colleagues write, “it is possible that the prolonged door-to-balloon time in the hypothermia group may have attenuated the effect of hypothermia on infarct size.”

Even though observational studies have demonstrated the relationship between reperfusion delays and mortality in STEMI, they continue, “door-to-balloon times were short in both groups and within the range wherein further reductions in mortality may not be realized. It is thus unlikely that the 15-minute delay to reperfusion in the hypothermia arm is totally responsible for the absence of effect.”

Because hypothermia has consistently reduced infarct size in experimental models, especially before reperfusion, the authors suggest the need for “a large-scale, appropriately powered trial” on the topic.

They propose the higher rate of stent thrombosis in the study arm could be due to the “chronic use” of dual antiplatelet therapy, which resulted in fewer than 80% of patients in both groups receiving aspirin or ADP antagonists before PCI. The authors acknowledge, however, that there were no cases of stent thrombosis in the control arm.

In an email with TCTMD, Dr. Stone said the “increased complication rate was mainly due to stent thrombosis, which I doubt is specific to the modality of achieving hypothermia…. While this may have been due to [the] play of chance, it must be carefully examined in any future hypothermia study.”

Finding the Safest Technique

As for which specific method of achieving hypothermia is best, Dr. Stone said the answer remains elusive. “In general, rapid induction of hypothermia is desirable and to a level that can be accurately regulated,” he said.

According to the authors, peritoneal hypothermia may be related to several safety issues, including:

• Respiratory suppression due to decreased diaphragm excursion coupled with use of sedation and narcotics for shivering suppression
• Major organ bleeding after peritoneal puncture, especially given the use of potent antithrombotic and antiplatelet agents

“Such complications can be circumvented through careful patient selection (avoiding those with prior abdominal procedures or pathology) and with careful technique,” they write.

Dr. Stone cited a novel hypothermia system that delivers ice microcrystals to the pulmonary tree to rapidly induce hypothermia. “This system will need to progress to large-scale studies in humans, but the concept is very attractive,” he said.

Pharmacology Instead of Cooling?

In a telephone interview with TCTMD, Benjamin S. Abella, MD, MPhil, of the University of Pennsylvania (Philadelphia, PA), said “cooling doesn’t occur in isolation. There are other actions taking place, and I don't think we fully understand how all these things interact.”

For example, he said, “there are some data that have appeared suggesting that drug absorption orally… may be altered by temperature.”

Dr. Abella explained that the risk/benefit ratio of increased adverse events vs reduced infarct size depends on what the adverse events are and their long-term consequences. “It's going to be a tailored situation,” he said. “It's going to be hard to generalize.”

Moreover, “it's going to be hard to say that one therapy, temperature goal, or technique is going to be good for all patients,” he commented. “It reflects the fact that we’re early in the whole evaluation of temperature in patient care and that we’re starting with blanket treatments that are not very nuanced or patient specific.”

Going forward, goals for STEMI patients will need to be more strictly defined, Dr. Abella said. “It depends what the science is going to show. Right now there is unfortunately no superb technique to reaching a lower body temperature in a time scale required before [catheterization]. That’s why we need more innovation and more device trials to see if that's possible and see if that matters.”

Ideally, he added, a pharmacological approach will be developed that would take the place of cooling.

“We don’t really understand how temperature modulation improves reperfusion injury—what specific pathways are involved…. I would love to see a world 10 years from now where we [can rapidly infuse] a drug on the way to the cath lab that produces much, if not all, of the benefit of temperature reduction… so that the patient is protected or will have the benefit that they might have had with the slower, more cumbersome temperature management techniques,” Dr. Abella concluded.

Note: Dr. Stone and several coauthors are either faculty or staff members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:
Nichol G, Strickland W, Shavelle D, et al. Prospective, multicenter, randomized, controlled pilot trial of peritoneal hypothermia in patients with ST-segment–elevation myocardial infarction. Circ Cardiovasc Interv. 2015;Epub ahead of print.

Related Stories:

• VELOCITY: Hypothermia for STEMI Results in More Adverse Events, No Reductions in Infarct Size
• Two Trials Look at Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Patients
• CHILL-MI: Therapeutic Hypothermia Most Effective in Early Anterior STEMI