Reducing Infarct Size and Reperfusion Injury in STEMI

Presented at the 15th Biennial International Andreas Gruentzig Society Meeting, February 3-7, 2019

Program Agenda               Faculty Disclosures              Vendor Acknowledgment

4.2  /  IAGS 2019
Session 1: Coronary Session 2: STEMI
Reducing Infarct Size and Reperfusion Injury in STEMI
Problem Presenter: H. Vernon Anderson, MD


Statement of problem or issue

For the 90% of STEMI patients that do not have cardiogenic shock or cardiac arrest, the main determinant of survival and future clinical status is infarct size. Ischemic time is the main factor governing infarct size, but modern STEMI systems-of-care have brought ischemic times down on average to low values that may not be able to be further reduced. Other therapies besides shorter treatment times must be developed to further reduce infarct size and optimize future clinical status.


Gaps in knowledge

Basic science investigations have identified and elaborated in great detail multiple interconnected biochemical and cellular pathways that are involved in ischemia-reperfusion. Yet despite extensive research, no effective pharmacotherapies have emerged. Other strategies must still be discovered to minimize myocardial injury and promote healing in already damaged myocardium, while also protecting adjacent uninjured but at-risk myocardium. 


Possible solutions and future directions

Two promising approaches with potential benefit have emerged. The first is pre-reperfusion left ventricular (LV) support. Preliminary studies show that initiating LV support (unloading the LV) with an intra-aortic balloon pump (IABP) or Impella prior to reperfusion can reduce infarct size, but not when LV support is initiated after reperfusion. Important questions that arise are whether reperfusion should be deliberately delayed while providing LV support, and what the proper balance might be between delay to reperfusion and infarct size reduction. The preliminary data suggest that 30 minutes of LV support prior to reperfusion may be optimal, while additional delay beyond 30 minutes results in increased infarct size despite the LV support. A small clinical pilot trial of 50 anterior-STEMI patients was encouraging for this approach, no apparent danger signals surfaced with 30 minutes delay in reperfusion, and larger clinical studies are planned.

The second area of interest is hypothermia, also termed ‘targeted temperature management.’ Preliminary animal studies demonstrate a graded, dose-dependent effect of temperature reduction on salvage (protection) of ischemic myocardium. A meta-analysis of patient-level data from randomized clinical trials confirmed this dose relationship, and furthermore indicated that 35°C was the appropriate threshold temperature: cooling to <35°C reduced infarct size by 27% in anterior-STEMI compared to controls (P<.02), whereas cooling that remained ≥35°C did not reduce anterior-STEMI infarct size. With inferior-STEMI, which on average were smaller than anterior-STEMI, cooling to <35°C reduced infarct size by 13% compared to controls (P=.34), which seems substantial but did not reach significance. And like anterior-STEMI, cooling that remained ≥35°C did not change inferior-STEMI infarct size. In a novel pilot study of 60 STEMI patients, regional myocardial hypothermia was achieved by infusion of cold saline through a coronary balloon angioplasty catheter. The solution temperature was 4°C, and distal coronary temperature was monitored via the thermistor-containing guidewire. Infarct size was measured by cardiac MRI on day 7. With anterior-STEMI, infarct size was reduced by 9%-points compared to controls (P=.023), whereas with non-anterior-STEMI, infarct size was reduced by 4%-points (P=.054), which just missed significance. Additional studies using this innovative technique are planned.