4.2 Therapies to Minimize Myocardial Injury During STEMI

These proceedings summarize the educational activity of the 17th Biennial Meeting of the International Andreas Gruentzig Society held January 30 to February 2, 2024 in Chiang Rai, Thailand.

Faculty Disclosures     Vendor Acknowledgments

2024 IAGS Summary Document

Statement of the problem or issue

Many therapies have been investigated for reducing infarct size, and almost all have been failures in human clinical studies. One of the problems is that everything works in a pig model, but never works in humans. Nevertheless, the work of Bart Meyns and his colleagues in Belgium has demonstrated in an animal model that unloading the left ventricle during reperfusion is associated with a significant decrease in infarct size¹ (Figure 1).

Figure 1. Infarct size in an animal model with and without LV unloading during reperfusion. From: J Am Coll Cardiol. 2003;41:1087-1095.

We used these concepts and data to perform a pilot trial in patients with anterior STEMI. Patients were randomly assigned to LV support with immediate reperfusion or LV support with reperfusion delayed for 30 minutes in order to unload the ventricle. Results stratified by myocardium at risk (sum of ST segment elevation) are shown in Figure 2.

Figure 2. Final infarct size by estimated area at risk, Door-To-Unload Pilot Trial. From: Circulation. 2019;139(3):337-346.

Gaps in current knowledge

We know there is a difference between LAD and non-LAD infarcts. With right coronary (RCA) or circumflex (LCX) occlusions, that is, non-anterior infarcts, the infarctions are all smaller, usually <10% of LV mass, and there is less time-dependence on reperfusion. On the other hand, with LAD (anterior) infarcts, which comprise about 40% of the treated STEMI population, there is definitely a time dependency on reperfusion. Reperfusion <2 hours after symptom onset results in smaller infarct size, between 2-to-3 hours infarct size doubles compared to <2 hours, and after about 3 hours there is little or nothing to be gained with reperfusion. So, it will be important to focus on early reperfusion for patients with larger anterior infarcts.

One of the gap areas we have, though, is the relationship between final infarct size and long-term clinical outcomes. There are studies that indicate long-term outcomes are improved in patients with smaller infarct sizes³ (Figure 3).

Figure 3. Event-free survival at 2 years by final infarct size. From: JACC Cardiovasc Imaging. 2014;7(9):930-939.

Possible solutions and future directions

Building upon the results of the D-T-U-Pilot trial, this concept of unloading the left ventricle for 30 minutes prior to reperfusion is being examined in the multicenter STEMI-DTU clinical trial.⁴ This trial should be completed before the end of 2024, and data should be forthcoming.

References

1. Meyns B, Stolinski J, Leunens V, Verbeken E, Flameng W. Left ventricular support by catheter-mounted axial flow pump reduces infarct size. J Am Coll Cardiol. 2003;41(7):1087-1095. doi: 10.1016/s0735-1097(03)00084-6
2. Kapur NK, Alkhouli MA, DeMartini TJ, et al. Unloading the left ventricle before reperfusion in patients with anterior ST-segment-elevation myocardial infarction. Circulation. 2019;139(3):337-346. doi: 10.1161/CIRCULATIONAHA.118.038269
3. van Kranenburg M, Magro M, Thiele H, et al. Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 2014;7(9):930-939. doi: 10.1016/j.jcmg.2014.05.010
4. Primary unloading and delayed reperfusion in ST-elevation myocardial infarction: the STEMI-DTU Trial (DTU-STEMI). NCT03947619. ClinTrials.gov.