4.3 Therapies to Improve Microvascular Function During STEMI and PCI

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

Infarct size in STEMI, and therefore clinical outcomes too, ultimately depend on the microvasculature of the myocardium, a subject that is actively being studied both in the acute setting and the chronic setting. There are several risk factors that can lead to potential microvascular dysfunction during and after primary PCI for STEMI. Microvascular dysfunction includes clogging of the microvasculature with platelet plugs, solid fibrin, and cellular debris. There may be embolization of thrombotic material or fragments of calcific plaque material, along with abnormal vasomotor function including vasospasm. A recent review illustrates some of the potential mechanisms causing microvascular obstruction (MVO)¹ (Figure).

Figure. Possible mechanisms of microvascular dysfunction in myocardial infarction. From: Nat Rev Cardiol. 2024;21:283-298 doi:10.1038/s41569-023-00953-4. 

Gaps in current knowledge

Numerous investigations have led to increasing data suggesting that many possible therapies that once seemed very promising might instead be neutral, if not harmful. Some of these are listed in the Table.

Table. Potential therapies to prevent microvascular dysfunction in myocardial infarction.

PPCI = primary percutaneous coronary intervention; GP= glycoprotein; LV = left ventricular.

Several potent antiplatelets agents and anticoagulants, for example, thrombolytics like alteplase and GP IIb/IIIa inhibitors, are now thought to be harmful when used routinely, with no benefit to the microvasculature, and they are now reserved for select settings such as large residual thrombus burden or persistent no-reflow. Potent P2Y12 antagonists were once thought to help improve outcomes, but pre-loading with large doses doesn't seem to matter. Recent analyses have found they can be given before, during, or after primary percutaneous coronary intervention (PPCI), and outcomes are the same. Vasoactive medications like adenosine or other vasodilators were studied in clinical trials and were found to be harmful in most patients. Aspiration thrombectomy is potentially harmful when performed routinely, and so it too is reserved for selected cases. Some early data on mechanical thrombectomy suggested this therapy was safe, but it does not appear that pivotal outcomes trials that might support routine use will be undertaken.  Clinical investigators examining intermittent coronary sinus occlusion (PICSO) presented pivotal trial findings at TCT-2023, and these data indicated no benefit in patients with STEMI.² Ongoing studies include the utility of percutaneous LVAD during PPCI, as well as studies of super-saturated oxygen (SSO₂).^3,4 Therefore, at present, there are no compelling data on how to prevent MVO from occurring in STEMI patients, or how to treat it.

Possible solutions and future directions

There is no doubt that potential therapies to prevent microvascular dysfunction in STEMI will continue to be created and tested. The door-to-unload (DTU) and AMIHOT trials appear to be the most promising underway at this time. Other novel potential pharmacotherapies that could help relieve MVO, targeting the harmful effects of endothelial damage, myocardial edema, and microvascular spasm, possibly used in conjunction with mechanical approaches, await development with the hope that this serious complication of STEMI can be ameliorated.

References

1. Galli M, Niccoli G, De Maria G, et al. Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction. Nat Rev Cardiol. 2024;21(5):283-298. doi: 10.1038/s41569-023-00953-4
2. De Maria GL. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) in acute myocardial infarction: PICSO-AMI-I trial. Presented at: TCT 2023. October 25, 2023. San Francisco, CA.
3. https://clinicaltrials.gov/study/NCT03000270
4. https://clinicaltrials.gov/study/NCT04743245