Intravascular Imaging and Coronary Microvascular Dysfunction After Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction

Coronary microvascular dysfunction (CMD) is a pathogenic condition that encompasses a range of structural and/or functional changes occurring within the coronary microcirculation, which comprises various vessels with a cross-sectional diameter <500 µm:^1–3 pre-arteriolar vessels, ranging from 100 to 500 µm in diameter; intramural arterioles with a diameter <100 µm; and the capillaries. This intricate network of vessels facilitates more than 70% of the coronary resistance during physiological conditions, and thus any changes can result in an inability to increase coronary blood flow against increasing oxygen demand, and subsequent myocardial ischemia.^1–3 Because of advancements in comprehending the pathophysiologically complex mechanisms of CMD, and the spread of noninvasive and invasive diagnostic procedures, CMD is being increasingly given attention as a significant contributor to myocardial ischemia among patients presenting with not only microvascular angina, but also obstructive coronary artery disease (CAD), epicardial coronary artery spasm, takotsubo syndrome, cardiomyopathies, and heart failure.^1–3 In general, the diagnostic criteria for CMD are: (1) decreased coronary flow reserve as represented by an increased coronary perfusion response to adenosine, (2) coronary microvascular spasm (reproducible chest pain/discomfort and ischemic ECG changes during spasm provocation test, without epicardial coronary artery spasm), (3) increased index of microcirculatory resistance, and (4) coronary slow-flow phenomenon (TIMI frame count >25).¹ Furthermore, CMD can be classified into 4 types according to the different clinical scenarios: (1) CMD in the absence of myocardial diseases and obstructive CAD, (2) CMD in myocardial diseases, (3) CMD in obstructive CAD, and (4) iatrogenic CMD.^2,4

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The CMD in patients presenting as acute coronary syndrome is categorized as Type 3, and the acute form of CMD is mainly caused by coronary microvascular obstruction (CMVO). The pathogenesis of CMVO is complex and involves multiple, interacting mechanisms that include distal atherothrombotic embolization, ischemia-reperfusion injury resulting in endothelial cell death and cardiomyocyte death, myocardial edema leading to microvascular compression from the outside, and individual susceptibility associated with pre-existing CMD.⁵ Previous studies showed that CMVO assessed by cardiovascular magnetic resonance (CMR) after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients was an independent risk factor for an adverse outcome mainly driven by exacerbation of heart failure.⁶ In addition, the index of microcirculatory resistance (IMR) measured at the end time point of primary PCI for STEMI was associated with smaller infarct size quantified using CMR at 6 months, with significant regression in infarct size,⁷ and was a prognostic factor for long-term outcome in STEMI patients undergoing primary PCI.⁶ Therefore, IMR can be helpful in grading the degree and severity of CMVO.⁷

There are several reports of evaluation of the association between CMVO and observed coronary artery plaque using intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in patients with STEMI. Shiono et al⁸ conducted an observational study to examine the predictive capability of IVUS regarding CMVO after primary PCI in patients with STEMI. They found that the presence of attenuated plaque, characterized by a maximum attenuation angle >180° and attenuation length of 5 mm, was significantly associated with the occurrence of CMVO after primary PCI. Satogami et al⁹ investigated the association between plaque rupture, as assessed by OCT, and the occurrence of CVMO as well as the grade of transmural extent of infarction (TEI) in STEMI patients following PCI. Their study findings indicated that the no-reflow phenomenon, distal embolization, greater TEI, and CMVO were more frequently observed in patients in the plaque rupture group. Another post-hoc subanalysis from an OCT registry showed that the maximal thrombus-to-lumen area ratio was significantly associated with CMVO assessed by cardiac magnetic resonance at 30 days post-STEMI.¹⁰

In this issue of the Journal, Feng et al¹¹ present their post-hoc analysis of patients who were admitted to the Second Affiliated Hospital of Harbin Medical University among the subjects of a prospective, multicenter randomized controlled trial, the SALVAGE trial. They included 235 patients who were diagnosed with STEMI and underwent PCI with preprocedural OCT assessment. Microvascular perfusion was assessed by the TIMI myocardial perfusion frame count (TMPFC) before and after PCI, and CMD was defined as TMPFC ≥95.5. Using the TMPFC, the study population were divided into 3 groups: improving (TMPFC changed from ≥95.5 to ≤95.5), stable (TMPFC did not exceed the critical value), and worsening TMPFC group (TMPFC changed from ≤95.5 to ≥95.5, or from ≥95.5 to even greater value). The CMD increased from 11.9% before PCI to 20.4% after PCI. The OCT findings showed that less intracoronary thrombosis, lower plaque rupture, and fewer lipid-rich plaques were observed in the improving TMPFC group than in the other 2 groups.¹¹ The authors make the insightful observation that assessment of culprit coronary plaque by OCT can be useful in both predicting the risk and capturing the underlying mechanisms of the acute form of CMD during primary PCI for STEMI, although some confounding factors could not be adjusted in the multivariable analysis because of limited sample size.

Regarding the treatment for prevention of CMD occurrence after PCI, several drugs have been investigated in previous studies targeting STEMI and stable angina;^12–14 however, no definite evidence of efficacy has been established. Based on the existing reports and the OCT findings of this study, distal embolization can be considered as a potential cause of the acute form of CMD. Therefore, the combination of medication and distal protection device, rather than their individual use, may be potentially beneficial. However, due to limited clinical research evidence, effective prevention remains a challenge for future investigation.

IRB Information

Name of the ethics committee: N/A. Reference number: N/A.

Disclosures

K.T. is a member of Circulation Journal’s Editorial Team. The other authors reports no conflicts.

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