Of Occlusions, Inclusions, and Exclusions: Time to Reclassify Infarctions?

Classification of myocardial infarction (MI) has hitherto been on the basis of the presence or absence of ST-segment–elevation on the ECG. The landmark FTT (Fibrinolytic Therapy Trialists’) collaborative group meta-analysis and the subsequent study of patient subpopulations revealed that the largest benefit of immediate reperfusion therapy was in individuals with ST-segment–elevation MI (STEMI) with a tendency toward net harm in patients who had either ST depression or a normal ST-segment on their ECG.¹ Apart from being on the basis of extensive clinical trial data, the classification also had the advantages of practical application. Patients with STEMI can be quickly identified by bedside ECG and often have complete angiographic occlusion of a culprit vessel. Although this has remained the standard for decades, ST-segment–elevation may not encompass the entire population of patients with acute MI with occlusion or who may benefit from emergent revascularization.

Angiographic Occlusion: the Real Question?

Several recent studies demonstrate that a substantial fraction of patients with acute MI in the absence of ST-segment–elevation (non-STEMI [NSTEMI]) have an acute occlusion of their culprit artery on invasive coronary angiography. These have been termed occlusion MIs (OMIs) and have triggered much debate about the classification of MIs. In a meta-analysis by Khan et al involving >40,000 patients with NSTEMI, the prevalence of a totally occluded culprit artery was 25%.² Other studies have demonstrated a similar frequency of total occlusion of the culprit artery in patients with NSTEMI. This subset of NSTEMI behave in a manner similar to overt STEMI. In the aforementioned meta-analysis by Khan et al, patients with NSTEMI and total occlusion displayed significantly higher major adverse cardiac event rates and all-cause mortality compared with those without total occlusion.² Another large study of 1957 patients with NSTEMI demonstrated that OMIs result in double the infarct size and a 72% higher risk of 6-month mortality.³

These findings question the basis of the dichotomy that is STEMI versus NSTEMI. Although the STEMI/NSTEMI dichotomous classification scheme has served the cardiology community well over the last several decades, it is likely that the constituent pathophysiological event determining prognosis and natural history is acute vessel occlusion itself rather than ST elevation. Our current interpretation of ECGs in acute coronary syndromes bares hidden testament to the same. Several “STEMI equivalents” have been defined over the decades, most of which are electrocardiographic patterns almost in contravention to the existing STEMI criteria. However, in essence, these actually denote angiographic occlusion. Standout examples are the Wellens pattern, new-onset left bundle-branch block (particularly when meeting Sgarbossa criteria), hyperacute T waves, the de Winter pattern, and precordial ST depressions of an isolated posterior wall infarction. In addition, the recently described “South African flag sign” and “Aslanger Pattern” with their noncontiguous or isolated ST elevations have thrown more light on the chasm between ST elevation and the real underlying question.

Recent studies suggest this could be a major issue. Meyers et al studied 467 patients with high-risk acute coronary syndromes, 108 of whom had OMI on angiography. ECGs did not demonstrate ST-segment–elevation in up to 40% of those patients.⁴ Predictably, a large proportion of missed patients with OMI did not receive emergent revascularization.⁴ In the DIFFOCULT study (Diagnostic Accuracy of Electrocardiogram for Acute Coronary Occlusion Resulting in Myocardial Infarction), in comparison with the ST elevation algorithm, 28% of 1000 patients with electrocardiographically diagnosed NSTEMI were reclassified as having OMI by cardiologists.⁵ The follow-up of this group showed larger infarct sizes and higher event rates versus those NSTEMIs without an occluded culprit, raising the possibility that earlier revascularization may improve outcomes for OMI not meeting STEMI criteria.⁵ Conversely, patients with ST elevation from causes other than MI (STEMI mimics) such as myocarditis may be offered fibrinolytic therapy, which may be harmful.

Gaps in Evidence

Although intriguing, these studies are retrospective, and we must have additional data on OMIs before changing clinical practice. In particular, several unknowns need to be better understood. First, what is the timing of occlusion in OMIs? Unlike the vast evidence accrued with the evolutionary pattern of ECGs in STEMI, the natural history of OMIs has yet to be delineated. Specifically, we need to better understand the progress of acute vessel occlusion in OMIs (and distinguish acute from subacute or chronic occlusion) that leads to ECG changes and, subsequently, NSTEMI. Answers to this question may also help us understand why some OMIs manifest with ST elevation whereas some do not. Second, we need to develop new approaches for rapid and accurate identification of OMIs. Some of this might involve using old tools like the ECG but in different ways. For instance, novel analytic tools like artificial intelligence may be able to better identify subtle ECG changes and classify patients with OMI on the ECG that exceed human interpretation. Currently, however, most automated software applications are designed to identify STEMI, not OMI. In addition, novel extended ECG platforms with up to 80 leads have been developed, which may help to identify occult acute circumflex artery occlusions. Other approaches could involve imaging tests like computed tomography coronary angiography that may be used rapidly in the emergency department. Results from the recent follow-up study of the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) have shown computed tomography angiography to be equivalent to invasive coronary angiography in differentiating obstructive and nonobstructive coronary artery disease in patients with NSTEMI. Last, we need to better understand the potential benefit of treatments like urgent revascularization in OMIs. Evaluating treatments will ultimately require randomized trials that test primary percutaneous coronary intervention, fibrinolytic therapy, or other anticoagulant agents in those with probable OMI against current standards of care (Figure). Addressing these unanswered questions will be necessary to better understand the clinical implications of OMIs within the overall spectrum of acute coronary syndromes.

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Conclusions

Classification of acute MI into STEMI and NSTEMI is imperfect. Traditional ST elevation criteria exclude a sizeable fraction of patients with OMI who may benefit from urgent revascularization. Novel diagnostic methods using the ECG or computed tomography angiography may identify a clear subset of patients who may derive maximum benefit from emergent revascularization, suggesting a critical need for future studies in this area.

Acknowledgments

All authors were involved in conceptualization, drafting, and revision of the article.

Footnotes