Left main coronary artery stenosis, atherothrombotic disease, or occlusion

Left main coronary artery (LMCA) occlusion is a rare but catastrophic manifestation of acute coronary syndromes. The LMCA supplies an extensive myocardial territory via the left anterior descending (LAD) and left circumflex (LCx) arteries; thus, acute obstruction can precipitate rapid hemodynamic deterioration, cardiogenic shock, malignant ventricular arrhythmias, or sudden cardiac death. Fewer than approximately 1% of patients with ST-elevation myocardial infarction (STEMI) who reach the catheterization laboratory are found to have complete LMCA occlusion—likely because many do not survive without immediate reperfusion. Prompt recognition of LMCA involvement is therefore essential. The 12-lead electrocardiogram (ECG) is an immediately available diagnostic tool that can provide critical clues to LMCA occlusion or severe stenosis prior to coronary angiography. This chapter reviews the electrocardiographic features suggestive of significant LMCA disease—including acute occlusions, subtotal stenoses, and atherothrombotic lesions—and discusses associated clinical presentations, prognostic implications, and management strategies relevant to cardiologists.

Pathophysiology and Clinical Significance

Occlusion of the left main coronary artery (LMCA) abruptly interrupts blood flow to both the left anterior descending (LAD) and left circumflex (LCx) coronary artery territories, resulting in extensive myocardial ischemia or infarction involving the anterior, septal, and lateral walls, and frequently the posterior wall if the LCx supplies the posterior descending artery (PDA) in a left-dominant circulation. This produces an infarction affecting multiple vascular territories—essentially a simultaneous large anterior and lateral ST-elevation myocardial infarction (STEMI), often with inferior or posterior involvement depending on coronary dominance. Clinically, patients present in extremis, with severe chest pain, diaphoresis, hypotension, pulmonary edema, malignant arrhythmias, and rapid progression to cardiogenic shock. Ventricular fibrillation or asystole may occur early due to the massive ischemic burden. Complete LMCA occlusion is frequently fatal within minutes if reperfusion is not achieved, hence its designation as the “widow-maker.” Patients who survive long enough for electrocardiographic evaluation often have some residual antegrade flow or collateral circulation that limits infarct size; in such cases, ECG patterns may provide critical clues to an LMCA culprit lesion. In contrast, a critical but subtotal LMCA stenosis (functional insufficiency) may cause subendocardial ischemia during exertion or increased myocardial demand, serving as a warning sign of impending total occlusion. These patients may present with non–ST-elevation acute coronary syndrome (NSTE-ACS), refractory angina, or hemodynamic instability, and are at high risk for progression to complete occlusion. In both acute total occlusion and critical high-grade stenosis, the ECG may demonstrate characteristic changes that should alert clinicians to the presence of LMCA or equivalent disease and the urgent need for revascularization.

Classic Electrocardiographic Patterns Indicative of Left Main Coronary Artery Disease

Several characteristic electrocardiographic (ECG) patterns have been described in association with acute left main coronary artery (LMCA) occlusion or severe LMCA stenosis. These patterns typically reflect either diffuse subendocardial ischemia, as seen in incomplete occlusion or critical stenosis, or extensive transmural myocardial infarction, as occurs in complete occlusion. The principal ECG manifestations include:

Figure: A 12-lead ECG from a patient with acute left main coronary artery occlusion. Note the pronounced ST-segment elevation in lead aVR (~2 mm) (red arrow) with concomitant 1 mm ST elevation in V1, while diffuse ST depressions are present in leads I, II, aVL, aVF, and V3–V6 . This pattern of aVR elevation with widespread ST depression is highly suggestive of left main (or severe multivessel) ischemia.

• Diffuse ST-Segment Depression with ST Elevation in aVR: The most widely recognized electrocardiographic manifestation of left main coronary artery (LMCA) ischemia is widespread horizontal ST-segment depression in multiple leads—typically six or more, often including leads I, II, aVL, aVF, and V4–V6—accompanied by ST-segment elevation in lead aVR. This pattern reflects global subendocardial ischemia. Because lead aVR is electrically opposite to the left-sided leads (I, II, aVL, V5–V6), diffuse ST-segment depression, particularly in the lateral leads, produces reciprocal ST-segment elevation in aVR. In the setting of critical LMCA stenosis (subtotal occlusion), inadequate coronary flow to meet myocardial oxygen demand results in this characteristic pattern: pronounced, diffuse ST-segment depression (most prominent in the lateral leads) with reciprocal ST-segment elevation in aVR, and often in V1, another rightward-oriented lead. Clinically, this ‘diffuse ischemia’ pattern is observed in high-risk non–ST-elevation myocardial infarction (NSTEMI) or unstable angina (UA) and indicates a large myocardial territory at risk. Classic diagnostic criteria include ST-segment elevation in aVR ≥1 mm and ST-segment elevation in aVR greater than or equal to that in V1. When these criteria are met in the context of ongoing ischemic symptoms, they are highly predictive of LMCA disease or severe multivessel coronary artery disease (CAD). In a landmark study, ST-segment elevation in aVR ≥1 mm was the strongest independent ECG predictor of severe LMCA or triple-vessel disease requiring coronary artery bypass grafting (CABG) in NSTEMI patients. Similarly, aVR elevation ≥1 mm in conjunction with multilead ST-segment depression demonstrates approximately 75–93% specificity for LMCA or triple-vessel disease in non–ST-elevation acute coronary syndromes (NSTE-ACS). Importantly, the absence of ST-segment elevation in aVR essentially excludes significant LMCA stenosis; if aVR is isoelectric or shows depression during an acute coronary syndrome, critical LMCA disease is highly unlikely. Therefore, lead aVR should always be carefully evaluated in ACS patients. Although historically referred to as the ‘forgotten lead,’ ST-segment changes in aVR provide crucial diagnostic and prognostic information.
• Extensive Anterior–Lateral ST Elevation (“Spatially Extensive STEMI”): While many left main coronary artery (LMCA) lesions present with the subendocardial ischemia pattern described above, a subset—particularly complete occlusions without collateral circulation—produce a frank STEMI pattern involving multiple myocardial territories. In such cases, the ECG demonstrates ST-segment elevation in the anterior precordial leads and high lateral leads, constituting an anterolateral STEMI. Classically, ST elevation is observed in leads V2–V6, I, and aVL, often with concomitant elevation in V1 and aVR. A large study identified this as a distinct STEMI pattern of LMCA occlusion: approximately one-third of LMCA occlusions exhibited ST elevation from V1 (or V2) through V6 and in leads I and aVL. This pattern reflects transmural injury across the extensive territory supplied by the left main artery. The ECG appearance is essentially that of a combined extensive anterior wall myocardial infarction (MI) and lateral wall MI. For example, ST elevation may be present in V3–V4 (anterior) and in leads I and aVL (lateral), sometimes accompanied by ST depression in the inferior leads due to reciprocal changes from lateral STEMI—a combination suggesting a very proximal occlusion (LMCA or proximal left anterior descending [LAD] artery with left circumflex [LCx] involvement). When both the LCx (lateral wall) and LAD (anterior wall) territories are infarcting, the patient is experiencing a “double” STEMI, most often due to LMCA occlusion, or less commonly, simultaneous proximal LAD and LCx occlusions. Clinically, an ECG showing widespread ST elevation (anterior and lateral) in a patient with hemodynamic collapse should prompt strong consideration of LMCA occlusion, particularly if there is no ST elevation in the inferior leads (helping to exclude a wraparound LAD supplying the inferior wall or right coronary artery involvement). These extensive STEMI cases frequently demonstrate intraventricular conduction disturbances—such as new right bundle branch block (RBBB) with left anterior fascicular block (LAFB)—secondary to septal infarction. Up to approximately 37% of acute LMCA occlusions are associated with LAFB, and about 17% present with combined RBBB and LAFB (bifascicular block), reflecting injury to the left bundle branch system from septal involvement. A prolonged QRS duration or new bundle branch block in the setting of anterolateral MI should heighten suspicion for a very proximal lesion (LMCA or proximal LAD). In summary, an ECG demonstrating STEMI in multiple territories simultaneously (e.g., anteroseptal and high lateral) should be presumed to represent LMCA occlusion until proven otherwise. Unfortunately, truly complete LMCA occlusion is often rapidly fatal, and few such ECGs are recorded; those that are captured typically represent patients in extremis, often in ventricular fibrillation or profound cardiogenic shock.
• “aVR + aVL” Pattern: In addition to the classic diffuse subendocardial ischemia pattern and the multi-territory STEMI pattern, investigators have described an intermediate ECG presentation characterized by concurrent ST-segment elevation (STE) in leads aVR and aVL (occasionally also in lead I), accompanied by relative ST-segment depression in the precordial leads. In one analysis of left main coronary artery (LMCA) occlusions, approximately 15% of cases demonstrated STE in both aVR and aVL, with minimal or absent STE in the chest leads. This configuration may be interpreted as a combination of high lateral myocardial injury (STE in aVL and I) and diffuse subendocardial ischemia (STE in aVR with anterior ST depression). In that study, the pattern was associated with specific collateral flow characteristics, and STE in both aVR and aVL was identified as a strong predictor of LMCA occlusion. Clinically, the presence of simultaneous STE in aVR and aVL (particularly ≥1 mm), together with widespread ST depression, should prompt strong suspicion for LMCA involvement or combined proximal left anterior descending (LAD) and left circumflex (LCx) artery disease. Although uncommon, this pattern highlights that LMCA occlusion can occasionally mimic an inferior NSTEMI (due to the frequent association of aVL STE with inferior ST depression) or a high lateral STEMI. Careful scrutiny will typically reveal the diffuse distribution of ST-segment changes—often involving multiple leads—which distinguishes it from an isolated single-vessel occlusion.

Mechanistic insight: The pathophysiological mechanisms underlying ST-segment changes in left main coronary artery (LMCA) ischemia help explain the characteristic electrocardiographic patterns. In the setting of a critical but not completely occlusive LMCA stenosis, ischemia is typically subendocardial (partial-thickness) and involves a broad expanse of the left ventricular myocardium. This produces a consistent pattern of widespread ST-segment depression, most prominent in the lateral and inferior leads, accompanied by reciprocal ST-segment elevation in lead aVR (and occasionally in V1). This constellation has been termed the “LMCA insufficiency” pattern. In contrast, complete proximal LMCA occlusion results in transmural infarction involving both the left anterior descending (LAD) and left circumflex (LCx) territories. This manifests as ST-segment elevation in leads reflecting the anterior septum (V1–V4) and the lateral wall (I, aVL, V5–V6) simultaneously. In such cases, lead aVR may also demonstrate ST-segment elevation, not solely as a reciprocal phenomenon, but due to direct injury of the basal interventricular septum, which is oriented toward aVR. The basal septum is typically supplied by the first septal perforator branch of the LAD; infarction in this region generates a primary injury current directed toward aVR. Thus, ST-segment elevation in aVR can arise from two distinct mechanisms: (1) reciprocal changes secondary to diffuse subendocardial ischemia (the most common mechanism), and (2) direct transmural infarction of the basal septum in the context of a proximal LAD or LMCA occlusion. Clinically, if ST elevation in aVR is accompanied by concurrent ST elevation in V1–V3 (anteroseptal leads), this suggests a proximal LAD occlusion involving the septum, which may result from either LMCA occlusion or a very proximal LAD thrombus. Conversely, if aVR shows ST elevation while the precordial leads predominantly exhibit ST depression, the mechanism is more likely purely reciprocal, reflecting diffuse subendocardial ischemia—more typical of critical LMCA stenosis or severe triple-vessel coronary artery disease rather than complete occlusion. Careful recognition of these electrocardiographic nuances can aid in distinguishing LMCA lesions from isolated proximal LAD occlusions.

Differentiating Left Main Coronary Artery Occlusion from Other Electrocardiographic Patterns

The ECG patterns described above—particularly the aVR sign, characterized by ST-segment elevation in lead aVR accompanied by diffuse ST-segment depression—are not entirely specific for left main coronary artery disease, as they indicate severe myocardial ischemia that may arise from other etiologies. Clinicians should carefully consider and differentiate the following scenarios:

• Proximal LAD Occlusion: An occlusion of the proximal left anterior descending artery (LAD), occurring before the first septal branch (S1), can produce ST-segment elevation in lead aVR due to infarction of the basal interventricular septum. In the setting of an anterior ST-elevation myocardial infarction (STEMI), ST elevation ≥1 mm in lead aVR is highly specific for an LAD occlusion located very close to its origin, proximal to S1. A proximal LAD occlusion typically produces ST-segment elevation in leads V1–V4 (anteroseptal leads) in addition to aVR elevation, resulting in an anteroseptal STEMI pattern with concomitant aVR elevation. In contrast, the classic electrocardiographic pattern of a left main coronary artery (LMCA) subocclusion usually demonstrates ST elevation in aVR without significant ST elevation in V2–V4; these leads instead often exhibit ST depression. Therefore, a useful diagnostic clue is as follows: if aVR shows ST elevation while V2–V4 demonstrate ST depression, consider LMCA disease or multivessel subendocardial ischemia; if both aVR and V1–V3 show ST elevation, a proximal LAD occlusion is more likely—although an acute LMCA occlusion can also produce this pattern by causing simultaneous LAD and left circumflex (LCx) territory infarction. Another distinguishing feature is the relative magnitude of ST elevation in aVR compared with V1. A well-known teaching point is that ST elevation in aVR greater than that in V1 favors LMCA disease, whereas ST elevation in V1 equal to or exceeding that in aVR suggests an isolated LAD occlusion. This criterion was first described by Yamaji et al., who observed that in acute LMCA obstruction, lead aVR tends to exhibit greater ST elevation than V1. Pathophysiologically, this is plausible: an isolated LAD occlusion produces marked ST elevation in V1–V4, whereas LMCA insufficiency causes diffuse subendocardial ischemia with widespread ST depression (limiting V1 elevation) but still results in aVR elevation via reciprocal changes. Thus, an aVR > V1 pattern should be considered a red flag for LMCA or severe multivessel disease. Nevertheless, there is overlap in the ECG manifestations of proximal LAD and LMCA occlusions, and in equivocal cases, the clinical context and urgent coronary angiography remain essential for definitive diagnosis.
• Severe Triple-Vessel Disease: Extensive chronic coronary artery disease (CAD) with critical stenoses in all three major epicardial vessels—the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA)—can closely mimic the electrocardiographic pattern of left main coronary artery (LMCA) subocclusion. In the setting of multivessel disease, an episode of demand ischemia or a non–ST-elevation myocardial infarction (NSTEMI) may precipitate diffuse subendocardial ischemia throughout the left ventricle, producing widespread ST-segment depressions with concomitant ST-segment elevation in lead aVR. Indeed, the ECG manifestations of severe triple-vessel CAD and LMCA disease are often indistinguishable. Both conditions signify a large myocardial territory at risk and frequently necessitate surgical revascularization via coronary artery bypass grafting (CABG). As noted in the literature, because the acute management is similar—urgent coronary angiography followed by likely CABG—the inability to differentiate between severe triple-vessel disease and LMCA disease on ECG alone is of limited practical consequence; the critical point is recognizing that either scenario represents a high-risk presentation and should not be misinterpreted as benign. In clinical practice, the presence of ST-segment elevation in aVR with diffuse ST-segment depression should prompt the consideration of LMCA or equivalent multivessel ischemia, both of which require intensive management. Ancillary diagnostic clues may be obtained from echocardiography—distinguishing global from regional wall-motion abnormalities—or from serial cardiac troponin measurements; however, definitive differentiation mandates coronary angiography. It is worth noting that some reports suggest that ST-segment elevation in lead aVL (accompanied by diffuse ST depression) may favor LMCA or proximal LAD disease, whereas ST depression in aVL with aVR elevation may be more consistent with multivessel disease, possibly reflecting differences in ischemic vector orientation. Nonetheless, such distinctions are subtle. The essential clinical message remains: ST-segment elevation in aVR with widespread ST-segment depression should be considered indicative of either LMCA occlusion or severe multivessel CAD until proven otherwise.
• Diffuse Demand Ischemia (Non-Cardiac or Secondary Causes): Diffuse subendocardial ST-segment depression with concomitant ST-segment elevation in lead aVR can occur in states of severe myocardial oxygen supply–demand mismatch, such as profound anemia, tachyarrhythmias, or hypotension (e.g., during cardiac arrest or shock of non-cardiac origin). For example, a patient in supraventricular tachycardia may exhibit transient ST-segment depressions with aVR elevation due to rate-related ischemia, effectively “stress-testing” the myocardium at a high heart rate. Similarly, post–cardiac arrest patients or those with severe hypoxemia may demonstrate this pattern as a result of global subendocardial hypoperfusion. In such cases, the ECG abnormalities often resolve once the tachyarrhythmia is controlled or hemodynamic parameters are restored. Clinicians should be cautious not to misinterpret these findings as indicative of acute left main coronary artery syndrome (LMCA ACS) when the primary pathology is an arrhythmia or shock from another etiology—the clinical context is paramount. If the pattern emerges during a tachyarrhythmia, an ECG should be repeated after rate control; resolution of ST-segment changes supports a diagnosis of transient demand ischemia. Conversely, persistence of marked ST-segment depression with aVR elevation after normalization of heart rate or blood pressure strongly suggests underlying fixed coronary artery disease. Distinguishing primary ACS from secondary ischemia is essential. Features favoring primary LMCA ACS include severe chest pain, significant cardiovascular risk factors, elevated cardiac troponin levels, and ST-segment changes disproportionate to the degree of tachycardia. In cases of diagnostic uncertainty, urgent cardiology consultation is warranted, as failure to identify a critical left main lesion may be fatal.

It is important to note that pericarditis—a condition historically associated with characteristic changes in lead aVR (PR-segment elevation and ST-segment depression)—exhibits an almost inverse electrocardiographic pattern compared with left main coronary artery (LMCA) ischemia. In pericarditis, the ECG typically demonstrates diffuse, concave upward ST-segment elevation with PR-segment depression in multiple leads, accompanied by ST-segment depression in lead aVR rather than elevation. This pattern is generally straightforward to differentiate from the LMCA ischemic pattern of widespread ST-segment depression with concomitant ST-segment elevation in lead aVR. However, clinicians should be aware that not all diffuse ST-segment depression is of ischemic origin; for example, hyperkalemia or the digitalis effect may produce ST-segment depression in the lateral leads, mimicking ischemia. Therefore, ECG findings must always be interpreted within the appropriate clinical context.

Clinical Presentation and Outcomes in Acute Coronary Syndromes Involving the Left Main Coronary Artery

Presentation: Patients with acute left main coronary artery (LMCA) occlusion typically present in extremis. The clinical history often describes the abrupt onset of severe, pressure-like chest pain, which may be accompanied by syncope or presyncope due to a sudden reduction in cardiac output or the occurrence of malignant ventricular arrhythmias. On physical examination, signs of cardiogenic shock are common, including hypotension, cool and clammy skin, altered mental status, and, in some cases, bradycardia or tachyarrhythmias. Pulmonary edema may develop secondary to acute left ventricular failure. Cardiac auscultation may reveal an S4 gallop or a soft systolic murmur suggestive of papillary muscle dysfunction. These patients frequently require immediate resuscitative intervention. Indeed, many individuals with LMCA occlusion present as out-of-hospital cardiac arrest and are successfully resuscitated; in such cases, an emergent post–return of spontaneous circulation (ROSC) electrocardiogram (ECG) may demonstrate characteristic ischemic patterns. Ventricular fibrillation is a common early manifestation of massive myocardial infarction; conversely, some patients present with profound bradycardia or pulseless electrical activity (PEA) when ischemia induces vagal reflexes or results in severe pump failure. Cardiac troponin concentrations in LMCA-related myocardial infarction are typically markedly elevated due to the extensive infarct size, although initial values may be only modestly increased if cardiac arrest or death occurs early in the clinical course.

Outcomes: The prognosis of true left main coronary artery (LMCA) occlusion is poor in the absence of rapid intervention. Reported in-hospital mortality rates for acute LMCA ST-elevation myocardial infarction (STEMI) vary widely, ranging from approximately 40% to as high as 70% in some series. Even in cases of critical LMCA non–ST-elevation acute coronary syndrome (NSTE-ACS) due to subtotal occlusion, the risk of myocardial infarction and death remains substantial without prompt revascularization. The magnitude of ST-segment elevation in lead aVR has been correlated with adverse outcomes: for example, an aVR elevation of ≥0.5 mm has been associated with a fourfold increase in mortality in ACS, and an elevation of ≥1 mm with an approximately six- to sevenfold increase. Marked aVR elevation (≥1.5–2 mm) is often associated with particularly high mortality; one study reported mortality rates of 20–75% in such patients, depending on the clinical presentation. These striking figures reflect the fact that an ECG pattern of ST elevation in aVR with diffuse ST depression typically indicates either LMCA or equivalent multivessel critical ischemia—a condition that, if not rapidly corrected, can result in extensive myocardial necrosis and pump failure. Patients meeting the ‘left main pattern’ criteria frequently require mechanical circulatory support, such as intra-aortic balloon counterpulsation or percutaneous left ventricular assist devices, in addition to pharmacologic therapy, as a bridge to revascularization, particularly when presenting with cardiogenic shock.

Conversely, if recognized promptly and managed aggressively, patients can survive an acute left main coronary artery (LMCA) event. Case reports describe patients with the classic ECG pattern who were taken directly to coronary angiography; when a left main thrombus is rapidly stented or emergent coronary artery bypass grafting (CABG) is performed, some patients recover satisfactory ventricular function. Early revascularization is critical—every minute of LMCA occlusion results in substantial myocardial loss. Patients with critical but subocclusive LMCA stenosis, without evidence of myocardial infarction, can achieve excellent outcomes if they undergo prompt surgical revascularization before infarction occurs. CABG confers a significant survival advantage in patients with substantial LMCA disease, whether in the context of acute coronary syndrome (ACS) or stable ischemic heart disease. Accordingly, current clinical guidelines designate significant LMCA disease as an unequivocal indication for revascularization. In stable patients, exercise stress testing may reveal evidence of LMCA disease—most notably, exercise-induced ST-segment elevation in lead aVR accompanied by widespread ST-segment depression in other leads, which is a strong predictor of LMCA or proximal left anterior descending (LAD) artery stenosis. Detection of ≥1 mm ST-segment elevation in aVR at peak exercise should prompt immediate concern for LMCA disease and consideration of invasive coronary evaluation. In such cases, timely CABG can prevent the occurrence of acute myocardial infarction.

In summary, patients exhibiting ECG evidence of left main coronary artery (LMCA) involvement constitute a particularly high-risk subset of acute coronary syndrome (ACS). Without prompt intervention, in-hospital mortality is substantial; however, rapid recognition and timely reperfusion can be life-saving. In the long term, survivors of LMCA infarction frequently exhibit markedly reduced left ventricular ejection fraction or progress to chronic heart failure as a consequence of the extensive myocardial injury. Therefore, optimal management includes prevention through early identification and revascularization of critical LMCA stenosis before complete occlusion occurs.

Management Considerations and Clinical Algorithms

Recognition of electrocardiographic patterns indicative of left main coronary artery (LMCA) occlusion or critical stenosis has direct and immediate implications for patient management and triage.

• Emergent vs. Urgent Revascularization: Traditionally, only ST-elevation myocardial infarction (STEMI) criteria—defined as ≥1–2 mm ST-segment elevation in two anatomically contiguous leads—trigger immediate cardiac catheterization laboratory activation. However, left main coronary artery (LMCA) occlusion, or its equivalent, may present without classical STEMI criteria, for example with diffuse ST-segment depression and concomitant ST-segment elevation in lead aVR (technically classified as an NSTEMI). There is ongoing debate as to whether this electrocardiographic pattern should be regarded as a “STEMI equivalent.” Many experienced clinicians treat it as such, particularly in the presence of hemodynamic instability. The 2022 ACC Expert Consensus Decision Pathway on the evaluation and disposition of acute chest pain acknowledges that certain high-risk ECG patterns (e.g., posterior MI, de Winter T-waves) warrant emergent intervention; however, ST-segment elevation in aVR was not formally designated as a STEMI equivalent. Instead, the consensus recommends managing diffuse ST depression with aVR elevation as a high-risk non–ST-elevation acute coronary syndrome (NSTE-ACS), meriting urgent—rather than immediate—angiography, unless the patient’s clinical status (e.g., cardiogenic shock) necessitates immediate intervention. In practical terms, a patient with ongoing chest pain and the classic aVR-positive/ST-depression pattern should undergo coronary angiography as soon as possible, ideally within less than two hours, analogous to an NSTEMI with refractory ischemia. The 2023 ESC guidelines for ACS similarly note that widespread ST depression with ST elevation in aVR and/or V1 suggests multivessel ischemia or LMCA obstruction, particularly in the context of shock, and recommend expedited invasive management. Thus, while isolated ST elevation in aVR may not automatically trigger a formal STEMI protocol, in practice such patients should be triaged to the catheterization laboratory with the highest urgency. In the presence of instability—hypotension, acute heart failure, or malignant arrhythmias—emergent activation is warranted, as this presentation carries a lethality comparable to STEMI. In stable, pain-free patients with this ECG pattern, urgent angiography within hours is indicated, rather than delayed evaluation over days. The proposed “Occlusion MI (OMI) vs. Non-Occlusion MI” paradigm seeks to bypass the STEMI/NSTEMI dichotomy; under this framework, an ECG suggestive of potential LMCA occlusion would prompt immediate reperfusion therapy, even in the absence of classic STEMI criteria. Many tertiary centers have adopted protocols to fast-track such patients to the catheterization laboratory, recognizing their exceptionally high mortality risk.
• Antiplatelet and anticoagulation considerations: In the context of non–ST-elevation acute coronary syndrome (NSTE-ACS), patients are frequently pretreated with P2Y₁₂ receptor inhibitors (such as clopidogrel or ticagrelor) as part of the initial medical management. However, when left main coronary artery disease is suspected—based on electrocardiographic findings or echocardiographic evidence—it may be prudent to defer P2Y₁₂ loading until the coronary anatomy has been delineated. This precaution is warranted because, if urgent coronary artery bypass grafting (CABG) is required—as is often the case with significant left main lesions—proceeding to surgery within 24 hours of P2Y₁₂ administration substantially increases perioperative bleeding risk. Several authors specifically recommend avoiding clopidogrel in patients with non–ST-elevation myocardial infarction (NSTEMI) who demonstrate ST-segment elevation in lead aVR ≥1 mm, as these patients frequently require surgical revascularization. In such cases, management with intravenous unfractionated heparin and, when appropriate, glycoprotein IIb/IIIa inhibitors while awaiting coronary angiography is a reasonable strategy. If angiography reveals a lesion suitable for percutaneous coronary intervention (PCI) and stenting is undertaken, P2Y₁₂ inhibition can be initiated at that time. Conversely, if surgical revascularization is indicated, the patient can proceed to CABG without the delay necessitated by recent P2Y₁₂ exposure. This individualized approach requires close coordination among emergency medicine, interventional cardiology, and cardiothoracic surgery teams, and may improve outcomes by avoiding unnecessary surgical delays. In all suspected cases of left main ACS, aspirin and anticoagulation should be administered in accordance with standard ACS protocols, as these confer established clinical benefit.
• Hemodynamic support: Given the rapid clinical deterioration often observed in these patients, clinicians should maintain a low threshold for initiating hemodynamic support. Historically, intra-aortic balloon pump (IABP) therapy has been employed in cases of cardiogenic shock due to left main coronary artery (LMCA) occlusion to augment coronary perfusion pending revascularization. More recently, percutaneous left ventricular assist devices (e.g., Impella) and, in extreme cases, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been utilized in LMCA myocardial infarction complicated by cardiogenic shock. In patients with borderline blood pressure or clinical evidence of impaired end-organ perfusion, early involvement of a dedicated shock team and initiation of mechanical circulatory support prior to or during percutaneous coronary intervention (PCI) can be life-saving. Although detailed discussion of device selection is beyond the scope of this ECG-focused review, the imperative for early recognition of LMCA occlusion is clear: such patients frequently require not only standard acute coronary syndrome pharmacotherapy, but also urgent mechanical support and expedited revascularization.
• Revascularization strategy: Once a left main coronary artery (LMCA) culprit lesion is identified, the optimal revascularization approach depends on the clinical scenario. In the setting of acute myocardial infarction with hemodynamic collapse, primary percutaneous coronary intervention (PCI) to the left main—often as an emergency or ‘bail-out’ stenting procedure—is frequently performed as a life-saving measure, as it can restore coronary flow more rapidly than emergent coronary artery bypass grafting (CABG). However, PCI in an unprotected LMCA carries substantial risk and is often a temporizing measure. If the patient stabilizes, CABG is generally recommended for long-term management of LMCA disease, particularly in the presence of multivessel coronary artery disease, owing to its demonstrated survival benefit. In stable patients with significant LMCA stenosis, surgical revascularization remains the treatment of choice to improve survival compared with medical therapy alone. Consequently, many patients undergo PCI as a bridge (‘salvage’ stenting) followed by CABG in the ensuing days or weeks, unless PCI is deemed definitive. In certain cases, such as subtotal LMCA stenosis detected prior to infarction, urgent CABG can be performed before myocardial damage occurs. A critical point for cardiologists is to involve the cardiothoracic surgery team early when an ECG pattern suggestive of LMCA involvement is recognized. Even prior to coronary angiography, alerting the surgical team to a suspected LMCA lesion can expedite definitive management. In selected situations where surgery is contraindicated or PCI is preferred—for example, in distal LMCA bifurcation thrombus with experienced PCI operators available—a percutaneous approach with appropriate hemodynamic support may serve as definitive therapy. Ultimately, each case requires individualized decision-making, but timely intervention is only possible if the diagnosis is made promptly.

To support clinical decision-making, several diagnostic algorithms and scoring systems have been investigated. For example, a 2022 study evaluated a combination of ECG criteria—ST-segment elevation (STE) in both leads aVR and aVL, together with the absence of STE in lead V1, representing an anterolateral subendocardial ischemic pattern—and found that this combination yielded approximately 95% specificity for acute left main coronary artery (LMCA) occlusion. The addition of fascicular block criteria, specifically the presence of left anterior fascicular block (LAFB) or right bundle branch block (RBBB) with concomitant LAFB, increased specificity to nearly 99%. Although overall sensitivity remained modest (approximately 39% when all criteria were applied), these findings underscore that certain ECG ‘red flags’ in combination—such as STE in aVR and aVL, diffuse ST depression, fascicular conduction blocks, and QRS complex widening—can be highly suggestive, and in some cases virtually diagnostic, of acute LMCA occlusion. In practice, clinicians may apply a streamlined mental algorithm at the bedside to integrate these findings.

• Step 1: Determine whether the ECG demonstrates ST-segment elevation in lead aVR ≥1 mm accompanied by widespread ST-segment depression, particularly involving six or more leads, including the lateral leads. If present, this pattern should raise suspicion for left main coronary artery (LMCA) occlusion or an equivalent critical coronary artery disease (CAD) lesion.
• Step 2: Assess lead V1. If ST-segment elevation (STE) in lead aVR exceeds that in V1, or if V1 demonstrates no STE, this finding favors left main coronary artery (LMCA) occlusion or severe three-vessel disease over isolated left anterior descending (LAD) artery occlusion. If V1 also exhibits STE—particularly when anteroseptal leads V1–V3 show STE—consider proximal LAD occlusion as an alternative etiology, although LMCA involvement remains possible.
• Step 3: Assess for conduction blocks or QRS complex prolongation. The emergence of a new left anterior fascicular block (LAFB) or bifascicular block in this clinical context strongly suggests the presence of a large proximal lesion, most likely involving the left main coronary artery (LMCA).
• Step 4: Assess the patient’s clinical status. In the presence of hemodynamic instability (e.g., hypotension, cardiogenic shock) or severe, persistent chest pain accompanied by this ECG pattern, initiate immediate reperfusion protocols, including urgent activation of the catheterization laboratory and consideration of mechanical circulatory support. If the patient is hemodynamically stable, arrange for urgent coronary angiography within 1–2 hours and provide interim medical management, avoiding administration of contraindicated agents such as P2Y₁₂ receptor inhibitors until coronary anatomy is defined.
• Step 5: Upon arrival in the catheterization laboratory, if an LMCA culprit lesion is confirmed, promptly involve the cardiothoracic surgery team. If percutaneous coronary intervention (PCI) is undertaken, it may serve as a bridge to coronary artery bypass grafting (CABG). Revascularization strategy should be individualized according to the patient’s coronary anatomy and hemodynamic stability, ensuring that the left main lesion is definitively treated—either by stenting or surgical bypass—prior to hospital discharge.

By adopting this approach, clinicians can enhance the early detection and management of left main coronary artery occlusion—a time-critical condition. It is important to recognize that not all patients with acute coronary syndromes (ACS) will conform neatly to the STEMI versus NSTEMI classification; careful attention to lead aVR and the overall pattern of ST-segment deviations can reveal a ‘hidden’ STEMI equivalent. As a key clinical message: diffuse ST-segment depression accompanied by ST-segment elevation in lead aVR in a patient with ischemic symptoms should be managed with the same urgency as an extensive myocardial infarction. Prompt recognition of this ECG pattern and expedited triage for revascularization can be life-saving, transforming a lesion with a grave prognosis into one with a favorable outcome when treated without delay.

Conclusion

In summary, the electrocardiographic manifestations of left main coronary artery (LMCA) occlusion or critical stenosis typically reflect global myocardial ischemia. The most characteristic pattern consists of diffuse ST-segment depression with reciprocal ST-segment elevation in lead aVR (and frequently in V1), or an anterolateral STEMI pattern involving multiple leads (I, aVL, V2–V6). Additional supportive findings include ST-segment elevation in lead aVR ≥1 mm (particularly when exceeding that in V1), new conduction disturbances such as left anterior fascicular block (LAFB) or right bundle branch block (RBBB), and severe, widespread ischemic changes. Patients with LMCA occlusion usually present in extremis, often with cardiogenic shock or cardiac arrest, and prognosis is highly dependent on prompt recognition and intervention. Although the aVR sign is not entirely specific—since proximal left anterior descending (LAD) artery occlusion or severe triple-vessel disease may produce similar ECG changes—its presence invariably indicates a high-risk acute coronary syndrome (ACS) requiring urgent, aggressive management. Current guidelines recommend expedited invasive evaluation in such scenarios. Vigilance for both subtle and overt ECG indicators of LMCA ischemia enables clinicians to activate appropriate diagnostic and therapeutic pathways, avoid potentially harmful pharmacologic interventions, mobilize interventional and surgical teams without delay, and provide timely hemodynamic support, thereby improving survival prospects. The ECG, obtainable within minutes of patient contact, remains an indispensable tool in the otherwise dire context of LMCA occlusion.