Shock, syncope and severe chest pain

• Sinus tachycardia with two premature supraventricular complexes (“PSVC”) – these are probably atrial in origin as they are both preceded by abnormal P waves (hidden within the preceding T-waves)
• Overall ventricular rate = 108 bpm
• Left axis deviation
• PR interval normal (~160ms)
• Broad QRS (~120ms) secondary to non-specific interventricular conduction delay (not characteristic of LBBB or RBBB); the QRS appears wider than it actually is in some leads due to the upsloping ST segments
• Widespread ST depression in I, II, aVF and V2-6 with T-wave inversion in aVL
• Marked ST elevation in aVR (> 3mm at the J-point)
• In comparison, there is minimal ST elevation in V1 (i.e. STE in aVR > V1)

In a patient presenting with ischaemic chest pain, the combination of:

• Widespread ST depression
• ST elevation in aVR ≥ 1mm
• ST elevation in aVR ≥ V1

Is strongly suggestive of left main coronary artery (LMCA) occlusion or severe multi-vessel disease.

ST elevation in aVR: Left Main Coronary Artery Occlusion?

This ECG demonstrates the classical pattern of LMCA occlusion:

• Widespread horizontal ST depression, most prominent in leads I, II and V4-6
• ST elevation in aVR ≥ 1mm
• ST elevation in aVR ≥ V1

However, ST elevation in aVR is not entirely specific to LMCA occlusion. It may also be seen with:

• Proximal left anterior descending artery (LAD) occlusion
• Severe triple-vessel disease (3VD)

Mechanism of STE in aVR

• Lead aVR is electrically opposite to the left-sided leads I, II, aVL and V4-6; therefore ST depression in these leads will produce reciprocal ST elevation in aVR.
• Lead aVR also directly records electrical activity from the right upper portion of the heart, including the right ventricular outflow tract and the basal portion of the interventricular septum; infarction in this area could theoretically produce ST elevation in aVR.

ST elevation is aVR is thought to result from two possible mechanisms:

• Diffuse subendocardial ischaemia (producing reciprocal change in aVR)
• Transmural ischaemia / infarction of the basal interventricular septum (e.g. due to a proximal occlusion within the left coronary system)

NOTE: The basal septum is supplied by the first septal perforator artery (a very proximal branch of the LAD), so ischaemia/infarction of the basal septum would imply involvement of the proximal LAD or LMCA.

Predictive Value of STE in aVR

In the context of widespread ST depression + symptoms of myocardial ischaemia:

• STE in aVR ≥ 1mm indicates proximal LAD / LMCA occlusion or severe 3VD
• STE in aVR ≥ 1mm predicts the need for CABG
• STE in aVR ≥ V1 differentiates LMCA from proximal LAD occlusion
• Absence of ST elevation in aVR almost entirely excludes a significant LMCA lesion

In the context of anterior STEMI:

• STE in aVR ≥ 1mm is highly specific for LAD occlusion proximal to the first septal branch

In patients undergoing exercise stress testing:

• STE of ≥ 1mm in aVR during exercise stress testing predicts LMCA or ostial LAD stenosis

Magnitude of ST elevation in aVR is correlated with mortality in patients with acute coronary syndromes:

• STE in aVR ≥ 0.5mm was associated with a 4-fold increase in mortality
• STE in aVR ≥ 1mm was associated with a 6- to 7-fold increase in mortality
• STE in aVR ≥ 1.5mm has been associated with mortalities ranging from 20-75%

Over the past 18 years, multiple studies have examined the utility of ST elevation in aVR for predicting severe coronary artery disease (proximal LAD/LMCA/3VD) and mortality in patients with acute coronary syndromes and those undergoing exercise stress testing. Some of the important studies are summarised below…

Gorgels et al. (1993)

• Population: 113 patients with unstable angina, including 20 patients with LMCA stenosis and 24 patients with 3VD.
• Findings: Patients with LMCA or 3VD frequently demonstrated ST-segment depression in multiple leads (typically I, II and V4-V6) plus ST-segment elevation in lead aVR during attacks of angina.

Engelen et al. (1999)

• Population: 100 patients with anterior STEMI.
• Findings: STE in aVR of any magnitude was 43% sensitive and 95% specific for LAD occlusion proximal to the first septal branch.

Yamaji et al. (2001)

• Population: 16 patients with acute LMCA occlusion, 46 patients with acute LAD occlusion and 24 patients with acute RCA occlusion.
• Findings:
  • STE in aVR (≥ 0.5mm) occurred with a significantly higher incidence in the LMCA group (88%) than in the LAD (43%) or RCA (8%) groups.
  • Magnitude of STE in aVR was significantly greater in the LMCA group (1.6 ± 1.3 mm) than the LAD group (0.4 ± 1.0 mm).
  • In contrast, magnitude of STE in V1 was less in the LMCA group (0.0 ± 2.1 mm) than in the LAD group (1.4 ± 1.1 mm).
  • STE in aVR ≥ V1 distinguished the LMCA group from the LAD group with 81% sensitivity, 80% specificity and 81% accuracy.

Barrabes et al. (2003)

• Population: 775 patients with first presentation of acute NSTEMI
• Findings:
  • Two-thirds of patients with STE in aVR ≥ 1 mm had either LMCA occlusion or severe 3VD.
  • Degree of STE in aVR was an independent predictor of mortality: STE of ≥ 1 mm was associated with a six- to seven-fold increase in in-hospital mortality (odds ratio of death = 6.6).
  • Magnitude of STE in aVR was also closely associated with rates of recurrent ischemic events and heart failure.
  • STE in aVR predicted the need for CABG – coronary grafting was required in 22% of patients with aVR STE > 1mm compared to 5% of those without.

Rostoff et al. (2005)

• Population: 150 patients with acute coronary syndromes – 46 with LMCA obstruction, 104 with occlusion of a different vessel
• Findings: STE in aVR was twice as common in patients with LMCA occlusion as those without (69.6% vs 34.6%).

Kosuge et al. (2005) 

• Population: 310 patients with non-ST-elevation acute coronary syndromes.
• Findings:
  • STE in aVR  ≥ 0.5 mm was the strongest predictor of LMCA or 3VD (78% sensitivity, 86% specificity, 57% PPV and 95% NPV).
  • STE in aVR was superior to the presence of ST depression in other leads for predicting LMCA/3VD.

Aygul et al. (2008)

• Population: 950 patients with STEMI (any type).
• Findings:
  • STE in aVR ≥ 0.5 mm predicted proximal LAD or LMCA occlusion (with 50% sensitivity, 91% specificity, 55% PPV, 89% NPV).
  • STE in aVR ≥ 0.5 mm was also an independent predictor of mortality (in-hospital mortality was 19% in those with ≥ 0.5 mm STE in aVR compared to only 5% in those without).
  • Patients with STE in aVR also had higher heart rates, lower systolic BPs, lower ejection fractions and worse Killip class at the time of admission.

Wong et al. (2011)

• Population: 15, 315 patients with STEMI enrolled in the HERO-2 trial (heparin vs bivalirudin for acute MI).
• Findings: STE ≥1.5 mm in aVR was associated with a two-fold increase in 30-day mortality for both inferior and anterior STEMI, compared to the baseline mortality rate of 10.8%.

Uthamalingam et al. (2011)

• Population: 454 patients undergoing both exercise stress testing (standard Bruce protocol) and cardiac catheterization within 6 months, including 75 patients with LMCA or ostial LAD stenosis.
• Findings: STE of ≥ 1mm in aVR during stress testing predicted LMCA or ostial LAD stenosis with sensitivity 75%, specificity 81% and overall accuracy 80%.

Kosuge et al. (2011)

• Population: 572 patients with acute NSTEMI.
• Findings:
  • Degree of STE in aVR was the strongest independent predictor of severe LMCA occlusion / 3VD requiring CABG (odds ratio 29.1), followed by positive troponin T level (odds ratio 1.27).
  • STE ≥ 1.0 mm in aVR identified severe LMCA occlusion /3VD with 80% sensitivity, 93% specificity, 56% PPV, and 98% NPV.

Proximal LAD occlusion

This ECG shows:

• ST elevation in aVR and V1 of similar magnitude.
• Widespread ST depression (V3-6, I, II, III, aVF)

This patient had a severe ostial LAD thrombus that was close to the left main (This ECG is reproduced from Dr Smith’s ECG Blog)

Severe Multi-Vessel Disease

This ECG shows:

• ST elevation in aVR and V1, of similar magnitude
• ST depression in multiple leads (V5-6, I, II, aVL, aVF)
• Evidence of anteroseptal STEMI – ST elevation with Q wave formation in V1-3

It would be reasonable to suspect a proximal LAD occlusion based on this ECG. However, this patient actually had severe multi-vessel disease. Angiography demonstrated a chronic total occlusion of his circumflex artery, with critical stenoses of his proximal LAD, RCA and ramus intermedius. Surprisingly, in this case the culprit vessel was thought to be the RCA, which had been collateralising his chronically occluded circ

Implications for therapy in acute coronary syndromes

Given the ability of STE in aVR to predict critical coronary lesions and death, this ECG pattern is increasingly being recognised as a “STEMI equivalent” that requires emergent reperfusion therapy to prevent cardiogenic shock and death. Furthermore, the presence or absence of STE in aVR may potentially inform the decision to give thienopyridine platelet inhibitors (e.g. clopidogrel, prasugrel) during an acute coronary syndrome:

• Clopidogrel treatment ≤ 7 days before CABG is associated with an increase in major bleeding, haemorrhage-related complications, and transfusion requirements.
• Prasugrel is associated with even more bleeding than clopidogrel.
• If urgent CABG (within 7 days) is likely, then there is an argument for omitting thienopyridines during the initial management of an acute coronary syndrome (or at least using clopidogrel instead of prasugrel).

In the study by Kosuge et al. (2011)

• STE in aVR ≥ 1 mm was a strong predictor of severe LMCA / 3VD requiring CABG.
• Conversely, patients with < 1mm ST elevation in aVR had a negligible risk of severe LMCA / 3VD requiring CABG.

Based on this data:

• Patients with < 1mm STE in aVR may safely receive clopidogrel/prasugrel during the initial treatment of their ACS as they are unlikely to proceed to urgent CABG.
• Patients with ≥ 1 mm STE in aVR may potentially require early CABG; therefore these patients should ideally be discussed with the interventional cardiologist (± cardiac surgeon) before thienopyridines are given.

• There was some initial resistance to urgent angiography as the junior cardiology registrar failed to appreciate the significance of the ECG changes.
• Luckily for the patient, the astute Emergency Physician persisted…
• Shortly after showing the ECG to his boss, a rather panicky cardiology registrar ran into ED and whisked the patient off to the cath lab!
• Coronary angiogram showed a complete ostial occlusion of the LMCA, with acute thrombus. The remainder of the coronary arteries were normal, apart from some minor irregularities in the RCA.
• The patient stabilised after PCI to the LMCA.
• An intra-aortic balloon pump (IABP) was inserted at the time of angiography and remained in situ for two days while the patient recovered from his cardiogenic shock.
• Troponin peaked at 220 μg/L.
• The patient made a good recovery – echocardiography performed six days later showed normal LV size with only mild segmental systolic dysfunction and an ejection fraction of 48%.
• He was transferred to a private hospital for ongoing management, so I am not sure whether he ultimately required CABG.

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