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Three Part Question

In [patients with suspected acute coronary syndromes and an ECG that is non-diagnostic for STEMI] does [ST elevation in lead aVR] accurately identify [acute myocardial infarction caused by LMCA stenosis]?

Clinical Scenario

A 60-year-old man presents to the emergency department with typical cardiac chest pain but is now pain free. His ECG is not diagnostic of ST elevation myocardial infarction (STEMI) but shows 1.5 mm ST segment elevation in lead aVR. Having visited a number of educational websites, you recognise that this finding may signify left main coronary artery (LMCA) occlusion. Concerned about the potential risks associated with both failure to recognise such an important and potentially life-threatening diagnosis and with those associated with over-diagnosis, over-investigation and over-treatment, you wonder whether the presence of ST elevation in aVR is a specific marker of that diagnosis.

Search Strategy

he following databases were searched using the Ovid interface: EBM Reviews—Cochrane Database of Systematic Reviews 2005–November 2014, EBM Reviews—ACP Journal Club 1991–December 2014, EBM Reviews—Database of Abstracts of Reviews of Effects 4th Quarter 2014, Ovid MEDLINE(R) 1946–January Week 2 2014 and Embase 1974–2014 Week 02.

The following search strategy was employed:
(exp ST segment elevation/OR exp ST segment elevation myocardial infarction/OR exp Angina, Unstable/OR exp Percutaneous Coronary Intervention/OR exp Acute Coronary Syndrome/OR exp heart infarction/OR exp Coronary Artery Disease/OR exp Myocardial Infarction/) AND (aVR.mp.) AND (anterior interventricular artery.mp. OR left main coronary artery.mp. OR left coronary artery.mp. OR LCA.mp. OR LMCA.mp. OR left main stem.mp. OR left main stem coronary artery.mp. OR LMS.mp. OR left main trunk.mp.) limit to human and English language.

Search Outcome

In total, 185 papers were identified, of which 44 were duplicates leaving 141 titles and abstracts for review. We excluded conference abstracts where insufficient data were available to enable the evidence to be appraised. This yielded a total of 12 papers for appraisal. One of these was a systematic review that summarised the evidence from five of the papers

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Hirano et al, 2006 Japan	140 patients with AMI (selected from a total of 2190 with AMI). Divided into four groups according to culprit artery (LMCA stenosis was one group)	Retrospective diagnostic cohort study	Prevalence of STE in aVR (≥0.05 mV) among patients with LMCA culprit lesions (defined as ‘occluded or severe narrowing and ulceration with or without thrombus’)	STE present in 80% of the LMCA group, compared with 22.9% of patients with LAD stenosis; 3% with LCX stenosis and 5.7% with RCA stenosis)	Unclear selection criteria presenting high risk for selection bias Method for ECG interpretation unclear Unclear whether ECG measurements were blinded to angiography Small numbers
Kühl and Berg, 2009 Denmark	Five studies, including 1336 patients, reporting on aVR for identifying culprit lesions in AMI. All studies included consecutive patients with NSTEMI	Systematic Review	Test characteristics from Barrabés et al 3 (n=775, nine of whom had LMCA stenosis; aVR STE defined as ≥0.1 mV)	Sensitivity 77% Specificity 64% PPV 5% NPV 99%	The studies each used different definitions of ST elevation in aVR and coronary stenosis in the LMCA. Coronary angiography was undertaken at a variable period after the index event in each study. Thus, the studies were too heterogeneous to allow pooling (and meta-analysis) of data The primary outcome was LMCA stenosis but patients did not necessarily also have AMI
			Test characteristics from Hengrussamee et al 4 (n=26, five of whom had LMCA stenosis; aVR STE defined as ≥0.05 mV)	Sensitivity 80% Specificity 76% PPV 44% NPV 94%
			Test characteristics for Kosuge et al 5 (n=310, 60 of whom had LMCA stenosis or 3-vessel disease; aVR STE defined as ≥0.05 mV)	Sensitivity 78% Specificity 86% PPV 57% NPV 95%
			Test characteristics for Rostoff et al 6 (n=134, 44 of whom had LMCA stenosis; aVR STE defined as ≥0.05 mV)	Sensitivity 68% Specificity 73% PPV 56% NPV 83%
			Test characteristics for Yu et al 7 (n=91, nine of whom had LMCA stenosis; aVR STE defined as ≥0.1 mV)	Sensitivity 89% Specificity 84% PPV 38% NPV 99%
Kosuge et al, 2011 Japan	572 consecutive patients in a Coronary Care Unit who underwent angiography following diagnosis of NSTEMI. 112 patients had LMCA occlusion or 3-vessel disease	Retrospective diagnostic cohort study	Test characteristics of STE in aVR (with diffuse ST depression) for predicting severe LMCA stenosis or 3-vessel disease (0.05 mV cut-off)	Sensitivity 91% Specificity 79% PPV 32% NPV 99%	A large number of those with global ST depression and STE in aVR did not receive the reference standard investigation. Screening relied on correct diagnosis. Retrospective. Single centre
			Test characteristics of STE in aVR (with diffuse ST depression) for predicting severe LMCA stenosis or 3-vessel disease (0.1 mV cut-off)	Sensitivity 80% Specificity 93% PPV 56% NPV 98%
Taglieri et al, 2012 Italy	140 patients with NSTEMI who had ECGs with ST depression and STE in aVR (92 of these patients had coronary angiography) and 237 patients with NSTEMI who had normal ECGs (237 of whom had angiography; controls)	Retrospective diagnostic cohort study	Proportion of patients with STE in aVR and global ST depression who had culprit lesions on angiography	LMCA lesion: 29% (n=27) 3-vessel disease: 44% (n=40)	Verification bias: a large proportion of patients did not undergo coronary angiography Screening relied on correct diagnosis Retrospective
			Odds of culprit LMCA disease in patients with global ST depression and STE in aVR	OR 4.72 (95% CI 2.31 to 9.64, p<0.001)
			Risk of inpatient mortality for patients with global ST depression and STE in aVR	Hazard ratio 2.29 (95% CI 1.44 to 3.64, p<0.001) compared with those with normal ECGs
Nough et al, 2012 Iran	400 consecutive patients with typical cardiac chest pain within the previous 6 hours who were admitted to a Coronary Care Unit All patients underwent coronary angiography	Prospective diagnostic cohort study	Prevalence of STE in aVR	124 (31%) had STE ≥0.05 mV in aVR 43 (10.8%) had STE ≥0.1 mV in aVR	Selected population (patients in a Coronary Care Unit undergoing coronary angiography) Purely angiographic outcome (we do not know if the patients also had AMI)
			Prevalence of LMCA stenosis (>50%) stratified by the presence or the absence of STE in aVR	No STE: 6.9% 0.05–0.1 mV STE: 17.4% ≥0.1 mV STE: 41.9%
			Calculated test characteristics of STE in aVR (0.5 mm cut-off) for LMCA stenosis [Not reported by authors]	Sensitivity 63% Specificity 74% PPV 26% NPV 93%
			Calculated test characteristics of STE in aVR (1 mm cut-off) for LMCA stenosis [Not reported by authors]	Sensitivity 35% Specificity 93% PPV 42% NPV 91%
Daly et al, 2012	116 patients with acute ischaemic-type chest pain who had an ECG and body surface potential map on arrival followed by a troponin test at ≥12 h and coronary angiography showing LMCA stenosis (≥70%; over a 10-year recruitment period) 92 (79%) of these patients had AMI (defined as troponin T ≥0.03 ng/mL NB, this was a subgroup of patients with LMCA stenosis from a larger cohort of 2810 patients	Prospective diagnostic cohort study	Test characteristics of STE in aVR (≥0.05 mV) for diagnosing AMI among patients with LMCA stenosis	Sensitivity 23% Specificity 92% PPV 85% NPV 21%	This study only included patients with proven LMCA stenosis. It cannot determine diagnostic performance in a less differentiated cohort. Potential for selection bias: patients only included if it was possible to record body surface potential mapping
Knotts et al, 2013	133 patients identified from a hospital ECG database who had ST depression in 7 or more leads and STE in aVR. 57 went on to have coronary angiography	Retrospective diagnostic cohort study	The presence of occlusion on coronary angiography among patients with STE in aVR and ST depression in at least 7 leads	18% (n=10) had LMCA stenosis 5% (n=3) had left main equivalent (stenosis of both the proximal LAD and the proximal LCX) stenosis Thus, a total of 23% of patients had either LMCA stenosis or LMCA equivalent stenosis	Single reviewer for ECGs Only 43% of those with characteristic ECG changes received the reference standard Small numbers, single centre Selected from an ECG database. Only 83% of patients who underwent coronary angiography had suspected acute coronary syndromes
			Requirement for coronary intervention among patients with STE in aVR and ST depression in at least 7 leads	51% (n=29) required revascularisation 25% (n=14) had PCI and 28% (n=16) had CABG

Comment(s)

All the papers appraised note an association between this pattern and severe stenosis of the LMCA or 3-vessel disease. However, the evidence identified from nine cohort studies consistently shows that lone ST elevation in lead aVR has little diagnostic value for identifying patients with stenosis of the LMCA. Both sensitivity and specificity are suboptimal to guide clinical decision making. The evidence suggests that diagnostic performance may improve when there is accompanying diffuse ST depression. Kosuge et al 8 found that such changes have a specificity of 93% for LMCA stenosis or 3-vessel disease, although the positive predictive value in that sample was only 58%, which limits the value of the finding for ‘ruling in’ LMCA stenosis. As such, taken alone this finding could not be used to guide the need for primary percutaneous coronary intervention, for example. However, as patients with LMCA stenosis are at particularly high risk, ST elevation in aVR may help to identify patients for early aggressive investigation.

Editor Comment

AMI, acute myocardial infarction; CABG, coronary artery bypass graft; LAD, left anterior descending; LCX, left circumflex; LMCA, left main coronary artery; NPV, negative predictive value; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; PPV, positive predictive value; STE, ST segment elevation.

Clinical Bottom Line

ST elevation in aVR can identify high-risk patients with LMCA stenosis for early intensive investigation, particularly when found alongside widespread ST depression. It has insufficient utility to identify patients who require immediate revascularisation.

References

1. Hirano T , Tsuchiya K , Nishigaki K , et al . Clinical features of emergency electrocardiography in patients with acute myocardial infarction caused by left main trunk obstruction. Circ J 2006;70:525–9.
2. Kühl JT , Berg RMG . Utility of lead aVR for identifying the culprit lesion in acute myocardial infarction. Ann Noninvasive Electrocardiol 2009;14:219–25.
3. Barrabés JA , Figueras J , Moure C , et al Prognostic value of lead aVR in patients with a first non–ST-segment elevation acute myocardial infarction. Circulation 2003;108:814–19.
4. Hengrussamee K , Kehasukcharoen W , Tansuphaswadikul S Significance of lead aVR ST segment elevation in acute coronary syndrome. J Med Assoc Thai 2005;88:1382–7.
5. Kosuge M , Kimura K , Ishikawa T , et al . Predictors of left main or three-vessel disease in patients who have acute coronary syndromes with non-ST-segment elevation. Am J Cardiol 2005;95:1366–9.
6. Rostoff P , Piwowarska W , Konduracka E , et al Value of lead aVR in the detection of significant left main coronary artery stenosis in acute coronary syndrome. Kardiol Pol 2005;62:128–35; discussion 136–7.
7. Yu F , Fu X , Wei Y , et al . Relationship of acute left main coronary artery occlusion and ST-segment elevation in lead aVR. Chin Med J 2004;117:459–60.
8. Kosuge M , Ebina T , Hibi K , et al . An early and simple predictor of severe left main and/or three-vessel disease in patients with non-ST-segment elevation acute coronary syndrome. Am J Cardiol 2011;107:495–500.
9. Taglieri N , Marzocchi A , Saia F , et al . Short- and long-term prognostic significance of ST-segment elevation in lead aVR in patients with non-ST-segment elevation acute coronary syndrome. Am J Cardiol 2011;108:21–8.
10. Nough H , Jorat MV , Varasteravan HR , et al . The value of ST-segment elevation in lead aVR for predicting left main coronary artery lesion in patients suspected of acute coronary syndrome. Rom J Intern Med 2012;50:159–64.
11. Daly MJ , Adgey JA , Harbinson MT . Improved detection of acute myocardial infarction in patients with chest pain and significant left main stem coronary stenosis. QJM 2012;105:127–35.
12. Knotts RJ , Wilson JM , Kim E , et al. Depression with ST elevation in aVR: Is this pattern specific for global ischemia due to left main coronary artery disease? J Electrocardiol 2013;46:240–8.