Sunday, July 5, 2020

Should ST elevation in lead aVR with concern for acute coronary syndrome prompt emergent coronary angiography?

Authors: Akilesh Honasoge, MD, Robert Brown, MD, Samantha Yarmis, MD, Mark Sutherland, MD, Megan Donohue, MD, Hannah Goldberg, MD

Editors: Kami M. Hu, MD FAAEM, Kelly Maurelus, MD FAAEM

Originally published: Common Sense
May/June 2020

Emergent management of traditional ST elevation myocardial infarction (STEMI) has been well defined over the past few decades, including fibrinolytic therapy and/or emergent coronary angiography with percutaneous intervention (PCI) when able.1 There has not been, however, a clear consensus on acute management of ST elevation (STE) in lead aVR. When examined in isolation, STE in aVR carries a broad differential including, but not limited to, myopericarditis, massive pulmonary embolism, global ischemia from hemorrhagic shock, left ventricular hypertrophy, left bundle branch block (LBBB), thoracic aortic dissection, and left main coronary artery (LMCA) disease.2 However, when a patient’s clinical history and presentation is concerning for acute coronary syndrome (ACS), what is the most appropriate emergent intervention? The most recent update to the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline on STEMI management was in 2013 and was the first American guideline to include mention of STE in lead aVR as a concern. The statement is rather broad, however, stating “multi-lead ST depression with coexistent ST elevation in lead aVR has been described in patients with left main or proximal left anterior descending artery occlusion.”1 The 2017 European Society of Cardiology (ESC) guidelines make the stronger assertion that ST depression greater than 1 mm in 8 or more surface leads coupled with STE in aVR and/or V1 “suggests multivessel ischemia or left main coronary artery obstruction.”3 The guidelines go on to recommend that ongoing symptoms of myocardial ischemia with this atypical sign should prompt primary PCI similar to patients with a LBBB meeting Sgarbossa’s criteria, but these recommendations have not reached widespread adoption in the United States. The following studies look at the outcomes of coronary angiography with STE in aVR to answer the following question:

Question: What are the coronary angiogram findings and clinical outcomes of coronary angiography associated with ST elevation in aVR?

Harhash AA, Huang JJ, Reddy S, et al. aVR ST Segment Elevation: Acute STEMI or Not? Incidence of an Acute Coronary Occlusion. Am J Med 2019;132(5):622-630.

The investigators sought to clarify the incidence of acute coronary thrombus versus severe nonocclusive multivessel disease in patients presenting with ST elevation in aVR and multi-lead ST depression (STE-aVR). They reasoned that a high incidence of acute coronary occlusion would support the 2013 ACCF/AHA recommendation for emergent coronary reperfusion within 90 minutes of identification of these EKG findings.

They performed a retrospective analysis of four years of STEMI team activations for emergent cardiac catheterization at University of Arizona’s two academic hospitals. Two blinded cardiologists retrospectively reviewed all ECGs originally determined to be STEMI and based on which the catheterization lab was activated. A separate, blinded interventional cardiologist then reviewed the coronary angiograms to determine incidence of acute coronary artery occlusion requiring intervention.

The authors looked at secondary outcomes which included a comparison of presentations in cardiac arrest, survival to discharge, and the presence of severe coronary artery disease (defined as greater than 70% stenosis) without occlusion. Data was presented as means with standard deviations for normally distributed continuous variables or as median values with interquartile ranges for skewed data.

Of 854 consecutive patients for which a STEMI team was activated, 847 had ECGs available and 99 (12%) were determined to have STE-aVR. Of these patients, 63 of the 99 had STE in leads other than aVR, most predominantly V1, but none had STE in two or more contiguous leads which would have met traditional STEMI criteria. Of the 99 patients, 79 underwent emergent coronary angiography with eight of these (10%) having evidence of an acute thrombotic coronary occlusion thought to be a culprit lesion, 47 (59%) having evidence of severe coronary artery disease (45% of which was 3-vessel), 13 (16%) having mild-moderate disease and 19 (24%) having angiographically normal coronaries. Twenty-nine patients had in-hospital PCI and seven patients underwent in-hospital coronary artery bypass grafting (CABG). Of the eight patients who had an acute coronary thrombus, none involved the LMCA or LAD.

The overall mortality rate of patients with STE-aVR was 31%, with the highest mortality rate among the patients who presented in cardiac arrest (67% vs 11% of those who did not present in arrest, p<0.001). The in-hospital outcomes of these 99 patients revealed a relatively sick population, with 47% requiring mechanical ventilation (19% in the non-arrest population) and 15% developing cardiogenic shock. Comparison of mortality made by randomly selecting 190 other non-aVR STEMI cases, from the same period, were found to have an in-hospital mortality rate of 6.2%.

The authors conclude that the incidence of disease requiring emergent intervention is low in the STE-aVR population, but 20 of the study group participants, arguably some of the sicker patients, did not undergo coronary angiography, potentially underestimating the actual incidence of acute coronary thrombosis. The authors compare the STE-aVR and non-aVR STEMI group mortality without other comparisons of illness severity, and do not confirm the actual incidence of acute thrombotic occlusion in the non-aVR group. There is no report for the specific incidence of PCI or CABG for the patients with STE-aVR and severe disease. The study suffers from a low number of ECGs with STE-aVR and is confounded by the presence other ST segment elevations in the study group. The authors suggest that STE in aVR is a poor predictor for the need for revascularization yet a predictor of increased mortality. Due to the limited size of the study, however, no definitive conclusions can be reached from these data.

Kosuge M, Kimura K, Ishikawa T, et al. Combined Prognostic Utility of ST segment in Lead aVR and Troponin T on Admission in Non-ST-Segment Elevation Acute Coronary Syndromes. Am J Cardiol 2006;97:334-9.

This study looked at a composite 90-day outcome with the goal of establishing an early risk stratification system for patients using the presence of STE in aVR and laboratory testing including troponin T (a group defined by this study as an NSTEMI group). The study was a retrospective cohort study that examined patients admitted to a single coronary care unit in Japan between 2001 and 2004. Patients were included if they had typical cardiac chest discomfort lasting at least 5 minutes within the 48 hours prior to hospital admission. Other inclusion criteria included an ECG on arrival and angiography during admission. Exclusion criteria included preexisting LBBB, RBBB, left ventricular hypertrophy (LVH), ventricular pacing, STE in leads other than aVR, Q wave MI on admission, or recent PCI within six months. All patients were followed for 90 days after admission. A total of 333 patients were included in the study; 69% were male, and the mean age was 67 years. Of the included patients, a total of 78 patients (23%) had a history of revascularization, 66 patients (20%) having had prior PCI and 21 patients (6.3%) having had prior CABG. There were 115 patients (35%) with a history of diabetes mellitus, and 213 patients (64%) with a history of hypertension.

A single cardiologist who was blinded to other data evaluated admission ECGs. STE was defined as ≥0.5 mm in any lead. A troponin T ≥0.1 ng/ml was defined as positive. Cardiac catheterizations were performed at a median of three days after admission. A single cardiologist who was blinded to other data evaluated angiograms. Clinically significant stenosis was defined as stenosis of ≥50% in the LMCA or ≥75% in ≥1 major epicardial vessel or its main branches. The primary end-point of this study was a composite of death, myocardial infarction or reinfarction, or urgent revascularization within 90 days.

Overall, 90 of the 333 (27%) patients had STE in aVR. On admission, when compared with patients without, patients with STE in aVR had a significantly higher CRP (0.838 vs 0.474, p=0.04), CK-MB (19 vs 13, p<0.01), and more often had a positive troponin T (52% vs 26%, p<0.01). Patients with STE in aVR were significantly more likely to have LMCA disease (12% vs 0.4%, p<0.01) or composite LMCA/3-vessel disease (51% vs 7%, p<0.01), with a higher rate of in-hospital PCI or CABG (87% vs 59%, p<0.01). The composite 90-day outcome of death, myocardial infarction/reinfarction, or urgent revascularization occurred more frequently in the STE in aVR group (40% vs 6%, p<0.01). Most importantly, a multivariate analysis demonstrated that ST segment elevation in aVR and a positive troponin T were the only statistically significant independent predictors of death or MI at 90 days (p=0.03 and p=0.04, respectively). The other variables examined such as age, gender, prior MI, prior revascularization, Killip class, coronary risk factors, systolic blood pressure, heart rate, CRP, CK-MB, and non-aVR ST segment depression, did not show statistical significance as predictors for the composite outcome.

Further subgroup analysis found a stepwise increase in the rate of the composite 90-day outcome with either STE in aVR, a positive troponin, or both. Rates of this 90-day outcome were 4% (- STE in aVR, - troponin), 13% (- STE in aVR, + troponin), 33% (+ STE in aVR, - troponin), and 47% (+ STE in aVR, + troponin). The authors conclude that both ST elevation in aVR and elevated troponin are independent predictors of adverse outcomes and that the combination of both provides a stronger predictor of adverse outcomes than either one alone. They note that left main or triple vessel disease can cause the ST segment vector to be directed to the right, leading to ST elevation in aVR and providing an explanation for why this specific ECG finding is indicative of extensive myocardial ischemia.

There are several limitations to this study. The study was a retrospective analysis of patients admitted to a single medical center. In addition, 10 of the 343 patients were lost to follow up and excluded from analysis. While the study provides some useful information in the patient population included, there were several subpopulations that were excluded, namely those with common preexisting ECG abnormalities such as LBBB, RBBB, and left ventricular hypertrophy, potentially limiting the generalizability of the study’s findings in these subpopulations.

Yamamoto M, Witsch T, Kubota S, Hara H, Hiroi Y. Diagnostic value of lead aVR in electrocardiography for identifying acute coronary lesions in patients with out-of-hospital cardiac arrest. Resuscitation 2019;142:97-103.

These authors looked to retrospectively evaluate the outcomes of cardiac catheterization in post-cardiac arrest patients without traditional STEMI criteria but demonstrating ST elevation in lead aVR after return of spontaneous circulation (ROSC). Both the 2013 ACCF/AHA guidelines and the 2017 ESC guidelines provide a class 1B recommendation for emergent PCI in a post-ROSC patient with a traditional STEMI, especially with a prearrest clinical course suggestive of a primary cardiac cause or an initial rhythm of ventricular fibrillation or ventricular tachycardia.i,iii Emergency physicians in recent years may be trending towards a more aggressive approach to post-ROSC patients with STE in aVR and widespread ST depressions, despite these patients not meeting traditional STEMI criteria, perhaps looking towards the 2017 ESC guidelines as more up-to-date guidance.

In a single center retrospective observational study, the authors screened 286 consecutive post-arrest patients in whom ROSC had been achieved, looking at the 111 patients with a presumed cardiac cause of arrest who also then underwent coronary angiography. After excluding patients with post-ROSC ECG findings of STEMI, LBB, or LVH, a total of 74 patients were included in the study. The study investigators measured ST elevation immediately after and within a few hours of ROSC and compared them in patients with and without lesions on post-arrest angiography. ST elevation was considered significant if >0.5 mm, and coronary artery stenosis of 50% or greater was considered clinically significant.

Of the 74 patients, 85% were male, 88% had a witnessed arrest, and 73% of patients had an initial rhythm of ventricular tachycardia or ventricular fibrillation. The median time to ROSC was 13 minutes. Coronary angiography was performed within 24 hours in 50% of these patients. The initial ECG was obtained within 10 minutes of ROSC with the early follow-up ECG acquired at a median time of 137 minutes post-ROSC. Angiography found acute culprit lesions in 20 patients (27%), stable coronary artery disease in 23 patients (31%), and 31 patients (42%) had no significant coronary stenosis. PCI with intervention was performed on 28 patients (38%) during their hospitalization, while two patients (3%) underwent CABG.

The authors found that STE in aVR immediately post-ROSC was not predictive of the presence of a culprit lesion. The authors did find, however, that patients with acute culprit lesions on angiography were significantly less likely to have a decrease in the degree of aVR ST elevation on their repeat ECG, compared to those without (0.1 mm versus 0.5 mm, respectively, p=0.01). Patients with a culprit lesion also trended towards having more leads with ST depression (5 vs 2 leads on initial EKG, 4 vs 0 leads on follow-up EKG) although this result was not statistically significant. Interestingly, patients treated with epinephrine prior to the initial ECG had statistically higher STE in aVR (0.8 mm vs 0.2 mm, p<0.001). No difference was found between other medications given. Patients with STE in aVR ≥0.5 mm on the early follow up ECG also had a significantly higher incidence of 3-vessel coronary artery disease (67% vs 21%, p<0.001), chronic total occlusion (50% vs 7.1%, p<0.001), as well as higher SYNTAX scores for coronary complexity (34% vs 0%, p<0.001). The authors found that STE in aVR on follow-up EKG had an independent odds ratio of 4.41 (95% CI: 1.12-17.4) for predicting acute coronary lesions post-cardiac arrest.

Although this study did not find immediate STE in aVR post-ROSC to be diagnostically useful, persistent aVR elevation on repeat ECG may indicate a higher likelihood of culprit coronary lesion. Limitations of this study include a small sample size and a male-dominated patient population with a large portion of the initially-screened patients excluded from final analysis. While it should certainly not be the sole factor in the decision to pursue coronary angiography, patients with continued ST elevation in aVR on a subsequent ECG one to two hours after ROSC should be strongly considered for urgent cardiac catheterization.

Lee GK, Hsieh YP, Hsu SW, et al. Value of ST-segment change in lead aVR in diagnosing left main disease in Non-ST-elevation acute coronary syndrome-A meta-analysis. Ann Noninvasive Electrocardiol. 2019;24(6):e12692.

This meta-analysis sought to use existing data to define an odds ratio of left main coronary artery (LMCA) disease based on ST deviations in lead aVR, noting that although multiple prior studies had contended that STE in lead aVR was suggestive of LMCA disease, the results across available studies were inconsistent.

The authors performed a wide literature search for articles through October 22, 2018 using multiple online databases including PubMed, Web of Science, Cochrane Library, MEDLINE, and China National Knowledge Infrastructure (CNKI). Search keywords included “aVR,” “aVR lead,” “ST,” “non‐ST‐segment elevation,” “myocardial infarction,” and “left main.” The authors initially identified 676 potentially relevant published articles. After removing duplicate articles as well as excluding articles that provided only prediction of clinical prognosis, only ECG analysis, case reports/conference abstracts, or were irrelevant, they were left with 175 articles. Of those 175 articles, 148 were excluded due to being gray literature, a duplicated or overlapping report, or providing insufficient data. Of note, 28 of these articles were excluded because they “had no left main coronary artery lesion or LMCA total occlusion” noted on search.

After these exclusions a final 27 articles were included for analysis, for a total of 7,870 cases with STE in lead aVR <0.05 mV and 2,582 cases with STE ≥0.05 mV. Nine of the articles also further defined outcomes between STE in aVR and LMCA disease with 4,426 patients subdivided into STE <0.05 mV (none), STE 0.05-0.1 mV (minor STE), and STE ≥0.1mV (overt STE). For each study they collected data on rates of acute myocardial infarction, severity of STE in aVR, and angiography results to be included in the final meta-analysis. Odds ratio was determined using the Z test. Two models for dichotomous outcomes were used, the random‐effects model (using DerSimonian and Laird's method) and the fixed‐effects model (using Mantel‐Haenszel's method). Heterogeneity was also calculated, and studies were weighted based on their Newcastle‐Ottawa score. Finally, a sensitivity analysis was conducted and demonstrated that the overall result was not influenced by a single study.

The pooled results of these studies showed that STE in aVR ≥0.05 mV (both minor and overt STE) was associated with a higher incidence of myocardial infarction (OR 3.12, 95% CI: 1.73-5.62) and LMCA disease compared to no STE (OR 6.64, 95% CI 4.80-9.17). The degree of STE in aVR was associated with the prevalence of LMCA disease; the pooled odds ratio for minor STE compared to no STE was 2.57 (95% CI: 1.97-3.36), and for overt STE was 6.17 (95% CI: 4.31-8.84). Overall, the prevalence of LMCA disease was 12% (95% CI: 8%-16%), with a higher prevalence in either minor or overt STE (26%, 95% CI: 18%-34%) than the no STE group (5%, 95% CI: 3%-7%).

This meta-analysis, the largest aggregation of these data to date, found a statistically significant association between STE in aVR and the presence of LMCA disease. It is a major limitation, however, that 28 articles were excluded because they had either “no left main coronary artery lesion or LMCA total occlusion.” As with all meta-analyses, it is possible that studies arriving at negative conclusions were performed and not ultimately reported, and while the authors tried to mitigate its effects using a random-effects model, there was significant heterogeneity between studies. Overall, this paper points to a strong correlation between ST elevation in lead aVR and LMCA disease but does not provide guidance on the urgency with which these patients should undergo coronary angiography.

The literature demonstrates that with respect to coronary artery disease, patients with ST-segment elevation in lead aVR are at an overall higher risk for more severe disease. They may have higher rates of LMCA and triple-vessel disease4-7 as well as poorer outcomes, including a higher in-hospital mortality rate,5-8 worse composite 90-day outcomes,5 and worse cardiac function.7 Current existing literature does not, however, provide clear guidance on the acuity with which these patients should undergo coronary angiography. It can be argued that, as with STEMI, the goal of emergent angiography and PCI is rapid revascularization of perfusion-starved myocardium. Although limited by size, the study by Harhash et al. finds a rate of acute thrombotic coronary occlusion of about 10% in these patients, none involving the LMCA or LAD.4 Yamamoto et al. propose that for out-of-hospital cardiac arrest patients with STE in aVR, the persistence of this finding a few hours after ROSC is suggestive of a culprit lesion that may benefit from acute intervention.6 It could be argued that emergent angiography and revascularization may improve patients’ clinical outcomes even without an acute culprit lesion. There is no data to help answer the latter question in this specific patient population. It is worth noting that the severity of STE in aVR and the number of concurrent ST segment depressions appear to correlate in a stepwise fashion with the incidence and severity of underlying coronary artery disease. These findings together could be used to risk-stratify patients from the Emergency Department to help determine the urgency with which should undergo coronary angiography. Overall, the best approach is likely a multidisciplinary conversation between the emergency physician and the cardiology consultant with the mutual understanding that these patients are high risk regardless of the approach taken.

Question: What are the coronary angiogram findings and clinical outcomes of coronary angiography associated with ST elevation in aVR?

When seen in acute coronary syndrome with elevated cardiac markers, ST-segment elevation in lead aVR with multi-lead ST depression portends a high risk of left main or multivessel coronary disease and worsened in-hospital and 90-day outcomes. The limited data appears to show a direct correlation between amount of STE and disease. The scarce data available on emergent angiography of these patients does not show a clear benefit for all-comers to the ED with chest pain and STE in aVR.

It seems prudent that emergency physicians base their decision to activate the catheterization lab on the patient’s presentation, history, cardiology consultation, troponin, persistent STE in aVR after ROSC, or has uncontrolled anginal chest pain despite aggressive management (similar to patients with NSTEMI).

  1. O'gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-425.
  2. Lipinski MJ, Mattu A, Brady WJ. Evolving Electrocardiographic Indications for Emergent Reperfusion. Cardiol Clin. 2018;36(1):13-26.
  3. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177.
  4. Lee GK, Hsieh YP, Hsu SW, Lan SJ, Soni K. Value of ST-segment change in lead aVR in diagnosing left main disease in Non-ST-elevation acute coronary syndrome-A meta-analysis. Ann Noninvasive Electrocardiol. 2019;24(6):e12692.
  5. Harhash AA, Huang JJ, Reddy S, et al. aVR ST Segment Elevation: Acute STEMI or Not? Incidence of an Acute Coronary Occlusion. Am J Med. 2019;132(5):622-630.
  6. Kosuge M, Kimura K, Ishikawa T, et al. Combined Prognostic Utility of ST segment in Lead aVR and Troponin T on Admission in Non-ST-Segment Elevation Acute Coronary Syndromes. Am J Cardiol 2006;97:334-339
  7. Yamamoto M, Witsch T, Kubota S, Hara H, Hiroi Y. Diagnostic value of lead aVR in electrocardiography for identifying acute coronary lesions in patients with out-of-hospital cardiac arrest. Resuscitation. 2019;142:97-103.
  8.  Barrabes et al. Prognostic Value of Lead aVR in Patients with a First Non-ST-Segment Elevation Acute Myocardial Infarction. Circulation 2003; 108: 814-819.

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