To activate or not to activate?

Written by Pendell Meyers, with edits by Steve Smith

I was texted this ECG with no clinical information:
(This will be called ECG-2)
What do you think?

I replied "Actually I think this might be a false positive."

The ECG shows sinus rhythm with relatively normal QRS complex followed by large STE in V1-V3, with ~4mm STE in V2. There are no pathologic Q-waves, no terminal QRS distortion. I do not think there is any STD in the inferior leads; there is a tiny amount of PR depression (normal) and the J-point is exactly on line with the PR interval. In lead III the T-wave does slope downward at first, but I just didn't think this was convincing morphology to be called reciprocal STD.

I was left with concerning anterior STE which may be a normal variant or may be LAD occlusion, so I used the SubtleSTEMI app on my phone:

3 variable


I sent it immediately to Dr. Smith with no clinical information. He saw it on his phone without the QT (so could not use the formulas), and responded: "That is a really tough one. But I think it is actually a normal variant. My best guess, but I am not sure. Did you use the formulas?"

It turns out this was from a male in his 50s with history of smoking and HTN but no known CAD who presented due to chest pain radiating to the right cheek and right arm, which had awoken him from sleep early in the morning. By the time he arrived in the ED, his pain had apparently spontaneously resolved.

Here was his initial ED ECG earlier that morning (ECG-1):

There is a small amount of STE in V1 and V2, but much less than the ECG above. This ECG is easily within normal limits.

The patient had an initial undetectable troponin and was placed in the observation unit for serial troponins and CTCA vs. stress test.

While waiting in the observation unit, the patient suddenly complained of returning chest pain.  This is when ECG-2 was recorded; here it is again:

The following ECG (ECG-3) was recorded 10 minutes later:
Similar findings with dramatic STE in V2. There is no reciprocal STD.

The treating clinicians interpreted his return of pain with dynamic ECG changes and dramatic STE in the anterior leads as a "STEMI," and activated the cath lab (appropriately).

Here is the result:
Normal left circulation (except for a 40% D1 nonculprit stenosis according to the report).

Normal right circulation.

Non-obstructive CAD, no coronary occlusion. Repeat ECG after cath was unchanged. Serial troponins were all undetectable. Echo was done and was unremarkable.

What do you think the final diagnosis was in the chart?

"Pericarditis," of course. He was treated with colchicine and discharged. This patient likely did not have pericarditis. It is much more likely that this ECG is simply a normal variant. Normal variants can change dramatically and dynamically as above. It is an unfortunate truth that we have shown on this blog many times.

Let me be clear: we are not advocating that this patient should not have been cathed emergently. Any patient with a concerning clinical picture or ECG may deserve emergent cath. Dynamic and dramatic STE in general does in fact have a significant rate of true positive acute coronary occlusion. Additionally, diagnostic cath (without any coronary intervention) is a very low risk procedure. But expert ECG interpretation can often predict the false positives in the group of dramatic ECG findings.

Would I have activated the cath lab? Assuming his clinical appearance was as concerning as it sounds on paper, I still think it would have been perfectly reasonable to do so, although in the back of my mind I would suspect a false positive. And that is completely acceptable and likely good care, because the ECG cannot identify all acute coronary occlusion. I would make sure that I am not overlooking the possibility of other dangerous etiologies of chest pain including dissection and PE before letting the patient roll away to the cath lab.

When this specific population (benign early repolarization vs. subtle LAD occlusion) was studied, R-wave amplitude in V4 was the most important predictor variable, more important than STE. QRS amplitude in V2 and QTc were also as important as STE. This is because acute coronary occlusion does not follow the rules of the "STEMI criteria." Instead, you must become expert in ECG interpretation by learning from cases such as these.

Smith comment: 

1. Is there an alternative to activating the cath lab if you suspect normal variant?  Yes. If you can get a rapid high quality, bubble contrast enhanced echocardiogram, read by an expert, and, while the patient has symptoms and ECG findings, it shows no wall motion abnormality (WMA), then you can be certain that it is normal variant.

2.  Caveat: However, frequently clinicians do such an echocardiogram after symptoms and ECG findings have resolved. This is hazardous! Although there is usually some residual stunning (WMA),  sometimes the ischemia was so brief that the wall motion completely recovers.  This would be a false negative echo and leave the patient with an unstable plaque and thrombus in the coronary artery that would then not be intervened upon.

Scary ST Elevation. What is it?

911 was called for an 18 year old who had altered mental status after using K2 (a recreational drug).  The medics put the patient on the monitor and saw ST elevation.  They then recorded a prehospital 12-lead (not shown, as it is identical to the ED ECG), which showed marked ST Elevation.  The computer diagnosed "Pericarditis."  They were very worried, and brought the patient to the "Stabilization Room" for critically ill patients.

On arrival, I looked at the prehospital ECG (again, identical to the ED ECG shown below):
What did I think?

I immediately said "Normal Variant ST Elevation," and directed the patient to our "Special Care Unit" for altered mental status from drugs and alcohol.

This is not pericarditis, nor is it STEMI.  Get to know this pattern just like you would get to know a friend.  I called him "Jack," and told the residents to get to know Jack.

Jack often has high voltage QRS, has marked J-waves (they look almost like Osborn waves).  There is a relatively short QT interval.  The ST Elevation is towards leads II and V5.  Thus, there is no reciprocal ST depression in aVL. [In fact, these could be Osborn waves, but they were not: the patient was not hypothermic.]

Although the T-wave is negative in aVL, it is NOT T-wave inversion, as the QRS-T angle is narrow (QRS axis is 85 degrees, almost directly inferior; T-wave axis is 68 degrees -- angle is only 17 degrees.  Both these measurements are accurately made by the computer algorithm.)

How do I know it is not pericarditis?  First, the patient denied any chest pain!  Second, normal variant STE is far more common that pericarditis.  There are J-waves, no PR depression, and no Spodick's sign (downsloping T-P segment -- of questionable reliability).

It is very common for Normal Variant STE to be misdiagnosed as pericarditis.  Does this have adverse consequences??  It may.  Take a look at this case that was written by Pendell Meyers when he was a medical student: due to misdiagnosis of the ECG as "pericarditis", a patient's chest pain was misattributed to pericarditis and the correct diagnosis of pulmonary embolism was ignored:

31 Year Old Male with RUQ Pain and a History of Pericarditis. Submitted by a Med Student, with Great Commentary on Bias!

ST-Elevation in aVR with diffuse ST-Depression: An ECG pattern that you must know and understand!

This case comes from Sam Ghali  (@EM_RESUS). 

A 60-year-old man calls 911 after experiencing sudden onset chest pain, palpitations, and shortness of breath. Here are his vital signs:

HR: 130-160, BP: 140/75, RR:22, Temp: 98.5 F, SaO2: 98%

This is his 12-Lead ECG:

He is in atrial fibrillation with a rapid ventricular response at a rate of around 140 bpm. There are several abberantly conducted beats. There is ST-Elevation in aVR of several millimeters and diffuse ST-Depression with the maximal depression vector towards Lead II in the limb leads and towards V5 in the precordial leads.

ECG reading is all about pattern recognition. And this particular pattern of ST-Elevation in aVR with diffuse ST Depression is a very important ECG pattern that you must be able to recognize. But what's probably more important than being able to recognize the pattern, is understanding what it represents. There appears to be a common misconception that the ST-Elevation in aVR in this case possibly represents "STEMI", or acute transmural (full-thickness) ischemia. If this were the case the patient would most likely be dead or at the very least in profound cardiogenic shock. The key to understanding what this pattern represents lies in understanding that the ST-Elevation in aVR is reciprocal to the diffuse ST-Depression - and that this diffuse ST-Depression represents global subendocardial ischemia!

So the real question that you must answer is: 
What is causing the global subendocardial ischemia?

It is critical to realize that more often than not the cause is global myocardial strain from a Non-ACS etiology! (profound sepsis, tachycardia, anemia, hypoxemia, etc). It is also very important to understand that in these Non-ACS settings, you can see this pattern with or without underlying coronary artery disease.

But of course it could be ACS. And if it is, then you are dealing with Left Main, Proximal LAD, or even multi-vessel plaque instability. But keep in mind that even if it is ACS you are still dealing subendocardial and not transmural ischemia.

Here is a subcostal view of the bedside Echo obtained from our patient in the ED:
There is good global function

So what is causing the diffuse subendocardial ischemia in our patient? 

 When the heart rate is significantly elevated as in this case, it is reasonable to suspect that the ischemia is likely tachycardia-induced, or "demand ischemia." So given the normal EF noted on Echo, (and by the way I would strongly recommend assessing the EF of any patient before deciding to give any negative inotropic medications) the decision was made to administer a Diltiazem bolus and infusion and to reassess after rate control was established. Rate controlled was gained as the patient's heart rate came down very nicely into the 80's. He felt much better and his symptoms were all but completely relieved.

Smith comment: it is also critical to assess volume before giving negative inotropes and negative chronotropes.  This tachycardia could be a response to poor LV filling.  Indeed the neither LV nor RV appear to be filling very well.  If the atrial fib with RVR is resulting in a rate so fast that the rate is the cause of poor LV filling, then there should be some increased filling pressures, possible pulmonary edema, and evidence of fluid overload.   Assessment of IVC filling would be helpful, and, if it is collapsed, then administration of fluids first (or blood if this is a GI bleed) is indicated.  If this does not result in a slower heart rate, then an AV nodal blocker is indicated, such as Diltiazem.  

Furthermore, since this patient has no history of atrial fib, and it is a critical situation, electrical cardioversion is both safer and more effective than an AV nodal blocker such as Diltiazem.

See these 2 posts

Atrial fibrillation with RVR: use POCUS to assess volume; then sinus vs. SVT: use of Lewis leads

Here is the repeat ECG obtained 25 minutes after the first one:
The rhythm is still A-Fib. The heart rate has come down more than 65 points. But despite the dramatic decrease in heart rate, the pattern of global subendocardial ischemia persists! (ST-Elevation in aVR with diffuse ST-depression that has a maximum depression vector towards leads II and V5)

If this repeat ECG had shown resolution of the global subendocardial ischemia pattern, it would be reasonable to conclude that it was likely the result of a-fib with an uncontrolled ventricular response. But because this pattern persisted after rate control and in the absence of any other evidence of clinical causes, one must assume that the etiology of the pattern is indeed ACS - meaning there has been acute plaque instability in either the left main coronary artery, Proximal LAD, or multi-vessel involvement. 

The patient was started on heparin in addition to the aspirin he received en route and the Cardiology team was consulted. (Of note, it is important not to start these patients on dual anti-platelet therapy as there is a high likelihood that they will require CABG.) The decision was made to proceed urgently to the cath lab for angiography. 

Cardiac Cath Results:

Left Main: There is a 90-95% stenosis of the distal left main including the ostium of LAD and Left Circumflex arteries.  
LAD: There is a focal 80% stenosis just after the takeoff of the first diagonal branch.

Circumflex: Severe disease at its ostium and moderate disease in the remainder of the proximal segment.

RCA: 100% chronic total occlusion at its proximal segment.

In discussion with the interventional cardiologist who performed the cath there was thought to be evidence of likely a component of acute thrombus at the 90-95% left main stenosis, suggesting Left Main ACS!

Case Resolution:

The patient was referred for CABG and ended up doing quite well.

Take Home Points:

1. The key to ECG reading is pattern recognition. The pattern of ST-Elevation of at least 1mm in lead aVR + diffuse ST-Depression with a maximal depression vector towards leads II & V5 is a pattern you must know. It represents global subendocardial ischemia.

2. When you see this pattern you should divide the differential for the diffuse subendocardial ischemia into two main categories: ACS vs Non-ACS. Do not automatically assume that it is ACS. I have seen this mistake made many times as ACS becomes the focus, at the expense of appropriate resuscitation addressing the underlying cause. It is very important to keep in mind that the etiology is far more likely to be Non-ACS than ACS!

See this case: 

Diffuse Subendocardial Ischemia on the ECG. Left main? 3-vessel disease? No!

3. The key to determining the etiology is through history, physical exam, clinical picture, laboratory data, Echo, and vigilant monitoring and frequent reassessment.  If you have identified and addressed potentially reversible causes of the ischemia, and the ECG pattern persists then you are dealing with ACS until proven otherwise.

4. Refrain from using dual-antiplatelet therapy in these patients as there is a high likelihood they will require CABG.

5. Remember that if this ECG pattern does represent ACS, the ST-Elevation in aVR is not the result of direct injury (or transmural ischemia) and that the ST-Elevation in aVR is reciprocal to the diffuse ST-Depression. Therefore these ACS cases do not represent "STEMI".  However, while there is not great data to guide the timing of cath for these patients, I would advocate going to the cath lab with a much stronger sense of urgency than for other "NSTEMIs".  The reasoning is that ACS is a very dynamic process and without the advantage of optimal medical therapy (a second platelet inhibitor should be withheld) there is a higher chance of the culprit vessel suddenly occluding and evolving to transmural ischemia. If this happens in the Proximal LAD, Left Main, or in the setting of Multi-vessel involvement the myocardial territory in jeopardy is so large that there is a good chance the patient will arrest and die before any reperfusion can be established!

6.  Smith comment: With diffuse subendocardial ischemia, you may not see any wall motion abnormality.  Global function can even be normal, although it may be globally depressed as well.  A normal bedside echo does not help in: 1) differentiating the cause of the STE in aVR 2) ruling out ACS.

Here is the section on aVR written by Smith in: Miranda et al. "New Insights into the Use of the 12-lead ECG in Acute MI in the ED" (Canadian J Cardiol 34(2):132-145; Feb 2018)

Lead aVR in ACS 62

Many experts consider the ECG pattern of STE in aVR, with diffuse STD elsewhere (referred to herein as the aVR STE pattern), to be representative of LM ATO.7 The 2013 ACC/AHA STEMI guidelines consider this a STEMI equivalent,in which thrombolytic therapy is not contraindicated (evidence level B, no specific class of recommendation).  18 However, these conclusions are on the basis of studies in which LM lesions were not true subtotal or complete occlusion (ie, TIMI 0/1 flow).62,63 The interventional community defines occlusive LM disease as >50% according to fractional flow reserve, or 75% stenosis,64 but urgent or emergent intervention on lesions not meeting these thresholds is only imperative if it is a thrombotic lesion and the patient has refractory ischemic symptoms (ie, not resolved by nitrates, antiplatelet, and antithrombotic therapies; see 3 examples in Supplemental Fig. S7).

Although nearly half of patients with 1 mm STE in aVR due to ACS will require coronary artery bypass surgery for revascularization,62 the infarct artery is often not the LM, but rather the LAD or severe 3-vessel disease. More importantly, such ECG findings are frequently due to nonocclusive etiologies (eg, baseline LVH, demand ischemia secondary to respiratory failure, aortic stenosis, hemorrhagic shock). Knotts et al. reported that only 23% of patients with the aVR STE pattern had any LM disease (fewer if defined as 50% stenosis). Only 28% of patients had ACS of any vessel, and, of those patients, the LM was the culprit in just 49% (14% of all cases).57 It was a baseline finding in 62% of patients, usually due to LVH.

Thus, a number of expert reviews emphasize the low specificity of the aVR STE pattern, preferring to label it as circumferential subendocardial ischemia; in this syndrome, STE in aVR is reciprocal STE, reciprocal to an STD vector toward leads II and V5.10,12,62 

The aVR STE pattern is also not sensitive for LM ATO. However, anterior STEMI with combined new right bundle branch block and left anterior fascicular block is highly suggestive of LM ATO (see example 12-lead ECG in Supplemental Fig. S8).65,66

It should be re-emphasized that true LM ATO (ie, TIMI flow 0) is rare in the ED, because most either die before arrival or are recognized clinically because of cardiogenic shock. Thus, reported specificities of STE in aVR for LM ATO result in very low positive predictive values. Of those who do get to the ED, many present with clear STE.62,65,66

The ACC/AHA states that thrombolytics are not contraindicated for diffuse STD associated with  STE in aVR.  Because of the poor specificity of this pattern for LM ATO, we suggest that thrombolytics should only be considered for those with profound STD that is clearly due to ACS, is refractory to all other medical management, and only when PCI is completely unavailable.

Lead aVR in STEMI
 Some patients whose ECGs already meet conventional STEMI criteria might also have STE in lead aVR. This finding does not alter the need to pursue emergent reperfusion, although it might suggest a poorer prognosis.62,67  In a patient with otherwise diagnostic STE, additional STE in aVR does not represent LM ATO and is not helpful in diagnosing the infarct-related artery or the site of occlusion.68  Less than 3% of anterior STEMI has LM ATO, and most are recognized clinically because of cardiogenic shock.69,70


62. Smith SW. Updates on the electrocardiogram in acute coronary syndromes.  Curr Emerg Hosp Med Rep 2013;1:43-52.

63. Jong GP, Ma T, Chou P, et al. Reciprocal changes in 12-lead electrocardiography
can predict left main coronary artery lesion in patients with acute myocardial infarction. Int Heart J 2006;47:13-20.

64. Stone GW, Sabik JF, Serruys PW, et al. Everolimus-eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med 2016;375:2223-35.

65. Fiol M, Carrillo A, Rodriguez A, et al. Electrocardiographic changes of ST-elevation myocardial infarction in patients with complete occlusion of the left main trunk without collateral circulation: differential diagnosis and clinical considerations. J Electrocardiol 2012;45:487-90.

66. Widimsky P, Rohac F, Stasek J, et al. Primary angioplasty in acute myocardial infarction with right bundle branch block: should new onset right bundle branch block be added to future guidelines as an indication for reperfusion therapy? Eur Heart J 2012;33:86-95.

67. Kukla P, Bryniarski L, Dudek D, Krolikowski T, Kawecka Jaszcz K. Prognostic significance of ST segment changes in lead aVR in patients with acute inferior myocardial infarction with ST segment elevation. Kardiol Pol 2012;70:111-8.

68. 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.

69. Zoghbi GJ, Misra VK, Brott BC, et al. ST elevation myocardial infarction due to left main culprit lesions: percutaneous coronary intervention outcomes. J Am Coll Cardiol 2010;55:A183.E1712.

70. Kurisu S, Inoue I, Kawagoe T, et al. Electrocardiographic features in patients with acute myocardial infarction associated with left main coronary artery occlusion. Heart 2004;90:1059-60.