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Journal of Electrocardiology 46 (2013) 240 – 248

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Diffuse ST depression with ST elevation in aVR: Is this pattern specific for

global ischemia due to left main coronary artery disease?
Robert J. Knotts, MD, a James M. Wilson, MD, a, b Edward Kim, MD, a
Henry D. Huang, MD, a Yochai Birnbaum, MD a, b,⁎
a
The Section of Cardiology, The Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
b
Texas Heart Institute, St Luke's Episcopal Hospital, Houston, Texas, USA

Abstract Background and Purpose: We assess whether the electrocardiographic (ECG) pattern of ST
depression in N 7 body surface leads combined with ST elevation in aVR and V1 is predictive of left
main coronary artery (LMCA) stenosis or left main equivalent (LMEQ) disease.
Methods: We collected 133 patients showing this particular ECG pattern. Patients with left bundle
branch block, ventricular rhythm or ventricular paced rhythm were excluded.
Results: Only 28% of the patients had non-ST elevation acute coronary syndrome (NSTE-ACS).
ECGs were classified as chronic, dynamic or no prior in 28%, 48% and 24%, respectively. A total of
57 patients (44%) underwent coronary angiography (CA). No significant coronary artery disease was
found in 26%. LMCA/LMEQ disease was found in only 23% of these patients. The positive
predictive value of the ECG pattern was not improved after exclusion of patients with
intraventricular conduction abnormalities and left ventricular hypertrophy or in patients with
dynamic ECG changes.
Conclusions: This ECG pattern is not always caused by LMCA/LMEQ disease; therefore, the term
“suspect circumferential subendocardial ischemia” may be preferred. Other medical conditions may
also be associated with a similar ECG pattern.
© 2013 Elsevier Inc. All rights reserved.
Keywords: Diffuse ST depression; Left main stenosis; Lead aVR

Introduction suggest “ischemia due to multivessel or LMCA obstruction”. 1

In this document, presence of typical symptoms is not
Diffuse ST segment depression in the inferior and
mentioned and the guidelines are read as a “stand alone”
anterolateral leads that is associated with ST segment
recommendation for ECG interpretation either at bed side or
elevation in leads aVR and V1 (Figs. 1-4) is thought to
off line. Moreover, there is no specification as to what is an
represent circumferential subendocardial ischemia, suggest-
ECG that is “otherwise unremarkable”. For example, does the
ing an injury vector directed toward the ventricular chamber.
presence of Q waves or QRS axis deviation considered
When accompanied by angina at rest, this ECG is believed to
“remarkable”? Furthermore, it is unclear whether in patients
have a 75% predictive accuracy of left main coronary artery
with diffuse ST depression with ST elevation in aVR as a
(LMCA) occlusion or three-vessel coronary artery disease. 1
chronic stable pattern, the same association with LMCA exist.
The current recommendation by the American Heart
These recommendations were endorsed by the recently
Association/American College of Cardiology Foundation/
published 2012 European Society of Cardiology Guidelines
Heart Rhythm Society (AHA/ACCF/HRS) for “resting
for the management of ST elevation acute myocardial
ECGs that reveal ST-segment depression greater than 0.1
infarction. 2 Dual antiplatelet therapy is recommended by the
mV in 8 or more body surface leads coupled with ST-
guidelines for all patients presenting with acute coronary
segment elevation in aVR and/or V1 but are otherwise
syndromes (ACS), regardless of whether they are to receive
unremarkable,” is that the automated interpretation should
percutaneous coronary intervention (PCI) or medical treatment
⁎ Corresponding author. The Department of Medicine, Section of
alone. 3 Oral P2Y12 receptor inhibitors, such as clopidogrel,
Cardiology, Baylor College of Medicine, One Baylor Plaza, MS: BCM620, prasugrel and ticagrelor, improve clinical outcomes in patients
Houston, TX 77030, USA. with ACS, but are associated with an increased risk of
E-mail address: ybirnbau@bcm.edu operative bleeding when administered within five days of
0022-0736/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jelectrocard.2012.12.016
 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248 241

Fig. 1. ECG of an 87-year-old man showing sinus rhythm with right bundle branch block and left anterior fascicular block. Patient was known to have severe
aortic stenosis. Patient presented with chest pain and was diagnosed as having a non-ST elevation myocardial infarction. There is ST depression with negative T
waves in the inferior leads and leads V3–V6 and ST elevation in leads aVR and V1. Subsequent coronary angiography revealed 70% diameter stenosis of his left
main coronary artery, 50% stenosis in the distal left anterior descending artery and 50% distal right coronary artery stenosis. Patient underwent aortic valve
replacement and coronary artery bypass grafting with left internal mammary artery graft to the left anterior descending artery and a saphenous vein graft to the
obtuse marginal branch.

coronary artery bypass graft (CABG) surgery. Since most of depression with ST elevation in lead aVR may be seen in
the patients with LMCA disease or left main equivalent patients with cardiomyopathies as well as left ventricular
(LMEQ, proximal narrowing in both the left anterior hypertrophy with repolarization changes and in numerous
descending and left circumflex arteries) will likely need other medical conditions that may or may not be associated
CABG surgery, some authors have recommended withholding with circumferential subendocardial ischemia. Diffuse ST
P2Y12 receptor inhibitors in patients presenting with such depression with ST elevation in aVR is not even the most
ECG pattern until the treatment plan has been established. 4 common ECG pattern seen in patients presenting with LMCA
Thus, early identification of patients with ACS due to LMCA obstruction. 5–7 This study assesses the diagnostic accuracy of
or LMEQ disease is of extreme importance. However, in our the criteria defined by the 2009 AHA/ACCF/HRS recom-
experience, the same ECG pattern of diffuse ST segment mendations as written. 1 The main objectives of this study were

Fig. 2. ECG of a 31-year-old woman with known non-ischemic cardiomyopathy (non-compaction) and recurrent ventricular tachycardia for which a defibrillator
was implanted. The ECG shows sinus rhythm with left ventricular hypertrophy. There is ST depression with negative T waves in leads I, II, III, aVF and V4-V6.
There is ST elevation in lead aVR, V1 and V2. This pattern was present in several previous ECGs in the preceding 4 months. Coronary angiography did not reveal
any significant coronary artery disease. Echocardiogram showed left ventricular ejection fraction of 38% with global hypokinesis.
242 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248

Fig. 3. ECG of a 67-year-old man with a history of coronary artery disease (two myocardial infarction in the past), severe aortic stenosis, and symptomatic
peripheral artery disease who came with progressive symptoms of effort induced angina. ECG shows sinus tachycardia, ST depression in leads I, II, III, aVF,
V3–V6 with positive T waves. There is ST elevation in leads aVR and V1. These changes were not present in a previous ECG done several months earlier.
Cardiac markers were negative. Coronary angiography revealed significant LMCA and right coronary artery stenosis. The patient underwent CABG and aortic
valve replacement.

to assess 1) the prevalence of acute ischemia caused by LMCA tricular conduction delay affect the accuracy of predicting
or LMEQ disease among patients having the ECG pattern of LMCA/LMEQ by this particular ECG pattern. In the present
diffuse ST depression along with ST elevation in lead aVR; 2) study, we used a common situation in which the cardiologist is
what other medical conditions are associated with such an analyzing ECGs from various areas of a tertiary hospital (in
ECG pattern; and 3) whether ECG confounders, such as left patients, intensive care units, as well as outpatient clinics)
ventricular hypertrophy (LVH) or various forms of intraven- without complete access to patients' clinical data.

Fig. 4. ECG of a 55-year-old man with known coronary artery disease and pulmonary hypertension secondary to scleroderma was admitted due to non STE-
myocardial infarction. During hospitalization he developed chest pain and ECG shows sinus rhythm with right axis deviation with ST depression and negative T
waves in leads I, II, III, aVF, V3–V6. There was also ST elevation in lead aVR. The ST deviation was not present on his admission ECG. Urgent coronary
angiography revealed 70% proximal stenosis in his left anterior descending artery. No other lesions were identified. The patient underwent PCI with stenting.
 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248 243

Methods Table 1
Demographic and clinical data of the patients that underwent (CA) or did not
We collected 142 electrocardiograms (ECGs) with dates undergo (No CA) coronary angiography.
ranging from March 2, 2008 to April, 13 2011 from the ones CA No CA P value
sent for routine reading at the St. Luke's Episcopal Hospital n 57 76
ECG laboratory and read by one investigator (YB). ECGs Male 31 (54%) 26 (34%) p= 0.02
showing diffuse ST segment depression in N 7 leads with ST- Age (years) 65+ 17 66+ 17 p= 0.74
segment elevation in aVR were collected. Patients with left Race p= 0.99
bundle branch block, QRS duration of N 130 msec, Caucasian 33 44
African American 11 16
ventricular rhythm or ventricular paced rhythm were Hispanic 9 10
excluded. The polarity of the T waves in the leads with Asian 2 3
maximal ST depression was defined as positive if the Undefined 2 3
terminal part of the T wave was N 0.1 mV above the Chief indication
isoelectric line, or negative. Chest pain 29 (51%) 17 (22%) p=0.0006
Shortness of breath 9 (16%) 11 (14%) P=0.97
Demographic data, date of ECG, the indication for the Heart failure 1 (2%) 3 (4%) p=0.83
ECG, presence of elevated cardiac markers, diagnosis of Coronary artery disease 3 (5%) 2 (3%) p=0.84
cardiac conditions (non-ST elevation acute coronary syn- Abdominal pain 3 (5%) 4 (5%) p=0.69
drome [NSTE-ACS], non-ischemic dilated cardiomyopathy Dizziness 0 3 (4%) p=0.35
[NIDCM], ischemic cardiomyopathy, hypertrophic obstruc- Palpitations arrhythmia 2 (4%) 3 (4%) p=0.74
Syncope 2 (4%) 2 (3%) p=0.83
tive cardiomyopathy and hypertensive heart disease, and Hypertension 0 2 (3%) p=0.61
significant valvular disease), performance of coronary Peripheral artery disease 0 1 (1%) p=0.88
angiography (if so, number of diseased vessels [N 70% Abnormal ECG 0 5 (7%) p=0.13
diameter stenosis] and presence of left main stenosis N 50%), Other 8 (14%) 23 (30%) p=0.047
performance of revascularization (percutaneous intervention Suspect ACS on presentation 47 (83%) 39 (51%) p=0.0002
ECG changes p=0.59
[PCI] or CABG) following the ECG and the existence of Chronic 17 (30%) 20 (26%)
previous ECG (N 24 hours) with the same pattern or without Dynamic 25 (44%) 40 (53%)
this pattern were obtained from the patients' medical records. No prior 15 (26%) 16 (21%)
Angiographic data were broken up into LMCA, LMEQ LVH-ECG 14 (25%) 19 (25%) p=0.95
disease or three-vessel disease (3VD), two-vessel disease IVCD p=0.005
No 36 (63%) 57 (75%)
(2VD), one-vessel disease (1VD) or no significant coronary IncRBBB 1 9
artery narrowing. If the patients were post-CABG and the RBBB 7 3
grafts to the left anterior descending (LAD) and/or obtuse NSIVCD 9 2
marginals were patent we did not list them as LMCA or IncLBBB 4 5
LMEQ disease. The ECG patterns were classified as chronic T waves
+ 53 (93.0%) 44 (58%) p=0.000016
(present for at least 24 hours prior to selected ECG), dynamic − 4 (7.0%) 32 (42%)
(more significant changes or new pattern) or no prior ECG
ACs- acute coronary syndrome; IncLBBB- incomplete left bundle branch
obtained.
block; IncRBBB- incomplete right bundle branch block; IVCD- Interven-
tricular conduction delay; LVH- left ventricular hypertrophy; NSIVCD-
nonspecific IVCD; RBBB- right bundle.
Results
Out of the 142 patients that were chosen for our study, 9 respectively (Table 1). A quarter of the patients in each
(6.3%) had insufficient data. Of the remaining 133 patients, group had ECG criteria for LVH. There were no significant
57 (43%) underwent coronary angiography (CA) (Table 1). difference in the prevalence of intraventricular conduction
Demographic and clinical characteristics of the patients delay [incomplete right bundle branch block (incRBBB),
are shown in Table 1. The prevalence of men was higher complete right bundle branch block (RBBB), nonspecific
among patients undergoing CA than among those who did intraventricular conduction delay (IVCD) or incomplete left
not undergo CA; however, there was no difference in mean bundle branch block (incLBBB)] among groups. Interest-
age or race. The chief indication for the ECG was chest pain ingly, the majority of the patients (93%) in the CA group
in more than half of the patients that underwent CA had positive T waves, whereas only 60% of the patients
compared to only 20% in the group without CA. There who did not undergo CA had positive T waves (Table 1).
were no differences between the groups in the percentage of At discharge, ACS was diagnosed in 34 patients (60%)
patients having ECG for shortness of breath, palpitations or who underwent CA and in only 3 (4%) patients who did not
arrhythmia, syncope, heart failure or abdominal pain. ACS undergo CA (pb0.00001).
was clinically suspected in 83% of the patients who Medical diagnoses that were associated with the ECG
underwent CA and in only 50% of the patients who did not pattern are listed in Table 2. As mentioned above, only 37
undergo CA. The pattern of diffuse ST depression with ST (28%) patients were diagnosed with NSTE-ACS. Almost
elevation in lead aVR was chronic in 30% and 26% of the half of the patients had hypertensive heart disease.
patients who underwent or did not undergo CA, respec- Among the 57 patients that underwent CA, 24 (42%) had
tively. Dynamic changes were noted in 44% and 53%, a history of diabetes mellitus, 46 (81%) had hypertension, 39
244 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248

Table 2 or underwent a different procedure, such as septal

Medical diagnoses of patients. ablation for hypertrophic obstructive cardiomyopathy.
(n=133) CA results of the 35 patients that did not have prior
NSTE-ACS 37 (28%) CABG are also listed in Table 3. A total of 12 (34%) of these
NIDCM 4 (3%) patients had normal coronary arteries or no significant
Ischemic cardiomyopathy 10 (8%) coronary artery disease, while only 7 (20%) had LMCA
Unknown cardiomyopathy 5 (4%)
narrowing, 3 (9%) had LMEQ disease, and 5 (14%) had
Hypertrophic cardiomyopathy 4 (3%)
Hypertensive heart disease⁎ 60 (45%) 3VD. Thus, 15 patients (43%) had three vessel disease,
CNS disorders 13 (10%) LMCA or LMEQ, without a significant difference from the
NIDCM- non-ischemic dilated cardiomyopathy; NSTE-ACS- Non ST
whole group. Sixteen patients (46%) needed revasculariza-
elevation acute coronary syndrome. tion (6 patients (17%) underwent PCI and 10 (29%) CABG),
⁎ Only 112 patients had echocardiographic data to verify the diagnosis while the rest (54%) were treated either medically or
of left ventricular hypertrophy. underwent a different procedure.
In 34 patients who underwent CA (60%), the initial
presentation was suspicious of ACS. The prevalence of
(68%) had known coronary artery disease and 21 (37%) LMCA, LMEQ or three vessel disease was comparable to
had known cardiomyopathy. Twenty-two patients (39%) that of the whole group (Table 3). As expected, more patients
had prior CABG and 19 (33%) had a history of prior presented with ACS underwent revascularization (74%),
PCI. A total of 38 (67%) of the patients that underwent with 41% undergoing PCI and 35% CABG.
CA presented with either chest pain or shortness of Among the patients that underwent CA, 43 patients (75%)
breath; 22 (58%) of these patients were diagnosed with did not have ECG criteria for LVH. There were no
NSTE-ACS; 4 (9.1%) developed ST elevation myocardial significant differences in the prevalence of LMCA, LMEQ
infarction later on during their hospitalization. Angio- or three vessel disease between patients without LVH criteria
graphic results of the patients that underwent CA are and the whole group (Table 3). Among the patients without
listed in Table 3. Of note, 15 (26%) of these patients had LVH, 22 (51%) underwent revascularization with 26%
normal coronary arteries or no significant coronary artery undergoing PCI and 28% CABG.
disease, while only 10 (18%) had LMCA narrowing, 3 A total of 23 patients that underwent CA (40%) had no
(5%) patients had LMEQ disease, and 10 (18%) had ECG confounders (ECG is “otherwise unremarkable”).
3VD. Thus, three vessel disease, LMCA or LMEQ was LMCA disease was found in only 3 of them (13%),
present in only 23 patients (40%). Significant left anterior LMEQ in 2 (9%) and three vessel disease in 5 (22%). The
descending narrowing (N 70% luminal diameter stenosis) prevalence of three vessel disease, LMCA or LMEQ was
was detected in 22 patients (39%), significant left 43%, not different from that of the whole group. A total of 16
circumflex artery narrowing in 19 patients (33%), patients (70%) underwent revascularization with 30%
significant right coronary artery narrowing in 24 patients undergoing PCI and 43% CABG.
(42%). One patient with prior CABG had N 70% luminal Most of the patients that underwent CA had positive T
narrowing of the left internal mammary artery and 6 had waves (53 patients). Among the 4 patients with negative T
significant narrowing of saphenous vein grafts. A total of waves, one had three vessel disease, one LMCA and two
29 patients (51%) needed revascularization, with 14 nonsignificant coronary artery disease (Table 4).
(25%) undergoing PCI and 16 (28%) undergoing Among the 57 patients that underwent CA, 25 (44%) had
CABG, while the other half were either treated medically dynamic ECG changes and in 17 patients (30%) the pattern

Table 3
Angiographic data and treatment of the 57 patients that underwent CA.
All patients No prior CABG Suspect ACS No LVH No ECG confounders
n 57 35 (61%) 34 (60%) 43 (75%) 23 (40%)
Men 31 (57%) 19 (54%) 18 (53%) 21 (49%) 13 (56%)
Age (years) 65+ 17 63+19 68+14 68+ 16 63+16
# of vessel
0 15 (26%) 12 (34%) 1 (3%) 11 (26%) 5 (22%)
1 9 (16%) 4 (11%) 7 (21%) 7 (16%) 5 (22%)
2 10 (18%) 4 (11%) 10 (29%) 7 (16%) 3 (13%)
3 10 (18%) 5 (14%) 7 (21%) 7 (16%) 5 (22%)
LMCA 10 (18%) 7 (20%) 7 (21%) 8 (19%) 3 (13%)
LMEQ 3 (5%) 3 (9%) 2 (6%) 3 (7%) 2 (9%)
LMCA/LMEQ 13 (23%) 10 (29%) 9 (26%) 11 (26%) 5 (22%)
LMCA/LMEQ/3VD 23 (40%) 15 (43%) 16 (47%) 18 (42%) 10 (43%)
Treatment
PCI 14 (25%) ⁎ 6 (17%) 14 (41%)⁎ 11 (26%)⁎ 7 (30%)⁎
CABG 16 (28%) 10 (29%) 12 (35%) 12 (28%) 10 (43%)
⁎ One patient underwent both PCI and CABG.
 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248 245

Table 4 cavity, the same electrical vector that causes ST segment

Angiographic data and treatment of patients with positive versus negative T depression in leads V5 and V6 (that are oriented towards the
waves.
left ventricular apex) will be recorded by lead aVR as ST
All patients Positive T waves Negative T waves segment elevation. 11 These reciprocal changes may be seen
n 57 53 4 in situations where the left ventricular end diastolic pressure
# of vessel is elevated. Gorgels et al. suggested that ischemia of the
0 15 (26%) 13 (25%) 2 (50%)
basal interventricular septum should cause ST elevation in
1 9 (16%) 9 (17%) 0
2 10 (18%) 10 (19%) 0 leads aVR and V1. 12 Thus, both proximal LAD obstruction
3 10 (18%) 9 (17%0 1 (25%) and LMCA occlusion should cause ST segment elevation in
LMCA 10 (18%) 9 (17%) 1 (25%) leads aVR and V1. 12 Kosuge et al. reported that ST elevation
LMEQ 3 (5%) 3 (6%) 0 in aVR has a sensitivity of 78%, specificity of 86%, positive
LMCA/LMEQ 13 (23%) 12 (23%) 1 (25%)
predictive value (PPV) of 57%, negative predictive value
LMCA/LMEQ/3VD 23 (40%) 21 (40%) 2 (50%)
(NPV) of 95% and predictive accuracy of 84% for predicting
LMCA or 3VD in a retrospective study of 310 patients with
of diffuse ST segment depression with ST elevation in aVR NSTE-ACS. 4
was a chronic pattern. Previous ECG was unavailable in 15
Diffuse ST depression
patients (26%). There was no difference in the prevalence of
LMCA (p=0.11), LMEQ (p=0.50) or LMCA/LMEQ/three Nikus et al. describe that the ECG pattern of widespread
vessel disease (p=0.41) among the groups. However, LMCA ST-segment depression and inverted T waves, maximally in
or LMEQ (p=0.18) tended to occur more often in the group leads V4–5 is associated with LMCA disease, LMEQ
with dynamic ECG changes (Table 5). Patients who had coronary artery disease, or severe there vessel disease. 13 In
dynamic ECG changes underwent more often revasculari- 50 patients with NSTE-ACS this pattern had a sensitivity of
zation than patients with stable or unknown ECG pattern (p= 100%, specificity of 57%, PPV of 24% and NPV of 100%
0.09), with more patients in with dynamic ECG changes for severe 3VD. While a sensitivity of 91%, specificity of
needed CABG (p=0.134). 79%, PPV of 76% and NPV of 92% were reported for
LMCA or LMEQ coronary artery disease. This pattern had a
sensitivity of 93%, specificity of 100%, PPV of 100% and
Discussion NPV of 92% for severe 3VD, LMCA or LMEQ coronary
The LMCA supplies blood to a majority of the artery disease. 13 In another study, Nikus and Sclarovsky
anterolateral and septal aspects of the left ventricle as it describe “transient ST depression with negative T waves
branches into the LAD and left circumflex arteries. A seen maximally in leads V4 and V5” as a pattern associated
decrease in blood flow after LMCA narrowing affects a with significant LMCA/3VD. The pattern had a PPV of
significant region of the heart, producing electrical distur- 100% and an NPV of 92% in a prospective study of 25
bances visible by ECG due to myocardial ischemia/injury. patients. ST elevation in aVR was explained as reciprocal
Isolated ST segment elevation in lead aVR as well as diffuse changes to the ST depression in leads V4 and V5, which are
ST segment depression with/without ST segment elevation electrically opposite to aVR. 13 Taglieri et al. describe the
in aVR has been described previously as patterns consistent predictive value of isolated diffuse ST depression compared
with either LMCA or triple vessel stenosis. 1,7,8
Table 5
Isolated ST elevation in aVR and V1 Angiographic data and treatment of patients with dynamic versus stable
ECG changes.
Gorgels et al were the first to report that ST elevation in All Dynamic Stable Prior ECG
lead aVR, together with ST depression in leads I, II and V4– patients ECG ECG unknown
V6 were predictive of LMCA or three vessel disease, changes pattern
especially when the total magnitude of ST changes exceeded n 57 25 (44%) 17 (30%) 15 (26%)
12 mm. 9 Yamaji et al. reported that ST elevation in lead aVR Men 31 (57%) 14 (56%) 10 (59%) 7 (47%)
(N 0.05 mV) that was greater than ST elevation in lead V1 Age (years) 65+17 67+ 16 62+ 19 66+14
“distinguished” LMCA obstruction from LAD and right # of vessel
0 15 (26%) 4 (16%) 7 (41%) 4 (27%)
coronary artery obstruction with 81% and 88% sensitivity,
1 9 (16%) 5 (20%) 1 (6%) 3 (20%)
80% and 92% specificity and 81% and 90% accuracy, 2 10 (18%) 4 (16%) 2 (12%) 4 (27%)
respectively.N 0.15 mV ST elevation in lead aVR predicted 3 10 (18%) 4 (16%) 3 (18%) 3 (20%)
mortality with 75% sensitivity, 75% specificity and 75% LMCA 10 (18%) 6 (24%) 4 (24%) 0
accuracy in patients with ACS. 10 The positive end of lead LMEQ 3 (5%) 2 (8%) 0 1 (7%)
LMCA/LMEQ 13 (23%) 8 (32%) 4 (24%) 1 (7%)
aVR points toward the patient's right shoulder, so if the
LMCA/LMEQ/3VD 23 (40%) 12 (48%) 7 (41%) 4 (27%)
LMCA is obstructed, the septal branches of the LAD would Treatment
also be affected. It is believed that LMCA obstruction leads PCI 14 (25%)⁎ 7 (28%)⁎ 3 (18%) 4 (27%)
to ischemia/injury of the basal septum with a resultant right CABG 16 (28%) 10 (40%) 2 (12%) 4 (27%)
superior pointing injury vector causing ST segment elevation Revascularization 29 (51%) 16 (64%) 5 (29%) 8 (53%)
in lead aVR. 10 Since lead aVR faces into the left ventricular ⁎ One patient underwent both PCI and CABG.
246 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248

to ST depression plus ST elevation in lead aVR in 0.05 mV”. 8 Nikus et al recommended that urgent CA
identifying LMCA disease and in-hospital as well as one- should be considered if the patient is hemodynamically
year cardiovascular mortality in patients with NSTE-ACS. unstable or ischemic symptoms persist, but there are not
They concluded that only diffuse ST depression plus ST enough data to recommend urgent CA based on the ECG
elevation in lead aVR was useful in identifying LMCA findings alone. 5,8
disease and mortality. Multivariable analysis showed an The current study questions the accuracy of interpreting
odds ratio (4.72; 95% CI 2.31 to 9.64; p b 0.001) for this the ECG pattern of diffuse ST segment depression with ST
combined pattern to predict LMCA obstruction. 14 The same elevation in aVR as a sign of diffuse three vessel disease or
analysis was completed for prediction of mortality, provid- LMCA/LMEQ disease, using the above mentioned recom-
ing a hazard ratio (1.52; 95% CI 1.44 to 3.64; p b 0.001), mendations. Here we collected consecutive patients with
favoring the combined pattern over isolated diffuse ST ECGs showing diffuse ST depression and ST elevation in
deviation as well. 14 Hanna and Glancy describe that during lead aVR. LMCA or LMEQ disease was found in only 23%
an episode of ischemic chest pain, a pattern of diffuse ST of the patients that underwent CA. Thus, the positive
depression in eight or more leads combined with ST predictive value of the ECG pattern for LMCA/LMEQ was
elevation in aVR and V1 has a 75% predictive accuracy for significantly lower in our cohort than that reported in
LMCA or 3-VD. 15 previous studies. 13 In contrast to the previous studies, most
However, as abovementioned, diffuse ST depression may of our patients were not diagnosed with ACS. Interestingly,
not even be the most common ECG pattern seen in patients the prevalence of LMCA/LMEQ was not higher among
presenting with LMCA obstruction. Atie et al reported that patients with presentation compatible with ACS as compared
only 60% of the patients with NSTE-ACS due to LMCA to all the 57 patients that underwent CA. It should be
obstruction had ST elevation in lead aVR and 67% had remembered that in about 30% of the patients with acute
maximal ST depression in lead V4. 16 The average number of myocardial infarction, presentation can be atypical, espe-
leads with ST-T changes was only 6.4, suggesting that in cially in the elderly, diabetic patients and women. 2,18
many patients there were less than 6 leads with ST Shortness of breath, hypotension, epigastric pain and
depression. 16 More recently, Taglieri et al reported that arrhythmia, all can be manifestation of ACS are common
only 24 out of 57 patients (42%) with NSTE-ACS due to in patients with cardiomyopathies, hypertensive heart
LMCA stenosis had ST elevation in lead aVR with ST disease and significant valvular disease that cause diffuse
depression in other leads. 14 ST elevation, predominantly in ST depression with ST elevation in aVR. Moreover, the
the precordial leads is probably the most frequent ECG prevalence of LMCA/LMEQ was not significantly higher
presentation in patients with complete occlusion of the among patients with dynamic ECG changes as compared to
LMCA, followed by right bundle branch block. 5–7,17 those with chronic pattern of diffuse ST depression and ST
The current recommendations by the AHA/ACCF/HRS elevation in aVR. It should be remembered that the amount
for “resting ECGs that reveal ST-segment depression greater of ST depression in patients with repolarization abnormal-
than 0.1mV in 8 or more body surface leads coupled with ities (LVH, cardiomyopathies, intraventricular conduction
ST-segment elevation in aVR and/or V1 but are otherwise delay, etc) is dependent on the heart rate and the degree of
unremarkable” are that the automated interpretation should QRS prolongation and therefore, may show dynamic
suggest “ischemia due to multivessel or left main coronary changes. In the present study, presence of symptoms
artery obstruction”. 1 Although in the text it is written that “It suggestive of ACS or dynamic ECG changes did not
has been reported that in patients with angina at rest, ST- improve the association between the ECG pattern and the
segment depression in 8 or more body surface ECG leads, presence of LMCA, LMEQ or three vessel disease.
combined with ST elevation in aVR and V1, is associated An important component of the recommendations is that
with a 75% predictive accuracy of 3-vessel or left main the ECG should be “otherwise unremarkable”. 1 There is no
stenosis”, 1 the recommendations do not mentioned symp- specification what is actually considered “unremarkable”. It
toms during ECG recording. Obviously, currently we cannot is clear that repolarization changes secondary to LVH or left
add symptoms or risk factors to the computerized automated bundle branch block may cause diffuse ST depression with
interpretation. Thus, the current recommendations suggest ST elevation in lead aVR. We did not include patients with
that the ECG should be interpreted independent of the left bundle branch block or QRS duration of N 130 msec in
clinical presentation. our cohort. Interestingly, after exclusion of the 14 patients
Nikus et al. on behalf of an International Society of with ECG signs of LVH, the prevalence of LMCA, LMEQ
Holter and Non-Invasive Electrocardiology (ISHNE) work- and/or three vessel disease did not significantly changed
ing group recommended that the AHA/ACCF/HRS recom- compared to the whole cohort. Even when we included only
mendation is supported by prior studies, “but needed minor patients without ECG confounders, the percentage of
modifications: 1.) The presence of left ventricular hyper- patients with LMCA, LMEQ and/or three-vessel disease
trophy, left bundle branch block with QRS N 130 msec and/ did not increase. Obviously, diffuse coronary artery disease
or tachycardia (rate N 100/min) invalidates these criteria. 2.) may result in pathological Q waves, QRS widening and QRS
The number of required leads with ST depression should be axis changes. Moreover, hypertension, a major risk factor for
reduced from 8 to 7. 3.) The threshold for ST depression in coronary artery disease, may results in LVH. As these
the V leads should be adjusted for age and gender. 4.) The changes are considered “abnormal”, excluding high-risk
threshold for ST elevation in aVR should be specified as patients with such abnormalities decreases the clinical
 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248 247

applicability of the ECG sign by excluding a large number of We cannot exclude the possibility that small vessel
high-risk patients. disease or supply/demand imbalance leads to diffuse
Nikus et al emphasized the importance of the T wave subendocardial ischemia in some of our patients. It has
polarity in leads V4-V5 in predicting LMCA/LMEQ previously been reported that other medical conditions, such
disease. Patients with negative T waves had higher as hypothermia 25 and various neurological disorders 26 may
prevalence of LMCA/LMEQ and poorer outcome than present with such transient ECG pattern. Thus, the term
patients with positive T waves. 13,19 Hence, the position “circumferential subendocardial ischemia” as suggested by
manuscript by Nikus et al suggests that “sudden occlusion Samuel Sclarovsky or “circumferential subendocardial
of the LMCA may present as widespread ST depression stress” may be better than “ischemia due to multivessel or
and inverted T waves with ST elevation in lead aVR.” 5 We left main coronary artery obstruction”. 1
used strict criteria for the definition of T wave polarity.
Investigators are using different definitions for the polarity
Study limitations
of the T waves. 20 For example, Nikus et al considered the
T wave to be positive or negative if it was 1 mm or more This is a retrospective review of patients based on ECGs
above or below the isoelectric line, measured more than that were identified during routine reading at the St. Luke's
120 ms after the J point. 13 As ST depression may affect the Episcopal Hospital ECG laboratory. Just over half of our
initial part of the T wave and during ischemia QRS may patients presented with chest pain and/or shortness of breath.
prolonged, we defined negative T wave based on the All ECGs met the pattern of diffuse ST depression with
terminal part of the T wave. Interestingly, most of our elevation in aVR, which is the pattern described by the
patients had positive T waves per this definition. Moreover, current AHA/ACCF/HRS guidelines. We did not limit
two out of the four patients with negative T waves did not ourselves to patients presenting with clinical scenario that
have significant coronary artery disease. Indeed, diffuse may be compatible with ACS, as we tested the accuracy of
horizontal, and especially upsloping ST depression with the ECG pattern for predicting LMCA or LMEQ-induced
prominent tall positive T waves may signify different ischemia. Larger prospective studies are needed to confirm
coronary anatomy (regional subendocardial ischemia) 21; our results and assess the predictive value of this particular
however, small positive terminal T waves may carry the ECG pattern for LMCA/LMEQ disease in patients with and
same significance as negative T waves. Further studies are without typical clinical presentations. An alternative ap-
needed to clarify this issue, especially to see if the proach to compare the incidence of such ECG pattern among
definition used by Nikus et al. 13 has better prediction. patients with ACS with or without LMCA/LMEQ/3VD has
Although the prevalence of LMCA, LMEQ or diffuse been reported (27). However, it is obvious that not all
three-vessel disease was relatively high in our patients, it is patients with such coronary anatomy have diffuse ischemia
clear that not all patients with such ECG pattern had LMCA/ due to LMCA or LMEQ lesions. They may have culprit
LMEQ disease. When combined with the right clinical lesions leading to ACS in more distal locations. In many
scenario, this ECG pattern is associated with high prevalence patients with NSTE-ACS, ischemia is intermittent and may
of LMCA/LMEQ disease. It is plausible that in patients not be detected by sporadic ECG recordings. In others, such
presenting with typical symptoms, this ECG pattern is more pattern may be related to etiologies other than acute diffuse
predictive for LMCA/LMEQ, especially if their baseline subendocardial ischemia.
ECG is completely normal. 5,8 Gorgels et al have shown that
during chest pain the number of leads with ST depression
and the amount of ST deviation in the ECG correlate with the
Conclusion
number of diseased coronary arteries. 9 The authors men-
tioned that the absolute shift of ST deviation from the The Texas Heart Institute at St Luke Episcopal Hospital is
baseline ECG, obtained when the patient did not have a tertiary center for heart disease, treating numerous patients
symptoms, is important as ST abnormalities could be present with complex heart diseases, cardiomyopathies and heart
at the baseline ECG even if the patient is free of ischemia. 9 failure. In our patient population, the pattern of diffuse ST
In particular, they suggested that ST depression in leads I, II depression in N 7 leads with ST elevation in aVR was
and V4–V6 and ST elevation in lead aVR are predictive of associated with acute coronary syndromes in only in 28% of
LMCA or three vessel disease. 9 However, if the above- the patients.
mentioned recommendations are adopted, urgent activation Although coronary artery disease is prevalent among the
of the catheterization laboratory for patients with atypical patients that were selected to undergo CA, only 23% of the
presentation (shortness of breath, epigastric pain, hypoten- patients had LMCA/LMEQ disease. We cannot exclude that
sion, etc.) solely based on ECGs showing diffuse ST this pattern represents “circumferential subendocardial
depression with ST elevation in lead aVR in order not to ischemia” due to “small vessel disease”, vasospasm or
misdiagnose acute myocardial infarction due to LMCA/ altered supply/demand ratio. Yet, the AHA/ACCF/HRS
LMEQ/three-vessel disease, will probably lead to high rate recommendation for interpreting this ECG pattern as
of false activation. Similar high rates of false activation of the representing “ischemia due to multivessel or left main
catheterization laboratory have been shown for patients with coronary artery obstruction,” implying that these patients
atypical symptoms presenting with presumably new left should be referred for urgent coronary angiography based on
bundle branch block. 22–24 the ECG pattern alone may not be supported by our findings
248 R.J. Knotts et al. / Journal of Electrocardiology 46 (2013) 240–248

and the term “circumferential subendocardial ischemia” is 12. Nikus KC, Eskola MJ, Virtanen VK, et al. ST-depression with negative
probably more accurate. t waves in leads V4–v5 – a marker of severe coronary artery disease in
non-ST elevation acute coronary syndrome: A prospective study of
angina at rest, with troponin, clinical, electrocardiographic, and
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