Manuscript type: original article
Angiographic and clinical outcomes among patients with acute coronary syndromes presenting
with isolated anterior ST-segment depression
Mohamed Salem, MD,PhD, Amal Hassan *, MSc, Amr Abo Elftoh *, MD, Hamza Kabil, MD,
and Hesham Abou-Elainen, MD
Department of Cardiology, Benha Faculty of Medicine, Benha University, Benha, Kalubia,
Egypt, and department of Cardiology, Shebin Elkom teaching Hospital *, Shebin Elkom,
Menoufia, Egypt
Short running head: Acute coronary syndrome
Corresponding author:
Dr. Mohamed Salem
Department of Cardiology, Benha Faculty of Medicine, Benha University, Benha, Egypt
Tel. 0020133106725, Mobile . 01092773227
E.mail. masalem@yahoo.com
Scientific e mail: mohamed.abdo01@fmed.bu.edu.eg
WWW. Bu.edu.eg
WWW.fac.bu.edu.eg
Conflict of interest: No
Disclosure of funding received for this work: No
1
Abstract
Objectives. To evaluate both angiographic and clinical outcomes in patients with acute coronary
syndrome (ACS) presenting with isolated anterior ST-segment depression on 12-lead
electrocardiogram (ECG).
Background. Acute coronary syndrome is an umbrella term used to cover a spectrum of events
caused by acute myocardial ischemia.
Methods. The study included 50 consecutive patients with ACS. All patients had isolated ST
depression in the anterior leads on admission ECG. Coronary angiography and cardiac
biomarkers were done at baseline. According to TIMI flow grade in the culprit artery and the
result of cardiac markers, patients were subdivided into 3 groups. Group I : TIMI flow grade 0/1
and positive markers, Group II: TIMI flow grade 2/3 and positive markers, Group III: TIMI
flow grade 2/3 and negative markers. In- Hospital and 30 days outcome were reported.
Results. Based on coronary angiography finding and results of cardiac markers, 12 patients
(24%) had totally occluded culprit artery plus positive markers, 10 patients (20%) had TIMI flow
II/III plus subtotal occlusion in the culprit artery and positive markers. While 28 patients (56%)
patients had TIMI flow II/III and negative markers. In hospital and 30 days outcomes did not
differ between groups.
Conclusion. Among patients with ACS presenting with isolated anterior ST segment depression,
about one quarter had an occluded culprit artery and elevated cardiac markers.
Key words. Acute coronary syndrome, coronary angiography, Cardiac Biomarkers
2
Introduction
The presence of ST segment elevation, especially when accompanied with reciprocal changes in
a patient with typical symptoms is highly predictive of evolving acute myocardial infarction
(AMI)
(1)
. Not all patients who develop myocardial necrosis have an abnormal ECG, thus, a
normal ECG doesn't rule out AMI, because the new sensitive biomarkers can detect very small
quantities of myocardial necrosis in a range where ECG abnormalities may not be observed
(2)
.
Common ECG findings in unstable angina and non ST-segment elevation MI (UA/NSTEMI)
include ST-segment depression, transient ST-segment elevation and T-wave inversion. However
approximately 20% of patients with NSTEMI confirmed by cardiac markers have no ischemic
ECG changes. The limited sensitivity and specificity of 12 lead ECG in diagnosing STEMI is
exemplified by the clinical scenario of isolated anterior ST-segment depression
(2)
. This
electrocardiographic finding can represent pathophysiology across the spectrum of ACS: 1)
plaque rupture with a patent artery and no elevation of cardiac biomarkers leading to UA; 2) a
patent artery supplying the anterior myocardium with elevated cardiac biomarkers (NSTEMI); or
3) acute thrombotic occlusion of the posterior circulation with elevated cardiac biomarkers
(STEMI). Previous studies have demonstrated that acute thrombotic occlusion of a vessel
supplying the posterior wall is particularly challenging to diagnose, both because of its
inconsistent presentation on the ECG and the relatively small contribution of the posterior wall to
the QRS complex in the traditional anterior chest leads
(3)
. In this study, we aimed to evaluate
both angiographic and clinical outcomes in patients with ACS presenting with isolated anterior
ST-segment depression on ECG.
Patients and methods
3
Study design
This single arm longitudinal study included 50 consecutive patients with ACS who were
admitted to the coronary care unit at Shebin Elkom teaching Hospital during the period from
November 2011 to June 2012. All patients had isolated ST segment depression in anterior leads
on admission ECG. We aimed to evaluate both angiographic and clinical outcomes in this
category of patients. Key inclusion criteria were patients with ACS with electrocardiographic
evidence of ≥1mm ST segment depression in leads V1-V4 at least, patients with chest pain of ≥
10 minutes duration. Key exclusion criteria were patients with ST segment depression or
elevation in other leads, patients with hemodynamic or electrical unstability, chronic renal or
hepatic failure, and malignancy.
A) Baseline evaluation
Baseline evaluation included a review of medical history, clinical examination, laboratory
investigations, 12 lead ECG. Review of medical history included: demographic data (age, sex),
risk factors for coronary artery disease (diabetes mellitus, hypertension, smoking, dyslipidemia,
family history of ischemic heart disease), prior medical history (prior myocardial infarction,
unstable angina, heart failure, arrhythmia), prior coronary intervention, cardiac medications.
Cardiac markers including CK, CK-MB, and cardiac Troponins were analyzed on admission and
6 hours later
B) Study medications
All patients received the standard anti-ischemic (B- Blockers, nitrates) and antithrombotic
measures (low molecular weight heparin, aspirin, and loading plus maintenance dose of
clopidogrel)
4
C) Coronary angiography
All patients had coronary angiography which was done according to the standard technique of
cardiac catheterization and angiography. The culprit artery was detected and TIMI Flow was
graded in each patient:
TIMI 0: Complete occlusion with no distal run off.
TIMI I: some penetration of contrast agent beyond the point of obstruction but with poor
distal run off.
TIMI II: perfusion of the entire vessel with good but delayed distal run off.
TIMI III: full perfusion of the entire vessel with normal distal run off.
D) Study protocol
According to TIMI flow grade in the culprit artery and the result of cardiac markers, patients
were sub divided into 3 groups. Group I: TIMI flow grade 0/1 and positive markers, Group II:
TIMI flow grade 2/3 and positive markers, and Group III: TIMI flow grade 2/3 and negative
markers.
E) Study follow up
1- In- Hospital outcome including: mortality, re infarction, recurrent chest pain, arrhythmias,
heart failure.
2- 30 days outcome including all cause mortality, re infarction, heart failure and re ischemia,
and need for target vessel revascularization.
5
Statistical analysis
The data collected were tabulated and analyzed by SPSS version 11. Quantitative data were
expressed as mean ±SD. One way ANOVA test was used for between groups analysis.
Qualitative data were expressed as number and percentage and analyzed by chi-square test. P< 0,
05 was considered to indicate statistical significance.
Results
Study population
The mean age was 50 ± 5.7 years (48± 4.8, 51 ± 6.1, 50 ±2.2, in group I , II , III respectively,
p=0.51 ). Sixty two % were males, 62 % had diabetes mellitus, 52 % were smokers, 36 % had
hypertension, 62 % had dyslipidemia, and 30% had family history of coronary artery disease.
Two % had prior MI, 38 % had prior angina, and 4 % had prior coronary intervention. Between
groups analysis did not show significant difference. Table 1.
6
Table1.Baseline characteristics
variable
All patients
Group I
Group II
Group III
n=50
n=12
n=10
n=28
P
value
Mean ±SD
50±5.7
48±4.8
51±6.1
50±2.2
0.51
Male sex, n(%)
31(62%)
8 (67%)
3 (30%)
20 (71%)
0.66
Diabetes mellitus
31(62%)
9(75%)
6(60%)
16(48%)
0.66
Hypertension
18(36%)
6(50%)
5(50%)
7(25%)
0.20
Smoker
26(52%)
8(66.7%)
3(30%)
15(35.6%)
0.2
Dyslipidemia
31(62%)
8(67%)
5(50%)
18(65%)
0.77
Family history of 15 (30%)
CAD
5(45%)
6(60%)
4(12%)
0.77
Prior MI
1(2%)
0(0%)
0(0%)
1(3.5%)
0.7
Prior angina
19(38%)
7(49%)
6(60%)
6(21%)
0.02
Prior coronary
intervention
2(4%)
0(0%)
0(0%)
2(7%)
0.5
Age, years
CAD= Coronary Artery Disease, MI= myocardial infarction
7
Clinical presentation on admission
Chest pain was the most common symptom (78%) on admission, dyspnea was reported in 12%,
and pulmonary edema in 10%. Between groups analysis did not show significant differences.
ECG on admission
All patients had ST segment depression in the anterior leads, 40% of patients had 1mm ST
segment depression (41%, 40%, 39%, in group I, II, III, respectively, P=0.9) , while 60% had >
1mm ST segment depression (58%, 60%, 61%, in group I, II, III, respectively, p=0.9). 42% of
all patients had ST depression from V1 to V4 (41%, 50%, 39% in group I, II, III, respectively
P=0.4), while 58% had ST depression extending from V1-V6 (58%, 50%, 61%, in group I, II, III,
respectively, p= 0.5) Table 2.
Table 2. ECG on admission
variable
ST segment
All patients
Group I
Group II
Group III
No= 50
No= 12
No= 10
No= 28
P value
21 (42%)
5 (41%)
5 (50%)
11 (39%)
0.4
29 (58%)
7 (58%)
5 (50%)
17 (61%)
0.5
20 (40%)
5 (41%)
4 (40%)
11 (39%)
0.9
30 (60%)
7 (58%)
6 (60%)
17 (61%)
0.9
depression V1-V4
ST segment
depression V1-V6
1mm ST segment
depression
> 1mm ST segment
depression
8
Clinical findings on admission
The mean heart rate was 79±12 bpm, the mean systolic blood pressure was 130±22 mmHg, the
mean diastolic blood pressure was 81 ± 14 mmHg, 18% had third heart sound, 16% had bilateral
basal crepitations, and 18% had systolic murmur. There were no significant differences between
groups.
Cardiac biomarkers
Cardiac troponin T was positive in 22 patients (44%), with a mean value 0.59±0.76 ug/l. The
mean cardiac troponin was 1.2±0.84ug/l, 0.12±0.09ug/l in group I, II respectively (P=0.001).The
mean CK-MB was 45.0±5.54U/L. Between groups analysis showed that CK-MB was 50±10,
40±0.00 U/L in group I, II, respectively, p=0.42.
Angiographic findings
The mean time between admission to CCU and coronary angiography was 72±12 hours, range
from 12 hours to one week. The mean total TIMI flow was 2.5±0.43. The culprit artery was
occluded in 12 (24%) patients with TIMI flow 0/1. TIMI flow grade II/III was reported in 10
patients (20%) in whom subtotal occlusion in the culprit artery was detected. However, 28
patients (56%) had TIMI flow grade II/III without evidence of significant coronary stenosis or
thrombosis. None of patients with occluded culprit artery had negative cardiac markers. Based
on coronary angiography findings and results of cardiac markers, 12 patients (24%) had totally
occluded culprit artery plus positive markers, 10 patients (20%) had TIMI flow II/III with
subtotal occlusion in the culprit artery and positive markers. While 28 patients (56%) patients
had TIMI flow II/III and negative markers. In group I, LCX, LAD, RCA were the culprit artery
in 42%, 33%, 25%, respectively. In group II, LCX, LAD, RCA were the culprit artery in 20%,
9
60%, 20% respectively. There was no significant correlation between the degree of ST segment
depression on ECG and TIMI flow grade on coronary angiography. figure 1.
60%
% of patients
50%
40%
30%
20%
10%
0%
TIMI 0/1+ve. CTNT
TIMI 2/3+ve. CTNT
TIMI 2/3-ve. CTNT
Figure 1 . Combined angiographic and biomarkers findings.
In- Hospital outcome
Recurrent chest pain was reported in 7 (14%) patients, ventricular arrhythmias in 6 (12%)
patients, heart failure developed in 5(10%) patients. In group I , chest pain was reported in 3
(25%) patients, ventricular arrhythmias in 3 (25%) patients, heart failure in 2 (17%) patients. In
group II, chest pain had developed in 2 (20%) patients, arrhythmias in 1 (10%) patient, heart
failure in (10%) patients. In group III, chest pain had developed in 2(7.1%) patients, arrhythmias
in 2 (7.1%) patients, heart failure in 2 (7 %) patients. Between groups analysis did not show
significant differences in the above mentioned adverse events.
10
30 days outcome
There was no mortality during the entire study period. Re-infarction (NSTEMI) was reported in
one patient from group II. Heart failure was reported in 4 patients (2 patients from group I, 1
patient from group II , and 1 patient from group III ). Between groups analysis did not show
significant differences in the above mentioned adverse events.
Discussion
Among ACS patients with anterior ST-segment depression in this study, about one-quarter had an
occluded culprit artery and elevated cardiac biomarkers. However, this was not associated with
worse short term clinical outcome compared to patients with patent culprit artery. In this study,
the mean time from admission to CCU and coronary angiography was 72 hours. It is possible that
a significant improvement in clinical outcome would be observed if the presence of an occluded
artery had been diagnosed at the time of presentation and an emergent intervention was done.
Current American College of Cardiology/American Heart Association guidelines recommend a
door-to-balloon time of less than 90 min for STEMI patients undergoing primary PCI. Multiple
studies have demonstrated that treatment delays result in greater morbidity and mortality (4). This
was in agreement with Pride et al 2010
(5)
who reported that among patients with ACS and
isolated ST segment depression in the anterior leads, 26% had an occluded culprit artery (TIMI
flow grade 0/1) and elevated cardiac troponins. In addition, our findings corroborate findings
from an analysis of NSTEMI patients enrolled in the PARAGON-B (Platelet IIb/IIIa Antagonism
for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network) trial,
in which 27% of patients had an occluded culprit artery at the time of coronary angiography
(6)
.
That such patients were more likely to have culprit lesions in the posterior circulation is not
surprising, as the difficulty in diagnosing MI involving the posterior circulation is well
11
documented
(5)
. Boden et al 1987
, reported that 46% of patients initially classified as having
(7)
anterior non–Q-wave MIs were later found to have posterior STEMI as evidenced by evolution of
ECG changes and cardiac biomarkers.
In this study, LCX, LAD, and RCA were the culprit artery in 42%, 33%, 25% of patients who
had occluded culprit artery respectively. Pride et al 2010 (5), in their study showed that the culprit
artery was most often the left circumflex artery (48%) in this category of patients with ACS and
isolated ST segment depression in the anterior leads. De Winter et al, 2008
(8)
stated that when
left circumflex artery is occluded, myocardial infarction may affect an electrocardiographically
silent area of the heart, and the traditional 12-lead ECG may be entirely normal. However, LAD
was the culprit artery in about one third of our patients with occluded culprit artery. Evidence
from literature suggests that 2% of patients with proximal left anterior descending coronary artery
occlusion may present with anterior ST-segment depression (8)
The mean value of cardiac troponin was higher (1.2±0.84ug/l) in patients with occluded culprit
artery compared to those with patent artery (0.12±0.09 ug/l). This may denote larger infarction
size in patients with occluded culprit artery. Pride et al 2010 (5), reported that peak serum CK-MB
concentrations were 3.3 times the upper limit of normal among patients with an occluded culprit
artery and 1.5 times the upper limit of normal among patients with a patent artery irrespective of
biomarker positivity . When stratified by culprit artery, the difference in enzymatic estimate of
infarct size was significantly higher among patients with an occluded artery regardless of the
artery involved. In our study, we did not report significant differences between groups neither in
hospital nor in 30 days outcomes. This was in disagreement with the results of Pride et al 2010 (5),
who reported that the 30-days incidence of the composite of death and MI was significantly
higher among patients with an occluded artery (8.6%) than among those with a patent culprit
12
artery and either elevated cardiac troponins (6.3%) or not (2.9%) (p = 0.006). Moreover, DeWinter et al 2008
(8)
, in their study, the incidence of MI was significantly higher among patients
with an occluded artery than those with patent artery with either elevated or not elevated cardiac
markers (9%, 6%, 3%) respectively. This discrepancy in results may be explained by the small
sample size in our study (50 patients) when compared to 1198 patients in the study done by Pride
et al 2010 (5).
Conclusion
Among patients with ACS presenting with isolated anterior ST segment depression , about one
quarter of patients had an occluded culprit artery and elevated cardiac markers.
Recommendations
1-
It is reasonable to perform emergency coronary angiography and percutaneous coronary
intervention when available in patients with ACS presented with isolated ST-segment depression
in anterior leads
2-
Larger sample size is recommended in further studies for better assessment of clinical
outcome.
Study limitation
1- Small sample size.
2- Short follow up period.
References
13
1. Alpert J, Thygesen K, Antman E, et al: Myocardial infarction redefined--a consensus document
of The Joint European Society of Cardiology/American College of Cardiology Committee for the
redefinition of myocardial infarction. J Am Coll Cardiol 2000 ;36 (3): 959- 969.
2. Somers M, Brady W, Perron A, et al .The prominent T wave: electrocardiographic differential
diagnosis. Am J Emerg Med 2002; 20(3): 243-251.
3. McClelland A, Owens C, Menown I, et al . Comparison of the 80-lead body surface map to
physician and to 12-lead electrocardiogram in detection of acute myocardial infarction. Am J
Cardiol 2003;92:252-257.
4. Antman E, Aobe D, Armstrong P, et al, ACC/AHA guidelines for the management of patients
with
ST-elevation
myocardial
infarction:
a
report
of
the
American
College
of
Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to
Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).
J Am Coll Cardiol 2004;44:E 1-211.
5. Pride Y, Tung P, Mohanavelu S, et al. Angiographic and clinical outcomes among patients with
acute coronary syndromes presenting with isolated anterior ST-segment depression: a TRITONTIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet
Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) substudy. JACCCardiovasc Interv 2010 ; 3(8):806-811.
6. Wang T, Zhang M, Fu Y. et al. Incidence, distribution, and prognostic impact of occluded culprit
arteries among patients with non-ST-elevation acute coronary syndromes undergoing- diagnostic
angiography. Am Heart J 2009;157: 716-723.
14
7. Boden W, Kleiger R, Gibson R, et al. Electrocardiographic evolution of posterior acute
myocardial infarction: importance of early precordial ST-segment depression. Am J Cardiol
1987;59: 782-787.
8. De Winter R, Verouden N, Wellens H, et al. A new ECG sign of proximal LAD occlusion. N
Engl J Med 2008;359:2071-2073.
15
16
17
18
19
20