Clopidogrel should be initiated as soon as possible in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) except those who urgently require coronary artery bypass grafting (CABG). The present study assessed the ability to predict severe left main coronary artery and/or 3-vessel disease (LM/3VD) that would most likely require urgent CABG based on only clinical factors on admission in 572 patients with NSTE-ACS undergoing coronary angiography. Severe LM/3VD was defined as ≥75% stenosis of LM and/or 3VD with ≥90% stenosis in ≥2 proximal lesions of the left anterior descending coronary artery and other major epicardial arteries. Patients were divided into the 3 groups according to angiographic findings: no LM/3VD (n = 460), LM/3VD but not severe LM/3VD (n = 57), and severe LM/3VD (n = 55). Severe LM/3VD was associated with a higher rate of urgent CABG compared to no LM/3VD and LM/3VD but not severe LM/3VD (46%, 2%, and 2%, p <0.001). On multivariate analysis, degree of ST-segment elevation in lead aVR was the strongest predictor of severe LM/3VD (odds ratio 29.1, p <0.001), followed by positive troponin T level (odds ratio 1.27, p = 0.044). ST-segment elevation ≥1.0 mm in lead aVR best identified severe LM/3VD with 80% sensitivity, 93% specificity, 56% positive predictive value, and 98% negative predictive value. In conclusion, ST-segment elevation ≥1.0 mm in lead aVR on admission electrocardiogram is highly suggestive of severe LM/3VD in patients with NSTE-ACS. Selected patients with this finding might benefit from promptly undergoing angiography, withholding clopidogrel to allow early CABG.
Dual antiplatelet therapy with clopidogrel and aspirin should be initiated as soon as possible in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS). However, such combination therapy can increase perioperative bleeding in patients undergoing early coronary artery bypass grafting (CABG). Therefore, one might consider with-holding clopidogrel until coronary angiography and definition of the coronary anatomy. The proportion of patients with NSTE-ACS who undergo CABG during hospitalization is 9% to 21%. CABG can often be deferred for several days, and few patients require urgent CABG. Ideally, clopidogrel should be withheld in the minority of patients who urgently require CABG and should be given to the remaining majority of patients. We previously examined clinical factors related to left main coronary artery and/or 3-vessel disease (LM/3VD) that would most likely lead to CABG in patients with NSTE-ACS but did not evaluate severity of coronary lesions in that study. In the present study, we assessed the ability to predict “severe” LM/3VD, which would most likely to require urgent CABG, using only clinical factors on admission in patients with NSTE-ACS.
Methods
We studied 572 consecutive patients (mean age 67 ± 11 years, range 30 to 92, 397 men and 175 women) who were admitted to Yokohama City University Medical Center (Yokohama, Japan) coronary care unit and fulfilled the following criteria: (1) typical chest discomfort attributed to cardiac ischemia, lasting ≥5 minutes, occurring within 24 hours before hospital admission, and involving an unstable pattern of pain including pain at rest, new onset, severe or frequent angina, or accelerating angina ; (2) no conditions precluding evaluation ST-segment changes on electrocardiogram (ECG) such as left or right bundle branch block, left ventricular hypertrophy, or ventricular pacing; (3) fully assessable ECGs on admission; and (4) fully assessable angiographic data during hospitalization. We excluded patients with nonischemic or atypical pain, persistent new ST-segment elevation in leads other than lead aVR, recent (<6 months) percutaneous coronary intervention, or previous CABG. All patients gave informed consent. The study protocol was approved by the internal review board of Yokohama City University Medical Center.
Standard 12-lead ECGs were recorded on admission at a paper speed of 25 mm/s and an amplification of 10 mm/mV. All ECGs were examined by a single investigator who was blinded to all other clinical data. ST-segment shifts were measured 80 ms after the J-point for ST-segment depression and 20 ms after this point for ST-segment elevation using the preceding TP segment as a baseline. ST-segment deviation was considered present if deviation was ≥0.5 mm in any lead.
A qualitative assay for cardiac-specific troponin T (detection limit 0.1 ng/ml of cardiac-specific troponin T; Roche Diagnostics, Tokyo, Japan) was performed on admission. Troponin T ≥0.1 ng/ml was defined as positive. Blood samples for measuring hemoglobin, plasma high-sensitivity C-reactive protein levels, and estimated glomerular filtration rate were also taken on admission. Japanese equations were used to calculate estimated glomerular filtration rate from serum creatinine level. Brain natriuretic peptide was simultaneously measured in 360 patients. Creatine kinase-MB levels were measured on admission, at 3-hour intervals during the first 24 hours, and in any patient with suspected reinfarction.
All patients underwent cardiac catheterization a median of 3 days after admission. Urgent cardiac catheterization was performed in patients with unstable hemodynamics from ischemic attacks or with ischemic attacks that could not be controlled by intensive drug treatment. Type and timing of revascularization were left to the discretion of the treating physician. All coronary angiograms were evaluated by a single investigator who was blinded to all other clinical data. Stenosis ≥50% in the diameter of the LM or stenosis of ≥75% in ≥1 major epicardial vessel or its main branches was considered clinically significant. Severe LM/3VD was defined as (1) ≥75% stenosis of the LM, (2) 3VD with ≥90% stenosis of the proximal portion of the left anterior descending coronary artery and ≥90% stenosis of the right coronary artery and/or left circumflex coronary artery, and (3) definitions 1 and 2. Patients were categorize according to presence (n = 112) or absence (n = 460) of LM/3VD, and the former group was subdivided according to severity of coronary lesions: nonsevere LM/3VD (n = 57) and severe LM/3VD (n = 55).
Demographic data, risk factors for coronary artery disease, and data from physical examination on admission were collected. Major adverse events such as death, myocardial (re)infarction, or urgent revascularization were also recorded for all patients. Myocardial infarction was diagnosed according to cardiac enzyme levels or electrocardiographic criteria. Enzymatic evidence of myocardial infarction was defined as an increase of creatine kinase-MB to higher than the upper limit of normal if the previous creatine kinase-MB level was in the normal range or 50% above the previous level if the previous level was above the normal range. Electrocardiographic evidence of myocardial infarction was defined as new clinically significant Q waves in ≥2 contiguous leads distinct from the enrollment myocardial infarction. Patients were followed for 30 days after admission.
Results are expressed as mean ± SD or as frequency (percentage), and high-sensitivity C-reactive protein and brain natriuretic peptide levels are expressed as median and interquartile range. Data were compared by 1-way analysis of variance, Kruskal-Wallis test, and chi-square analysis. Differences were considered statistically significant at p value <0.05. Multivariate logistic regression analysis was used to identify clinical predictors of severe LM/3VD among the variables associated (p <0.05) with this diagnosis on univariate analysis. Odds ratios and 95% confidence intervals were calculated. In addition, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy of predictors of severe LM/3VD identified on multivariate analysis were determined. SPSS statistical software (SPSS, Inc., Chicago, Illinois) was used for all analyses.
Results
Baseline characteristics are listed in Table 1 . Patients with LM/3VD, especially severe LM/3VD, had a more rapid heart rate, higher prevalences of Killip class ≥II, diabetes mellitus, positive troponin T, and higher levels of high-sensitivity C-reactive protein, creatine kinase-MB, and brain natriuretic peptide than did patients without LM/3VD. LM/3VD was associated with lower levels of hemoglobin and estimated glomerular filtration rate. There were no significant differences in other clinical variables among the 3 groups.
| LM/3VD | p Value | |||
|---|---|---|---|---|
| No LM/3VD | Nonsevere | Severe | ||
| (n = 460) | (n = 57) | (n = 55) | ||
| Age (years) | 66 ± 11 | 69 ± 10 | 68 ± 11 | 0.06 |
| Men | 322 (70%) | 39 (68%) | 36 (66%) | 0.78 |
| Systolic blood pressure on admission (mm Hg) | 150 ± 25 | 150 ± 32 | 141 ± 26 | 0.07 |
| Heart rate on admission (beats/min) | 76 ± 17 | 81 ± 20 | 89 ± 23 | <0.001 |
| Killip class ≥II on admission | 26 (6%) | 9 (16%) | 17 (31%) | <0.001 |
| Symptom onset ≤6 hours | 356 (78%) | 43 (75%) | 49 (89%) | 0.13 |
| Previous myocardial infarction | 86 (19%) | 18 (32%) | 12 (22%) | 0.07 |
| Previous percutaneous coronary intervention | 90 (20%) | 15 (26%) | 5 (9%) | 0.06 |
| Risk factors | ||||
| Hypertension | 304 (66%) | 42 (74%) | 38 (69%) | 0.49 |
| Diabetes mellitus | 136 (30%) | 29 (51%) | 30 (55%) | <0.001 |
| Smoking | 229 (50%) | 22 (39%) | 23 (42%) | 0.18 |
| Hyperlipidemia ⁎ | 230 (50%) | 25 (44%) | 29 (53%) | 0.61 |
| Family history of coronary artery disease | 120 (26%) | 13 (23%) | 16 (29%) | 0.75 |
| Hemoglobin on admission (g/dl) | 14 ± 2 | 13 ± 2 | 13 ± 2 | 0.033 |
| High-sensitivity C-reactive protein on admission (mg/dl) | 0.131 (0.061–0.323) | 0.180 (0.079–0.453) | 0.253 (0.099–0.801) | 0.005 |
| Positive troponin T on admission | 135 (29%) | 28 (49%) | 33 (60%) | <0.001 |
| Creatine kinase-MB on admission (IU/L) | 14 ± 16 | 18 ± 24 | 27 ± 36 | <0.001 |
| Estimated glomerular filtration rate on admission (ml/min/1.73 m 2 ) | 68 ± 25 | 58 ± 28 | 58 ± 26 | 0.004 |
| Brain natriuretic peptide on admission (pg/ml) † | 67 (26–179) | 187 (81–429) | 230 (67–571) | <0.001 |
| (n = 297) | (n = 32) | (n = 31) | ||
| Cardiac procedures and outcomes at 30 days | ||||
| Death | 1 (0.2%) | 1 (2%) | 2 (4%) | 0.010 |
| Myocardial (re)infarction | 14 (3%) | 3 (5%) | 5 (9%) | 0.23 |
| Death/myocardial (re)infarction | 15 (3%) | 4 (7%) | 7 (13%) | 0.004 |
| Urgent percutaneous coronary intervention | 29 (6%) | 7 (12%) | 5 (9%) | 0.22 |
| Urgent coronary artery bypass surgery | 7 (2%) | 1 (2%) | 25 (46%) | <0.001 |
| Urgent revascularization (percutaneous coronary intervention or coronary artery bypass surgery) | 36 (8%) | 8 (14%) | 30 (55%) | <0.001 |
| Cardiac procedures | ||||
| Percutaneous coronary intervention | 272 (59%) | 36 (63%) | 14 (25%) | <0.001 |
| Coronary artery bypass surgery | 27 (6%) | 13 (23%) | 40 (73%) | <0.001 |
| Any revascularization (percutaneous coronary intervention or coronary artery bypass surgery) | 291 (63%) | 49 (86%) | 54 (98%) | <0.001 |
⁎ Fasting total cholesterol concentration ≥220 mg/dl, fasting triglyceride concentration ≥150 mg/dl, or use of antihyperlipidemic therapy.
Urgent CABG was more frequently done in patients with severe LM/3VD (46%). In contrast, urgent CABG was done in only 2% of patients with LM/3VD but not severe LM/3VD.
Electrocardiographic findings are presented in Table 2 . Compared to patients without LM/3VD, those with LM/3VD, especially severe LM/3VD, had a higher prevalence and a larger amount of ST-segment depression, a larger number of leads other than lead aVR with ST-segment depression, and a higher prevalence and greater magnitude of ST-segment elevation in lead aVR. Figure 1 shows a representative ECG of a patient with severe LM/3VD.
| Variable | LM/3VD | p Value | ||
|---|---|---|---|---|
| No LM/3VD | Nonsevere | Severe | ||
| (n = 460) | (n = 57) | (n = 55) | ||
| ST-segment depression ≥0.5 mm | 288 (63%) | 53 (93%) | 55 (100%) | <0.001 |
| Maximal ST-segment depression (mm) | 0.8 ± 1.0 | 1.7 ± 1.1 | 2.6 ± 1.7 | <0.001 |
| Sum of ST-segment depressions (mm) | 2.6 ± 3.6 | 6.7 ± 5.1 | 10.5 ± 7.3 | <0.001 |
| Number of leads with ST-segment depression ≥0.5 mm | 2.5 ± 2.5 | 5.1 ± 2.6 | 6.1 ± 2.2 | <0.001 |
| ST-segment elevation ≥0.5 mm in lead aVR | 68 (15%) | 39 (68%) | 50 (91%) | <0.001 |
| ST-segment elevation in lead aVR (mm) | 0.1 ± 0.3 | 0.6 ± 0.5 | 1.2 ± 0.7 | <0.001 |
In multivariate models, degree of ST-segment elevation in lead aVR was the strongest predictor of severe LM/3VD, followed by positive troponin T ( Table 3 ). Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy of ST-segment elevation in lead aVR and positive troponin T for severe LM/3VD are presented in Table 4 . ST-segment elevation ≥1.0 mm in lead aVR best identified severe LM/3VD.
| Variable | Odds Ratio (95% CI) | p Value | |
|---|---|---|---|
| Univariate | Multivariate | ||
| Systolic blood pressure | 0.020 | 0.07 | |
| Heart rate | <0.001 | 0.29 | |
| Killip class ≥II | <0.001 | 0.29 | |
| Previous percutaneous coronary intervention | 0.045 | 0.80 | |
| Diabetes mellitus | 0.001 | 0.08 | |
| High-sensitivity C-reactive protein | <0.001 | 0.30 | |
| Positive troponin T | 1.27 (1.10–2.78) | <0.001 | 0.044 |
| Creatine kinase-MB | <0.001 | 0.33 | |
| Estimated glomerular filtration rate | <0.001 | 0.32 | |
| Maximal ST-segment depression | <0.001 | 0.053 | |
| Sum of ST-segment depressions | <0.001 | 0.055 | |
| Number of leads with ST-segment depression ≥0.5 mm | <0.001 | 0.24 | |
| Degree of ST-segment elevation in lead aVR | 29.1 (9.54–49.8) | <0.001 | <0.001 |
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