Guidelines recommend coronary angiography in patients with non–ST-elevation myocardial infarction (NSTEMI) within 24 to 72 hours, a requirement that cannot always be met. The aim of this study was to evaluate the potential use of contrast echocardiography in prioritizing these patients by identifying those with NSTEMI and angiographically severe coronary artery disease (CAD). Echocardiography was performed before coronary angiography in 110 patients with NSTEMI (67 ± 12 years old, 31% women). Segmental myocardial perfusion and wall motion was scored using a 17-segment left ventricular model. CAD was assessed by quantitative coronary angiography. In the total study population, median troponin T level was 0.27 μg/L (0.13 to 0.86) and Thrombolysis In Myocardial Infarction risk score 3.1 ± 1.5. By quantitative coronary angiography 15% had normal coronary angiographic findings, whereas 1-, 2-, and 3-vessel disease were present in 35%, 27%, and 23%, respectively. Severe CAD (left main stem stenosis, 3-vessel disease, or multivessel disease including proximal stenosis in left anterior descending artery) was found in 42%. Number of segments with hypoperfusion increased with CAD severity from 4.1 ± 2.0 in patients with normal coronary arteries to 5.9 ± 2.4, 7.8 ± 3.5, and 10.4 ± 2.8 in patients with 1-, 2-, and 3-vessel disease, respectively (p <0.01). In multiple logistic regression analysis risk of severe CAD increased by 39% for every additional hypoperfused segment by echocardiography independent of wall motion abnormalities and Thrombolysis In Myocardial Infarction risk score. In conclusion, contrast echocardiography may be used for prediction of angiographic CAD severity in patients with NSTEMI awaiting coronary angiography.
Patients with non–ST elevation acute myocardial infarction (NSTEMI) represent a heterogenous group with different short- and long-term risks for death, complications, and new cardiovascular events. Early invasive treatment has been found cost effective in intermediate- and high-risk patients with NSTEMI, and current guidelines recommend Thrombolysis In Myocardial Infarction (TIMI) risk score to prioritize and identify intermediate- and high-risk patients with NSTEMI. However, the relation between TIMI risk score and angiographic coronary artery disease (CAD) has been less studied, and recent publications have demonstrated that TIMI risk score may underestimate angiographic CAD severity, in particular in patients classified as having intermediate risk. Myocardial perfusion assessment by contrast echocardiography has been demonstrated to improve risk stratification in patients hospitalized with acute chest pain and suspected acute coronary syndrome. The aim of this study was to evaluate the potential use of contrast echocardiography in prioritizing patients with NSTEMI awaiting coronary angiography by identifying patients with angiographically severe CAD.
Methods
In total 204 patients were hospitalized with NSTEMI at the Department of Heart Disease, Haukeland University Hospital from March through December 2008. Hemodynamically unstable patients, patients who developed ST-segment elevation on electrocardiogram, patients with mechanical valve prosthesis or severe pulmonary disease, and patients with NSTEMI in whom coronary angiography was found contraindicated were excluded, leaving 126 patients eligible for the study. Of these, 12 patients declined to participate in the study and another 4 were excluded: 3 patients because of development of hemodynamic unstable disease and 1 patient who refused to undergo planned coronary angiography. Thus, the final study population consisted of 110 consecutive patients with NSTEMI. Cardiovascular risk factors did not differ between the 110 included patients and the total NSTEMI cohort eligible for coronary angiography during the recruitment period. All patients had acute chest pain and/or dyspnea in combination with increased serum troponin T level. All patients gave written informed consent to participate and the study protocol was approved by the regional ethics committee.
Medical history including previous cardiovascular disease and risk factors was recorded at admission. Laboratory testing included repeated measurements of serum troponin T. Serum troponin T >0.03 μg/L was regarded as increased. A 12-lead electrocardiogram was obtained in all patients and interpreted according to current guidelines. Individual TIMI risk score was calculated.
Echocardiography was performed before coronary angiography using an Acuson Sequoia C512 (Siemens, Mountain View, California) echocardiograph. Contrast-enhanced real-time low-mechanical index imaging with destruction replenishment technique was performed using a Cadance Coherent Contrast Imaging System (Siemens). Perflutren Lipid Microsphere ultrasound contrast (Luminity, Lantheus Medical Imaging, North Billerica, Massachusetts) was administered as repeated intravenous bolus doses of Luminity 0.1 to 0.4 ml diluted in saline 50 ml as required to maintain stable contrast enhancement of the left ventricular (LV) cavity. No severe adverse events occurred, but 3 patients reported transient low back pain. Contrast-enhanced LV wall motion and myocardial perfusion were assessed offline by a single experienced reader blinded to demographic data, TIMI risk score, and angiographic findings. Wall motion and myocardial perfusion were visually scored as normal or abnormal in apical 2-, 3-, and 4-chamber views using a 17-segment LV model. LV structure and systolic function were assessed according to American Society of Echocardiography and European Association of Echocardiography standards. Overall, perfusion could not be assessed in 5 LV segments because of rib shadowing and attenuation. Aortic and mitral regurgitations were assessed using color Doppler.
Coronary angiography was performed in all patients and evaluated offline by a digitalized automatic edge detection algorithm (QAngio XA 7.1, MEDIS Medical Imaging Systems, Leiden, the Netherlands). Analysis was performed by 1 reader blinded to echocardiographic results. The tip of the catheter was used for calibration. An artery diameter decrease ≥50% was regarded as significant stenosis. The most severe stenosis in each main coronary artery was reported. Presence of left main stem stenosis, 3-vessel disease, or multivessel disease including the proximal left anterior descending coronary artery was classified as angiographically severe CAD.
Statistical analysis was performed with SPSS 15.0 (SPSS, Inc., Chicago, Illinois). Continuous variables are reported as mean ± SD or median and 25fth to 75fth percentile as appropriate, and categorical variables as number and percentage. Comparison between groups was performed by unpaired t test, chi-square statistics, or analysis of variance with Scheffe post hoc analysis as appropriate. An association between angiographically severe CAD and myocardial hypoperfusion, wall motion abnormality, and TIMI risk score was assessed by logistic regression analysis, reported as odds ratio (OR) and 95% confidence interval (CI), and compared by receiver operator characteristics curve analysis reporting area under the curve with 95% CI. A 2-tailed p value <0.05 was considered statistically significant in uni- and multivariate analyses.
Results
Clinical characteristics of the study population are listed in Table 1 , where 26% of patients had >3 known cardiovascular risk factors. Sixty-six percent had a TIMI risk score >3, consistent with high risk for cardiovascular events. TIMI risk score increased with increasing severity of CAD ( Figure 1 , Table 2 ). LV ejection fraction was well preserved in most patients, but 25% of patients had an ejection fraction <50%. Significant aortic stenosis by Doppler echocardiography was found in 6%, mild aortic regurgitation in 27%, and mild-moderate mitral regurgitation in 30%. Pulmonary hypertension was detected by echocardiography in 5%.
| Thrombolysis In Myocardial Infarction risk score | 3.11 ± 1.49 |
| Age | 67 ± 12 |
| Women | 34 (30%) |
| Previous known coronary artery disease | 38 (35%) |
| Previous myocardial infarction | 33 (30%) |
| Previous coronary artery bypass surgery | 10 (9%) |
| Previous percutaneous coronary intervention | 19 (17%) |
| Family history of coronary artery disease ⁎ | 44 (40%) |
| Hypertension † | 49 (45%) |
| Diabetes mellitus | 21 (19%) |
| Current smoker | 31 (28%) |
| Hypercholesterolemia ‡ | 55 (50%) |
| Electrocardiographic ST depression | 32 (29%) |
| Troponin T level ⁎ | 0.27 (0.13–0.86) |
| Left ventricular ejection fraction (%) | 56 ± 12 |
⁎ First-degree relative with coronary artery disease before age 55 years in men or 65 years in women.
† Blood pressure >140/90 mm Hg or on antihypertensive treatment.
‡ Total cholestreol level >6.5 mmol/L or on cholesterol-lowering treatment.
| Variable | Number of Coronary Arteries Narrowed | |||
|---|---|---|---|---|
| 0 (n = 16) | 1 (n = 39) | 2 (n = 30) | 3 (n = 25) | |
| Thrombolysis In Myocardial Infarction risk score | 2.3 ± 0.9 | 3.3 ± 1.4 | 3.5 ± 1.6 ⁎ | 3.7 ± 1.4 ⁎ |
| Troponin T level (μg/L) | 0.14 (0.06–0.23) | 0.36 (0.17–0.98) | 0.24 (0.09–0.77) | 0.28 (0.18–0.91) |
| Wall motion abnormality (left ventricular segments) | 2.1 ± 3.2 | 3.0 ± 2.6 | 3.9 ± 3.4 | 5.4 ± 4.8 ⁎ |
| Myocardial hypoperfusion (left ventricular segments) | 4.1 ± 2.0 | 5.9 ± 2.4 | 7.8 ± 3.5 † | 10.4 ± 2.8 † ‡ |
† p < 0.01 compared to no significant stenosis group.
Average degree of coronary artery stenosis was 82 ± 14%. Angiographically severe CAD was found in 42% of patients. Troponin T level did not differ among groups of patients with 0-, 1-, 2-, and 3-vessel disease ( Figure 1 , Table 2 ) or between groups of patients with angiographically severe and nonsevere CAD ( Table 3 ). Wall motion abnormality and myocardial hypoperfusion were found in 75% and 99% of patients, respectively. Median number of LV segments with wall motion abnormality was 4 and that with hypoperfusion was 7, respectively. These differed significantly between groups of patients with different extents of angiographic CAD ( Figure 1 , Table 2 ) and between groups of patients with angiographically severe and nonsevere CAD ( Table 3 ).
| Variable | CAD | |
|---|---|---|
| Severe (n = 46) | Nonsevere (n = 64) | |
| Age (years), mean ± SD | 71 ± 12 † | 65 ± 12 |
| Women | 24% | 36% |
| Previous myocardial infarction | 37% | 25% |
| Hypertension | 44% | 45% |
| Diabetes mellitus | 22% | 17% |
| Left ventricular ejection fraction (%) | 53 ± 12 | 56 ± 11 |
| Thrombolysis In Myocardial Infarction risk score | 3.5 ± 1.4 | 3.1 ± 1.4 |
| Troponin T level (μg/L) | 0.25 (0.13–0.65) | 0.30 (0.14–0.96) |
| Wall motion abnormality (segments) | 4.7 ± 4.3 ⁎ | 2.9 ± 2.8 |
| Myocardial hypoperfusion (segments) | 9.1 ± 3.3 † | 5.8 ± 2.9 |
Of the 16 patients without significant CAD, 3 had wall motion abnormality in 1 segment to 2 segments and 4 patients had wall motion abnormality in >2 LV segments. In the latter group, 2 had Takotsubo cardiomyopathy, 1 a coronary thrombus without significant quantitative coronary angiography stenosis, and 1 had undergone percutaneous coronary intervention during a previous MI. In the 2 patients with Takotsubo cardiomyopathy, delayed perfusion in all apical segments involved in the apical ballooning was found. Decreased perfusion was also found in patients with coronary thrombus and previous percutaneous coronary intervention for acute MI consistent with peripheral microembolization affecting microcirculation.
Perfusion scoring by contrast echocardiography (OR 1.40, 95% CI 1.21 to 1.62, p <0.01) and segmental wall motion scoring (OR 1.16, 95% CI 1.03 to 1.30, p <0.05) predicted severe angiographic CAD in univariate logistic regression analysis, whereas TIMI risk score did not (OR 1.25, 95% CI 0.95 to 1.64, p = NS). In multiple logistic regression analysis, risk of having angiographically severe CAD increased by 39% for every additional LV segment with hypoperfusion independent of TIMI risk score and wall motion abnormality ( Table 4 ). Replacing TIMI risk score with the individual score components in a subsequent model did not change the results ( Table 4 ). Perfusion scoring was superior to wall motion scoring in identifying patients with angiographically severe CAD in receiver operator characteristics curve analysis ( Figure 2 ). Combining TIMI risk score >3 and perfusion scoring by contrast echocardiography did not increase the ability to predict severe angiographic CAD ( Figure 2 ). In another multiple logistic regression analysis, ≥6 hypoperfused LV segments by echocardiography was associated with a sevenfold higher risk for having severe angiographic CAD (OR 6.82, 95% CI 2.41 to 19.32, p <0.01) independent of TIMI risk score (OR 1.28, 95% CI 0.94 to 1.73, p = 0.116), and LV ejection fraction (OR 1.02, 95% CI 0.97 to 1.05, p = 0.537).
