17 November 2015: Clinical Research
Relation of Angiographic Thrombus Burden with Severity of Coronary Artery Disease in Patients with ST Segment Elevation Myocardial Infarction
Hakan Duman A , Mustafa Çetin F , Murtaza Emre Durakoğlugil E , Hüsnü Değirmenci C , Hikmet Hamur D , Mehmet Bostan B , Zakir Karadağ D , Yüksel Çiçek B
DOI: 10.12659/MSM.895157
Med Sci Monit 2015; 21:3540-3546
Abstract
BACKGROUND: We planned to investigate the relationship of thrombus burden with SYNTAX score in patients with ST elevation myocardial infarction (STEMI).
MATERIAL AND METHODS: We retrospectively enrolled 780 patients who underwent PPCI in our clinic due to STEMI. Clinical, laboratory, and demographic properties of the patients were recorded. Angiographic coronary thrombus burden was classified using thrombolysis in myocardial infarction (TIMI) thrombus grades.
RESULTS: Patients with high thrombus burden were older, with higher diabetes prevalence longer pain to balloon time, higher leukocyte count, higher admission troponin, and admission CK-MB concentrations. SYNTAX score was higher and myocardial perfusion grades were lower in patients with high thrombus burden. Multivariate logistic regression analysis revealed SYNTAX score as the strongest predictor of thrombus burden. ROC analysis demonstrated a sensitivity of 75.5%, specificity of 61.2%, and cut-off value of >14 (area under the curve (AUC): 0.702; 95% confidence interval [CI]: 0.773–0.874;P<0.001) for high thrombus burden.
CONCLUSIONS: SYNTAX score may have additional value in predicting higher thrombus burden besides being a marker of coronary artery disease severity and complexity.
Keywords: Biomarkers - blood, Coronary Angiography, Coronary Artery Disease - surgery, Forecasting, Myocardial Infarction - surgery, percutaneous coronary intervention, ROC Curve, Thrombosis - pathology
Background
ST segment elevation myocardial infarction (STEMI) is still an important cause of cardiovascular mortality, and morbidity. Without doubt, coronary thrombosis is the main physiopathologic mechanism of STEMI. Moreover, higher thrombotic burden in infarct related artery (IRA) is related to stent thrombosis, distal embolization, no-reflow phenomenon, and long-term mortality [1–4].
No-reflow phenomenon poses as a major problem in patients with STEMI undergoing primary percutaneous coronary intervention (primary PCI, PPCI). Although the thrombotic lesion in IRA is successfully stented, tissue level perfusion remains low with increased cardiovascular morbidity, and mortality [5,6]. Thus, identification of factors that could increase no-reflow and potential remedies of this phenomenon is clinically significant.
SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score is an angiographic scoring system, which grades coronary artery disease severity and complexity [7]. Even though SYNTAX score is primary utilized for selection of elective revascularization strategies, there is growing data implicating additional clinical value in STEMI. Recent studies revealed that pre-PPCI SYNTAX score is associated with no-reflow phenomenon and long-term mortality in STEMI [8–11]. Moreover, SYNTAX score independently predicted angiographically visible distal embolization in patients undergoing PPCI [12]. These results implicate an association between pre-PPCI thrombus burden and SYNTAX score. Therefore, we planned to investigate this relationship in patients with STEMI.
Material and Methods
STUDY POPULATION:
We retrospectively enrolled 780 patients who underwent PPCI in our clinic due to STEMI between April 2009 and February 2015. Our study was approved by the local ethics board.
Our study included patients who had the diagnosis of STEMI according to recent STEMI guideline, and underwent PPCI [13]. The clinical, demographic, and laboratory data of the patients were obtained using patient records and registries. Heart rate, Killip class, previous medications, pain to balloon time and door to balloon time, serum creatinine, lipid panel, and hematological indices of all patients were recorded during hospital admission. Data regarding coronary angiography were gathered through re-evaluation of stored media. The patients were treated according to relevant guidelines [13,14]. Tirofiban was used at a dose of 10 mg/kg bolus and 0.15 mg/kg/min intravenous infusion if preferred by the physician. Experienced operators performed all PPCI procedures.
We excluded cases that underwent fibrinolytic therapy (n=15), emergent cardiovascular bypass surgery (n=18), and patients with end stage renal failure (n=11), malignancy (n=3), culprit left main coronary lesion (n=3), and spontaneous coronary dissection (n=1).
SYNTAX score was calculated using SYNTAX Score Calculator 2.11 software downloaded from http://www.syntaxscore.com [7,15].
CLINICAL DEFINITIONS:
Hypertension was defined as systemic blood pressure >140/90 mmHg or the use of antihypertensive medication. Hypercholesterolemia was accepted if a serum total cholesterol level >200 mg/dL, or with the use of a cholesterol lowering agent. Diabetes mellitus was acknowledged as an HbA1c >6.5%, a plasma glucose level ≥126 mg/dL (7.0 mmol/L) after an overnight fast, or the use of antidiabetic medications. Positive family history of coronary artery disease was defined as documented evidence of premature coronary artery disease in a first degree relative (men <55 and women <65 years of age).
Killip Classification was noted as follows: Class I: No evidence of heart failure. Class II: Findings of mild to moderate heart failure (S3 gallop, rales < half-way up lung fields or elevated jugular venous pressure). Class III: Pulmonary edema. Class IV: Cardiogenic shock defined as systolic blood pressure <90 and signs of hypoperfusion such as oliguria, cyanosis, and sweating.
ANGIOGRAPHIC DEFINITIONS:
Three experienced investigators who were blinded to clinical parameters of the patients’ carefully reviewed coronary angiograms. The TIMI flow grades were determined by the consensus of the three investigators. Angiographic thrombus burden was classified as follows: Grade 0: no thrombus, Grade 1: Possible thrombus, Grade 2: the thrombus’ greatest dimension is <1/2 vessel diameter, Grade 3: Greatest dimension >1/2 to <2 vessel diameters, Grade 4: Greatest dimension >2 vessel diameters, Grade 5: total vessel occlusion due to thrombus [3]. The patients were stratified into low thrombus burden (Grades 1, 2 and 3) and high thrombus burden groups (4 and 5) according to final thrombus score.
Postprocedural final thrombolysis in myocardial infarction (TIMI) flow grade, TIMI myocardial perfusion grade (TMPG), corrected TIMI frame count (cTFC), and TMPG were noted as previously defined. [16–18]. TIMI flow grade <3, and final myocardial blush grade <2 were described as angiographic no-reflow.[19].
STATISTICAL ANALYSES:
Continuous variables are expressed as mean ± standard deviation, whereas categorical variables are expressed as percentage. Comparison between groups was made using the Student t test, Mann-Whitney U test or chi-square tests, as appropriate. Multiple logistic regression analysis was performed to identify the independent predictors of high thrombus burden using variables. Two-tailed P values <.05 were considered to indicate statistical significance. Statistical analyses were performed using SPSS, version 18.0 for Windows. In order to predict cutoff value of SYNTAX score, receiver operating characteristics (ROC) curve analysis was performed by MedCalc statistic software (version 13.2.0, Mariakerke, Belgium).
Results
The study population consisted of 780 patients with STEMI (mean age 56±11, 52.8% male). The mean SYNTAX score was 18±9.5. We formed two groups according to the final TIMI thrombus grade; 299 (%38.3) patients had low thrombus burden whereas 481 subjects (%61.7) had high thrombus burden. The comparisons of basic clinical and laboratory findings between groups thrombus burden were presented in Table 1. Patients with high thrombus burden were older (57.1
The discriminatory value of SYNTAX score for high thrombus burden was assessed by ROC analysis and revealed a sensitivity of 75.5%, specificity of 61.2%, and cut-off value of >14 (area under the curve (AUC): 0.702; 95% confidence interval [CI]: 0.773–0.874; P<0.001) (Figure 1).
Multivariate logistic regression analysis was performed in order to determine the independent predictors of high thrombus burden. SYNTAX score (odds ratio: 2.45,95% confidence interval: 1.36–4.39, P <0.001), age (odds ratio: 1.01,95% confidence interval: 1.00–1.03, P <0.01), DM (odds ratio: 0.58, 95% confidence interval: 0.58–0.40, P <0.004), WBC (odds ratio: 1.11,95% confidence interval: 1.04–1.18, P<0.001), baseline troponin levels (odds ratio: 1.16, 95% confidence interval: 1.05–1.29, P<0.004) were found as significant independent predictors for HTB in patients with STEMI (Table 3).
Discussion
LIMITATIONS:
The main limitation of our study is the retrospective design. We could not assess inflammation by using additional markers such as high-sensitive C reactive protein. Even though we utilized the TIMI thrombus grade, a well-known and widely used classification, this grading may not be the perfect and ideal. Lastly, we did not utilize thrombus aspiration in our study.
Conclusions
Age, diabetes mellitus, admission troponin and leukocyte concentrations, and SYNTAX score are independently associated with TIMI thrombus burden in patients undergoing PPCI for STEMI. Angiographic no-reflow is more frequent in patients with high thrombus burden. SYNTAX score may have additional value in predicting higher thrombus burden besides being a marker of coronary artery disease severity and complexity.
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