The no-reflow phenomenon has been shown to have a significant effect on clinical outcomes in patients with acute ST-segment elevation myocardial infarction. Angiographic features incorporated in the SYNTAX Score (SXScore) obtained on diagnostic angiography during primary percutaneous coronary intervention (PPCI) may be associated with the occurrence of myocardial no-reflow. The aim of this study was to assess the ability of the SXScore to predict no-reflow during PPCI. The SXScore was applied to 669 consecutive patients presenting with acute ST-segment elevation myocardial infarction from November 2006 to February 2008. Angiographic analysis of the PPCI procedure was used to determine no-reflow. The median SXScore was 16 (range 9.5 to 23). No-reflow occurred in 77 patients (12%). On univariate logistic regression analysis, the SXScore showed a strong association (for each 10-unit increase in SXScore, odds ratio 1.42, 95% confidence interval 1.16 to 1.76, p <0.001). On multivariate logistic regression in a model including clinical variables, SXScore was an independent predictor of no-reflow (odds ratio 1.29, 95% confidence interval 1.02 to 1.63, p <0.001). Classification and regression tree analysis identified SXScore >21 as the best cutoff, with patients having double the risk for no-reflow compared to those with SXScore ≤21 (events 9% vs 18%, p = 0.006). In conclusion, the SXScore obtained in the diagnostic phase of PPCI for acute ST-segment elevation myocardial infarction can identify patients at risk for developing no-reflow.
Myocardial no-reflow after primary percutaneous coronary intervention (PPCI) is associated with a increased incidence of clinical events and a poor survival rate after acute ST-segment elevation myocardial infarction (STEMI). Patients at high risk for no-reflow include older subjects, those with previous coronary artery bypass surgery, and those presenting with higher Killip classes and longer ischemic times. Angiographic characteristics of patients with STEMI at higher risk for subsequent no-reflow include occlusion of the infarct-related artery (IRA), a high thrombus burden, saphenous graft as the culprit vessel, and multivessel disease. Such angiographic characteristics can be quantified by the SYNTAX Score (SXScore). The SXScore obtained in the diagnostic phase of PPCI, incorporates information including the patency of the IRA, the area of myocardium at risk supplied by the culprit vessel at the level of occlusion, as well as information on the complexity of the lesion and extent and severity of coronary artery disease. Patients with STEMI with high SXScores are at increased risk for adverse events, including mortality, and the prognostic value of the score is independent and additive to other risk scores based on clinical variables such as the Thrombolysis In Myocardial Infarction (TIMI) and Primary Angioplasty in Myocardial Infarction (PAMI) scores. The mechanisms that relate a high SXScore to adverse cardiovascular events in this patient population are unclear and may in part be mediated by a higher rate of failure to achieve adequate myocardial reperfusion during PPCI. We hypothesized that with its additional angiographic characterization of patients presenting for PPCI, the SXScore can stratify patients at risk for developing myocardial no-reflow.
Methods
From November 2006 to February 2008, 736 consecutive patients who underwent PPCI for STEMI at our institution were screened for inclusion in the MI SXScore study. All patients in the referral area of the Thoraxcenter, Erasmus Medical Center (Rotterdam, The Netherlands) who had symptoms of acute myocardial infarction (<12 hrs duration) were assessed clinically and using 12-lead electrocardiography by paramedical personnel or peripheral hospital medical staff members. Pretreatment with aspirin, clopidogrel, and heparin was administered before hospital admission. Urgent diagnostic angiography was followed by PPCI using standard techniques. Drug-eluting stents were implanted as the first-line choice of stent. Treatment for complications such as cardiogenic shock and cardiac arrest was performed according to guidelines.
The SXScore was calculated as previously described. In short, SXScore I was obtained from the diagnostic angiogram before any intervention, and SXScore II was calculated after wiring the IRA. The principal difference between SXScore I and SXScore II is a reduction of 5 points attributed to total occlusion of the IRA in patients in whom simple wiring of the occluded vessel resulted in restoration of TIMI flow of 2 or 3. Patients with previous coronary artery bypass grafting in whom the SXScore could not be calculated were excluded from the study. All coronary lesions with diameter stenoses ≥50% in vessels ≥1.5 mm were scored using the SXScore algorithm, which is available at http://www.syntaxscore.com . The SXScore for each patient was calculated by a team of 2 interventional cardiologists. In case of disagreement with regard to the significance of a lesion, quantitative coronary angiography was applied, and the lesion was included if it was ≥50% stenosis. On agreement between the 2 cardiologists, the data were entered into a dedicated software program.
The investigators calculating the SXScores were blinded to patients’ clinical characteristics. The scoring was done prospectively at each stage so that the investigators were blinded to the next-stage film, to the procedural data, and to the clinical outcomes. No changes in values were allowed once scores were assigned. In this study, SXScore I was the score of interest, because we hypothesized that the score obtained in the diagnostic or preintervention phase is associated with no-reflow. Therefore, unless stated otherwise, “SXScore” refers to SXScore I.
TIMI flow and corrected TIMI frame count were assessed as previously reported. Myocardial blush grade was assigned as described by van ‘t Hof et al. Angiographic epicardial artery no-reflow was defined as an acute temporary or persistent reduction in coronary flow (TIMI flow grade 0 or 1) in the absence of dissection, thrombus, spasm, or high-grade residual stenosis at the target lesion. Slow flow was recorded if there was a temporary reduction from TIMI flow grade 3 to grade 2. Distal embolization was defined as visible downstream movement of a contrast filling defect from the site of the culprit lesion. Distal occlusion was defined as a distal filling defect with an abrupt “cutoff” in one of the peripheral coronary artery branches of the infarct-related vessel distal to the site of angioplasty.
Survival data for all patients were obtained from the municipal registry. A health questionnaire was subsequently sent to all living patients with specific questions on re-admission and major adverse cardiac events. For patients with adverse events at other centers, medical records, discharge summaries and, when necessary, angiographic films were systematically reviewed. General practitioners, referring cardiologists, and patients were contacted as necessary for additional information. Events were adjudicated by 2 experienced interventional cardiologists according to the following definitions. STEMI was diagnosed when patients had symptoms of acute myocardial infarction lasting ≥30 minutes and accompanied by >1-mm (0.1-mV) ST-segment elevation in ≥2 contiguous leads and later confirmed by creatine kinase and creatine kinase-MB increases and/or troponin increase. Target vessel revascularization was defined as any percutaneous coronary intervention of the index IRA. Major adverse cardiac events were defined as a composite of death, recurrent myocardial infarction, and target vessel revascularization.
The no-reflow phenomenon was defined by ≥1 of the following: final TIMI flow grade <3, final myocardial blush grade <2, temporary epicardial coronary no-reflow, distal coronary occlusion, and a final corrected TIMI frame count of >100 frames/s.
Continuous variables are expressed as mean ± SD or as medians and interquartile ranges, and categorical variables are presented as absolute numbers and percentage. Continuous variables were compared using Student’s unpaired t tests or Mann-Whitney nonparametric U tests. Categorical variables were compared using chi-square statistics or Fisher’s exact tests as appropriate. Observed unadjusted and adjusted measures of association were obtained using logistic regression models and are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Separate logistic regression analyses were performed to identify independent predictors of no-reflow using all clinical variables. These univariate predictors were entered into a second logistic regression model to obtain the adjusted OR. The multivariate model consisted of SXScore and the clinical variables: age, gender, out-of-hospital cardiac arrest, Killip class, cardiogenic shock, pulse rate, and blood pressure. The effects of procedural characteristics, including thrombus aspiration, glycoprotein IIb/IIIa inhibitor use, and balloon predilatation and postdilatation, on no-reflow and on the relation of SXScore and no-reflow were further explored using a Cox regression model including these variables. Classification and regression tree analysis was performed to determine the best SXScore value cutoff that stratified patients at high versus low risk for developing no-reflow. To assess which of the angiographic characteristics best affected the association of SXScore and no-reflow, a separate logistic regression analysis in a multivariate model with the angiographic variables IRA, TIMI flow before wiring, thrombus grade after wiring, number of vessels diseased, chronic total occlusion, and bifurcation was performed.
The cumulative incidence of adverse events according to the presence of no-reflow was estimated according to the Kaplan-Meier method, and curves were compared using the log-rank test. A p value <0.05 was considered to indicate statistical significance. All statistical analyses were performed using SPSS version 17.0 (SPSS, Inc., Chicago, Illinois).
Results
From the initial 736 patients screened, 27 were excluded because of unavailability of a complete diagnostic coronary angiogram, and 21 were excluded because they had undergone previous coronary artery bypass grafting. Survival status and follow-up could not be obtained in 19 patients. Thus, the final number of patients included in our analysis was 669. The median SXScore was 16 (range 9.5 to 23). Differences in the baseline clinical characteristics in patients with low and high SXScores are listed in Table 1 . Patients with a higher SXScores (≥16) were older, more often male, and more often had type 2 diabetes, and smoking and previous myocardial infarction were more prevalent in this group. Patients presenting in the acute phase with higher pulse rates, cardiogenic shock, and higher Killip classes more often had higher SXScores.
| Variable | Lower SXScore (<16) | Higher SXScore (≥16) | p Value |
|---|---|---|---|
| (n = 332) | (n = 337) | ||
| Age (years) | 63 ± 13 | 67 ± 12 | <0.01 |
| Men | 221 (67%) | 248 (74%) | 0.047 |
| Diabetes mellitus | 22 (7%) | 41 (12%) | 0.014 |
| Type I | 11 (3%) | 17 (5%) | 0.26 |
| Type II | 12 (4%) | 25 (7%) | 0.03 |
| Hypertension | 101 (30%) | 123 (37%) | 0.096 |
| Hypercholesterolemia ⁎ | 64 (19%) | 76 (23%) | 0.3 |
| Smokers | |||
| Current | 155 (47%) | 125 (37%) | 0.012 |
| Former | 46 (14%) | 45 (13%) | 0.036 |
| Renal failure † | 4 (1%) | 14 (4%) | 0.018 |
| Family history of coronary artery disease | 121 (36%) | 89 (26%) | <0.01 |
| Body mass index (kg/m 2 ) | 27 ± 4 | 27 ± 4 | 0.74 |
| Previous myocardial infarction | 25 (8%) | 60 (18%) | <0.01 |
| Previous percutaneous coronary intervention | 30 (9%) | 34 (10%) | 0.64 |
| Symptom onset–to–balloon time >90 minutes | 257 (84%) | 264 (87%) | 0.27 |
| Out-of-hospital cardiac arrest | 13 (4%) | 18 (5%) | 0.38 |
| Pulse rate (beats/min) | 77 ± 16 | 80 ± 19 | 0.037 |
| Blood pressure (mm Hg) | |||
| Systolic | 124 ± 26 | 123 ± 27 | 0.29 |
| Diastolic | 75 ± 14 | 75 ± 16 | 0.45 |
| Cardiogenic shock | 19 (6%) | 36 (11%) | 0.02 |
| Killip class 2–4 | 18 (5%) | 34 (10%) | 0.024 |
⁎ Fasting total serum cholesterol level >5.5 mmol/L (210 mg/dl) or use of lipid-lowering therapy.
Table 2 lists the differences in angiographic and procedural characteristics between patients with low and high SXScores. The left main stem and the left anterior descending coronary artery were more commonly the culprit vessels in patients with high SXScores, whereas the left circumflex coronary artery and the right coronary artery were more commonly the IRAs in low-SXScore patients. Furthermore, the IRA more often had poor anterograde flow (TIMI grade 0 or 1) in patients with high SXScores. Multivessel disease, chronic total occlusions, and bifurcations were more often present in patients with higher scores, and this reflected a higher rate of multivessel and bifurcation stenting and a longer total stent length implanted. There was no difference in the procedural use of thrombectomy, glycoprotein IIb/IIIa inhibitors, or balloon predilatation or postdilatation between the 2 groups. The use of an intra-aortic balloon pump was necessary in twice as many patients with SXScores ≥16 compared with those with scores <16.
| Variable | Lower SXScore (<16) | Higher SXScore (≥16) | p Value |
|---|---|---|---|
| (n = 332) | (n = 337) | ||
| Anterior STEMI | 127 (38%) | 177 (53%) | <0.001 |
| Infarct-related coronary artery | |||
| Left main | 6 (2%) | 36 (11%) | <0.01 |
| Left anterior descending | 111 (34%) | 169 (50%) | <0.01 |
| Left circumflex | 63 (19%) | 46 (14%) | 0.06 |
| Right | 156 (47%) | 119 (35%) | <0.01 |
| Initial TIMI flow grade 0 or 1 in IRA | 157 (48%) | 253 (75%) | <0.01 |
| Stent thrombosis (cause) | 12 (4%) | 13 (4%) | 0.86 |
| Number of diseased coronary arteries | |||
| 1 | 222 (67%) | 59 (18%) | <0.01 |
| 2 | 91 (27%) | 115 (34%) | 0.06 |
| 3 ⁎ | 18 (5%) | 163 (48%) | <0.01 |
| Left main disease | 6 (2%) | 36 (11%) | <0.01 |
| Chronic total occlusion | 4 (1%) | 42 (13%) | <0.01 |
| Stent implantation | 311 (94%) | 305 (91%) | 0.096 |
| Balloon predilatation | 60 (18%) | 60 (17%) | 0.91 |
| Total stent length (mm) | 28 (18–40) | 30 (23–51) | <0.01 |
| Stent diameter (mm) | 3.0 ± 0.5 | 3.0 ± 0.5 | 0.83 |
| Bifurcation treatment in IRA | 47 (14%) | 76 (23%) | <0.01 |
| Balloon postdilatation | 63 (19%) | 61 (18%) | 0.73 |
| Thrombectomy | 62 (19%) | 62 (19%) | 0.93 |
| Glycoprotein IIb/IIIa inhibitors | 73 (22%) | 74 (22%) | 0.99 |
| Inotropic agents | 14 (4%) | 17 (5%) | 0.61 |
| Intra-aortic balloon pump | 15 (5%) | 30 (9%) | 0.024 |
| Multivessel stenting | 26 (8%) | 43 (13%) | 0.036 |
| Final TIMI flow grade 0 or 1 | 7 (2%) | 21 (6%) | <0.01 |
| Corrected TIMI frame count at end (frames/s) | 24 (16–36) | 26 (18–40) | 0.052 |
| Myocardial blush grade 0 or 1 | 3 (1%) | 19 (6%) | <0.01 |
⁎ Includes patients with left main disease plus 1-vessel disease.
The no-reflow phenomenon occurred in 77 patients (12%) included in the analysis. The components used to define the composite end point are listed in Table 3 . On univariate logistic regression analysis, the SXScore showed a strong association with no-reflow (for each 10-unit increase in SXScore, unadjusted OR 1.42, 95% CI 1.16 to 1.76, p <0.001). The other univariate predictors of no-reflow were age, gender, out-of-hospital arrest, Killip class, shock, pulse rate, and blood pressure. After adjusting for these predictors in multivariate logistic regression, the SXScore was an independent predictor of no-reflow (per 10-unit increase in SXScore, adjusted OR 1.29, 95% CI 1.02 to 1.63, p <0.001; Table 4 ).
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