Relationship Between the Angiographically Derived SYNTAX Score and Outcomes in High-Risk Patients Undergoing Percutaneous Coronary Intervention
Numerous scores have been designed to predict outcomes of percutaneous coronary intervention (PCI).1–6 These scores include clinical, demographic and angiographic parameters and are particularly helpful to predict in-hospital events. Recently, the investigators of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial developed and validated a score for severity of coronary artery disease (CAD) based entirely on angiographic characteristics (presence of total occlusion, bifurcation or trifurcation, angle and involvement of branch vessels, calcification, lesion length, ostial location, tortuosity and presence of thrombus).7,8 The SYNTAX score can be calculated using an interactive Web program and is the summation of the individual scores for each lesion with > 50% diameter stenosis by visual estimation in a vessel > 1.5 mm in diameter. It was used predominantly in patients with very complex CAD, such as left main coronary stenosis or 3-vessel CAD in clinical trials or registries comparing PCI to coronary artery bypass grafting (CABG)9–11 and it was found to reliably predict major adverse cardiac events (MACE).
Since the SYNTAX score was designed to characterize risk in patients with very severe CAD, but not in those with less critical CAD, we set out to evaluate the relationship between the SYNTAX score and mortality or repeat revascularization in patients with less severe CAD treated in routine clinical practice. In order to increase the rate of observed events, we chose a population of patients considered at high risk for ischemic events because of the presence of diabetes mellitus or chronic kidney disease.12
Methods
Data for patients undergoing PCI at our institution are prospectively entered into a computerized database based on the reporting system of the American College of Cardiology National Cardiovascular Database Registry (ACC NCDR). We included for this analysis all patients undergoing their first PCI between 1/1/2006 and 12/31/2007. In order to select a population with higher risk for cardiovascular death, only patients with diabetes mellitus or chronic kidney disease (CKD; serum creatinine ≥ 1.5 mg/dl) were included. Patients with previous CABG or those undergoing primary PCI for ST-elevation myocardial infarction (MI) were excluded. The authors separately evaluated the SYNTAX score and concordance was evaluated in a subset of 160 patients, for which paired assessments were performed (SJB and RA, SJB and AJP). The study endpoint was all-cause mortality or repeat revascularization, assessed by the Social Security Administration Death Index (SSDI, updated on 4/14/2010)13 and local electronic medical records.
Continuous and categorical variables were summarized with means and proportions, respectively. The concordance correlation coefficient (Lin) was determined for the two pairs of observers. Survival analysis was performed using Kaplan-Meier methodology with log-rank testing. A multivariable Cox proportional hazard model was developed to assess the impact on all-cause mortality, or revascularization, of the following variables: age, gender, extent of CAD (number of diseased vessels), SYNTAX score, ejection fraction, prior MI, diabetes mellitus, CKD (defined as serum creatinine ≥ 1.5 mg/dl, or as creatinine clearance
The institutional review board (IRB) approved the local PCI registry and allowed the use of aggregate data for clinical research.
Results
We identified 482 patients who underwent elective or urgent PCI in the specified period 
and fulfilled the inclusion and exclusion criteria. We had excluded 102 patients with previous CABG and 19 because of STEMI. During the study period 2,404 PCI procedures were performed. The baseline characteristics of the cohort are shown in Table 1. The mean duration of follow up was approximately 3 years (1,027 ± 311 days, median 1,070 days). The mean SYNTAX score was 11 ± 8, median of 9 (5–15), tertiles 12. The maximum score was 63. The 
score was not normally distributed (p 14
The estimated 1-, 2- and 3-year survival rates and 95% confidence intervals (CI) were 0.94 (0.91–0.96), 0.88 (0.85–0.91) and 0.85 (0.82–0.88), respectively. There were 79 deaths overall (16.4%), including 3 periprocedural deaths prior to hospital discharge. The mortality rate was 13.3% and 19.7% in patients with scores below and above the median (i.e., 9), 
respectively, p = 0.04. The mortality rate according to tertiles of SYNTAX scores is shown in Figure 2 (p = 0.60). Using the multivariable regression model described above (c-statistic 0.70), the strongest independent predictor of death was creatinine clearance (hazard ratio [HR] 0.82 [0.74–0.90], p
Repeat PCI was performed in 113 patients (23.4%). The estimated cumulative rate at 3 years was 19.2%, 32.2% and 33.2%, in increasing tertiles of score, p 
same multivariable model as above, the SYNTAX score was not associated with repeat PCI. Excluding patients with staged PCI, only the extent of CAD (HR 1.8 per vessel, p = 0.04), and prior MI (HR 2.0, p = 0.05) were independently predictive of repeat PCI for de-novo or restenotic lesions. None of the patients underwent surgical revascularization after their initial PCI.
Discussion
In this single-institution experience, we report the use of the SYNTAX score outside randomized clinical trials in patients who had less than critical CAD (involving the left main coronary artery or all 3 vessels) but had high-risk clinical features and underwent non-emergency PCI. We found that at a median follow up of 3 years, all-cause mortality was predominantly predicted by the degree of renal dysfunction, ejection fraction and previous myocardial infarction. The SYNTAX score, which could be reliably and consistently calculated by the investigators, did not independently predict outcome. The mortality rate in our cohort was approximately 5% per year. A higher SYNTAX score was associated with a higher rate of repeat PCI, but this association became insignificant after adjustment for important baseline characteristics.
Previous reports of the SYNTAX score utilization focused on patients with much more severe CAD. Valgimigli et al calculated retrospectively the SYNTAX score in the 306 patients with 3-vessel CAD enrolled in the Arterial Revascularization Therapies Study (ARTS II).11 The score varied between 4 and 54.5. The mean and median score were 22.7 and 22, respectively, significantly higher than in our cohort. It was independently associated with the rate of major adverse cardiovascular and cerebral events (MACCE) at 1 year, and demonstrated better discrimination and fit than the American Heart Association/American College of Cardiology (ACC/AHA) modified lesion classification scheme. There was no separate analysis for mortality in this study. Recently, Capodanno et al reported on 255 patients treated with PCI for left main coronary stenosis over 5.5 years.10 The scores ranged from 8–57, with a mean of 24.8 and a median of 24. At 1.5 years, the SYNTAX score independently predicted mortality (HR 1.15, p = 0.003). The same group extended these findings in 819 patients treated with PCI or CABG for left main coronary stenosis over 5.5 years.9 Only the patients with a score > 34 had lower 2-year mortality rate with CABG than with PCI. In the SYNTAX trial,8 the SYNTAX score was prospectively calculated by an independent angiographic core laboratory. The tertiles of score were 0–22 (mean 17), 23–32 (mean 27) and ≥ 33 (mean 42). The incidence of MACCE was significantly higher for PCI than for CABG in the highest score tertile, but there was no multivariable adjustment or separate analysis for mortality. Finally, the Austrian Multivessel TAXUS Stent (AUTAX) registry analyzed the predictive value of the score for MACCE in 440 patients with multivessel CAD treated with PCI.15 There was no independent association between the score and incidence of MACCE at 2 years. More similar to our study was the report from the “all-comers” Limus Eluted from A Durable versus ERodable Stent coating (LEADERS) trial, in which 1,397 patients undergoing elective PCI had their SYNTAX score calculated. The mean (14 ± 9) and median (12 [7–19]) scores were closer to those in our cohort. The score was significantly associated with the rate of MACE at 1 year, after adjustment for the presence of diabetes, acute coronary syndrome, use of beta-blockers and stent type. Mortality was higher in increasing tertiles of score (p = 0.002). There was a higher rate of target lesion revascularization in increasing tertiles of score.16
It is evident from the comparison of our series with most of the others that this report evaluates a cohort of patients with significantly less severe CAD than those previously reported, as is typical of large interventional cardiology practices. Unlike scores that integrate clinical and angiographic data,1,17 the SYNTAX score is more similar to the ACC/AHA lesion classification.18 We previously reported on the ability of the modified Mayo Clinic Risk Score (MCRS) and New York Risk Score (NYRS) to predict in-hospital death following PCI in routine clinical practice.19 Both these scores include age, creatinine level, ejection fraction and prior MI. These scores had good discriminatory ability (c-statistic of 0.82 and 0.83, respectively) for the population treated at our center, but were tested only for short-term survival. It is notable that three of the variables included in these scores were the independent predictors of 3-year death in our current study. Garg et al attempted to combine the SYNTAX and ACEF (age, creatinine and ejection fraction) scores in a clinical SYNTAX score in 512 patients from the Arterial Revascularization Therapies Study (ARTS)-II and showed only modest ability to improve prediction of MACE at 5 years, compared with each score alone.20
Important limitations should be integrated in the interpretation of these data. The SYNTAX score was initially correlated with MACE and not with mortality alone and, in our study it was calculated retrospectively in a relatively small cohort, and did not influence clinical decisions. We did not have consistently accurate information on the reasons for additional PCI or the medical management before and after the procedure. We could not obtain consistently reliable data on repeat PCI performed outside our institution and not reported to us by patients or their physicians. There was no reliable information on the incidence or MI or stroke during follow up and, thus, we cannot exclude the possibility that the SYNTAX score does predict MACCE, as in other studies. Finally, the SSDI is subject to important reporting and accuracy limitations, and most of our data on occurrence and timing of death reflect the information contained in it.
Despite these important limitations, we conclude that a detailed angiographic score is not independently predictive of 3-year all-cause mortality in patients with diabetes mellitus or CKD, but without previous CABG or critical CAD, undergoing non-emergency PCI. Repeat revascularization rates are higher in patients with increasing scores, but this association becomes insignificant after multivariable adjustment and removal of planned, staged procedures. A hybrid score, incorporating predictive characteristics such as degree of renal dysfunction, ejection fraction, clinical presentation and selected angiographic characteristics may prove to be a more useful tool to predict outcome and to select the appropriate revascularization strategy in large cohorts of patients with varying severity of CAD.
References
1. Wu C, Hannan EL, Walford G, et al. A risk score to predict in-hospital mortality for percutaneous coronary interventions. J Am Coll Cardiol 2006;47:654–660.
2. Shaw RE, Anderson HV, Brindis RG, et al. Development of a risk adjustment mortality model using the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) experience: 1998–2000. J Am Coll Cardiol 2002;39:1104–1112.
3. Resnic FS, Ohno-Machado L, Selwyn A, et al. Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention. Am J Cardiol 2001;88:5–9.
4. Ellis SG, Weintraub W, Holmes D, et al Relation of operator volume and experience to procedural outcome of percutaneous coronary revascularization at hospitals with high interventional volumes [see comments]. Circulation 1997;95:2479–2484.
5. Singh M, Lennon RJ, Holmes DR Jr, et al. Correlates of procedural complications and a simple integer risk score for percutaneous coronary intervention. J Am Coll Cardiol 2002;40:387–393.
6. Peterson ED, Dai D, DeLong ER, et al. Contemporary mortality risk prediction for percutaneous coronary intervention: Results from 588,398 procedures in the National Cardiovascular Data Registry. J Am Coll Cardiol 2010;55:1923–1932.
7. Sianos G, Morel MA, Kappenstein AP, et al. The SYNTAX score: An angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1:219–227.
8. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961–972.
9. Capodanno D, Capranzano P, Di Salvo ME, et al. Usefulness of SYNTAX score to select patients with left main coronary artery disease to be treated with coronary artery bypass graft. JACC Cardiovasc Interv 2009;2:731–738.
10. Capodanno D, Di Salvo ME, Cincotta G, et al. Usefulness of the SYNTAX Score for Predicting Clinical Outcome After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery Disease. Circ Cardiovasc Intervent 2009;2:302–308.
11. Valgimigli M, Serruys PW, Tsuchida K, et al. Cyphering the complexity of coronary artery disease using the syntax score to predict clinical outcome in patients with three-vessel lumen obstruction undergoing percutaneous coronary intervention. Am J Cardiol 2007;99:1072–1081.
12. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, et al. ACC/AHA/SCAI 2005 Guideline update for percutaneous coronary intervention — Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006;47:216–235.
13. Curb JD, Ford CE, Pressel S, et al. Ascertainment of vital status through the National Death Index and the Social Security Administration. Am J Epidemiol 1985;121:754–766.
14. Garg S, Girasis C, Sarno G, et al. The SYNTAX score revisited: A reassessment of the SYNTAX score reproducibility. Catheter Cardiovasc Interv 2009;75:953–956.
15. Gyongyosi M, Christ G, Lang I, et al. 2-year results of the AUTAX (Austrian Multivessel TAXUS-Stent) registry beyond the SYNTAX (synergy between percutaneous coronary intervention with TAXUS and cardiac surgery) study. JACC Cardiovasc Interv 2009;2:718–727.
16. Wykrzykowska JJ, Garg S, Girasis C, et al. Value of the SYNTAX score for risk assessment in the all-comers population of the randomized multicenter LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial. J Am Coll Cardiol 2010;56:272–277.
17. Singh M, Rihal CS, Lennon RJ, et al. Bedside estimation of risk from percutaneous coronary intervention: The new Mayo Clinic risk scores. Mayo Clin Proc 2007;82:701–708.
18. Ryan T, Faxon D, Gunnar R, Force AAT. Guidelines for percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1988;12:529–545.
19. Brener SJ, Colombo KD, Haq SA, et al. Precision and accuracy of risk scores for in-hospital death after percutaneous coronary intervention in the current era. Catheter Cardiovasc Interv 2010;75:153–157.
20. Garg S, Sarno G, Garcia-Garcia HM, et al. A new tool for the risk stratification of patients with complex coronary artery disease: the Clinical SYNTAX Score. Circ Cardiovasc Interv 2010;3:317–326.
From the Division of Cardiology, New York Methodist Hospital, Brooklyn, New York. Disclosure: A. Prasad reports that he was a cardiology fellow when the data were collected and this manuscript written. Manuscript submitted September 28, 2010, provisional acceptance given October 25, 2010, final version accepted November 11, 2010. Address for correspondence: Sorin J. Brener MD, FACC, Professor of Medicine, Director, Cardiac Catheterization Laboratory, NY Methodist Hospital, 506 6th Street, KP-2, Brooklyn, NY 11215. E-mail: sjb9005@nyp.org
