- Email: [email protected]
The SYNTAX Score and SYNTAX-Based Clinical Risk Scores
STATE OF THE ART
The SYNTAX Score and SYNTAX-Based Clinical Risk Scores Vasim Farooq, MBChB, MRCP, Salvatore Brugaletta, MD, and Patrick W. Serruys, MD, PhD Risk stratification is an important and essential component in appropriately informing patients electing to undergo coronary artery bypass graft or percutaneous coronary intervention. This process is an integral part of the SYNTAX pioneered Heart Team approach in selecting the most appropriate revascularization modality in patients with complex coronary artery disease. The SYNTAX score was pioneered as an anatomical-based risk score that aided in this decisionmaking process. The purpose of this review is to examine the SYNTAX score and subsequent risk models that have been developed on the basis of this landmark anatomical-based risk score. Semin Thoracic Surg 23:99-105 © 2011 Elsevier Inc. All rights reserved. Keywords SYNTAX score, clinical syntax score, modified ACEF, ACEF, Global Risk Risk stratification is an important and essential component in appropriately informing patients electing to undergo coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). This process is an integral part of the SYNTAX trial pioneered Heart Team approach in selecting the most appropriate revascularization modality in patients with complex (three-vessel or left main stem [LMS] disease) coronary artery disease and has recently been incorporated as a class I recommendation in recent myocardial revascularization guidelines.1 Despite the landmark Synergy between PCI with TAXUS and Cardiac Surgery (SYNTAX) trial having established that surgery was the standard of care for patients with LMS and/or multivessel disease, an important finding from this study was that patients with less complex disease, as defined by a low SYNTAX score (SXscore), were found to have equivalent outcomes to PCI surgery at 1-year and, as recently reported, 3-year follow-up.2,3 Within cardiothoracic surgical practice, the use of risk models to appropriately risk stratify patients is well-established, and they are predominantly related to clinical variables alone, with scores such as the
Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands. Address reprint requests to Patrick W. Serruys, MD, PhD, Department of Interventional Cardiology, Erasmus University Medical Centre, ’s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.08.001
EuroSCORE4,5 or Society of Thoracic Surgeons Score6 being in widespread contemporary use. The use of SXscore within this surgical population has been shown not to provide any additional predictive benefit and is likely related to the fact that bypass grafts are anastomosed distal to the coronary disease, regardless of the complexity of the proximal segments, provided there are suitable graftable targets.7,8 Within interventional cardiology practice, the SXscore has emerged as a useful risk model in identifying a subset of patients who could be safely and efficaciously treated with PCI, with comparable outcomes to CABG at up to 3 years.9 However, criticism has emerged that clinical factors are not being taken into account in the risk stratification of the PCI patient, and potentially important prognostic and morbidity information might be missing.7,10-12 The purpose of this review article is therefore to give a brief overview of the SXscore and the subsequent development of risk scores that have attempted to combine this anatomical-based risk score with clinical variables (Table 1). Emerging risk models such as the functional SYNTAX score and the novel concept of the patient empowered risk-benefit trade-off between PCI and CABG to help personalize the choice of revascularization modality are also explored. SYNTAX SCORE In 1981, Leaman et al13 developed a coronary scoring system that assessed the severity and extent of the underlying coronary artery disease. This system was based on the severity of luminal diameter 99
SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES Table 1. Summary of the SYNTAX-Based Risk Scores.* Clinical-Based Risk Scores† Are Listed Below Their Respective Combined SYNTAX and Clinical-Based Risk Scores No. of Variables Used to Calculate Risk Clinical Risk Score SYNTAX score* (SXscore)
Clinical 0
Angiographic 11 (per lesion)
0
11 (per lesion)
14
11
14
0
3
11 (per lesion)
ACEF score† (age, creatinine, ejection fraction)
3
0
Modified ACEF score† (age, creatinine clearance, ejection fraction) Global Risk*
3
0
17
11 (per lesion)
Additive EuroSCORE†
17
0
Functional Syntax score* Parsonnet ⫹ Syntax score* Parsonnet score†
Clinical Syntax score*
narrowing and weighted according to the usual flow to the left ventricle in each coronary vessel. Consequently, the most weight was given to the LMS, followed by the left anterior descending, circumflex, and right coronary arteries. This early pioneering work ultimately formed the basis of the SXscore.7,9 The SXscore is an anatomical risk– based score that takes into account features such as bifurcations, total occlusions, thrombus, calcification, small vessels, etc (Fig. 1). Each coronary lesion with ⬎50% luminal obstruction lumen in vessels ⱖ1.5 mm is separately scored and summated to provide the overall SXscore. This is calculated by using dedicated software that integrates the number of lesions with their specific weighting factors on the basis of the amount of myocardium distal to the lesion and morphologic features of each single lesion.7,9,13-14 Within the SYNTAX trial,2 the distribution of the SXscore was found to be Gaussian in the randomized PCI and CABG populations, with the curves almost 100
Outcomes Quantifies coronary artery disease complexity by tertiles of SXscore: correlated with clinical outcomes (death, MACCE) at 1year.3,7 FFR-guided SXscore calculation improved prognostic ability of the SXscore: death/MI, MACE at 1 year.19 MACCE and death at median follow-up of 973 days (PCI).24 Independent predictor of MACE after LMS intervention.23 Operative mortality after open heart surgery.22 MACCE and death in patients with complex coronary disease (ARTS II) after PCI at 5year follow-up.29 Predictor of cardiac death and MI at 1 year after PCI; inferior to the SXscore at predicting overall MACE and risk of repeat revascularization.25 Operative mortality in elective cardiac operations.26,27 Component of Clinical SYNTAX score.
Death and MACCE after unprotected LMS PCI.30,34 Evidence for predicting death or MACCE in high-risk tertiles for PCI.10-12,32 Operative mortality for all forms of cardiothoracic surgery.4,5
being superimposable on each other. Conversely, the mean SXscore in the nested registry patients, who were not acceptable for both CABG and PCI by the Heart Team and therefore not randomizable, was shifted to the right, reflecting more complex coronary anatomy in the nested registries compared to the randomized population (Fig. 2). When the scores of the randomized SYNTAX population were divided into tertiles, the upper boundary of the lowest tertile was 22 (low risk), the second tertile ranged from 23-32 (intermediate risk), and the lower boundary for the highest tertile was ⱖ33 (high risk). The SXscore has since been consistently shown to demonstrate poorer outcomes and to be an independent predictor of major adverse cardiac and cerebrovascular event (MACCE) in the high tertile group of risk for PCI at 1 year7 and within the ARTS II study population (consisting of a population with two-vessel [46%] or three-vessel [54%] disease) at up to 5 years of follow-up (Fig. 3).15
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES
Figure 1. The SYNTAX Score Algorithm. This is applied to each individual coronary lesion that has diameter stenosis ⬎50% and located in a vessel that is 1.5 mm in diameter. The individual lesion scores are added together to give the final SYNTAX score; in the example above the total score was 51.5.7,9,14,36 EuroIntervention. LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery. (Reprinted with permission from Serruys et al.7 Copyright 2009, with permission from Europa Edition.)
Early submitted work from the 3-year SYNTAX trial has indicated that the SXscore alone appears to be relatively poorly predictive of clinical events within the three-vessel disease population, unless combined with clinical variables (unpublished data). Three-vessel disease may be representative of patients with a more adverse risk profile who have evidence of systemic atherosclerotic disease; evidence to support this concept comes from the 10-year predicted Framingham risk scores, which demonstrated a significant and direct relationship with the prevalence and magnitude of coronary artery calcium scores.16 Consequently, the three-vessel disease population, in particular with moderate-high SXscores, may be at a greater longer-term cardiovascular and cerebrovascular risk and therefore might potentially benefit from CABG on prognostic and morbidity grounds because of the bypass grafts protecting the coronary vessel as opposed to PCI, which treats the individual lesion.3 Conversely, within the LMS population, a low-moderate SXscore has recently been shown to have comparable outcomes for PCI and CABG at 3 years.3 It may be hypothesized that the outcomes of the LMS population may be predominantly affected by the presence of three-vessel disease and its apparent associated comorbidity. FUNCTIONAL SYNTAX SCORE The Fractional Flow Reserve (FFR) versus Angiography for Guiding PCI in Patients with Multivessel Evaluation (FAME) study investigated the role of
FFR measurements to determine the functional significance of individual coronary lesions. By using FFR measurements to guide subsequent coronary intervention, a potential prognostic impact was observed when compared with angiographic guidance alone.17,18 Consequently, by incorporating FFR measurements into the SYNTAX score to form the recently dubbed functional SYNTAX score, it was shown in a retrospective subanalysis of almost 500 patients with multivessel disease from the FFR-guided arm of the FAME study that this improved the risk stratification
Figure 2. Distribution of the SXscore in the randomized (RCT) and nested registry CABG and PCI populations from the SYNTAX trial. Note how the distributions for both the randomized CABG and PCI populations are almost superimposable on each other, whereas the nested registries are shifted to the right.2,7 (Reprinted with permission from Serruys et al.7 Copyright 2009, with permission from Europa Edition.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES of patients when compared with the conventional angiographic-based approach to the calculation of the SXscore.19 The primary benefit appeared to be in reclassifying a significant proportion of the higherrisk groups into lower risk categories, while still maintaining a significantly higher event rate (death/ myocardial infarction [MI] and major adverse cardiovascular event [MACE] at 1 year) in the high-risk groups. The study, however, did not include LMS disease, and from a practical perspective even if validated in larger prospective populations, is perhaps more limited by the more invasive nature of the procedure. Noninvasive Functional SYNTAX Score Novel new techniques in development to potentially simplify the generation of the newly developed functional SYNTAX score include the use of noninvasive computed tomographic angiography that allows for the simultaneous assessment of anatomy and the measurement of the hemodynamic significance of lesions (Heartflow, Redwood City, CA). Validation of this technique is currently ongoing in the multicenter Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography (DeFACTO) trial. One of the main advantages of the proposed functional SYNTAX score is limiting the inevitable intervariability in coronary angiogram assessment, if visual assessment is used to assess the vessel/lesion size.7 Two-dimensional and potentially three-dimensional quantitative coronary angiography may, however, reduce the potential benefit seen in favor of FFR.20,21 The practice of visual assessment of vessel/ lesion size is representative of real-life practice and
Figure 3. Kaplan–Meier curves of freedom protocoldefined MACCE rate according to SYNTAX score tertiles. (Reprinted with permission from Serruys et al.15) (Color version of figure is available online at http:// www.semthorcardiovascsurg.com.)
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was also the basis of how the SXscores were calculated within the SYNTAX study. SYNTAX SCORE COMBINED WITH CLINICAL-BASED RISK SCORES SYNTAX Score and the Parsonnet Score By combining the Parsonnet score, an operative risk score published in 1989 consisting of 14 clinical variables,22 with the SXscore, it has been shown that this may potentially improve the performance of the SXscore alone. In 2005, Valgimigli et al23 demonstrated that the Parsonnet score was an independent predictor of MACE after LMS intervention from the Rotterdam RESEARCH and T-SEARCH registries. More recently, Chakravarty et al24 demonstrated that by adding the Parsonnet score as a covariate to the SYNTAX score, this improved the ability of the score in predicting MACCE after LMS PCI. Clinical Syntax Score The underlying rationale for the Clinical Syntax score was to combine the SXscore and a variant of the ACEF score (modified ACEF score).25 The ACEF score combines age, creatinine, and ejection fraction into a score and was proved to be comparable to the EuroSCORE in elective CABG patients.26,27 The modified ACEF score is calculated by using the formula: age/ejection fraction ⫹ 1 point for every 10 mL/min reduction in creatinine clearance below 60 mL/min/ 1.73 m2 (up to a maximum of 6 points); the rationale of this model was that by using creatinine clearance instead of serum creatinine to assess renal function, this potentially allowed for more accurate assessment of the underlying renal function.28 This model was applied to the ARTS II population treated with sirolimus eluting stents for multivessel (two- to three-vessel) coronary artery disease.29 By dividing the calculated Clinical SYNTAX scores into tertiles of risk, it was demonstrated that the risk model for predicting outcomes for MACCE and death at 5 years was superior to the SXscore or ACEF scores alone. One of the major limiting factors of the Clinical Syntax score was that despite being able to predict events in the high-risk tertile, the risk model was unable to discriminate between the clinical events for the low-risk and intermediate-risk tertiles; this was also demonstrated when applied to a different similar-sized registry by another group.30 Global Risk The SYNTAX trial established a complex interaction between the EuroSCORE and SXscore in preliminary unpublished data.31 Given that the Euro-
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES Table 2. The Additive EuroSCORE Is Calculated by Summating the Individual Scores From 17 Different Variables4 Additive EuroSCORE Patient factors Age Sex Chronic pulmonary disease Peripheral arteriopathy
Per 5 years or part thereof older than the age of 60 years Female Long-term use of bronchodilators or steroids for respiratory disease
1 1 1
Claudication/carotid stenosis ⬎50%/previous or planned intervention on the abdominal aorta, limb arteries, or carotids Neurological dysfunction Severely affected mobility or day-to-day function Previous cardiac surgery Previous opening of the pericardium Serum creatinine Preoperatively ⬎200 mol/L Active endocarditis Antibiotic therapy at time of surgery Critical preoperative state Preoperative cardiac arrest, ventilation, renal failure, inotropic support, intra-aortic balloon pump use, ventricular arrhythmia Cardiac factors Unstable angina Rest pain requiring intravenous nitrates Left ventricular function Moderate (30%-50%) Poor (⬍30%) Recent MI Within 90 days Pulmonary hypertension Systolic pulmonary artery pressure ⬎60 mm Hg Operative factors Emergency operation Performed before the start of next working day Other than isolated Major cardiac procedure other than or in addition to CABG CABG Surgery on thoracic aorta Postinfarct septal rupture
SCORE has been shown to be an independent predictor of MACE for both CABG and PCI as previously described,32,33 the need to combine the angiographic and clinical scores into one single approach has become evident.31 One of the main advantages of potentially combining the EuroSCORE and SXscore to give a “Global Risk” assessment is that the same risk model could be used in patients during the Heart Team approach in determining the optimal revascularization modality (CABG or PCI) for the patient. To facilitate this process it is the author’s opinion that the historically
2 2 3 2 3 3
2 1 3 2 2 2 2 3 4
accepted cutoffs for the level of risk (low, intermediate, and high) for the additive EuroSCORE, each of which has previously been demonstrated to have a different prognostic value,4,5,7,9,14 and the SYNTAX trial defined anatomical SXscore ranges7,9,14 should be incorporated into the Global Risk model (Tables 2-3.) In variants of this model with differing and inconsistent cutoff levels of risk for the SXscore and/or additive EuroSCORE in a nonrandomized population, it has recently been shown that this may poten tially improve the ability to predict outcomes in pa-
Table 3. The Global Risk Approach, Combining Historically Defined Tertiles of Risk for the EuroSCORE4,37 and the SYNTAX Trial Defined Ranges for the SXscore2,7
Low additive EuroSCORE (0-2) Intermediate additive EuroSCORE (3-5) High additive EuroSCORE (ⱖ6)
Low SYNTAX Score (ⱕ22) Low risk
Intermediate SYNTAX Score (23-32) Low risk
High SYNTAX Score (ⱖ33) Intermediate risk
Low risk
Low risk
Intermediate risk
Intermediate risk
Intermediate risk
High risk
Application of this risk model by the Heart Team in determining the optimal revascularization modality (CABG or PCI) may allow for improved risk stratification of patients compared to the SYNTAX score alone.
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES tients undergoing surgical or percutaneous LMS revascularization.30,34 The main goal of using the Global Risk model is therefore to combine anatomical and clinical variables to potentially further aid in the risk stratification of patients with three-vessel disease and/or LMS disease considering revascularization and to identify a low-risk group of percutaneous or surgically treated patients who would have comparable outcomes in terms of safety and efficacy. This concept has been recently applied by our group to the randomized and All-Comers SYNTAX population, the results of which are expected to be published soon. RISK/BENEFIT ANALYSIS Undoubtedly, both CABG and PCI allow for improvement in the quality of life of the patient. One of the main drawbacks of using contemporary risk models for both CABG and PCI is that the role of the individual patient, their personal preferences, and perception of risk might potentially be underestimated. To address this issue, the novel concept of a clinical model that balances the risks and benefits of the proposed revascularization procedure has recently emerged.35 The need for some individuals to remain active within their professional/personal lives may be vital, and they would thus be potentially more prepared to accept the longer-term risks of PCI, namely increased revascularization, to remain at their present functional state in exchange for them being free from the short-term morbidity effects associated with CABG such as pain from thoracotomy and vein harvesting sites. Individual patients may value this risk-benefit trade-off differently. For some, exchanging the increased risk of repeat PCI to obtain short-term pain relief and a rapid return to full mobility will be acceptable, whereas others may prefer to endure shortterm pain to obtain a higher probability of avoiding a subsequent revascularization with CABG. Patients may also prefer to risk undergoing multiple PCI procedures rather than a single CABG, or they may prefer to avoid the risk of requiring CABG after PCI and instead have CABG initially. Consequently, from the patient’s perspective, the balance between these conflicting considerations appears to play a crucial role
1. Wijns W, Kolh P, Danchin N, et al: Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 31:2501-2555, 2010 2. Serruys PW, Morice MC, Kappetein AP, et al:
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in the identification of the preferred revascularization strategy. Federspiel et al35 recently applied this concept to the Arterial Revascularization Therapies Study (ARTS I) population by quantifying the trade-off between the risks and benefits of PCI versus CABG, such as freedom of pain and improvements in health-related quality of life measures, for patients with multivessel disease. Although this study was performed on study data that were more than 10 years old in a population who had implantation of bare metal stents, the results were nevertheless supportive of this concept and have allowed for the first time a quantification of a level of risk that a patient would be able to accept to maintain their present functional state. Data from the SYNTAX trial on this very concept to reflect more contemporary practice with drug eluting stents are forthcoming. CONCLUSION Risk models incorporating clinical variables alone appear to be adequate for risk stratifying CABG patients, whereas a combination of clinical and anatomical variables is required for an effective, clinically useful risk model for PCI patients. Although the SXscore is prognostically useful in risk stratifying patients proposing to undergo PCI, it is clearly not the whole picture, and it is the authors’ view that clinical variables will ultimately prove to be the more important factors, with the added incremental benefits of anatomical variables. Risk models in development, such as the Global Risk, will allow for the simultaneous use of the same risk model in both surgical and percutaneously treated patients and may prove to be of clinical value. Novel concepts such as the Functional Syntax score, especially if this can be performed noninvasively, and the patient empowered risk-benefit trade-off are all further areas in current development in which additional clinically relevant information may become available.
Acknowledgments The first author wishes to thank the Dickinson Trust Travelling Scholarship, Manchester Royal Infirmary, Manchester, England, United Kingdom.
Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360:961-972, 2009 3. Kappetein AP, Feldman TE, Mack MJ, et al: Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left
main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 32:2125-2134, 2011 4. Nashef SA, Roques F, Michel P, et al: European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 16:9-13, 1999
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES 5. Roques F, Michel P, Goldstone AR, et al: The logistic EuroSCORE. Eur Heart J 24:881-882, 2003 6. Shahian DM, O’Brien SM, Filardo G, et al: The Society of Thoracic Surgeons 2008 cardiac surgery risk models: Part 1—Coronary artery bypass grafting surgery. Ann Thorac Surg 88: S2-S22, 2009 (suppl) 7. Serruys PW, Onuma Y, Garg S, et al: Assessment of the SYNTAX score in the Syntax study. EuroIntervention 5:50-56, 2009 8. Mohr FW, Rastan AJ, Serruys PW, et al: Complex coronary anatomy in coronary artery bypass graft surgery: Impact of complex coronary anatomy in modern bypass surgery? Lessons learned from the SYNTAX trial after two years. J Thorac Cardiovasc Surg 141:130140, 2011 9. Sianos G, Morel MA, Kappetein AP, et al: The SYNTAX Score: An angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1:219-227, 2005 10. Romagnoli E, Burzotta F, Trani C, et al: EuroSCORE as predictor of in-hospital mortality after percutaneous coronary intervention. Heart 95:43-48, 2009 11. Kim YH, Ahn JM, Park DW, et al: EuroSCORE as a predictor of death and myocardial infarction after unprotected left main coronary stenting. Am J Cardiol 98:1567-1570, 2006 12. Kim Y-H, Park D-W, Kim W-J, et al: Validation of SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score for prediction of outcomes after unprotected left main coronary revascularization. J Am Coll Cardiol Interv 3:612-623, 2010 13. Leaman DM, Brower RW, Meester GT, et al: Coronary artery atherosclerosis: Severity of the disease, severity of angina pectoris and compromised left ventricular function. Circulation 63:285-299, 1981 14. SYNTAX working-group: SYNTAX score calculator. Available at: http://www.syntaxscore. com. Launched May 19, 2009 15. Serruys PW, Onuma Y, Garg S, et al: 5-Year clinical outcomes of the ARTS II (Arterial Revascularization Therapies Study II) of the sirolimus-eluting stent in the treatment of patients with multivessel de novo coronary artery lesions. J Am Coll Cardiol 55:1093-1101, 2010 16. Okwuosa TM, Greenland P, Ning H, et al: Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) po-
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tential implications for coronary risk assessment. J Am Coll Cardiol 57:1838-1845, 2011 Tonino PA, Fearon WF, De Bruyne B, et al: Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol 55: 2816-2821, 2010 Pijls NH, Fearon WF, Tonino PA, et al: Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-Year follow-up of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol 56:177-184, 2010 Fearon WF: Functional Syntax score. Presented at Left Main Coronary Interventions Course, February 14, 2011, New York, NY Cutlip DE, Mehran R, Vranckx P: FAME and coronary stent investigations: Is there a kink in the wire? J Am Coll Cardiol 57:115-116, 2011, author reply 116 Yong AS, Ng AC, Brieger D, et al: Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve. Eur Heart J 32:345-353, 2011 Parsonnet V, Dean D, Bernstein AD: A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation 79:I3-I12, 1989 Valgimigli M, van Mieghem CAG, Ong ATL, et al: Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: Insights from the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital Registries (RESEARCH and T-SEARCH). Circulation 111:1383-1389, 2005 Chakravarty T, Buch MH, Naik H, et al: Predictive accuracy of SYNTAX score for predicting long-term outcomes of unprotected left main coronary artery revascularization. Am J Cardiol 107:360-366, 2011 Wykrzykowska JJ, Garg S, Onuma Y, et al: Value of age, creatinine, and ejection fraction (ACEF score) in assessing risk in patients undergoing percutaneous coronary interventions in the “All-Comers” LEADERS trial. Circ Cardiovasc Interventions 4:4756, 2011 Ranucci M, Castelvecchio S, Menicanti L, et al: Risk of assessing mortality risk in elective car-
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diac operations: Age, creatinine, ejection fraction, and the law of parsimony. Circulation 119:3053-3061, 2009 Ranucci M, Castelvecchio S: The ACEF score one year after: A skeleton waiting for muscles, skin, and internal organs. EuroIntervention 6:549-553, 2010 Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 16:31-41, 1976 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 Interventions 3:317-326, 2010 Capodanno D, Caggegi A, Miano M, et al: Global Risk classification and Clinical SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score in patients undergoing percutaneous or surgical left main revascularization. J Am Coll Cardiol Interv 4:287-297, 2011 Serruys PW: Integrating lessons from recent clinical trials into practice: Beyond the SYNTAX score. Presented at Transcatheter Therapeutics Asia Pacific, April 29, 2010, Seoul, South Korea Rodés-Cabau J, Deblois J, Bertrand OF, et al: Nonrandomized comparison of coronary artery bypass surgery and percutaneous coronary intervention for the treatment of unprotected left main coronary artery disease in octogenarians. Circulation 118:2374-2381, 2008 Min SY, Park DW, Yun SC, et al: Major predictors of long-term clinical outcomes after coronary revascularization in patients with unprotected left main coronary disease: Analysis from the MAIN-COMPARE study. Circ Cardiovasc Interventions 3:127-133, 2010 Capodanno D, Miano M, Cincotta G, et al: EuroSCORE refines the predictive ability of SYNTAX score in patients undergoing left main percutaneous coronary intervention. Am Heart J 159:103-109, 2010 Federspiel J, Stearns SC, van Domburg R, et al: Risk-benefit trade-offs in revascularisation choices. EuroIntervention 2011 Ong AT, Serruys PW, Mohr FW, et al: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study: Design, rationale, and run-in phase. Am Heart J 151:1194-1204, 2006 Gogbashian A, Sedrakyan A, Treasure T: EuroScore: A systematic review of international performance. Eur J Cardiothorac Surg 25:695-700, 2004
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The SYNTAX Score and SYNTAX-Based Clinical Risk Scores Vasim Farooq, MBChB, MRCP, Salvatore Brugaletta, MD, and Patrick W. Serruys, MD, PhD Risk stratification is an important and essential component in appropriately informing patients electing to undergo coronary artery bypass graft or percutaneous coronary intervention. This process is an integral part of the SYNTAX pioneered Heart Team approach in selecting the most appropriate revascularization modality in patients with complex coronary artery disease. The SYNTAX score was pioneered as an anatomical-based risk score that aided in this decisionmaking process. The purpose of this review is to examine the SYNTAX score and subsequent risk models that have been developed on the basis of this landmark anatomical-based risk score. Semin Thoracic Surg 23:99-105 © 2011 Elsevier Inc. All rights reserved. Keywords SYNTAX score, clinical syntax score, modified ACEF, ACEF, Global Risk Risk stratification is an important and essential component in appropriately informing patients electing to undergo coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). This process is an integral part of the SYNTAX trial pioneered Heart Team approach in selecting the most appropriate revascularization modality in patients with complex (three-vessel or left main stem [LMS] disease) coronary artery disease and has recently been incorporated as a class I recommendation in recent myocardial revascularization guidelines.1 Despite the landmark Synergy between PCI with TAXUS and Cardiac Surgery (SYNTAX) trial having established that surgery was the standard of care for patients with LMS and/or multivessel disease, an important finding from this study was that patients with less complex disease, as defined by a low SYNTAX score (SXscore), were found to have equivalent outcomes to PCI surgery at 1-year and, as recently reported, 3-year follow-up.2,3 Within cardiothoracic surgical practice, the use of risk models to appropriately risk stratify patients is well-established, and they are predominantly related to clinical variables alone, with scores such as the
Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands. Address reprint requests to Patrick W. Serruys, MD, PhD, Department of Interventional Cardiology, Erasmus University Medical Centre, ’s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.08.001
EuroSCORE4,5 or Society of Thoracic Surgeons Score6 being in widespread contemporary use. The use of SXscore within this surgical population has been shown not to provide any additional predictive benefit and is likely related to the fact that bypass grafts are anastomosed distal to the coronary disease, regardless of the complexity of the proximal segments, provided there are suitable graftable targets.7,8 Within interventional cardiology practice, the SXscore has emerged as a useful risk model in identifying a subset of patients who could be safely and efficaciously treated with PCI, with comparable outcomes to CABG at up to 3 years.9 However, criticism has emerged that clinical factors are not being taken into account in the risk stratification of the PCI patient, and potentially important prognostic and morbidity information might be missing.7,10-12 The purpose of this review article is therefore to give a brief overview of the SXscore and the subsequent development of risk scores that have attempted to combine this anatomical-based risk score with clinical variables (Table 1). Emerging risk models such as the functional SYNTAX score and the novel concept of the patient empowered risk-benefit trade-off between PCI and CABG to help personalize the choice of revascularization modality are also explored. SYNTAX SCORE In 1981, Leaman et al13 developed a coronary scoring system that assessed the severity and extent of the underlying coronary artery disease. This system was based on the severity of luminal diameter 99
SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES Table 1. Summary of the SYNTAX-Based Risk Scores.* Clinical-Based Risk Scores† Are Listed Below Their Respective Combined SYNTAX and Clinical-Based Risk Scores No. of Variables Used to Calculate Risk Clinical Risk Score SYNTAX score* (SXscore)
Clinical 0
Angiographic 11 (per lesion)
0
11 (per lesion)
14
11
14
0
3
11 (per lesion)
ACEF score† (age, creatinine, ejection fraction)
3
0
Modified ACEF score† (age, creatinine clearance, ejection fraction) Global Risk*
3
0
17
11 (per lesion)
Additive EuroSCORE†
17
0
Functional Syntax score* Parsonnet ⫹ Syntax score* Parsonnet score†
Clinical Syntax score*
narrowing and weighted according to the usual flow to the left ventricle in each coronary vessel. Consequently, the most weight was given to the LMS, followed by the left anterior descending, circumflex, and right coronary arteries. This early pioneering work ultimately formed the basis of the SXscore.7,9 The SXscore is an anatomical risk– based score that takes into account features such as bifurcations, total occlusions, thrombus, calcification, small vessels, etc (Fig. 1). Each coronary lesion with ⬎50% luminal obstruction lumen in vessels ⱖ1.5 mm is separately scored and summated to provide the overall SXscore. This is calculated by using dedicated software that integrates the number of lesions with their specific weighting factors on the basis of the amount of myocardium distal to the lesion and morphologic features of each single lesion.7,9,13-14 Within the SYNTAX trial,2 the distribution of the SXscore was found to be Gaussian in the randomized PCI and CABG populations, with the curves almost 100
Outcomes Quantifies coronary artery disease complexity by tertiles of SXscore: correlated with clinical outcomes (death, MACCE) at 1year.3,7 FFR-guided SXscore calculation improved prognostic ability of the SXscore: death/MI, MACE at 1 year.19 MACCE and death at median follow-up of 973 days (PCI).24 Independent predictor of MACE after LMS intervention.23 Operative mortality after open heart surgery.22 MACCE and death in patients with complex coronary disease (ARTS II) after PCI at 5year follow-up.29 Predictor of cardiac death and MI at 1 year after PCI; inferior to the SXscore at predicting overall MACE and risk of repeat revascularization.25 Operative mortality in elective cardiac operations.26,27 Component of Clinical SYNTAX score.
Death and MACCE after unprotected LMS PCI.30,34 Evidence for predicting death or MACCE in high-risk tertiles for PCI.10-12,32 Operative mortality for all forms of cardiothoracic surgery.4,5
being superimposable on each other. Conversely, the mean SXscore in the nested registry patients, who were not acceptable for both CABG and PCI by the Heart Team and therefore not randomizable, was shifted to the right, reflecting more complex coronary anatomy in the nested registries compared to the randomized population (Fig. 2). When the scores of the randomized SYNTAX population were divided into tertiles, the upper boundary of the lowest tertile was 22 (low risk), the second tertile ranged from 23-32 (intermediate risk), and the lower boundary for the highest tertile was ⱖ33 (high risk). The SXscore has since been consistently shown to demonstrate poorer outcomes and to be an independent predictor of major adverse cardiac and cerebrovascular event (MACCE) in the high tertile group of risk for PCI at 1 year7 and within the ARTS II study population (consisting of a population with two-vessel [46%] or three-vessel [54%] disease) at up to 5 years of follow-up (Fig. 3).15
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES
Figure 1. The SYNTAX Score Algorithm. This is applied to each individual coronary lesion that has diameter stenosis ⬎50% and located in a vessel that is 1.5 mm in diameter. The individual lesion scores are added together to give the final SYNTAX score; in the example above the total score was 51.5.7,9,14,36 EuroIntervention. LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery. (Reprinted with permission from Serruys et al.7 Copyright 2009, with permission from Europa Edition.)
Early submitted work from the 3-year SYNTAX trial has indicated that the SXscore alone appears to be relatively poorly predictive of clinical events within the three-vessel disease population, unless combined with clinical variables (unpublished data). Three-vessel disease may be representative of patients with a more adverse risk profile who have evidence of systemic atherosclerotic disease; evidence to support this concept comes from the 10-year predicted Framingham risk scores, which demonstrated a significant and direct relationship with the prevalence and magnitude of coronary artery calcium scores.16 Consequently, the three-vessel disease population, in particular with moderate-high SXscores, may be at a greater longer-term cardiovascular and cerebrovascular risk and therefore might potentially benefit from CABG on prognostic and morbidity grounds because of the bypass grafts protecting the coronary vessel as opposed to PCI, which treats the individual lesion.3 Conversely, within the LMS population, a low-moderate SXscore has recently been shown to have comparable outcomes for PCI and CABG at 3 years.3 It may be hypothesized that the outcomes of the LMS population may be predominantly affected by the presence of three-vessel disease and its apparent associated comorbidity. FUNCTIONAL SYNTAX SCORE The Fractional Flow Reserve (FFR) versus Angiography for Guiding PCI in Patients with Multivessel Evaluation (FAME) study investigated the role of
FFR measurements to determine the functional significance of individual coronary lesions. By using FFR measurements to guide subsequent coronary intervention, a potential prognostic impact was observed when compared with angiographic guidance alone.17,18 Consequently, by incorporating FFR measurements into the SYNTAX score to form the recently dubbed functional SYNTAX score, it was shown in a retrospective subanalysis of almost 500 patients with multivessel disease from the FFR-guided arm of the FAME study that this improved the risk stratification
Figure 2. Distribution of the SXscore in the randomized (RCT) and nested registry CABG and PCI populations from the SYNTAX trial. Note how the distributions for both the randomized CABG and PCI populations are almost superimposable on each other, whereas the nested registries are shifted to the right.2,7 (Reprinted with permission from Serruys et al.7 Copyright 2009, with permission from Europa Edition.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES of patients when compared with the conventional angiographic-based approach to the calculation of the SXscore.19 The primary benefit appeared to be in reclassifying a significant proportion of the higherrisk groups into lower risk categories, while still maintaining a significantly higher event rate (death/ myocardial infarction [MI] and major adverse cardiovascular event [MACE] at 1 year) in the high-risk groups. The study, however, did not include LMS disease, and from a practical perspective even if validated in larger prospective populations, is perhaps more limited by the more invasive nature of the procedure. Noninvasive Functional SYNTAX Score Novel new techniques in development to potentially simplify the generation of the newly developed functional SYNTAX score include the use of noninvasive computed tomographic angiography that allows for the simultaneous assessment of anatomy and the measurement of the hemodynamic significance of lesions (Heartflow, Redwood City, CA). Validation of this technique is currently ongoing in the multicenter Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography (DeFACTO) trial. One of the main advantages of the proposed functional SYNTAX score is limiting the inevitable intervariability in coronary angiogram assessment, if visual assessment is used to assess the vessel/lesion size.7 Two-dimensional and potentially three-dimensional quantitative coronary angiography may, however, reduce the potential benefit seen in favor of FFR.20,21 The practice of visual assessment of vessel/ lesion size is representative of real-life practice and
Figure 3. Kaplan–Meier curves of freedom protocoldefined MACCE rate according to SYNTAX score tertiles. (Reprinted with permission from Serruys et al.15) (Color version of figure is available online at http:// www.semthorcardiovascsurg.com.)
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was also the basis of how the SXscores were calculated within the SYNTAX study. SYNTAX SCORE COMBINED WITH CLINICAL-BASED RISK SCORES SYNTAX Score and the Parsonnet Score By combining the Parsonnet score, an operative risk score published in 1989 consisting of 14 clinical variables,22 with the SXscore, it has been shown that this may potentially improve the performance of the SXscore alone. In 2005, Valgimigli et al23 demonstrated that the Parsonnet score was an independent predictor of MACE after LMS intervention from the Rotterdam RESEARCH and T-SEARCH registries. More recently, Chakravarty et al24 demonstrated that by adding the Parsonnet score as a covariate to the SYNTAX score, this improved the ability of the score in predicting MACCE after LMS PCI. Clinical Syntax Score The underlying rationale for the Clinical Syntax score was to combine the SXscore and a variant of the ACEF score (modified ACEF score).25 The ACEF score combines age, creatinine, and ejection fraction into a score and was proved to be comparable to the EuroSCORE in elective CABG patients.26,27 The modified ACEF score is calculated by using the formula: age/ejection fraction ⫹ 1 point for every 10 mL/min reduction in creatinine clearance below 60 mL/min/ 1.73 m2 (up to a maximum of 6 points); the rationale of this model was that by using creatinine clearance instead of serum creatinine to assess renal function, this potentially allowed for more accurate assessment of the underlying renal function.28 This model was applied to the ARTS II population treated with sirolimus eluting stents for multivessel (two- to three-vessel) coronary artery disease.29 By dividing the calculated Clinical SYNTAX scores into tertiles of risk, it was demonstrated that the risk model for predicting outcomes for MACCE and death at 5 years was superior to the SXscore or ACEF scores alone. One of the major limiting factors of the Clinical Syntax score was that despite being able to predict events in the high-risk tertile, the risk model was unable to discriminate between the clinical events for the low-risk and intermediate-risk tertiles; this was also demonstrated when applied to a different similar-sized registry by another group.30 Global Risk The SYNTAX trial established a complex interaction between the EuroSCORE and SXscore in preliminary unpublished data.31 Given that the Euro-
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES Table 2. The Additive EuroSCORE Is Calculated by Summating the Individual Scores From 17 Different Variables4 Additive EuroSCORE Patient factors Age Sex Chronic pulmonary disease Peripheral arteriopathy
Per 5 years or part thereof older than the age of 60 years Female Long-term use of bronchodilators or steroids for respiratory disease
1 1 1
Claudication/carotid stenosis ⬎50%/previous or planned intervention on the abdominal aorta, limb arteries, or carotids Neurological dysfunction Severely affected mobility or day-to-day function Previous cardiac surgery Previous opening of the pericardium Serum creatinine Preoperatively ⬎200 mol/L Active endocarditis Antibiotic therapy at time of surgery Critical preoperative state Preoperative cardiac arrest, ventilation, renal failure, inotropic support, intra-aortic balloon pump use, ventricular arrhythmia Cardiac factors Unstable angina Rest pain requiring intravenous nitrates Left ventricular function Moderate (30%-50%) Poor (⬍30%) Recent MI Within 90 days Pulmonary hypertension Systolic pulmonary artery pressure ⬎60 mm Hg Operative factors Emergency operation Performed before the start of next working day Other than isolated Major cardiac procedure other than or in addition to CABG CABG Surgery on thoracic aorta Postinfarct septal rupture
SCORE has been shown to be an independent predictor of MACE for both CABG and PCI as previously described,32,33 the need to combine the angiographic and clinical scores into one single approach has become evident.31 One of the main advantages of potentially combining the EuroSCORE and SXscore to give a “Global Risk” assessment is that the same risk model could be used in patients during the Heart Team approach in determining the optimal revascularization modality (CABG or PCI) for the patient. To facilitate this process it is the author’s opinion that the historically
2 2 3 2 3 3
2 1 3 2 2 2 2 3 4
accepted cutoffs for the level of risk (low, intermediate, and high) for the additive EuroSCORE, each of which has previously been demonstrated to have a different prognostic value,4,5,7,9,14 and the SYNTAX trial defined anatomical SXscore ranges7,9,14 should be incorporated into the Global Risk model (Tables 2-3.) In variants of this model with differing and inconsistent cutoff levels of risk for the SXscore and/or additive EuroSCORE in a nonrandomized population, it has recently been shown that this may poten tially improve the ability to predict outcomes in pa-
Table 3. The Global Risk Approach, Combining Historically Defined Tertiles of Risk for the EuroSCORE4,37 and the SYNTAX Trial Defined Ranges for the SXscore2,7
Low additive EuroSCORE (0-2) Intermediate additive EuroSCORE (3-5) High additive EuroSCORE (ⱖ6)
Low SYNTAX Score (ⱕ22) Low risk
Intermediate SYNTAX Score (23-32) Low risk
High SYNTAX Score (ⱖ33) Intermediate risk
Low risk
Low risk
Intermediate risk
Intermediate risk
Intermediate risk
High risk
Application of this risk model by the Heart Team in determining the optimal revascularization modality (CABG or PCI) may allow for improved risk stratification of patients compared to the SYNTAX score alone.
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES tients undergoing surgical or percutaneous LMS revascularization.30,34 The main goal of using the Global Risk model is therefore to combine anatomical and clinical variables to potentially further aid in the risk stratification of patients with three-vessel disease and/or LMS disease considering revascularization and to identify a low-risk group of percutaneous or surgically treated patients who would have comparable outcomes in terms of safety and efficacy. This concept has been recently applied by our group to the randomized and All-Comers SYNTAX population, the results of which are expected to be published soon. RISK/BENEFIT ANALYSIS Undoubtedly, both CABG and PCI allow for improvement in the quality of life of the patient. One of the main drawbacks of using contemporary risk models for both CABG and PCI is that the role of the individual patient, their personal preferences, and perception of risk might potentially be underestimated. To address this issue, the novel concept of a clinical model that balances the risks and benefits of the proposed revascularization procedure has recently emerged.35 The need for some individuals to remain active within their professional/personal lives may be vital, and they would thus be potentially more prepared to accept the longer-term risks of PCI, namely increased revascularization, to remain at their present functional state in exchange for them being free from the short-term morbidity effects associated with CABG such as pain from thoracotomy and vein harvesting sites. Individual patients may value this risk-benefit trade-off differently. For some, exchanging the increased risk of repeat PCI to obtain short-term pain relief and a rapid return to full mobility will be acceptable, whereas others may prefer to endure shortterm pain to obtain a higher probability of avoiding a subsequent revascularization with CABG. Patients may also prefer to risk undergoing multiple PCI procedures rather than a single CABG, or they may prefer to avoid the risk of requiring CABG after PCI and instead have CABG initially. Consequently, from the patient’s perspective, the balance between these conflicting considerations appears to play a crucial role
1. Wijns W, Kolh P, Danchin N, et al: Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 31:2501-2555, 2010 2. Serruys PW, Morice MC, Kappetein AP, et al:
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in the identification of the preferred revascularization strategy. Federspiel et al35 recently applied this concept to the Arterial Revascularization Therapies Study (ARTS I) population by quantifying the trade-off between the risks and benefits of PCI versus CABG, such as freedom of pain and improvements in health-related quality of life measures, for patients with multivessel disease. Although this study was performed on study data that were more than 10 years old in a population who had implantation of bare metal stents, the results were nevertheless supportive of this concept and have allowed for the first time a quantification of a level of risk that a patient would be able to accept to maintain their present functional state. Data from the SYNTAX trial on this very concept to reflect more contemporary practice with drug eluting stents are forthcoming. CONCLUSION Risk models incorporating clinical variables alone appear to be adequate for risk stratifying CABG patients, whereas a combination of clinical and anatomical variables is required for an effective, clinically useful risk model for PCI patients. Although the SXscore is prognostically useful in risk stratifying patients proposing to undergo PCI, it is clearly not the whole picture, and it is the authors’ view that clinical variables will ultimately prove to be the more important factors, with the added incremental benefits of anatomical variables. Risk models in development, such as the Global Risk, will allow for the simultaneous use of the same risk model in both surgical and percutaneously treated patients and may prove to be of clinical value. Novel concepts such as the Functional Syntax score, especially if this can be performed noninvasively, and the patient empowered risk-benefit trade-off are all further areas in current development in which additional clinically relevant information may become available.
Acknowledgments The first author wishes to thank the Dickinson Trust Travelling Scholarship, Manchester Royal Infirmary, Manchester, England, United Kingdom.
Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360:961-972, 2009 3. Kappetein AP, Feldman TE, Mack MJ, et al: Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left
main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 32:2125-2134, 2011 4. Nashef SA, Roques F, Michel P, et al: European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 16:9-13, 1999
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SYNTAX SCORE AND SYNTAX-BASED CLINICAL RISK SCORES 5. Roques F, Michel P, Goldstone AR, et al: The logistic EuroSCORE. Eur Heart J 24:881-882, 2003 6. Shahian DM, O’Brien SM, Filardo G, et al: The Society of Thoracic Surgeons 2008 cardiac surgery risk models: Part 1—Coronary artery bypass grafting surgery. Ann Thorac Surg 88: S2-S22, 2009 (suppl) 7. Serruys PW, Onuma Y, Garg S, et al: Assessment of the SYNTAX score in the Syntax study. EuroIntervention 5:50-56, 2009 8. Mohr FW, Rastan AJ, Serruys PW, et al: Complex coronary anatomy in coronary artery bypass graft surgery: Impact of complex coronary anatomy in modern bypass surgery? Lessons learned from the SYNTAX trial after two years. J Thorac Cardiovasc Surg 141:130140, 2011 9. Sianos G, Morel MA, Kappetein AP, et al: The SYNTAX Score: An angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1:219-227, 2005 10. Romagnoli E, Burzotta F, Trani C, et al: EuroSCORE as predictor of in-hospital mortality after percutaneous coronary intervention. Heart 95:43-48, 2009 11. Kim YH, Ahn JM, Park DW, et al: EuroSCORE as a predictor of death and myocardial infarction after unprotected left main coronary stenting. Am J Cardiol 98:1567-1570, 2006 12. Kim Y-H, Park D-W, Kim W-J, et al: Validation of SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score for prediction of outcomes after unprotected left main coronary revascularization. J Am Coll Cardiol Interv 3:612-623, 2010 13. Leaman DM, Brower RW, Meester GT, et al: Coronary artery atherosclerosis: Severity of the disease, severity of angina pectoris and compromised left ventricular function. Circulation 63:285-299, 1981 14. SYNTAX working-group: SYNTAX score calculator. Available at: http://www.syntaxscore. com. Launched May 19, 2009 15. Serruys PW, Onuma Y, Garg S, et al: 5-Year clinical outcomes of the ARTS II (Arterial Revascularization Therapies Study II) of the sirolimus-eluting stent in the treatment of patients with multivessel de novo coronary artery lesions. J Am Coll Cardiol 55:1093-1101, 2010 16. Okwuosa TM, Greenland P, Ning H, et al: Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) po-
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