Editorial Angiology 1-3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714562244 ang.sagepub.com
Predictive Value of the Logistic Clinical SYNTAX Score Amisha Nibber, MD1, Khaled M. Ziada, MD1, and Thomas F. Whayne Jr, MD, PhD1
The SYNTAX score was developed for use in the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial as an objective and comprehensive angiographic tool to grade the complexity of coronary artery disease (CAD) before randomizing patients to coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The primary objective of the scoring system was to define technical complexity and feasibility of PCI.1 At the conclusion of the trial, additional advantages of the SYNTAX score were appreciated, that is, it was a strong predictor of adverse outcomes in the PCI group and it defined subsets of patients in whom PCI resulted in similar or inferior outcomes compared with CABG.2,3 Nevertheless, the SYNTAX scoring system has many limitations, the most important of which is its pure angiographic nature, that is, it does not incorporate clinical variables that influence procedural and patient outcomes. Additionally, it may include lesions that are not hemodynamically significant, and it does not predict outcomes of patients undergoing CABG in the original SYNTAX trial population.2-6 Since the development of the SYNTAX score, a number of risk models have been developed to enhance prognostic stratification in complex PCI.4 While employing the basic angiographic anatomical variables of the original score, the modified risk models incorporate major clinical variables known to influence outcomes of PCI patients in particular and CAD patients in general. The combination of the angiographic SYNTAX score with the clinical variables comprising the European System for Cardiac Risk Evaluation (EuroSCORE) (typically used for patients with CABG) led to the Global Risk Classification (GRC) model.7,8 The multiplication of the age, creatinine level, and ejection fraction score and the SYNTAX score resulted in Clinical SYNTAX score (CSS)9 and its logistic derivative, log CSS.10 More recently, the proposed SYNTAX score II includes the original anatomic score in addition to 7 clinical variables.11 These, as well as a few other, combined risk models were designed to optimize the selection of the revascularization approach, provide better prognostic information, and can be individualized rather than placing single patients into risk categories.
In this issue of Angiology, Ozturk et al attempt to use log CSS, a combined angiographic/clinical scoring system developed for and validated in PCI patients,10,12 for the prediction of saphenous vein graft (SVG) failure plus major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing CABG surgery.13 They included 267 patients who were followed up clinically with indicated coronary angiography at varying time points following CABG surgery. In addition to low ejection fraction, a high log CSS was found to be predictive of SVG failure (odds ratio 2.21, 95% confidence interval 1.02-4.75, P ¼ .04). Semiquantitatively, the incidence of graft failure increased in a stepwise fashion in intermediate and high tertiles of log CSS. Both the SYNTAX score and the log CSS were associated with an increased risk of MACCE (P ¼ .001 and P < .001, respectively). Although the sample is small and selected based on clinical events, the use of the log CSS in predicting outcomes of patients with CABG has not been previously reported. Traditionally, risk models of PCI and CABG have been distinct entities that are not used interchangeably. Given the fundamental differences between the 2 revascularization approaches, this is not surprising. Percutaneous coronary intervention is a segmental therapeutic approach in which the feasibility and procedural outcomes are directly linked to the nature and complexity of the target lesion and the target segment. Coronary artery bypass graft surgery involves the creation of a parallel conduit in which the target lesion and segment are not dealt with directly, hence the outcome is more related to the quality of the runoff distal vessel than it is related to the proximal diseased segment. As such, risk models that focus on the lesion characteristics, such as the SYNTAX score, are not expected to provide insight into the outcome of CABG surgery. Despite these
1
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA
Corresponding Author: Thomas F. Whayne Jr, University of Kentucky, 326 Wethington Bldg, 900 South Limestone St, Lexington, KY 40536, USA. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
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Angiology
fundamental differences, a few common features do exist between patients undergoing PCI and CABG surgery. First, both have advanced CAD, the outcome of which is more determined by patient-related or clinical characteristics such as age, ventricular function, renal function, and peripheral arterial disease. Second, patients with complex and multiple lesions are more likely to have more advanced stages of disease, thus those with higher lesion complexity are also more likely to have higher plaque burden and more diffuse disease affecting their distal vessels. These principles are clearly demonstrated by the application of the anatomic SYNTAX score and the more clinical or combined log CSS to the population with CABG by Ozturk et al.13 While the first was not helpful in predicting SVG failure, the second was highly predictive. Knowing the difference between the 2 scoring systems, it is clear that the enhanced risk stratification provided by the log CSS is primarily due to the impact of the clinical variables incorporated in the log CSS formula. Multiple other variables such as metabolic and inflammatory disorders may ultimately have to be considered in such formulas.14 Nevertheless, the potential effect of advanced target segment disease in patients with higher log CSS scores cannot be refuted with certainty, given the importance of this variable in predicting SVG failure. The small sample size does not allow for further dissection of the data to delineate the effect of other technical factors known to contribute to SVG failure.15 The association between the log CSS and MACCE in this article13 is not surprising, given the well-established impact of age, ejection fraction, and renal function on adverse outcomes in all subsets of patients with CAD. However, the association between the SYNTAX score and adverse events in this seems to contradict findings by others. In a larger sample, Mohr et al found no relationship between the scoring system and adverse outcomes.6 Several explanations for this discrepancy can be put forward. In this work by Ozturk et al,13 selection bias was introduced by including only patients who underwent repeat angiography for a clinical indication, whereas Mohr et al performed a systematic follow-up of a prospectively designed trial (the SYNTAX trial and the associated registry).6 The extended and uncontrolled timing of follow-up after CABG surgery may have also biased the sample toward those with more advanced disease, whereas the SYNTAX data set follow-up was uniformly done at 2 years. Finally, the small sample may have allowed for chance findings.13 In conclusion, this original application of the log CSS to a population with CABG and the demonstration of a predictive value of the risk model in defining the risk of SVG failure13 provide hope that a uniform risk model can be designed for risk stratification prior to coronary revascularization, regardless of the approach. The GRC and the SYNTAX II are other risk models that have undergone more robust validation.7,8,11 The data set of Ozturk et al13 provides a degree of validation for the log CSS model that may be easier to use by clinicians
attempting to select the optimal revascularization approach in patients with complex CAD. References 1. Sianos G, Morel MA, Kappetein AP, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. Eurointervention. 2005;1(2):219-227. 2. 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(10): 961-972. 3. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629-638. 4. Capodanno D. Beyond the SYNTAX score–advantages and limitations of other risk assessment systems in left main percutaneous coronary intervention. Circ J. 2013;77(5):1131-1138. 5. Serruys PW, Onuma Y, Garg S, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5(1):50-56. 6. 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. 2011;141(1):130-140. 7. 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. JACC Cardiovasc Interv. 2011;4(3): 287-297. 8. Serruys PW, Farooq V, Vranckx P, Girasis C, Brugaletta S, Garcia-Garcia HM, et al. A global risk approach to identify patients with left main or 3-vessel disease who could safely and efficaciously be treated with percutaneous coronary intervention: the SYNTAX Trial at 3 years. JACC Cardiovasc Interv. 2012;5(6):606-617. 9. 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(4): 317-326. 10. Farooq V, Vergouwe Y, Raber L, et al. Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score. Eur Heart J. 2012;33(24): 3098-3104. 11. Farooq V, van Klaveren D, Steyerberg EW, et al. Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. Lancet. 2013;381(9867):639-650. 12. Iqbal J, Vergouwe Y, Bourantas CV, Klaveren DV, Zhang YJ, Campos CM, et al. Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
Nibber et al
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based on patient-level data from 7 contemporary stent trials. JACC Cardiovasc Interv. 2014;7(5):464-470. 13. Ozturk D, Celik O, Cakmak HA, et al. Usefulness of the logistic clinical SYNTAX score in prediction saphenous vein graft failure in patients undergoing coronary artery bypass grafting [published online November 10, 2014]. Angiology. 2014. doi:10.1177/ 0003319714557539.
14. Katsiki N, Athyros VG, Karagiannis A, Wierzbicki AS, Mikhailidis DP. Should we expand the concept of coronary heart disease equivalents? Curr Opin Cardiol. 2014;29(4): 389-395. 15. Hess CN, Lopes RD, Gibson CM, et al. Saphenous Vein Graft Failure After Coronary Artery Bypass Surgery: Insights From PREVENT IV. Circulation. 2014;130(17):1445-1451.
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
Predictive Value of the Logistic Clinical SYNTAX Score Amisha Nibber, MD1, Khaled M. Ziada, MD1, and Thomas F. Whayne Jr, MD, PhD1
The SYNTAX score was developed for use in the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial as an objective and comprehensive angiographic tool to grade the complexity of coronary artery disease (CAD) before randomizing patients to coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The primary objective of the scoring system was to define technical complexity and feasibility of PCI.1 At the conclusion of the trial, additional advantages of the SYNTAX score were appreciated, that is, it was a strong predictor of adverse outcomes in the PCI group and it defined subsets of patients in whom PCI resulted in similar or inferior outcomes compared with CABG.2,3 Nevertheless, the SYNTAX scoring system has many limitations, the most important of which is its pure angiographic nature, that is, it does not incorporate clinical variables that influence procedural and patient outcomes. Additionally, it may include lesions that are not hemodynamically significant, and it does not predict outcomes of patients undergoing CABG in the original SYNTAX trial population.2-6 Since the development of the SYNTAX score, a number of risk models have been developed to enhance prognostic stratification in complex PCI.4 While employing the basic angiographic anatomical variables of the original score, the modified risk models incorporate major clinical variables known to influence outcomes of PCI patients in particular and CAD patients in general. The combination of the angiographic SYNTAX score with the clinical variables comprising the European System for Cardiac Risk Evaluation (EuroSCORE) (typically used for patients with CABG) led to the Global Risk Classification (GRC) model.7,8 The multiplication of the age, creatinine level, and ejection fraction score and the SYNTAX score resulted in Clinical SYNTAX score (CSS)9 and its logistic derivative, log CSS.10 More recently, the proposed SYNTAX score II includes the original anatomic score in addition to 7 clinical variables.11 These, as well as a few other, combined risk models were designed to optimize the selection of the revascularization approach, provide better prognostic information, and can be individualized rather than placing single patients into risk categories.
In this issue of Angiology, Ozturk et al attempt to use log CSS, a combined angiographic/clinical scoring system developed for and validated in PCI patients,10,12 for the prediction of saphenous vein graft (SVG) failure plus major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing CABG surgery.13 They included 267 patients who were followed up clinically with indicated coronary angiography at varying time points following CABG surgery. In addition to low ejection fraction, a high log CSS was found to be predictive of SVG failure (odds ratio 2.21, 95% confidence interval 1.02-4.75, P ¼ .04). Semiquantitatively, the incidence of graft failure increased in a stepwise fashion in intermediate and high tertiles of log CSS. Both the SYNTAX score and the log CSS were associated with an increased risk of MACCE (P ¼ .001 and P < .001, respectively). Although the sample is small and selected based on clinical events, the use of the log CSS in predicting outcomes of patients with CABG has not been previously reported. Traditionally, risk models of PCI and CABG have been distinct entities that are not used interchangeably. Given the fundamental differences between the 2 revascularization approaches, this is not surprising. Percutaneous coronary intervention is a segmental therapeutic approach in which the feasibility and procedural outcomes are directly linked to the nature and complexity of the target lesion and the target segment. Coronary artery bypass graft surgery involves the creation of a parallel conduit in which the target lesion and segment are not dealt with directly, hence the outcome is more related to the quality of the runoff distal vessel than it is related to the proximal diseased segment. As such, risk models that focus on the lesion characteristics, such as the SYNTAX score, are not expected to provide insight into the outcome of CABG surgery. Despite these
1
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA
Corresponding Author: Thomas F. Whayne Jr, University of Kentucky, 326 Wethington Bldg, 900 South Limestone St, Lexington, KY 40536, USA. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
2
Angiology
fundamental differences, a few common features do exist between patients undergoing PCI and CABG surgery. First, both have advanced CAD, the outcome of which is more determined by patient-related or clinical characteristics such as age, ventricular function, renal function, and peripheral arterial disease. Second, patients with complex and multiple lesions are more likely to have more advanced stages of disease, thus those with higher lesion complexity are also more likely to have higher plaque burden and more diffuse disease affecting their distal vessels. These principles are clearly demonstrated by the application of the anatomic SYNTAX score and the more clinical or combined log CSS to the population with CABG by Ozturk et al.13 While the first was not helpful in predicting SVG failure, the second was highly predictive. Knowing the difference between the 2 scoring systems, it is clear that the enhanced risk stratification provided by the log CSS is primarily due to the impact of the clinical variables incorporated in the log CSS formula. Multiple other variables such as metabolic and inflammatory disorders may ultimately have to be considered in such formulas.14 Nevertheless, the potential effect of advanced target segment disease in patients with higher log CSS scores cannot be refuted with certainty, given the importance of this variable in predicting SVG failure. The small sample size does not allow for further dissection of the data to delineate the effect of other technical factors known to contribute to SVG failure.15 The association between the log CSS and MACCE in this article13 is not surprising, given the well-established impact of age, ejection fraction, and renal function on adverse outcomes in all subsets of patients with CAD. However, the association between the SYNTAX score and adverse events in this seems to contradict findings by others. In a larger sample, Mohr et al found no relationship between the scoring system and adverse outcomes.6 Several explanations for this discrepancy can be put forward. In this work by Ozturk et al,13 selection bias was introduced by including only patients who underwent repeat angiography for a clinical indication, whereas Mohr et al performed a systematic follow-up of a prospectively designed trial (the SYNTAX trial and the associated registry).6 The extended and uncontrolled timing of follow-up after CABG surgery may have also biased the sample toward those with more advanced disease, whereas the SYNTAX data set follow-up was uniformly done at 2 years. Finally, the small sample may have allowed for chance findings.13 In conclusion, this original application of the log CSS to a population with CABG and the demonstration of a predictive value of the risk model in defining the risk of SVG failure13 provide hope that a uniform risk model can be designed for risk stratification prior to coronary revascularization, regardless of the approach. The GRC and the SYNTAX II are other risk models that have undergone more robust validation.7,8,11 The data set of Ozturk et al13 provides a degree of validation for the log CSS model that may be easier to use by clinicians
attempting to select the optimal revascularization approach in patients with complex CAD. References 1. Sianos G, Morel MA, Kappetein AP, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. Eurointervention. 2005;1(2):219-227. 2. 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(10): 961-972. 3. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629-638. 4. Capodanno D. Beyond the SYNTAX score–advantages and limitations of other risk assessment systems in left main percutaneous coronary intervention. Circ J. 2013;77(5):1131-1138. 5. Serruys PW, Onuma Y, Garg S, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5(1):50-56. 6. 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. 2011;141(1):130-140. 7. 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. JACC Cardiovasc Interv. 2011;4(3): 287-297. 8. Serruys PW, Farooq V, Vranckx P, Girasis C, Brugaletta S, Garcia-Garcia HM, et al. A global risk approach to identify patients with left main or 3-vessel disease who could safely and efficaciously be treated with percutaneous coronary intervention: the SYNTAX Trial at 3 years. JACC Cardiovasc Interv. 2012;5(6):606-617. 9. 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(4): 317-326. 10. Farooq V, Vergouwe Y, Raber L, et al. Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score. Eur Heart J. 2012;33(24): 3098-3104. 11. Farooq V, van Klaveren D, Steyerberg EW, et al. Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. Lancet. 2013;381(9867):639-650. 12. Iqbal J, Vergouwe Y, Bourantas CV, Klaveren DV, Zhang YJ, Campos CM, et al. Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
Nibber et al
3
based on patient-level data from 7 contemporary stent trials. JACC Cardiovasc Interv. 2014;7(5):464-470. 13. Ozturk D, Celik O, Cakmak HA, et al. Usefulness of the logistic clinical SYNTAX score in prediction saphenous vein graft failure in patients undergoing coronary artery bypass grafting [published online November 10, 2014]. Angiology. 2014. doi:10.1177/ 0003319714557539.
14. Katsiki N, Athyros VG, Karagiannis A, Wierzbicki AS, Mikhailidis DP. Should we expand the concept of coronary heart disease equivalents? Curr Opin Cardiol. 2014;29(4): 389-395. 15. Hess CN, Lopes RD, Gibson CM, et al. Saphenous Vein Graft Failure After Coronary Artery Bypass Surgery: Insights From PREVENT IV. Circulation. 2014;130(17):1445-1451.
Downloaded from ang.sagepub.com at UNIV NEBRASKA LIBRARIES on December 31, 2014
