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The SYNTAX II Score Predicts Mortality at 4 Years in Patients Undergoing Percutaneous Coronary Intervention
Abstract: Background. Short-term outcome after percutaneous coronary intervention (PCI) has improved dramatically, but the association between clinical or angiographic characteristics and long-term outcome remains less well described. The SYNTAX (Synergy Between PCI With TAXUS and Cardiac Surgery) II score has been designed to overcome the limitations of the purely angiographic SYNTAX I score by including clinical parameters and comorbidities. It has not been tested extensively in “real-world” PCI patients, outside of randomized clinical studies. Methods and Results. We identified unique patients undergoing PCI between January 1, 2011 and January 24, 2013 and followed for at least 60 days. We calculated the SYNTAX I and II scores for each patient and collected data at longest follow-up available for vital status, recurrent PCI, systolic heart failure, stroke, or Q-wave myocardial infarction. Cox proportional hazards regression was used to assess independent predictors of mortality. There were 831 patients followed for a mean of 4 years. The average age was 66 ± 10 years. Nearly 40% were women and 50% had diabetes mellitus. The mean follow-up interval was 4 years, during which 42 patients died (Kaplan-Meier rate, 4.3% [IQR, 3.0-6.2%]). The PCI-SYNTAX II score was significantly higher in patients who died than in survivors (43 ± 12 vs 32 ± 12, respectively; P<.001). The SYNTAX II score was the only variable associated with death at a mean follow-up of 4 years (hazard ratio per 1 point, 1.05 [95% confidence interval, 1.03-1.08]; P<.001). Conclusion. The SYNTAX II score, incorporating angiographic and clinical parameters, is a useful tool for risk stratification and prediction of 4-year mortality in “real-world” patients.
J INVASIVE CARDIOL 2018;30(8):290-294. Epub 2018 June 15.
Key words: PCI, SYNTAX II score, mortality
Percutaneous coronary intervention (PCI) is one of the most commonly performed procedures around the world and its outcomes have improved dramatically since its inception four decades ago.1 Many risk scores have been developed to predict in-hospital and longer-term outcomes after PCI.2 Some are based exclusively on angiographic parameters, others on clinical data, and a few combine the two types of information. Nearly 10 years ago, the SYNTAX (Synergy Between PCI With TAXUS and Cardiac Surgery) score was designed specifically to categorize patients enrolled in the SYNTAX trial, comparing PCI with coronary artery bypass grafting (CABG) in patients with multivessel (MV) coronary artery disease (CAD), with or without involvement of the left main coronary artery (LMCA).3 It consists solely of angiographic characteristics of lesions and is calculated using an application developed by the SYNTAX trial investigators considering the following: coronary dominance (left or right), segment involved (in right dominance, 8 for right coronary artery [RCA], 1 for LMCA, 7 for left anterior descending [LAD] coronary artery, and 8 for left circumflex [LCX] artery); and presence of chronic total occlusion, trifurcation or bifurcation, severe tortuosity, heavy calcifications, lesion length >20 mm, and thrombus. All lesions with stenosis >50% by visual estimation are scored, regardless of whether revascularization is performed or not. The score thus represents an objective assessment of burden of CAD, more detailed than the traditional classification of 1-vessel, 2-vessel, or 3-vessel CAD involvement. The SYNTAX II score (SS II) was developed in recognition of the principal limitation of the first SYNTAX score – ie, the lack of any demographic or comorbidity information complementing the angiographic assessment. It includes the SYNTAX I (angiographic) score described above, age, gender, creatinine clearance, LMCA stenosis >50%, and presence of peripheral arterial disease (PAD) or chronic obstructive pulmonary disease (COPD).4 Using 4-year data from the 1800-patient SYNTAX trial, the SS II discriminated well in all patients (CABG or PCI), with c-statistic for internal (SYNTAX trial) validation of 0.73 and for external (DELTA registry) validation of 0.72, which were substantially higher than for the anatomical SYNTAX score alone (c-statistic of 0.57 and 0.61, respectively).
Nevertheless, as these data were obtained from a randomized clinical trial (RCT), we sought to evaluate the utility of the SS II in real-world PCI patients treated at one large-volume institution.
Methods
We identified patients treated with PCI at our institution between January 1, 2011 and January 24, 2013. After excluding patients treated for acute ST-segment elevation myocardial infarction (STEMI), those with cardiogenic shock or cardiac arrest before index PCI (to eliminate very high early mortality), those with previous CABG or undergoing CABG during index hospital stay, and those with intraprocedural death, the SYNTAX I score (SS I) was calculated for each patient by one of three authors (SJB, AR, or AM). The concordance between the readers was assessed by blinded review of 20 randomly selected studies by the senior reviewer and one junior reviewer. Repeat PCI or CABG performed within 60 days of index PCI were reviewed to determine whether they constituted staged, planned revascularization (excluded from endpoint tallying) or not. The residual SYNTAX score (rSS) was calculated after initial PCI and all additional staged procedures.5 Delta SS (DSS) was calculated by subtracting rSS from initial SS I. Subsequently, the charts of all patients were reviewed for demographics, comorbidity assessment, and longest follow-up data available. The SS II score was calculated using the nomogram reported by Farouq et al.4 It is suitable for patients undergoing either surgical or percutaneous revascularization and can be a guide to choosing one of the strategies. We tabulated the PCI-SS II score for each patient. We used the institutional electronic medical record (CernerWorks) and contacted all patients and their physicians of record if follow-up data were not electronically available.
The endpoints considered were mortality, repeat revascularization, stroke, new systolic heart failure, or acute MI with new Q-waves.
All patients were enrolled in the institutional PCI registry at index PCI for state and national mandatory reporting and were offered the option to opt out of follow-up via written notification. Data were collected using the National Cardiovascular Database Registry version 4.0 tool. The institutional Investigational Review Board provides yearly waiver of individual consent if data from the registry are reported in aggregate without personal identifying features. Statistical analysis was performed using STATA SE 14 (StataCorp). The Cohen kappa coefficient was used for concordance between readers of SS.6,7 A logistic regression model was used to assess the independent contribution to Q-wave MI, new systolic heart failure, and repeat revascularization of the four following variables: SS II, rSS (or DSS), presentation with acute coronary syndrome, and diabetes mellitus (DM), in order to avoid over-fitting of the model. Even though DM was not found to predict mortality in SYNTAX, it is a well-established adverse prognostic indicator in patients with CAD.8 Survival analysis and Cox proportional hazards analysis with the same variables as described above were performed using the Kaplan-Meier technique. Stroke was not analyzed with regression modeling because of the small number of events.
Results
We initially identified 2020 procedures performed during the study period. The following exclusions were noted: prior CABG (n = 319); intraprocedural death (n = 3); cardiogenic shock or cardiac arrest before PCI (n = 21); CABG during index admission (n = 9); STEMI (n = 135); follow-up <60 days (n = 28); non-unique patients, including non-staged procedures (n = 271); and patients who could not be reached directly or via their physician of record and had no additional encounter in our electronic medical record (n = 403), leaving 831 patients eligible for the study (Figure 1). Their baseline characteristics are shown in Table 1. The average age was 66 ± 10 years. Nearly 40% were women and 50% had DM. The mean follow-up interval was 4 years, during which 42 patients died, resulting in an overall mortality rate of 4.3% (95% confidence interval [CI], 3.0-6.2) (Figure 2). The estimated mortality rate was 11.6% (95% CI, 7.5-17.7) in the 211 patients with chronic kidney disease (CKD) vs 2.0% (95% CI, 1.1-3.7) in those without CKD (defined as clearance <60 mL/min/1.73 m2) (P<.001). In addition, there were 15 strokes (1.8%), 41 Q-wave MIs (5.0%), 131 diagnoses of new systolic heart failure (16.1%), and 268 repeat unplanned PCIs (32.7%).
The kappa for concordance (for absolute variation of two points) of SS I reading between the senior reader and each of the junior readers was 0.64 and 0.66, respectively. The PCI-SS II was significantly higher in patients who died than in survivors (43 ± 12 vs 32 ± 12, respectively; P<.001). SS I was not different among these two groups (12 ± 8 vs 10 ± 8, respectively; P=.14). Similar results were noted for rSS (5 ± 7 vs 4 ± 5, respectively; P=.06) and DSS (7 ± 5 vs 7 ± 6, respectively; P=.72). SS I was not associated with death by univariate analysis (odds ratio per 1 point, 1.02 [95% CI, 0.98-1.06]; P=.29).
In the multivariable regression analysis (Table 2), SS II was the only variable associated with death at a mean follow-up of 4 years (hazard ratio per 1 point, 1.05 [95% CI, 1.03-1.08]; P<.001). DM (P=.27), ACS (P=.54), and rSS (P=.19) were not independent predictors of mortality. The c-statistic for the model was 0.75 (P<.001) and goodness-of-fit was acceptable (Hosmer-Lemeshow P=.36). Substituting DSS for rSS did not substantially affect the model results. SS II was also independently associated with the development of systolic heart failure.
We repeated the analyses by inputting outcomes data for the 431 patients with insufficient or no follow-up. There was no significant change in the results shown in Table 2.
Discussion
In a cohort of consecutive patients undergoing PCI in 2011-2012, we found that: (1) the SS II is an independent predictor of 4-year mortality. An increase of 5 points would predict a 30% increase in mortality; as SS I was not associated with mortality, the clinical parameters encapsulated in SS II must be responsible for this association; (2) CKD is confirmed again as a powerful modifier of outcomes in patients with CAD, while DM did not affect mortality; and (3) the SS II score predicts not just mortality, but also new systolic heart failure.
\The mean SS II in our cohort was 32 (median, 31), which would correspond to a predicted 4-year mortality of ~7% (Figure 3), significantly higher than what we observed. This is likely related to the fact that the extent of CAD was much lower in these patients than in those enrolled in the SYNTAX trial, as evidenced by the much lower SS I (11 vs 29, respectively). Furthermore, there were few patients with LMCA involvement in our cohort, compared with 33% in SYNTAX.
Cavalcante et al systematically analyzed patients with MV-CAD and DM enrolled in three trials – SYNTAX, PRECOMBAT, and BEST – in order to determine whether SS II could be validated in a non-SYNTAX RCT. SS II showed equally acceptable discrimination for 4-year mortality in patients with DM (c-statistic, 0.68) and without DM (c-statistic, 0.67).9 Our model for mortality had a higher discrimination (c-statistic, 0.75) and confirmed that DM was not an independent predictor of 4-year mortality.
Farooq et al expanded the SYNTAX II score to include body mass index, presentation with ACS, DM with insulin or oral agents, previous MI, and current smoking (Figure 4). They tested this expanded model in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial and found that the expanded (logistic clinical SYNTAX) score improved discrimination significantly for 1-year mortality compared to SS I (from 0.64 to 0.83; P<.01).10 These observations are relevant to our study because the mean SS I in ACUITY was 9, which is similar to our cohort.
Besides these large datasets in RCTs, there is little information on the utility of SS II in real-world practice. Salvatore et al calculated SS II in 100 ACS patients undergoing PCI (median SS II of 29, similar to our cohort) and found that SS II above the median was an independent predictor of major adverse cardiac and cerebral events (MACCE) at 1 year (hazard ratio, 2.74 [95% CI, 1.30-8.21]; P=.01), but was not a predictor of death alone, as our results indicated.11 The largest observational study comes from Song et al, who examined 4398 consecutive patients undergoing three-vessel and/or unprotected LMCA-PCI at a single center from January 2013 to December 2013.12 The SS II was divided in tertiles (with cut-off points at 20 and 26). Mortality was significantly higher in the upper tertile than in the intermediate or lower tertiles during the 2-year follow-up (2.7% vs 1.7% vs 0.5%, respectively; P<.001). Multivariate analysis showed that SS II was an independent predictor of 2-year mortality (hazard ratio, 1.66 [95% CI, 1.03-2.68]; P=.04). SS II had better discrimination for 2-year mortality than SS I (c-statistics 0.74 vs 0.62, respectively; P<.001). It was notable that even though this series addressed only patients with extensive CAD, their median SS II was lower than ours, suggesting a lower burden of comorbidity. Even the SS I average varied between only 12 and 19, all lower than the lowest tertile in the SYNTAX trial.
Study limitations. We recognize that the data presented in this manuscript have important limitations, some of which are inherent to observational studies. Our follow-up interval was not uniform (although 94% of the cohort had >1 year of follow-up) and we did not have access to the National Death Index to ascertain vital statuses of those we could not reach. It is possible that some non-fatal events were not reported in the electronic medical record or by the patients themselves, and we did not have precise timing of some non-fatal events that were reported to us. We did not have the ability to clearly identify causes of death, particularly when it occurred outside the hospital. Ultimately, only 40% of the procedures performed in this interval were finally considered for the study, limiting the generalizability of our findings.
Conclusion
Despite these limitations, we conclude that the SS II, incorporating anatomical, demographic, and clinical parameters, is a useful tool for risk stratification and prediction of 4-year mortality in a real-world group of patients with varying degrees of CAD undergoing PCI for various clinical indications. It is superior to the anatomical SS I and should be considered as a tool for advising patients on prognosis after PCI.
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From the New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Brener reports speaker’s bureau personal fees from Astra Zeneca. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 26, 2018, final version accepted April 5, 2018.
Address for correspondence: Sorin J. Brener MD, FACC, Professor of Medicine, NY Presbyterian Brooklyn Methodist Hospital, 506 6th Street, Brooklyn, NY 11215. Email: sjb9005@nyp.org
