• SYNTAX Score II 2020 Validated for 5-Year Mortality Risk

    The SYNTAX score II 2020 (SSII-2020) for predicting 5-year death has the potential to support decision making on revascularization in patients with three-vessel disease (3VD) or left main coronary artery disease (LMCAD), a new analysis reports.

    Published online Monday and in the Sept. 21 issue of the Journal of the American College of Cardiology, the study noted that current guidelines recommend a heart-team discussion when deciding upon the optimal revascularization strategy in patients with multivessel disease or LMCAD – noting that multiple factors are at play in the decision, including the individual risks for percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG) surgery based on the patient’s clinical comorbidities, and the anatomical complexity of their coronary artery disease (CAD).

    “The SYNTAX score II was developed using the predictors of 4-year mortality in the SYNTAX trial to support decision making, and its utility has been externally validated in real-world registries and randomized trial populations,” noted the researchers, led by Hironori Hara, MD, from the University of Amsterdam, National University of Ireland and The University of Tokyo.

    However, following the collection of mortality outcomes at 10-year follow-up in the SYNTAXES study, the SSII-2020 was developed.

    This new score predicts 5- and 10-year mortality rates and 5-year major adverse cardiac and cerebrovascular events (MACCE) rates for both revascularization modalities and the resulting absolute risk difference (ARD). However, the score does not make any formal binary recommendation on the preferred modality of revascularization.

    “The aim of the present study was to investigate the clinical prognostic value of the SSII-2020 score and to evaluate its ability to predict treatment benefit for CABG vs PCI to support clinical decision-making among patients with complex CAD,” the authors said.

    Study details

    Hara and colleagues analyzed 5-year mortality and MACCE in 7,362 patients with 3VD and/or LMCAD enrolled in Cohorts 2 and 3 of the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) PCI/CABG registry.

    The discriminative abilities of SSII-2020 were assessed using Harrell’s C statistic, and agreement between observed and predicted event rates following PCI or CABG and treatment benefit (ARD) for the outcomes were assessed by calibration plots.

    Relating to 5-year mortality, SSII-2020 predicted the prognosis after PCI and CABG well, said the team (C-index = 0.72, intercept = -0.11, slope = 0.92).

    When patients were grouped according to the predicted 5-year mortality, an ARD of less than 4.5% showed equipoise of PCI and CABG, while an ARD ≥4.5% favored CABG. The observed mortality rates after PCI and CABG were not significantly different in patients with lower predicted ARD (observed ARD: 2.1% [95% confidence interval [CI]: -0.4% to 4.4%]), and a significant difference in survival in favor of CABG was observed in patients with higher predicted ARD (observed ARD: 9.7% [95% CI: 6.1% to 13.3%]).

    However, for MACCE, the SSII-2020 could not recommend a specific treatment with sufficient accuracy, the researchers said.

    The team concluded that SSII-2020 for 5-year mortality well predicted the prognosis after PCI and CABG and, therefore, has the potential to support decision making on revascularization in patients with 3VD or LMCAD. However, they added that further research could enhance the predictive accuracy of the SSII-2020 and derivatives for longer-term outcomes and support clinical decisions involving the selection of revascularization methods for patients with left main or multivessel coronary disease.

    More than a Hollywood remake?

    Writing in an accompanying editorial, John J. Squiers, MD, and J. Michael DiMaio, MD, from the Baylor Scott & White The Heart Hospital in Plano, Texas, said the SYNTAX score has been widely applied in clinical trial design and clinical practice to objectively measure and stratify the anatomical CAD – noting that calculation of the SYNTAX score to inform heart-team decision-making for patients with multivessel CAD was also recommended in the 2014 American guidelines and 2018 European guidelines.

    “Perhaps taking a cue from Hollywood—an industry yet to find a commercially successful film that cannot be remade for a newer generation of movie-goers—the SYNTAX investigators have recently redeveloped the SSII-2020 using the 10-year outcomes,” said the expert commentators.

    “Like any worthwhile remake, the SSII-2020 incorporates many recognizable features of its predecessor but not without a twist—patient sex was discarded from the prior model, whereas diabetes and current smoking were added as predictive variables in the remake.”

    The editorialists said the new analysis by Hara and colleagues provides “a clinically useful interpretation” of their sophisticated analytic methods – noting that similar to the original validation paper, the new study reports erudite metrics such as C-index, slope, intercept and others that would be challenging to translate clinically into the internal discussion of a heart team, let alone into informative conversations with patients.

    “Fortunately, the authors have recognized this reality and provided a practical solution—one that should be the main take-away from the paper for most readers,” they said, noting that a unique feature of the SSII-2020 is that it predicts mortality risks for PCI and CABG individually, therefore allowing for quantitative comparisons – set out as ARDs – between these coronary revascularization therapies for any given patient.

    “Using an ARD cutoff of 4.5%, the authors have identified a subgroup of patients for whom CABG is most likely to improve survival,” they commented, adding that although ARD might not be a familiar statistic to many clinicians, the concept is readily understandable and made even easier by the availability of online and app-based SSII-2020 calculators.

    Real-world implementation

    Squiers and DiMaio said the use of SSII-2020 calculators can facilitate real-world, clinical implementation of a score that is the first validated for direct comparison of expected outcomes after CABG and PCI.

    “In particular, the SSII-2020 may provide objective data to inform and to support a heart team decision for maximally invasive CABG over minimally invasive PCI in appropriate patients,” they said.

    However, the experts noted that longer-term validation in diverse populations is required before use of the SSII-2020 can be recommended ubiquitously, but they conceded that such validation may be particularly challenging with currently available data given that most randomized trials have not (or will not) report 10-year outcomes and most real-world registries lack sufficient duration of follow-up.

    “As future randomized trials are designed, investigators should strongly consider prospectively capturing data necessary to calculate and validate the SSII-2020 in their study population,” they said.


    Hara H, Shiomi H, van Klaveren D, et al. External Validation of the SYNTAX Score II 2020. J Am Coll Cardiol 2021;78:1227-1238.

    Squiers JJ, DiMaio JM. SYNTAX Score II 2020: A Remake Worth the Price of Admission? J Am Coll Cardiol 2021;78:1239-1241.

    Image Credit: 7activestudio – stock.adobe.com

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