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  • Functional SYNTAX Score Predicts Similar Outcome with PCI, CABG for Half of 3-Vessel CAD Patients – FAME-3 Substudy

    Measuring functional SYNTAX score (FSS) in patients with angiographic three-vessel coronary artery disease (3VD) can predict half of patients who would have similar 1-year clinical outcomes whether they underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), according to a subgroup analysis of the FAME 3 trial.

    These data were reported by Yuhei Kobayashi, MD, of the New York Presbyterian Brooklyn Methodist Hospital, and colleagues, in a manuscript published Monday online and in the Sept. 11 issue of JACC: Cardiovascular Interventions.

    The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial demonstrated that fractional flow reserve (FFR)-guided PCI using current-generation drug-eluting stents did not meet the criteria for non-inferiority compared with CABG among patients with angiographic 3VD.

    The current American College of Cardiology/American Heart Association coronary revascularization guidelines recommend the evaluation of coronary artery disease complexity based on the traditional anatomic SYNTAX score and limiting PCI to patients with scores ≤22.

    The FSS incorporates physiological significance of lesions based on their FFR values to predict outcomes after PCI. This FAME 3 substudy investigated whether FSS identified a larger proportion of patients with more complex 3VD who underwent PCI and had a similar outcome to CABG.

    This prespecified subgroup analysis comprised the same patient population as FAME 3, an international, multicenter, randomized, controlled trial that included 48 sites. The major inclusion criteria were the presence of 3VD defined as ≥50% diameter stenosis of three epicardial coronary vessels, excluding the left main coronary artery, and amenable to revascularization by either PCI or CABG per local heart team discussion. Patients with a recent ST-segment elevation myocardial infarction (MI), cardiogenic shock, and a left ventricular ejection fraction <30% were excluded. 

    The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, MI, stroke, or any repeat revascularization at 1 year after the index procedure. Outcomes in patients without functionally significant 3VD were compared with those in patients with functionally significant 3VD and CABG. Finally, lesion-level analysis was performed to investigate the event rate from lesions deferred based on FFR and compared to the event rate in stented lesions.

    FFR was measured using a 0.014-inch pressure sensor guidewire (Abbott Vascular Inc.) in the usual fashion. For bifurcation lesions, the artery to be assessed with FFR was up to the operator’s discretion, although only one value was assigned to a bifurcation lesion. A default value of 0.50 was applied to chronic total occlusions that underwent revascularization without FFR assessment.

    The calculation of FSS was not feasible in the CABG arm, as only 10% of the patients underwent FFR assessment before CABG. To calculate FSS, the SYNTAX scores of lesions with a negative FFR (>0.80) were removed. The number of functionally significant vessels was also calculated, as some patients with angiographic 3VD had vessels without functionally significant lesions on FFR assessment.

    This study analyzed 733 patients who underwent PCI and 743 patients who underwent CABG with interpretable angiograms before the index procedure. Baseline characteristics were similar in patients with low and high FSSs, and 40% of the patients presented with acute coronary syndrome. The patients’ mean age was approximately 65 years and most (80.8%) were male and Caucasian (94.1%).

    Patients who underwent PCI had a mean FSS of 22.7±8.5, with 27% of patients reclassified from a SYNTAX score >22 to FSS ≤22. Upon incorporating FSS, 66.6% of the patients undergoing PCI had functionally significant 3VD. Patients with high FSS (>22) tended to have more anatomically complex disease, with a greater number of chronic total occlusions, bifurcation lesions, longer lesions, and heavily calcified lesions than patients with low FSS (≤22).

    Regarding the primary endpoint, patients randomized to PCI who had a low FSS had a significantly lower rate of MACCE at 1 year than those with a high FSS (6.3% vs. 15.1%, log-rank P <0.001), predominantly driven by a lower rate of revascularization. The MACCE rate in the low FSS group, which comprised 50% of all patients undergoing PCI, was similar to the MACCE rate in patients assigned to CABG (P = 0.77). The primary endpoint in patients without functionally significant 3VD who underwent PCI was similar to CABG (P = 0.97). The rates of MI and revascularization among all the deferred lesions were 0.5% and 3.2%, respectively.  

    In FAME 3, only one-third of the patients randomized to PCI had a low anatomic SYNTAX score ≤22, although these patients had a similar MACCE rate at 1 year compared with patients undergoing CABG.

    This substudy found that incorporation of the FSS resulted in a reclassification of disease complexity, with 50% of all PCI patients having low-complexity disease based on an FSS ≤22. Patients with a low FSS who underwent PCI had a similar MACCE rate at 1 year compared with patients assigned to CABG, and FSS was an independent predictor of MACCEs in patients randomized to PCI in the multivariable model. Additionally, the MACCE rate in patients randomized to PCI with one or two functionally nonsignificant vessels was similar to that in patients who underwent CABG.

    These findings support that FSS may identify more patients with 3VD who can achieve a similar outcome with PCI compared to CABG than the anatomic SYNTAX score. Furthermore, another important finding was that the rates of MI and revascularization were low in lesions in which PCI was deferred based on FFR, suggesting the safety of deferring PCI in functionally nonsignificant lesions, even in the setting of acute coronary syndrome or complex disease.

    Some limitations of this study include inadequate statistical power for comparisons among subgroups, a small number of unavailable angiograms for analysis, and the lack of FFR information in the CABG arm, although previous studies evaluating the role of FFR in guiding CABG have not shown a significant benefit compared to angiographic guidance alone.

    Overall, this FAME 3 substudy showed that the functional SYNTAX score identified a greater proportion of patients with angiographic 3VD who had a similar 1-year outcome with PCI compared with CABG. This study highlights the role of combining functional with anatomical information in determining an optimal revascularization strategy for patients.

    In an accompanying editorial, Patrick W. Serruys, MD, PhD, of the University of Galway, Ireland, one of the principal creators of the anatomic SYNTAX score, commended the investigators for the present study, as it highlighted the importance of functional revascularization in patients with angiographic 3VD, building upon prior work investigating functionally guided PCI.

    He concluded that interventional cardiologists and cardiothoracic surgeons should use state-of-the-art practices regarding appropriate patient selection, preprocedural functional evaluation, intravascular imaging to optimize PCI results, use of multiple arterial grafts during CABG, and postprocedural functional evaluation to improve patient outcomes.


    Kobayashi Y, Tatsunori T, Zimmermann FM, et al. Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Artery Disease. JACC Cardiovasc Interv. 2023;16:2112–2119.

    Serruys PW, Revaiah PC, Onuma Y. Refining and Personalizing Prediction: Anatomical to Functional Prognostic Scores in the Era of State-of-the-Art Revascularization. JACC Cardiovasc Interv. 2023;16:2120–2124.

    Image Credit: Kien –

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