γ-Glutamyl Transferase and Long-Term Survival in the SYNTAXES Trial: Is It Just the Liver?

BACKGROUND: Recently, machine learning algorithms have identified preprocedural γ-glutamyl transferase (GGT) as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX (Synergy Between PCI [Percutaneous Coronary Intervention] With Taxus and Cardiac Surgery) trial. The aim of the present study is to investigate the impact of preprocedural GGT on 10-year all-cause mortality in patients with complex coronary artery disease after revascularization. METHODS AND RESULTS: The SYNTAX trial was a randomized trial comparing PCI with coronary artery bypass grafting in 1800 patients with complex coronary artery disease. The present report is a post hoc subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) trial, an investigator-driven extended 10-year follow-up of the SYNTAX trial. The association between preprocedural GGT and 10-year all-cause mortality was investigated. The mean values of GGT for men and women were 43.5 (SD, 48.5) and 36.4 (SD, 46.1) U/L, respectively. In multivariable Cox regression models adjusted by traditional risk factors, GGT was an independent predictor for all-cause death at 10-year follow-up, and each SD increase in log-GGT was associated with a 1.24-fold risk of all cause death at 10-year follow-up (95% CI, 1.10-1.40). According to previously reported sex-related GGT thresholds, patients with higher GGT level had a 1.74-fold risk of all-cause death at 10-year follow-up (95% CI, 1.32-2.29) compared with patients with lower GGT level. CONCLUSIONS: Preprocedural GGT is an independent predictor of 10-year mortality after coronary revascularization in patients with complex coronary artery disease. In patients with elevated GGT, strong secondary prevention may be required after revascularization and must be studied prospectively. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT03417050.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Five-year outcomes in patients with multivessel coronary artery disease undergoing surgery or percutaneous intervention.

The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)-356 patients or percutaneous coronary intervention (PCI)-679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P < 0.01 and 26.8% vs. 12.6%, P < 0.01, respectively), while CABG-patients experienced stroke more often (7.3% vs. 3.1% for PCI, P < 0.01). In real-life practice with long-term follow-up, none of the two revascularization modalities implemented following HT decisions showed overwhelming superiority: occurrence of death and MI were similar, rates of RR favoured CABG, while incidence of strokes advocated PCI.

Impact of left ventricular ejection fraction on 10-year mortality in the SYNTAX trial.

BACKGROUNDS: The impact of reduced left ventricular ejection fraction (LVEF) on very long-term prognosis following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) has been debated. The aim of this study was to investigate the impact of LVEF at baseline on 10-year mortality in the SYNTAX trial. METHODS: Patients (n = 1800) were categorized into three sub-groups: reduced (rEF ≤ 40 %), mildly reduced (mrEF 41-49 %), and preserved LVEF (pEF ≥ 50 %). The SYNTAX score 2020 (SS-2020) was applied in patients with LVEF<50 % and ≥ 50 %. RESULTS: Ten-year mortalities were 44.0 %, 31.8 %, and 22.6 % (P < 0.001) in patients with rEF (n = 168), mrEF (n = 179), and pEF (n = 1453). Although no significant differences were observed, the mortality with PCI was higher than with CABG in patients with rEF (52.9 % vs 39.6 %, P = 0.054) and mrEF (36.0 % vs. 28.6 %, P = 0.273), and comparable in pEF (23.9 % vs. 22.2 %, P = 0.275). Calibration and discrimination of the SS-2020 in patients with LVEF<50 % were poor, whilst they were reasonable in those with LVEF≥50 %. The proportion of patients eligible for PCI who had a predicted equipoise in mortality with CABG was estimated to be 57.5 % in patients with LVEF≥50 %. CABG was safer than PCI in 62.2 % of patients with LVEF<50 %. CONCLUSIONS: Reduced LVEF was associated with an increased risk of 10-year mortality in patients revascularized either surgically or percutaneously. Compared to PCI, CABG was safe revascularization in patients with LVEF≤40 %. In patients with LVEF≥50 % individualized 10-year all-cause mortality predicted by SS-2020 was helpful in decision-making whilst the predictivity in patients with LVEF<50 % was poor.

Coronary computed tomography angiography-based SYNTAX score for comprehensive assessment of advanced coronary artery disease.

BACKGROUND: Since the initial attempt to adapt the anatomical SYNTAX score (aSS) to coronary computed tomography angiography (CCTA), CCTA imaging technology has evolved, and is currently used as a "decision-maker" for revascularization strategy in complex coronary artery disease (CAD) and has rendered necessary some updating of the aSS to the CCTA modality. OBJECTIVES: The aim is to provide updated definitions of the aSS derived from CCTA in patients with complex CAD undergoing CABG. METHODS: The modifications of CCTA-aSS are the following; (i) updated definition and detection criteria of total occlusion (TO) in CCTA based on length assessment, (ii) inclusion of scoring points for serial bifurcations located in one single coronary segment. (iii) inclusion of weighing score points for lesions located distal to a TO, not visualized on conventional coronary angiography, but visible in CCTA, (iv) removal of thrombus and bridging collateral items from the weighing score, considering the limited diagnostic capability of CCTA in detecting these specific lesion characteristics. RESULTS: the updated CCTA-aSS was tested in a first-in-man study using the sole guidance of CCTA for the planning and performance of bypass surgery in complex CAD (n â€‹= â€‹114). An interobserver analysis showed excellent reproducibility (ICC â€‹= â€‹0.96, 95 â€‹% confidence interval 0.94-0.97). CONCLUSION: The updated CCTA-aSS was implemented in a cohort of patients with complex CAD undergoing CABG with the sole guidance of CCTA and FFRCT and the Inter-reproducibility of the analysis of the updated score was found excellent. The prognostic value of the modified CCTA-aSS will be examined in future studies.

Can Machine Learning Aid the Selection of Percutaneous vs Surgical Revascularization?

BACKGROUND: In patients with 3-vessel coronary artery disease (CAD) and/or left main CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). OBJECTIVES: The aim of this study was to assess whether these individualized revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. METHODS: In the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) study, ML algorithms (Lasso regression, gradient boosting) were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG) and prespecified effect-modifiers: disease type (3-vessel or left main CAD) and anatomical SYNTAX score. The model's discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n = 1,800) and externally validated in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) registry (n = 7,362), and then compared with the original SYNTAX score II 2020 (SSII-2020). RESULTS: The hybrid gradient boosting model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI: 0.75-0.81) in cross-validation and 0.77 (95% CI: 0.76-0.79) in external validation. The ML models discriminated 5-year mortality better than the SSII-2020 in the external validation cohort and identified heterogeneity in the treatment benefit of CABG vs PCI. CONCLUSIONS: An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems-trained to collect large numbers of parameters-may harmonize decision making globally. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

CCTA-based CABG SYNTAX Score: a tool to evaluate completeness of coronary segment revascularization after bypass surgery.

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0-41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0-20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG.

Glagov revisited: coronary artery disease phenotype on non-invasive imaging provides rationale for implementing preventive pharmacotherapy-a case report.

Background: Glagov et al. showed that no reduction in vessel lumen occurred until the atherosclerotic plaque burden exceeded 40% of the vessel area. Most major adverse cardiac events occurring in the first 4 years after a myocardial infarction arise from untreated angiographically mild, non-flow-limiting lesions at the time of the index event. We report how computed tomography (CT) coronary angiography (CCTA) can be used to non-invasively risk stratify a patient with non-obstructive coronary artery disease (CAD) and guide further management. Case summary: A 69-year-old non-smoking female with hypertension, dyslipidaemia, and hypothyroidism presented with atypical chest pain. Electrocardiogram and left ventricular ejection fraction were normal. Her lipidic profile was normal. CCTA showed a lipid-rich plaque with very low attenuation (<30 HU) in the left main stem (LMS) extending into the proximal left anterior descending (LAD) and in the mid LAD artery. The maximum plaque burden in the LMS was 67% with a remodelling index of 1.375, and an area stenosis of 22%. Tissue characterization showed a lipid-rich plaque with a thin fibrous cap. The perivascular fat attenuation index (FAI) in the proximal LAD was suggestive of (-69 HU) inflamed perivascular fat. Shear stress analysis of the LMS plaque showed normal wall shear stress (WSS); however, the axial plaque stress was high. Her medications were intensified to rosuvastatin 20 mg once daily (OD) and ezetimibe 10 mg OD. The patient remained asymptomatic at 6 months follow-up. Discussion: Our case exemplifies the value of CCTA as a diagnostic 'one-stop shop' (CCTA, finite element analysis, computed tomographic density [CTD], tissue characterization analysis, FAI analysis, WSS and wall strain, and etc.) when stratifying a patient with non-obstructive CAD. With further development of novel potent anti-lipidaemic and anti-inflammatory drugs, non-obstructive lesions with adverse plaque and haemodynamic parameters will have the opportunity to be treated with additional preventive pharmacological therapy.

10 Years of SYNTAX: Closing an Era of Clinical Research After Identifying New Outcome Determinants.

The SYNTAX trial randomized patients equally eligible for coronary artery bypass grafting or percutaneous coronary intervention using the Heart Team approach. The SYNTAXES study achieved a follow-up rate of 93.8% and reported the 10-year vital status. Factors associated with increased mortality at 10 years were pharmacologically treated diabetes mellitus, increased waist circumference, reduced left ventricular function, prior cerebrovascular and peripheral vascular disease, western Europe and North American descent, current smoking, chronic obstructive pulmonary disease, elevated C-reactive protein, anemia, and an increase in HbA1c. Procedural factors associated with higher 10 years mortality include periprocedural myocardial infarction, extensive stenting, small stents, ≥1 heavily calcified lesion, ≥1 bifurcation lesion, residual SYNTAX score >8, and staged percutaneous coronary intervention. Optimal medical therapy at 5 years, use of statins, on-pump coronary artery bypass grafting, multiple arterial grafts, and higher physical component score and mental component score were associated with lower mortality at 10 years. Numerous scores and prediction models were developed to help individualize risk assessment. Machine learning has emerged as a novel approach for developing risk models.

Impact of on-pump and off-pump coronary artery bypass grafting on 10-year mortality versus percutaneous coronary intervention.

OBJECTIVES: The very long-term mortality of off-pump and on-pump coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in a randomized complex coronary artery disease population is unknown. This study aims to investigate the impact of on-pump and off-pump CABG versus PCI on 10-year all-cause mortality. METHODS: The SYNTAX trial randomized 1800 patients with three-vessel and/or left main coronary artery disease to PCI or CABG and assessed their survival at 10 years. In this sub-study, the hazard of mortality over 10 years was compared according to the technique of revascularization: on-pump CABG (n = 725), off-pump CABG (n = 128) and PCI (n = 903). RESULTS: There was substantial inter-site variation in the use of off-pump CABG despite baseline characteristics being largely homogeneous among the 3 groups. The crude rate of mortality was significantly lower following on-pump CABG versus PCI [25.6% vs 28.4%, hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65-0.96], while it was comparable between off-pump CABG and PCI (28.5% vs 28.4%, HR 0.98, 95% CI 0.69-1.40). After adjusting for the 9 variables included in the SYNTAX score II 2020, 10-year mortality remained significantly lower with on-pump CABG than PCI (HR 0.75 against PCI, P = 0.009). CONCLUSIONS: In the SYNTAXES trial, 10-year mortality adjusted for major confounders was significantly lower following on-pump CABG compared to PCI. There was no evidence for unadjusted difference between off-pump CABG and PCI, although the unadjusted estimated HR had a wide CI. Site heterogeneity in the technique used in bypass surgery has had measurable effects on treatment performance.

Impact of repeat revascularization within 5 years on 10-year mortality after percutaneous or surgical revascularization.

BACKGROUND: The SYNTAX trial demonstrated negative impact of repeat revascularization (RR) on 5-year outcomes following PCI/CABG in patients with three-vessel(3VD) and/or left main coronary artery disease(LMCAD). We aimed to investigate the impact of RR within 5 years, on 10-year mortality in patients with 3VD and/or LMCAD after PCI/CABG. METHODS: The SYNTAXES study evaluated the vital status out to 10 years of patients with 3VD and/or LMCAD. Patients were stratified by RR within 5 years and randomized treatment. The association between RR within 5 years and 10-year mortality was assessed. RESULTS: A total of 330 out of 1800 patients (18.3%) underwent RR within 5 years. RR occurred more frequently after initial PCI than after initial CABG (25.9% vs. 13.7%, p < 0.001). Overall, 10-year mortality was comparable between patients undergoing RR and those not (28.2% vs. 26.1%, adjusted HR: 1.17, 95%CI 0.93-1.48, p = 0.187). In the PCI arm, RR was associated with a trend toward higher 10-year mortality (adjusted HR: 1.29, 95%CI 0.97-1.72, p = 0.075), while in the CABG arm, the trend was opposite (adjusted HR: 0.74, 95%CI 0.46-1.20, p = 0.219). Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to initial CABG (33.5% vs. 17.6%, adjusted HR: 2.09, 95%CI 1.21-3.61, p = 0.008). CONCLUSION: In the SYNTAXES study, RR within 5 years had no impact on 10-year all-cause death in the population overall. Among patients requiring any repeat procedures, 10-year mortality was higher after initial treatment with PCI than after CABG. These exploratory findings should be investigated with larger populations in future studies. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; SYNTAXES Unique identifier: NCT03417050. URL: https://www. CLINICALTRIALS: gov ; SYNTAX Unique identifier: NCT00114972.

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft.

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology.

Impact of periprocedural major adverse events on 10-year mortality after revascularisation.

BACKGROUND: The long-term prognostic impact of a composite of periprocedural major adverse events (PMAE) following revascularisation for patients with complex coronary artery disease (CAD) has not yet been established. AIMS: This study aimed to assess the impact on 10-year mortality of non-fatal PMAE following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Other objectives were to evaluate 1) whether PMAE affect mortality predicted by the SYNTAX score II 2020 (SSII-2020) and 2) whether optimal medical therapy (OMT) positively affects the prognosis of patients with non-fatal PMAE. METHODS: The association between 10-year mortality and non-fatal PMAE occurring within 30 days of PCI or CABG in patients with three-vessel disease and/or left main disease enrolled in the SYNTAXES study was investigated. RESULTS: The main findings are that non-fatal PMAE occurred less frequently following PCI than CABG (11.2% vs 28.2%; p<0.001) and that non-fatal PMAE were an independent predictor of all-cause mortality in the first year post-procedure, but not at 5 or 10 years, in both treatment modalities. PMAE substantially alter the individual predictions of 10-year mortality by the SSII-2020. In patients with non-fatal PMAE, OMT may provide survival benefits during the first year post-procedure as well as in the long term. CONCLUSIONS: In patients with complex CAD, non-fatal PMAE were more common following CABG than PCI, but their prognostic impact was similar, being significant in the first year and then diminishing out to 10 years. Patients with non-fatal PMAE may therefore require more careful follow-up and additional preventive treatment in the first year post-procedure.

Appropriateness of the Modality of Revascularization According to the SYNTAX Score II 2020 in the FASTTRACK CABG Study: An Interim Report on Patient Selection.

BACKGROUND: Personalized long term vital prognosis plays a key role in deciding between percutaneous coronary intervention (PCI) and CABG in patients with complex coronary artery disease. The FASTTRACK CABG trial enrolls patients with the sole guidance of coronary computed tomographic angiography (CCTA) and fractional flow reserve CCTA (FFRCT). The feasibility/non-feasibility of this approach is determined by the surgeon request to have access to the invasive coronary angiography. METHODS: This interim analysis, which was requested by the Data and Safety Monitoring Board (DSMB), compared the treatment decision of the "on site" Heart team to the recommended treatment as per the SYNTAX Score II 2020 (SS-2020), which was prospectively assessed by the central core laboratory in the first 57 consecutive patients (half of the planned population) enrolled in this First in Man study. RESULTS: The average anatomical SYTAX Score is 35.6 ± 11.5. The SS-2020 predicted 5-year MACE and 10-year all-cause mortality are 14.7 % and 21.6 % following CABG, and 23.0 % and 30.4 % following PCI. Among the enrolled patients the SS-2020 predicts long-term PCI outcomes similar to CABG (absolute risk difference ≤0 % in favor of PCI) in only two patients whilst the remaining 55 patients had a predicted survival benefit with CABG. CONCLUSIONS: According to the SS-2020, the first 57 patients recruited into the FASTTRACK CABG trial received the appropriate modality of revascularization and the DSMB allowed the investigators to complete the study.

Impact of residual angina on long-term clinical outcomes after percutaneous coronary intervention or coronary artery bypass graft for complex coronary artery disease.

AIMS: The aim of this study was to investigate the impact on 10-year survival of patient-reported anginal status at 1 year following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in patients with left main coronary artery disease (LMCAD) and/or three-vessel CAD (3VD). METHODS AND RESULTS: In this post hoc analysis of the randomized SYNTAX Extended Survival study, patients were classified as having residual angina (RA) if their self-reported Seattle Angina Questionnaire angina frequency (SAQ-AF) scale was ≤90 at the 1-year follow-up post-revascularization with PCI or CABG. The primary endpoint of all-cause death at 10 years was compared between the RA and no-RA groups. A sensitivity analysis was performed using a 6-month SAQ-AF.At 1 year, 373 (26.1%) out of 1428 patients reported RA. Whilst RA at 1 year was an independent correlate of repeat revascularization at 5 years [18.3 vs. 11.5%; adjusted hazard ratio (HR): 1.54; 95% confidence interval (CI): 1.10-2.15], it was not associated with all-cause death at 10 years (22.1 vs. 21.6%; adjusted HR: 1.11; 95% CI: 0.83-1.47). These results were consistent when stratified by the modality of revascularization (PCI or CABG) or by anginal frequency. The sensitivity analysis replicating the analyses based on 6-month angina status resulted in similar findings. CONCLUSION: Among patients with LMCAD and/or 3VD, patient-reported RA at 1 year post-revascularization was independently associated with repeat revascularization at 5 years; however, it did not significantly increase 10-year mortality, irrespective of the primary modality of revascularization or severity of RA.

Geographic disparity in 10-year mortality after coronary artery revascularization in the SYNTAXES trial.

AIMS: To investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD). METHODS AND RESULTS: The SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10 years. Patients were stratified according to the region of recruitment: North America (N-A, n = 245), Eastern Europe (E-E, n = 189), Northern Europe (N-E, n = 425), Southern Europe (S-E, n = 263), and Western Europe (W-E, n = 678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p < 0.001), and less frequently male in N-A (65.3% vs 79.6%, p < 0.001). Diabetes (16.0% vs 25.4%, p < 0.001) and peripheral vascular disease (6.8% vs 10.9%, p = 0.025) were less frequent in N-E than W-E. Ejection fraction was highest in W-E (62% vs 56%, p < 0.001). Compared to W-E, the mean anatomic SYNTAX score was higher in S-E (29 vs 31, p = 0.008) and lower in N-A (26, p < 0.001). Crude ten-year mortality was similar in N-A (31.6%), and W-E (30.7%), and significantly lower in E-E (22.5%, p = 0.041), N-E (21.9%, p = 0.003) and S-E (22.0%, p = 0.014). Compared to W-E, adjusted mortality in N-E (HR 0.85, p = 0.019) and S-E (HR 0.72, p = 0.043) remain significantly lower after adjustment for pre- and peri-procedural factors, but no significant interaction (Pinteraction = 0.728) between region and modality of revascularization was seen. CONCLUSION: In the era of globalization, knowledge, and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies.

Effect of Patient-Reported Preprocedural Physical and Mental Health on 10-Year Mortality After Percutaneous or Surgical Coronary Revascularization.

BACKGROUND: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. METHODS: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. RESULTS: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73-0.97]; P=0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76-0.95]; P=0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS Pinteraction=0.033, MCS Pinteraction=0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55-5.30]; P=0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction (Pinteraction=0.002). CONCLUSIONS: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; SYNTAXES Unique identifier: NCT03417050. URL: https://www. CLINICALTRIALS: gov; SYNTAX Unique identifier: NCT00114972.

Mortality after multivessel revascularisation involving the proximal left anterior descending artery.

OBJECTIVE: We sought to investigate whether long-term clinical outcomes differ following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel disease (3VD) and lesions in the proximal left anterior descending artery (P-LAD). METHODS: This post-hoc analysis of the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) Extended Survival study included patients with 3VD who were classified according to the presence or absence of lesions located in the P-LAD. Ten-year all-cause death and 5-year major adverse cardiac or cerebrovascular events (MACCE) were assessed. RESULTS: Among 1088 patients with 3VD, 559 (51.4%) had involvement of P-LAD and their 10-year mortality was numerically higher following PCI versus CABG (28.9% vs 21.9%; HR: 1.39, 95% CI 0.99 to 1.95). Although patients without P-LAD lesions had significantly higher 10-year mortality following PCI compared with CABG, there was no evidence of a treatment-by-subgroup interaction (28.8% vs 20.2%; HR: 1.47, 95% CI 1.03 to 2.09, pinteraction=0.837). The incidence of MACCE at 5 years was significantly higher with PCI than CABG, irrespective of involvement of P-LAD (with P-LAD: HR: 1.86, 95% CI 1.36 to 2.55; without P-LAD: HR: 1.54, 95% CI 1.11 to 2.12; pinteraction=0.408). Individualised assessment using the SYNTAX Score II 2020 established that a quarter of patients with P-LAD lesions had significantly higher mortality with PCI than CABG, whereas in the remaining three-quarters CABG had similar mortality. CONCLUSIONS: Among patients with 3VD, the presence or absence of a P-LAD lesion was not associated with any treatment effect on long-term outcomes following PCI or CABG. TRIAL REGISTRATION NUMBER: SYNTAXES: NCT03417050; SYNTAX: NCT00114972.

Predicted and Observed Mortality at 10 Years in Patients With Bifurcation Lesions in the SYNTAX Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow-up. OBJECTIVES: The aim of this study was to investigate the impact of bifurcation lesions on individual predicted and observed all-cause 10-year mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. METHODS: In the SYNTAXES (SYNTAX Extended Survival) study, 10-year observed and individual predicted mortality derived from the SYNTAX score 2020 (SS-2020) was compared between patients with ≥1 bifurcation (n = 1,300) and those with no bifurcations (n = 487). RESULTS: Among patients treated with PCI, patients with >1 bifurcation lesion compared with those without bifurcation lesions had a significantly higher risk for all-cause death (19.8% vs 30.1%; HR: 1.55; 95% CI: 1.12-2.14; P = 0.007), whereas following CABG, mortality was similar in patients with and those without bifurcation lesions (23.3% vs 23.0%; HR: 0.81; 95% CI: 0.59-1.12; P = 0.207; Pinteraction = 0.006). In PCI patients, a 2-stent vs a 1-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51; 95% CI: 1.06-2.14; P = 0.021). According to the SS-2020, among those with ≥1 bifurcation, there was equipoise for all-cause mortality between PCI and CABG in 2 quartiles of the population, whereas CABG was superior to PCI in the 2 remaining quartiles. CONCLUSIONS: Bifurcation lesions require special attention from the heart team, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity and calculation of individualized 10-year prognosis using the SS-2020 may therefore be helpful in decision making. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).

External Validation of the FREEDOM Score for Individualized Decision Making Between CABG and PCI.

BACKGROUND: Although randomized trials have established that coronary artery bypass grafting (CABG) is, on average, the most effective revascularization strategy compared with percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease (MVD), individual patients differ in many characteristics that can affect the benefits and harms of treatment. The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus) score was developed to predict different outcomes with CABG vs PCI on the basis of 8 patient characteristics and the smoking-treatment interaction. OBJECTIVES: This study aimed to assess the ability of the 5-year major adverse cardiovascular event (MACE) model to predict treatment benefit of CABG vs PCI in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials. METHODS: This study identified 702 patients with diabetes and MVD to mirror the FREEDOM participants. Discrimination was assessed by C-index, and calibration was assessed by calibration plots in the PCI and CABG arms, respectively. The ability of the FREEDOM score to predict treatment benefit of CABG vs PCI was assessed. RESULTS: Overall, CABG was associated with a lower rate of 5-year MACE compared with PCI (12.4% vs 20.3%; log-rank P = 0.021) irrespective of a history of smoking (Pinteraction = 0.975). Both discrimination and calibration were helpful in the PCI arm (C-index: 0.69; slope: 0.96, intercept: -0.24), but moderate in the CABG arm (C-index: 0.61; slope: 0.61; intercept: -0.53). The FREEDOM score showed some heterogeneity of treatment benefit. CONCLUSIONS: The FREEDOM score could identify some heterogeneity of treatment benefit of CABG vs PCI for 5-year MACE. Until further prospective validations are performed, these results should be taken into consideration when using the FREEDOM score in patients with diabetes and MVD. (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972) (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease [BEST]; NCT00997828) (Future Revascularization Evaluation in Patients with Diabetes Mellitus [FREEDOM]; NCT00086450).