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Objectives: This study sought to evaluate the long-term differences in survival between multiple arterial grafts (MAG) and single arterial grafts (SAG) in patients who underwent coronary artery bypass grafting (CABG) in the SYNTAX study., Methods: The present analysis included the randomized and registry-treated CABG patients (n = 1509) from the SYNTAX Extended Survival study (SYNTAXES). Patients with only venous (n = 42) or synthetic grafts (n = 1) were excluded. The primary end point was all-cause death at the longest follow-up. Multivariable Cox regression was used to adjust for differences in baseline characteristics. Sensitivity analysis using propensity matching with inverse probability for treatment weights was performed., Results: Of the 1466 included patients, 465 (31.7%) received MAG and 1001 (68.3%) SAG. Patients receiving MAG were younger and at lower risk. At the longest follow-up of 12.6 years, all-cause death occurred in 23.6% of MAG and 40.0% of SAG patients [adjusted hazard ratio (HR) 0.74, 95% confidence interval (CI) (0.55-0.98); P = 0.038], which was confirmed by sensitivity analysis. MAG in patients with the three-vessel disease was associated with significant lower unadjusted and adjusted all-cause death at 12.6 years [adjusted HR 0.65, 95% CI (0.44-0.97); P = 0.033]. In contrast, no significance was observed after risk adjustment in patients with the left main disease, with and without diabetes, or among SYNTAX score tertiles., Conclusions: In the present post hoc analysis of all-comers patients from the SYNTAX trial, MAG resulted in markedly lower all-cause death at 12.6-year follow-up compared to a SAG strategy. Hence, this striking long-term survival benefit of MAG over SAG encourages more extensive use of multiple arterial grafting in selected patients with reasonable life expectancy., Trial Registration: SYNTAXES ClinicalTrials.gov reference: NCT03417050; SYNTAX ClinicalTrials.gov reference: NCT00114972., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aims: To evaluate the impact of various smoking status on 10-year all-cause mortality and to examine a relative treatment benefit of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) according to smoking habits., Methods and Results: The SYNTAX Extended Survival study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to CABG or PCI in the SYNTAX trial. In the present analysis, patients were divided into three groups (current, former, or never smokers), and the primary endpoint of 10-year all-cause mortality was assessed according to smoking status. Smoking status was available in 1793 (99.6%) patients at the time of randomization, of whom 363 were current smokers, 798 were former smokers, and 632 were never smokers. The crude rates of 10-year all-cause mortality were 29.7% in current smokers, 25.3% in former smokers, and 25.9% in never smokers (Log-rank P = 0.343). After adjustment for imbalances in baseline characteristics, current smokers had a significantly higher risk of 10-year all-cause mortality than never smokers [adjusted hazard ratio (aHR): 2.29; 95% confidence interval (CI): 1.60-3.27; P < 0.001], whereas former smokers did not. PCI was associated with a higher risk of all-cause mortality than CABG among current smokers (HR: 1.60; 95% CI: 1.09-2.35; P = 0.017), but it failed to show a significant interaction between revascularization strategies and smoking status (Pinteraction = 0.910)., Conclusion: Current smokers had a higher adjusted risk of 10-year all-cause mortality, whereas former smokers did not. The treatment effect of CABG vs. PCI did not differ significantly according to smoking status., Clinical Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972; SYNTAX Extended Survival. ClinicalTrials.gov reference: NCT03417050., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The EXCEL trial reported similar five-year rates of the primary composite outcome of death, myocardial infarction (MI), or stroke after percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) for treatment of obstructive left main coronary artery disease (LMCAD)., Aims: We sought to determine whether these outcomes remained consistent regardless of geography of enrolment., Methods: We performed a prespecified subgroup analysis based on regional enrolment., Results: Among 1,905 patients randomised to PCI (n=948) or CABG (n=957), 1,075 (56.4%) were recruited at 52 European Union (EU) centres, and 752 (39.5%) were recruited at 67 North American (NA) centres. EU versus NA patients varied according to numerous baseline demographics, anatomy, pharmacotherapy and procedural characteristics. Nonetheless, the relative rates of the primary endpoint after PCI versus CABG were consistent across EU versus NA centres at 30 days and 5 years. However, NA participants had substantially higher late rates of ischaemia-driven revascularisation (IDR) after PCI, driven predominantly by the need for greater target vessel and lesion revascularisation. This culminated in a significant difference in the relative risk of the secondary composite outcome of death, MI, stroke, or IDR at 5 years (p interaction =0.02)., Conclusions: In the EXCEL trial, the relative risks for the 30-day and five-year primary composite outcome of death, MI or stroke after PCI versus CABG were consistent irrespective of geography. However, five-year rates of IDR after PCI were significantly higher in NA centres, a finding the Heart Team and patients should consider when making treatment decisions. ClinicalTrials.gov identifier: NCT01205776.

Objectives: The aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)., Background: Limited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization., Methods: This substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG)., Results: The 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (P interaction  = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264)., Conclusions: At 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (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 [SYNTAX], NCT00114972)., Competing Interests: Funding Support and Author Disclosures The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-year follow-up, was funded by Boston Scientific. Both sponsors had no role in the study design, data collection, data analyses, and interpretation of the study data and were not involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom. Dr Serruys has received personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Merillife. Dr Hara has received a grant for studying overseas from the Japanese Circulation Society and a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Morice is a CEO and shareholder of CERC, a contract research organization based in Paris, with no role in this trial. Dr Kappetein is an employee of Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD)., Methods: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L)., Results: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually., Conclusion: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes., Methods and Results: The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227)., Conclusions: The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The optimal revascularisation strategy for patients with left main coronary artery disease is uncertain. We therefore aimed to evaluate long-term outcomes for patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG)., Methods: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane database using the search terms "left main", "percutaneous coronary intervention" or "stent", and "coronary artery bypass graft*" to identify randomised controlled trials (RCTs) published in English between database inception and Aug 31, 2021, comparing PCI with drug-eluting stents with CABG in patients with left main coronary artery disease that had at least 5 years of patient follow-up for all-cause mortality. Two authors (MSS and BAB) identified studies meeting the criteria. The primary endpoint was 5-year all-cause mortality. Secondary endpoints were cardiovascular death, spontaneous myocardial infarction, procedural myocardial infarction, stroke, and repeat revascularisation. We used a one-stage approach; event rates were calculated by use of the Kaplan-Meier method and treatment group comparisons were made by use of a Cox frailty model, with trial as a random effect. In Bayesian analyses, the probabilities of absolute risk differences in the primary endpoint between PCI and CABG being more than 0·0%, and at least 1·0%, 2·5%, or 5·0%, were calculated., Findings: Our literature search yielded 1599 results, of which four RCTs-SYNTAX, PRECOMBAT, NOBLE, and EXCEL-meeting our inclusion criteria were included in our meta-analysis. 4394 patients, with a median SYNTAX score of 25·0 (IQR 18·0-31·0), were randomly assigned to PCI (n=2197) or CABG (n=2197). The Kaplan-Meier estimate of 5-year all-cause death was 11·2% (95% CI 9·9-12·6) with PCI and 10·2% (9·0-11·6) with CABG (hazard ratio 1·10, 95% CI 0·91-1·32; p=0·33), resulting in a non-statistically significant absolute risk difference of 0·9% (95% CI -0·9 to 2·8). In Bayesian analyses, there was an 85·7% probability that death at 5 years was greater with PCI than with CABG; this difference was more likely than not less than 1·0% (<0·2% per year). The numerical difference in mortality was comprised more of non-cardiovascular than cardiovascular death. Spontaneous myocardial infarction (6·2%, 95% CI 5·2-7·3 vs 2·6%, 2·0-3·4; hazard ratio [HR] 2·35, 95% CI 1·71-3·23; p<0·0001) and repeat revascularisation (18·3%, 16·7-20·0 vs 10·7%, 9·4-12·1; HR 1·78, 1·51-2·10; p<0·0001) were more common with PCI than with CABG. Differences in procedural myocardial infarction between strategies depended on the definition used. Overall, there was no difference in the risk of stroke between PCI (2·7%, 2·0-3·5) and CABG (3·1%, 2·4-3·9; HR 0·84, 0·59-1·21; p=0·36), but the risk was lower with PCI in the first year after randomisation (HR 0·37, 0·19-0·69)., Interpretation: Among patients with left main coronary artery disease and, largely, low or intermediate coronary anatomical complexity, there was no statistically significant difference in 5-year all-cause death between PCI and CABG, although a Bayesian approach suggested a difference probably exists (more likely than not <0·2% per year) favouring CABG. There were trade-offs in terms of the risk of myocardial infarction, stroke, and revascularisation. A heart team approach to communicate expected outcome differences might be useful to assist patients in reaching a treatment decision., Funding: No external funding., Competing Interests: Declaration of interests MSS, BAB, SAM, and EB are members of the Thrombolysis in Myocardial Infarction Study Group, which has received grant support through Brigham and Women's Hospital (Boston, MA, USA) from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. MSS declares research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, Ionis, The Medicines Company, MedImmune, Merck, Novartis, Pfizer, and Quark Pharmaceuticals, and has consulted for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol Myers Squibb, CVS Caremark, DalCor, Dr Reddy's Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, Novo Nordisk, and Silence Therapeutics. BAB declares research grants through Brigham and Women's Hospital from Pfizer, Ionis, Quark, AstraZeneca/MedImmune, and Amgen, and consulting or personal fees from Philips, Abbott Vascular, CSI, Abiomed, Servier, Janssen, Quark, and Daiichi Sankyo. PWS declares consultancy or personal fees from SMT, Novartis, Philips, Xeltis, and Merillife. APK is an employee of Medtronic. S-JP declares grants from Abbott Vascular, Daiichi-Sankyo, ChongKunDang Pharm, Daewoong Pharm, and Edwards, and personal fees from Abbott Vascular and Edwards, all outside the submitted work. D-WP declares grants from Daiichi-Sankyo, ChongKunDang Pharm, Daewoong Pharm, and Abbott Vascular, and personal fees from Edwards, Abbott Vascular, and Medtronic, all outside the submitted work. EHC declares institutional research grants from Abbott, Biosensors, and Boston Scientific, and speaker fees from Abbott. NRH declares institutional research grants from Abbott, Biosensors, Bbraun, Boston Scientific, and Reva Medical, and speaker fees from Abbott, Reva Medical, and Terumo. GWS declares speaker honoraria from Cook and Infraredx; consultancy for Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds; that Columbia University (New York, NY, USA) received payments from Abbott for research activities related and not related to EXCEL and royalties for sale of the MitraClip; and that Mount Sinai Hospital (New York, NY, USA) receives research funding from Abbott. JFS was the North American Surgical Principal Investigator in the EXCEL trial. EB declares research grants through Brigham and Women's Hospital from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis, and consultancies with Amgen, Boehringer-Ingelheim/Lilly, Bristol Myers Squibb (MyoKardia), Cardurion, NovoNordisk, and Verve. All author authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The PROSE trial purpose is to investigate whether the incidence of thromboembolic-related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.-On-X) compared with a previous generation mechanical prosthesis (St Jude Medical-SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations., Methods: The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors., Results: The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population., Conclusions: The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations., (© 2021. The Author(s).)

Background: The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear., Methods and Results: This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62-1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057)., Conclusions: Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years., Trial Registration: SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear., Methods and Results: The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04-1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54-2.40; p < 0.001). The risk of 10 year all-cause death was similar between patients receiving PCI or CABG irrespective of the presence of prior CEVD (p -interaction  = 0.624)., Conclusion: Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050., (© 2021. The Author(s).)

Aims: To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD)., Methods: The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD., Results: Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08-1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83-1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p -interaction  = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11-4.23, p < 0.001) compared to those without CVD., Conclusions: The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050., (© 2021. The Author(s).)

Objectives: We investigated the impact of total stent length (TSL) and average nominal stent diameter (ASD) on 10-year mortality after percutaneous coronary intervention (PCI) in the SYNTAXES trial., Background: TSL and ASD in patients treated with PCI are associated with major adverse cardiovascular events. However, the treatment effect of PCI with extensive and/or small stenting as compared with coronary artery bypass grafting (CABG) for complex coronary artery disease has not been fully evaluated., Methods: Impacts on mortality of extensive stenting defined as TSL >100 mm and small stenting as ASD <3 mm were analyzed in 893 PCI patients and were compared to 865 CABG patients., Results: TSL as a continuous variable was significantly associated with 10-year mortality (adjusted hazard ratio [HR], 1.05 [1.01-1.09] per 10 mm increase). PCI patients with extensive stenting had a higher 10 year mortality than CABG patients (adjusted HR, 1.97 [1.41-2.74]) or not- extensive stenting PCI (adjusted HR, 1.94 [1.36-2.77]). Although ASD did not have a significant association with 10 year mortality (adjusted HR, 0.97 [0.85-1.11] per 0.25 mm increase), PCI with small stents was associated with a higher 10 year mortality, compared to CABG (adjusted HR, 1.66 [1.23-2.26]) and PCI performed with large stents (adjusted HR, 1.74 [1.19-2.53]). Patients treated with not-extensive and large stents had similar mortality rates (24.0 versus 23.8%) as those treated with CABG., Conclusions: Extensive and small stenting were associated with higher 10 year mortality, compared with CABG. When patients have to be treated with extensive or small stenting, revascularization with CABG should be preferred., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Objectives: To assess the safety and efficacy of using vascular closure devices (VCDs) in percutaneous coronary intervention (PCI) for left main coronary artery disease (LM-CAD)., Background: VCDs provide rapid hemostasis for patients undergoing PCI with transfemoral access (TFA); however, the safety and efficacy of VCDs continues to be debated., Methods: We analyzed data from the EXCEL trial in patients with LM-CAD in whom PCI was performed via TFA with vs without VCD. The primary endpoint was a composite of death, myocardial infarction (MI), or stroke. Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 30 days was also assessed. Propensity-score matching analysis was used., Results: Among 694 patients with LM-CAD undergoing TFA-PCI, 423 (61.0%) received VCDs (collagen plug, 320 [75.7%]; suture mediated, 55 [13.0%]; others, 48 [11.3%]). Patients with and without VCD use had similar 30-day rates of BARC type 2-5 bleeding (5.0% vs 6.7%, respectively; P=.30) and BARC type 3-5 bleeding (2.1% vs 3.7%, respectively; P=.20). There were no significant differences in the rates of death, MI, or stroke in patients with and without VCD use at 30 days (4.7% vs 4.1%, respectively; P=.74) or at 5 years (20.3% vs 24.2%, respectively; P=.16). These results were similar after adjustment., Conclusion: In the EXCEL trial, LM-CAD PCI via TFA using VCD was associated with similar 30-day rates of bleeding and comparable early and late major adverse cardiovascular events compared with manual compression.

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the "obesity paradox", possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m 2 ), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the "obesity paradox" following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG)., Methods: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR., Results: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43])., Conclusions: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.

Background: Intraoperative graft assessment with tools like Transit Time Flow Measurement (TTFM) is imperative for quality control in coronary surgery. We investigated the variation of TTFM parameters before and after protamine administration to identify new benchmark parameters for graft quality assessment., Methods: The database of the REQUEST ("REgistry for QUality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery") study was retrospectively reviewed. A per graft analysis was performed. Only single grafts (i.e., no sequential nor composite grafts) where both pre- and post-protamine TTFM values were recorded with an acoustical coupling index > 30% were included. Grafts with incomplete data and mixed grafts (arterio-venous) were excluded. A second analysis was performed including single grafts only in the same MAP range pre- and post- protamine administration., Results: After adjusting for MAP, we found a small increase in MGF (29 mL/min to 30 mL/min, p = 0.009) and decrease in PI (2.3 to 2.2, p <  0.001) were observed after the administration of protamine. These changes were especially notable for venous conduits and for CABG procedures performed on-pump., Conclusion: The small changes in TTFM parameters observed before and after protamine administration seem to be clinically irrelevant, despite being statistically significant in aggregate. Our data do not support a need to perform TTFM measurements both before and after protamine administration. A single TTFM measurement taken either before or after protamine may suffice to achieve reliable data on each graft's performance. Depending on the specific clinical situation and intraoperative changes, more measurements may be informative., Trial Registration: Clinical Trials Number: NCT02385344 , registered February 17th, 2015., (© 2021. The Author(s).)

Background: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial., Objectives: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG., Methods: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality., Results: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without., Conclusions: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (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)., Competing Interests: Funding Support and Author Disclosures The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-year follow-up, was funded by Boston Scientific Corporation. Both sponsors had no role in the study design, data collection, data analyses, and interpretation of the study data, nor were they involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom. Dr Serruys has received personal fees from Biosensors, Micell Technologies, Sino Medical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr Hara has received a grant for studying overseas from Japanese Circulation Society and a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Morice is a chief executive officer and shareholder of CERC, a contract research organization based in Paris that has no role in this trial. Dr Head has been an employee of Medtronic. Dr Kappetein has been an as employee of Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD., Methods: Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy., Results: COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56-2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59-1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67-0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p interaction  = 0.544)., Conclusions: COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Objectives: We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial., Background: The optimal LPS for LMCA PCI is unclear., Methods: We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3-year MACE; all-cause death, stroke, or myocardial infarction., Results: Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) (p trend  = .22). There were no significant differences in the 3-year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p = .50) or ischemia-driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p = .65). The adjusted 3-year rates of MACE did not differ according to LPS., Conclusions: The comparable 3-year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology., (© 2020 Wiley Periodicals LLC.)

Background: The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear., Objectives: The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD)., Methods: In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models., Results: Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; p interaction  = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; p interaction  = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: -0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients., Conclusions: Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (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 [SYNTAX]; NCT00114972)., Competing Interests: Funding Support and Author Disclosures The SYNTAX Extended Survival study, during extension of follow-up up to 10 years, was supported by the German Foundation of Heart Research (Frankfurt am Main, Germany). The SYNTAX trial, during 0- to 5-year follow-up, was funded by Boston Scientific Corporation (Marlborough, Massachusetts). The study funders had no role in the study design, data collection, data analyses, and interpretation of the study data, nor were involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Hara has received a grant for studying overseas from Japanese Circulation Society and a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr. Piek has received personal fees and nonfinancial support from Philips/Volcano, outside the submitted work. Dr. Head has served as an employee of Medtronic, outside the submitted work. Dr. Kappetein has served as an employee of Medtronic, outside the submitted work. Dr. Cohen has received grants from Boston Scientific, during the conduct of the study; and has received grants and personal fees from Boston Scientific, Medtronic, Abbott, and Svelte, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We compared the effect of bivalirudin or heparin and use or nonuse of glycoprotein IIb/IIIa inhibitors (GPI) on the outcome of left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the randomized EXCEL trial., Background: The optimal antithrombotic regimen to support PCI of the LMCA remains controversial because of low representation of this subset in clinical trials., Methods: The PCI cohort (n = 928) in EXCEL was divided according to bivalirudin versus heparin antithrombin treatment and compared for the primary composite endpoint of death, myocardial infarction (MI), or stroke at 30 days and 5 years., Results: Bivalirudin was used in 319 patients (34.4%). The composite endpoint at 30 days occurred in 7.2% versus 3.8% bivalirudin and heparin patients, respectively, p = .02; at 5 years, the composite endpoint occurred in 26.3% versus 19.9% bivalirudin and heparin patients, respectively, p = .02. Major bleeding was more frequent in bivalirudin patients (4.1% versus 1.3%, p = .008). There were no differences in stent thrombosis between the groups. Bivalirudin use was an independent predictor of the 30-day composite endpoint (OR 2.88, 95% CI 1.28-6.48, p = .01) but not of the 5-year composite endpoint (OR 1.30, 95% CI 0.84-2.02, p = .23). GPI use was infrequent (n = 67, 7.2%) and was not associated with adverse outcomes., Conclusion: Among patients undergoing LMCA PCI in the EXCEL trial, procedural use of bivalirudin was associated with greater rates of periprocedural MI and the 30-day composite endpoint without reducing bleeding complications. Five-year outcomes were similar. GPIs were used infrequently and were not associated with clinical outcomes., (© 2020 Wiley Periodicals, Inc.)

Prior studies in patients with noncomplex coronary artery disease have demonstrated the safety of percutaneous coronary intervention (PCI) in the outpatient setting. We sought to examine the outcomes of outpatient PCI in patients with unprotected left main coronary artery disease (LMCAD). In the EXCEL trial, 1905 patients with LMCAD and site-assessed low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus coronary artery bypass grafting. The primary end point was major adverse cardiovascular events (MACE; the composite of death, stroke, or myocardial infarction). In this sub-analysis, outcomes at 30 days and 5 years were analyzed according to whether PCI was performed in the outpatient versus inpatient setting. Among 948 patients with LMCAD assigned to PCI, 935 patients underwent PCI as their first procedure, including 100 (10.7%) performed in the outpatient setting. Patients who underwent outpatient compared with inpatient PCI were less likely to have experienced recent myocardial infarction. Distal left main bifurcation disease involvement and SYNTAX scores were similar between the groups. Comparing outpatient to inpatient PCI, there were no significant differences in MACE at 30 days (4.0% vs 5.0% respectively, adjusted OR 0.52 95% CI 0.12 to 2.22; p = 0.38) or 5 years (20.6% vs 22.1% respectively, adjusted OR 0.72, 95% CI 0.40 to 1.29; p = 0.27). Similar results were observed in patients with distal left main bifurcation lesions. In conclusion, in the EXCEL trial, outpatient PCI of patients with LMCAD was not associated with an excess early or late hazard of MACE. These data suggest that outpatient PCI may be safely performed in select patients with LMCAD., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The long-term clinical benefit after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with total occlusions (TOs) and complex coronary artery disease has not yet been clarified., Objectives: The objective of this analysis was to assess 10-year all-cause mortality in patients with TOs undergoing PCI or CABG., Methods: This is a subanalysis of patients with at least 1 TO in the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which investigated 10-year all-cause mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial, beyond its original 5-year follow-up. Patients with TOs were further stratified according to the status of TO recanalization or revascularization., Results: Of 1,800 randomized patients to the PCI or CABG arm, 460 patients had at least 1 lesion of TO. In patients with TOs, the status of TO recanalization or revascularization was not associated with 10-year all-cause mortality, irrespective of the assigned treatment (PCI arm: 29.9% vs. 29.4%; adjusted hazard ratio [HR]: 0.992; 95% confidence interval [CI]: 0.474 to 2.075; p = 0.982; and CABG arm: 28.0% vs. 21.4%; adjusted HR: 0.656; 95% CI: 0.281 to 1.533; p = 0.330). When TOs existed in left main and/or left anterior descending artery, the status of TO recanalization or revascularization did not have an impact on the mortality (34.5% vs. 26.9%; adjusted HR: 0.896; 95% CI: 0.314 to 2.555; p = 0.837)., Conclusions: At 10-year follow-up, the status of TO recanalization or revascularization did not affect mortality, irrespective of the assigned treatment and location of TOs. The present study might support contemporary practice among high-volume chronic TO-PCI centers where recanalization is primarily offered to patients for the management of angina refractory to medical therapy when myocardial viability is confirmed. (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 [SYNTAX]; NCT00114972)., Competing Interests: Funding Support and Author Disclosures The SYNTAXES study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-year follow-up, was funded by Boston Scientific Corporation. Both sponsors had no role in the study design, data collection, data analyses and interpretation of the study data, nor were involved in the decision to publish the final manuscript. The principal investigators and authors had complete scientific freedom. Dr. Hara has received a grant for studying overseas from the Japanese Circulation Society and a grant from the Fukuda Foundation for Medical Technology, outside the submitted work. Dr. Morice is a chief executive office and shareholder of the Cardiovascular European Research Center, a contract research organization based in Paris having no role in this trial. Dr. Head is an employee of Medtronic, outside the submitted work. Dr. Kappetein is an employee of Medtronic, outside the submitted work. Dr. Serruys has received personal fees from Biosensors, Micell Technologies, Sino Medical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Onuma has received institutional research grants related to his work as the chairman of cardiovascular imaging core labs of several clinical trials and a registry sponsored by industry, for which he receives no direct compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)

Objective: Several recent-generation surgical tissue valves have been found to have bleeding rates exceeding rates recommended by regulatory bodies. We explored bleeding events using data from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial for the Avalus valve (Medtronic, Minneapolis, Minn) to examine whether this end point remains relevant for the evaluation of bioprostheses., Methods: Patients (n = 1115) underwent aortic valve replacement. Bleeding and thromboembolic event episodes in patients within 3 years postimplant were analyzed for frequency, timing, and severity, focusing on patients taking antiplatelet/anticoagulant medications at the time of the event. Clinical and hemodynamic outcomes are also reported., Results: At 3 years, the Kaplan-Meier cumulative probability estimate of all-cause death was 7.2% (cardiac, 3.6%; valve-related, 1.1%). The Kaplan-Meier cumulative probability estimates of all and major hemorrhage were 8.7% and 5.2%, respectively. Ninety-nine bleeding events occurred in 86 patients: most occurred >30 days postsurgery. Among the 51 late major bleeds, in 5 cases the patients were taking anticoagulant/antiplatelet medication for prophylaxis after surgical aortic valve replacement at the time of the event, whereas the remaining patients were taking medications for other reasons. Age (hazard ratio, 1.035; 95% confidence interval, 1.004-1.068), peripheral vascular disease (hazard ratio, 2.135; 95% confidence interval, 1.106-4.122), renal dysfunction (hazard ratio, 1.920; 95% confidence interval, 1.055-3.494), and antithrombotic medication use at the time of the event (hazard ratio, 1.417; 95% confidence interval, 1.048-1.915) were associated with late bleeds (major and minor)., Conclusions: Overall clinical outcomes demonstrated low mortality and few complications except for major bleeding. Most bleeding events occurred >30 days after surgery and in patients taking antiplatelet and/or anticoagulation for indications other than postimplant prophylaxis., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Limited data exist regarding procedural and clinical outcomes of percutaneous coronary intervention (PCI) in patients with trifurcation disease of the distal left main (LM) coronary artery. We therefore aimed to examine the procedural methods and early and late outcomes among patients undergoing distal LM trifurcation versus bifurcation PCI in the EXCEL trial., Methods and Results: Patients with distal LM bifurcation disease randomised to PCI with everolimus-eluting stents in the EXCEL trial were categorised into those with and without trifurcation involvement. Angiographic and procedural characteristics in addition to clinical events up to five-year follow-up after PCI were compared. Among 605 patients with site-reported distal LM disease, 61 patients (10.1%) were identified with trifurcation anatomy. The five-year primary composite endpoint of death, myocardial infarction, or stroke occurred in 16.6% of patients with trifurcation disease compared with 22.5% of patients with distal bifurcation disease only (p=0.32). Ischaemia-driven target lesion revascularisation rates were also similar (11.9% vs 12.0%, p=0.94). No significant differences in definite or probable stent thrombosis were observed between treatment groups (1.7% vs 2.3%, p=0.76)., Conclusions: Despite the greater inherent complexity, procedural and long-term clinical outcomes following PCI of distal LM trifurcations with everolimus-eluting stents in a modest-sized cohort from the EXCEL trial were similar compared with treatment of distal LM bifurcation disease without trifurcations. These findings support PCI as a treatment strategy for selected patients with distal LM trifurcation disease. ClinicalTrials.gov Identifier: NCT01205776.

Background: The Cardiac Surgical Societies Valve Labeling Task Force consensus document acknowledged inconsistent sizing and labeling of prosthetic heart valves. This study compared the labeled size, internal diameter, and hemodynamics of different surgical and transcatheter valve types implanted into the same size annulus, measured by preprocedural computed tomography (CT)., Methods: Patients were retrospectively sorted into 3 CT annular diameter size groups: small (less than 23 mm), medium (23 to less than 26 mm), and large (26 mm or greater). Surgical valves were sorted into 4 categories based on tissue and design: (stentless porcine, standard stented bovine, wraparound stented bovine, and stented porcine). Comparisons were made within the surgical types and with a transcatheter valve. Echocardiograms were independently assessed and CTs were centrally measured., Results: We analyzed 726 surgical and 923 transcatheter valve paired data sets. Among the various valve types implanted into the same size CT annulus, there were significant differences regarding size, internal diameter, and hemodynamics within all 3 size groups. Root enlargement procedures occurred in 1.2% with no differences across valve types or size groups. Transcatheter valve hemodynamics were similar to stentless valves and were significantly better than all stented valves. There was no difference in hemodynamics between the 2 bovine stented valve types, and stented porcine valves were inferior to all valve types., Conclusions: This study documents that prosthetic heart valve sizing and labeling inconsistencies exist. Use of preoperative CT annular dimensions is the most accurate method to compare size, internal diameter, and hemodynamics of bioprosthetic aortic valves because it compares values among various valve types implanted into the same size annulus., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Randomised controlled trials are considered the gold standard for testing the efficacy of novel therapeutic interventions, and typically report the average treatment effect as a summary result. As the result of treatment can vary between patients, basing treatment decisions for individual patients on the overall average treatment effect could be suboptimal. We aimed to develop an individualised decision making tool to select an optimal revascularisation strategy in patients with complex coronary artery disease., Methods: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries between March, 2005, and April, 2007. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to either the percutaneous coronary intervention (PCI) group or coronary artery bypass grafting (CABG) group. The SYNTAXES study ascertained 10-year all-cause deaths. We used Cox regression to develop a clinical prognostic index for predicting death over a 10-year period, which was combined, in a second stage, with assigned treatment (PCI or CABG) and two prespecified effect-modifiers, which were selected on the basis of previous evidence: disease type (three-vessel disease or left main coronary artery disease) and anatomical SYNTAX score. We used similar techniques to develop a model to predict the 5-year risk of major adverse cardiovascular events (defined as a composite of all-cause death, non-fatal stroke, or non-fatal myocardial infarction) in patients receiving PCI or CABG. We then assessed the ability of these models to predict the risk of death or a major adverse cardiovascular event, and their differences (ie, the estimated benefit of CABG versus PCI by calculating the absolute risk difference between the two strategies) by cross-validation with the SYNTAX trial (n=1800 participants) and external validation in the pooled population (n=3380 participants) of the FREEDOM, BEST, and PRECOMBAT trials. The concordance (C)-index was used to measure discriminative ability, and calibration plots were used to assess the degree of agreement between predictions and observations., Findings: At cross-validation, the newly developed SYNTAX score II, termed SYNTAX score II 2020, showed a helpful discriminative ability in both treatment groups for predicting 10-year all-cause deaths (C-index=0·73 [95% CI 0·69-0·76] for PCI and 0·73 [0·69-0·76] for CABG) and 5-year major adverse cardiovascular events (C-index=0·65 [0·61-0·69] for PCI and C-index=0·71 [0·67-0·75] for CABG). At external validation, the SYNTAX score II 2020 showed helpful discrimination (C-index=0·67 [0·63-0·70] for PCI and C-index=0·62 [0·58-0·66] for CABG) and good calibration for predicting 5-year major adverse cardiovascular events. The estimated treatment benefit of CABG over PCI varied substantially among patients in the trial population, and the benefit predictions were well calibrated., Interpretation: The SYNTAX score II 2020 for predicting 10-year deaths and 5-year major adverse cardiovascular events can help to identify individuals who will benefit from either CABG or PCI, thereby supporting heart teams, patients, and their families to select optimal revascularisation strategies., Funding: The German Heart Research Foundation and the Patient-Centered Outcomes Research Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Numerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist., Objectives: The purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial., Methods: PMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression., Results: PMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these "enzyme-driven events" on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year., Conclusions: The rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (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 [SYNTAX]; NCT00114972)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use., Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial., Methods: The pre-specified protocol definition of PMI (PMI Prot ) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMI UD ) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMI UD , troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined., Results: PMI Prot occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMI UD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMI Prot and PMI UD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMI Prot was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (p interaction  = 0.86). Conversely, PMI UD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (p interaction  = 0.004). Results were similar for all-cause mortality and with varying PMI UD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality., Conclusions: The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMI Prot was associated with similar hazard after PCI and CABG, whereas PMI UD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Indexed effective orifice area (EOAi) charts are used to determine the likelihood of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR). The aim of this study is to validate whether these EOAi charts, based on echocardiographic normal reference values, can accurately predict PPM., Methods and Results: In the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial, 986 patients with aortic valve stenosis/regurgitation underwent AVR with an Avalus valve. Patients were randomly split (50:50) into training and test sets. The mean measured EOAs for each valve size from the training set were used to create an Avalus EOAi chart. This chart was subsequently used to predict PPM in the test set and measures of diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) were assessed. PPM was defined by an EOAi ≤0.85 cm2/m2, and severe PPM was defined as EOAi ≤0.65 cm2/m2. The reference values obtained from the training set ranged from 1.27 cm2 for size 19 mm up to 1.81 cm2 for size 27 mm. The test set had an incidence of 66% of PPM and 24% of severe PPM. The EOAi chart inaccurately predicted PPM in 30% of patients and severe PPM in 22% of patients. For the prediction of PPM, the sensitivity was 87% and the specificity 37%. For the prediction of severe PPM, the sensitivity was 13% and the specificity 98%., Conclusion: The use of echocardiographic normal reference values for EOAi charts to predict PPM is unreliable due to the large proportion of misclassifications., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Whether intervention should be performed in patients with asymptomatic severe aortic stenosis (AS) remains debated., Objective: To meta-analyze the natural history of asymptomatic severe AS and examine the association of early intervention with survival., Data Sources: PubMed, Embase, and Cochrane databases were searched from inception to February 1, 2020., Study Selection: Observational studies of adult patients with asymptomatic severe AS., Data Extraction and Synthesis: Two investigators independently extracted study and patient characteristics, follow-up time, events, and prognostic indicators of events. Random-effects models were used to derive pooled estimates., Main Outcomes and Measures: The meta-analysis on natural history was performed on the primary end point of all-cause death occurring during a conservative treatment period, with secondary end points consisting of cardiac death, death due to heart failure, sudden death, development of symptoms, development of an indication for aortic valve intervention, and aortic valve intervention. The primary end point for the meta-analysis of early intervention vs a conservative strategy was all-cause death during long-term follow-up. Finally, meta-analysis was performed on the association of prognostic indicators with the composite of death or aortic valve intervention found in multivariable models., Results: A total of 29 studies with 4075 patients with 11 901 years of follow-up were included. Pooled rates per 100 patients per year were 4.8 (95% CI, 3.6-6.4) for all-cause death, 3.0 (95% CI, 2.2-4.1) for cardiac death, 2.0 (95% CI, 1.3-3.1) for death due to heart failure, 1.1 (95% CI, 0.6-2.1) for sudden death, 18.1 (95% CI, 12.8-25.4) for an indication for aortic valve intervention, 18.5 (95% CI, 13.4-25.5) for development of symptoms, and 19.2 (95% CI, 15.5-23.8) for aortic valve intervention. Early intervention was associated with a significant reduction in long-term mortality (hazard ratio, 0.38; 95% CI, 0.25-0.58). Factors associated with worse prognosis were severity of AS, low-flow AS, left ventricular damage, and atherosclerotic risk factors., Conclusions and Relevance: Data from observational studies and a recent randomized clinical trial suggest that many patients with asymptomatic severe AS develop an indication for aortic valve intervention, and their deaths are mostly cardiac but not only sudden. Other end points besides sudden death should be considered during the decision to perform early intervention that are associated with improved survival.

Background: The poorer prognosis of coronary artery disease in females compared with males is related mainly to differences in baseline characteristics. In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, the effect of treatment with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting surgery (CABG) on mortality at 5 years differed significantly between females and males; however, the optimal revascularization beyond 5 years according to sex has not been evaluated., Objectives: The aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years., Methods: The SYNTAXES (SYNTAX Extended Survival) study evaluated vital status up to 10 years in 1,800 patients with de novo 3-vessel and/or left main coronary artery disease randomized to treatment with PCI or CABG in the SYNTAX trial. All-cause death at 10 years was separately evaluated in female and male patients with complex coronary artery disease., Results: Of 1,800 patients, 402 (22.3%) were female and 1,398 (77.7%) were males. Females had a higher 10-year mortality rate compared with males (32.8% vs. 24.7%; log-rank p = 0.002), but female sex was not an independent predictor of mortality (adjusted hazard ratio: 1.02; 95% confidence interval: 0.76 to 1.36). Mortality at 10 years tended to be lower after CABG than after PCI, with a similar treatment effect for female and male patients (adjusted hazard ratio for females: 0.90 [95% confidence interval: 0.54 to 1.51]; adjusted hazard ratio for males: 0.76 [95% confidence interval: 0.56 to 1.02]; p for interaction = 0.952)., Conclusions: Female sex was not an independent predictor of mortality at 10 years in patients with complex coronary artery disease. The interaction between sex and treatment with PCI or CABG that was observed at 5 years was no longer present at 10 years. (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 [SYNTAX], NCT00114972)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cigarette smoking is a well-known risk factor for coronary artery disease (CAD). However, the impact of smoking on outcomes after coronary revascularization, especially in patients with left main CAD (LMCAD) is less well understood. The EXCEL trial randomized 1,905 patients with LMCAD and visually assessed low or intermediate anatomical complexity (SYNTAX score ≤32) to PCI with everolimus-eluting stents or CABG. Patients were categorized according to smoking status (current, former, or never), and their outcomes at 5 years were compared by logistic regression with follow-up time included as a log-transformed offset variable. The primary endpoint was a composite of death, myocardial infarction, or stroke. Among 1893 patients with known smoking status at baseline, 416 (22%) were current smokers and 774 (41%) were former smokers. The crude rates of the primary endpoint were 19.5% for never smokers, 20.5% for former smokers (p = 0.61 vs never smokers), and 23.1% for smokers (p = 0.15 vs never smokers). Compared with never smokers, the adjusted risk of the primary endpoint was higher for current smokers (adjOR 1.82, 95% confidence interval [CI] 1.126 to 2.63; p = 0.001), but not for former smokers (adjOR 1.00, 95% CI 0.75 to 1.33, p = 0.10). The relative efficacy of PCI versus CABG for the 5-year primary endpoint was similar irrespective of smoking status (P interaction  = 0.22). In conclusion, current smokers in the EXCEL trial had a higher adjusted 5-year risk of the primary composite endpoint of death, myocardial infarction, or stroke than never smokers, whereas former smokers were not at increased risk. Active smoking was a risk factor after LMCAD revascularization irrespective of revascularization method., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The impact of final kissing balloon inflation (FKBI) after percutaneous coronary intervention (PCI) of bifurcation lesions on long-term clinical outcomes remains controversial. We sought to determine the impact of FKBI on four-year outcomes after PCI of distal left main (LM) bifurcation lesions., Methods and Results: The EXCEL trial compared PCI with everolimus-eluting stents and coronary artery bypass graft surgery (CABG) in patients with left main (LM) disease. We examined four-year clinical outcomes after PCI of distal LM bifurcation lesions according to use of FKBI. The primary endpoint was the composite rate of death, myocardial infarction (MI), or stroke. The major secondary endpoint was the composite rate of death, MI, stroke, or ischaemia-driven revascularisation (IDR). Among 948 patients randomised to PCI, 759 had distal LM lesions treated, 430 of which were treated with one stent and 329 of which were treated with two or more stents. The four-year rates of the primary and major secondary endpoints were similar with versus without FKBI in both the one-stent and ≥2-stent groups in both unadjusted and adjusted analyses., Conclusions: In the EXCEL trial, the performance of FKBI after PCI of distal LM bifurcation lesions was not associated with improved four-year clinical outcomes regardless of whether one stent or ≥2 stents were implanted.

Objective: It remains unclear how often coronary revascularization is necessary after aortic valve interventions, either by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement. However, these data are relevant for treatment and prosthesis choice. The authors sought to analyze the incidence and characteristics of coronary revascularization after SAVR during follow-up., Methods: Of 2256 patients undergoing isolated SAVR between 1987 and 2015, 420 patients (mean age 56.9 ± 15.5 years, 66.9% male) were followed at the Erasmus Medical Center. Incidence, predictors, and characteristics of coronary revascularization were analyzed. Cumulative incidence of revascularization was assessed using a competing risk approach., Results: Mean follow-up after SAVR was 17.2 years (total of 4541 patient-years). A total of 24 patients underwent 28 procedures of revascularization. The cumulative incidence of revascularization after SAVR was 0.5%, 2.2%, 4.1%, and 6.9% at 1, 5, 10, and 20 years, respectively. The linearized rate of revascularization was 6.2 per 1000 patient-years. Percutaneous coronary intervention was the most common revascularization method (64%; N = 18/28). Revascularization before SAVR (N = 36/420; of whom 27 percutaneous coronary intervention) was an independent predictor of revascularization during follow-up (hazard ratio, 6.6; 95% confidence interval, 2.6-17.1; P  < .001)., Conclusions: After SAVR, the rate of coronary revascularization was 6.9% (N = 24/420) at 20-year follow-up. Patients were at particular risk if they had undergone previous revascularization before SAVR. These data may furthermore be relevant to the transcatheter aortic valve replacement population., (© 2020 The Authors.)

Aims: Accurate risk prediction in patients undergoing revascularisation is essential. We aimed to assess the predictive performance of Society of Thoracic Surgeons (STS) risk models in patients with left main coronary artery disease (LMCAD) undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention with everolimus-eluting stents (PCI-EES)., Methods and Results: The predictive performance of STS risk models for perioperative mortality, stroke and renal failure was evaluated for their discriminative ability (C statistic) and calibration (Hosmer-Lemeshow goodness-of-fit-test; χ2 and p-values) among patients with LMCAD undergoing PCI-EES (n=935) and CABG (n=923) from the randomised EXCEL trial. STS risk scores, in CABG patients, showed good discrimination for 30-day mortality and average discrimination for stroke (C statistic 0.730 and 0.629, respectively) with average calibration. For PCI, STS risk scores had no discrimination for mortality (C statistic 0.507), yet good discrimination (C statistic 0.751) and calibration for stroke. The predictive performance for renal failure was good for CABG (C statistic 0.82), yet poor for PCI (C statistic 0.59)., Conclusions: In selected patients with LMCAD from the EXCEL trial, STS risk models showed good predictive performance for CABG yet lacked predictive performance for PCI for perioperative mortality and renal failure. The STS stroke risk model was surprisingly more discriminating in PCI compared to CABG. Improved and procedure-specific risk prediction instruments are needed to accurately estimate adverse events after LMCAD revascularisation by CABG and PCI. ClinicalTrials.gov Identifier: NCT01205776.

Aim: To evaluate the impact of left ventricular ejection fraction (LVEF) on 3-year outcomes in patients with left main coronary artery disease (LMCAD) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the EXCEL trial., Methods and Results: The EXCEL trial randomized patients with LMCAD to PCI with everolimus-eluting stents (n = 948) or CABG (n = 957). Among 1804 patients with known baseline LVEF, 74 (4.1%) had LVEF <40% [heart failure with reduced ejection fraction (HFrEF)], 152 (8.4%) LVEF 40-49% [heart failure with mid-range ejection fraction (HFmrEF)] and 1578 (87.5%) LVEF ≥50% (heart failure with preserved ejection fraction). Patients with HFrEF vs. HFmrEF vs. preserved LVEF experienced a longer postoperative hospital stay (9.0 vs. 7.0 vs. 6.0 days, P = 0.02) with greater peri-procedural complications after CABG, while hospital stay after PCI was unaffected by LVEF (1.5 vs. 2.0 vs. 1.0 days, P = 0.20). The composite primary endpoint of death, stroke, or myocardial infarction at 3 years was 29.3% (PCI) vs. 27.6% (CABG) in patients with HFrEF, 16.2% vs. 15.0% in patients with HFmrEF, and 14.5% vs. 14.6% in those with preserved LVEF, respectively (P interaction  = 0.90). Smoothing spline analysis demonstrated that the 3-year risk of all-cause death increased when LVEF decreased, both in patients undergoing CABG and PCI., Conclusion: In the EXCEL trial, the composite rate of death, stroke or myocardial infarction at 3 years was significantly higher in patients with HFrEF compared with HFmrEF or preserved LVEF, driven by an increased rate of all-cause death. No significant differences after PCI vs. CABG were observed among patients with HFrEF, HFmrEF and preserved LVEF. Longer-term follow-up could provide important insights on differences in clinical outcomes that might emerge over time., Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01205776., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Compared with randomized controlled trials (RCTs) in medical specialties, RCTs in cardiac surgery face specific issues. Individual and collective equipoise, rapid evolution of the surgical techniques, as well as difficulties in obtaining funding, and limited education in clinical epidemiology in the surgical community are among the most important challenges in the design phase of the trial. Use of complex interventions and learning curve effect, differences in individual operators' expertise, difficulties in blinding, and slow recruitment make the successful completion of cardiac surgery RCTs particularly challenging. In fact, over the course of the last 20 years, the number of cardiac surgery RCTs has declined significantly. In this review, a team of surgeons, trialists, and epidemiologists discusses the most important challenges faced by RCTs in cardiac surgery and provides a list of suggestions for the successful design and completion of cardiac surgery RCTs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease., Methods: The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years., Results: SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG., Conclusions: In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: We evaluated the influence of transit-time flow measurement with epicardial and epiaortic high-frequency ultrasound in patients undergoing coronary artery bypass grafting procedure., Methods: The Registry for Quality Assessment with Ultrasound Imaging and Transit-time Flow Measurement in Cardiac Bypass Surgery study is a multicenter, prospective study among 7 international centers performing coronary artery bypass grafting procedures. The primary end point was any change in the planned surgical procedure. Major secondary end points consisted of the rate and reason for surgical changes related to the aorta, in situ conduits, coronary targets, and completed grafts, and the rate of in-hospital mortality and major morbidity., Results: Between April 2015 and December 2017, 1046 patients were enrolled. Of those, 1016 were included in the final analyses. Mean age was 65.9 years, 14.0% were women, and diabetes was present in 39.6%. Off-pump procedures were performed in 39.6% and bilateral internal thoracic arteries in 30.5%. The primary end point occurred in 25.2% of patients (n = 256) and in 77% (197 out of 256) this was based on transit-time flow measurement and/or high-frequency ultrasound. Surgical changes were related to the aorta in 9.9%, to in situ conduits in 2.7%, and the coronary targets in 22.6%. Graft revision occurred in 7.8%, including revisions of the proximal and/or distal anastomosis in 6.6%. In-hospital adverse event rates were 0.6% for mortality, 1.0% for cerebrovascular events, and 0.3% for myocardial infarction., Conclusions: Surgical changes related to the aorta, conduits, coronary targets, and anastomosis were made in 25% of patients. This was associated with low operative mortality and low major morbidity. Transit-time flow measurement and high-frequency ultrasound may improve the quality, safety, and efficacy of coronary artery bypass grafting procedures and should be considered as a routine procedural aspect., (Copyright © 2019 The American Association for Thoracic Surgery. All rights reserved.)

Introduction: Sutureless biological valves for surgical aortic valve replacement (SAVR), characterized by the absence of anchoring sutures at the aortic annulus, are gaining popularity because of ease and reproducibility of implant, shorter operating times, and enhancement of minimally invasive approaches. The stentless configuration of the sutureless valve was designed to achieve optimal hemodynamic performance., Materials and Methods: PERSIST-AVR (PERceval Sutureless Implant versus STandard Aortic Valve Replacement) is a prospective, randomized, adaptive, open-label, international, postmarket trial (NCT02673697). The primary objective of the trial is to assess the safety and efficacy of the Perceval (LivaNova, London, UK) sutureless bioprosthesis among patients undergoing SAVR in the presence of severe aortic stenosis to demonstrate the noninferiority of Perceval as compared with standard sutured stented bioprosthetic aortic valve as an isolated procedure or combined with coronary artery bypass grafting. Sample size will be determined adaptively through interim analyses performed by an Independent Statistical Unit till a maximum of 1,234 patients, enrolled at ∼60 sites in countries where the device is commercially available. Patients will be followed up for 5 years after implant. The primary end point is the number of patients free from major adverse cardiac and cerebrovascular-related events at 1 year. Additional secondary outcomes will be assessed up to 5 years., Discussion: PERSIST-AVR is the first prospective, randomized study comparing in-hospital and postdischarge outcomes in a robust population of patients undergoing SAVR with either the Perceval sutureless bioprosthesis or a conventional sutured stented bioprosthesis up to 5 years., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

The incidence, recurrence rate, and prognostic significance of atrial fibrillation or flutter (AF) following hospital discharge after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. We sought to determine the 3-year incidence and clinical impact of postdischarge AF in patients with LMCAD treated with PCI or CABG. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI versus CABG. We analyzed the occurrence of postdischarge AF through 3 years and its time-adjusted association with adverse outcomes. A total of 1,802 patients without AF at baseline comprised the study cohort. Within 3 years, 227 episodes of AF occurred (29 [12.8%] in the PCI arm and 198 [87.2%] in the CABG arm, p <0.0001); of those, 63 (27.7%) occurred following discharge from the index hospitalization in 57 patients. In-hospital AF predicted postdischarge AF (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.42 to 6.10, p = 0.004). By multivariable analysis, time-updated postdischarge AF was an independent predictor of 3-year cardiovascular death (HR 4.91, 95% CI 1.92 to 12.60, p = 0.0009), stroke (HR 4.87, 95% CI 1.12 to 21.12, p = 0.035), and the composite outcome of death, stroke or myocardial infarction (HR 3.09, 95% CI 1.56 to 3.6-6.11, p = 0.001). Among patients with postdischarge AF, the rate of the primary composite outcome did not vary according to presence or absence of in-hospital AF (21.0% vs 23.8%, p = 0.78). In conclusion, postdischarge AF following CABG or PCI for LMCAD is associated with increased mortality and stroke. In-hospital atrial fibrillation is an independent predictor of AF following discharge., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to report the 2-year results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial and confirm the interim Bayesian analysis., Background: Transcatheter aortic valve replacement (TAVR) with a self-expanding valve was noninferior to surgery in patients with severe aortic stenosis and intermediate operative risk using Bayesian statistical methods. Novel Bayesian designs have been used to shorten the time to primary endpoint analysis in randomized clinical trials, although the predictive value of Bayesian analysis compared with frequentist approaches remains debated., Methods: The SURTAVI trial randomized 1,660 patients. An interim analysis was performed 1 year after the 1,400th patient was treated to estimate the primary 2-year endpoint of all-cause mortality or disabling strokes for all patients., Results: The Kaplan-Meier rate for the complete 2-year primary endpoint was 12.7% in the TAVR group and 12.6% in the surgery group (0.0% difference; 95% confidence interval: -3.4% to 3.5%), compared with 12.6% with TAVR and 14.0% with surgery (-1.4% difference; Bayesian credible interval: -5.2% to 2.3%) in the interim Bayesian analysis. A comparison of individual clinical, hemodynamic, and quality-of-life endpoints using Bayesian and frequentist methods found no significant differences., Conclusions: The complete analysis of all patients with aortic stenosis at intermediate risk for surgery in the SURTAVI trial confirmed the noninferiority, with respect to the frequency of all-cause mortality or disabling stroke, of TAVR to surgery, as determined in the interim Bayesian analysis. Follow-up will extend out to 10 years., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD)., Background: The impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown., Methods: All patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models., Results: During 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p < 0.0001) consistently after both PCI and CABG (p int  = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non-target lesion revascularization and non-target vessel revascularization were not., Conclusions: In the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The prognostic impact of resting heart rate (RHR) following revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (LMCAD) is unknown. We aimed to assess the effect of RHR at discharge on 3-year cardiovascular outcomes following PCI and CABG for LMCAD. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI with everolimus-eluting stents versus CABG. RHR was measured at discharge following the index hospitalization. The principal outcome measure was the composite endpoint of death, myocardial infarction (MI) or stroke at 3 years. Among 1,303 patients in sinus rhythm with available ECGs, the median (IQR) discharge RHR was 72 (62to 81) bpm. Median discharge RHR was higher after CABG versus PCI (78 [IQR 70 to 86] versus 65 [IQR 59 to 74] bpm, p <0.0001). At 3 years, 107 patients (8.2%) had a primary composite endpoint event including 61 patients (4.7%) who died. By multivariable analysis, discharge RHR assessed as a continuous variable (per 5 bpm) was an independent predictor at 3 years of the primary composite endpoint of death, MI, or stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.06 to 1.25, p = 0.0006); the secondary composite endpoint of death, MI, stroke, or ischemia-driven revascularization at 3 years (HR 1.12, 95% CI 1.05 to 1.19, p = 0.0007); all-cause mortality (HR 1.18, 95% CI 1.07 to 1.31, p = 0.002); and cardiovascular death (HR 1.16, 95% CI 1.00 to 1.33, p = 0.046). No significant interactions were present between RHR and treatment with PCI versus CABG for the primary (p int  = 0.20) or secondary (p int  = 0.47) composite endpoints. In patients with LMCAD undergoing revascularization, an increased RHR at discharge was associated with a higher risk for adverse cardiovascular outcomes at 3 years, irrespective of treatment modality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established., Methods: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction., Results: At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], -0.9 to 6.5; P = 0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, -1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, -1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, -1.9 percentage points; 95% CI, -3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, -0.8 percentage points; 95% CI, -2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0)., Conclusions: In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.)., (Copyright © 2019 Massachusetts Medical Society.)