Background:The clinical performance of left atrial appendage occlusion (LAAO) as a procedure and the long-term impact of its varied implantation configurations and anticoagulation regimens remain unclear. Objectives:This study sought to provide data in routine practice from a prospective multicenter registry. Methods:A total of 3,096 consecutive patients from 39 Chinese centers undergoing LAAO were enrolled between April 1, 2019, and October 31, 2020. Results:The baseline CHA2DS2-VASc and HAS-BLED scores were 4.0 ± 1.8 and 2.4 ± 1.2, respectively; mean age was 69 ± 9 years. One-year follow-up was completed in 3,013 (97.8%) patients. The ischemic endpoint of death, stroke, and systemic embolism occurred in 133 (4.51%) patients, and life-threatening, disabling, or major bleeding occurred in 71 (2.36%) patients. After inverse probability of treatment weighting, no significant association was found between anesthesia type (moderate sedation vs general anesthesia) or image guidance (transesophageal/intracardiac echocardiography vs fluoroscopy) and ischemic or bleeding events. In 1,295 (42.0%) cases, LAAO combined with catheter ablation was associated with a significantly lower rate of death, stroke, or systemic embolism than LAAO only (3.5% vs 5.2%, inverse probability of treatment weighting HR: 0.68; 95% CI: 0.47-0.99). The most common post-LAAO antithrombotic regimen was warfarin/direct oral anticoagulant monotherapy for 45 days, followed by single-/dual-antiplatelet therapy (38.1%). Conclusions:In Chinese centers, patients undergoing LAAO had low rates of ischemic and bleeding events at 1 year. Combining LAAO with catheter ablation was associated with a lower rate of ischemic events than LAAO only. (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With Atrial Fibrillation Using the Watchman Left Atrial Appendage Closure Technology [RECORD]; NCT03917563).

Abstract Background Intervention with drug-coated balloons (DCB) is based on a leave-nothing-behind concept and has been recommended as the first-line treatment modality for in-stent restenosis (ISR) and small-vessel disease. However, DCB treated for de novo lesions and comparison between DCB treatment for de novo lesions and ISR has not been fully elucidated. Purpose To report and compare 3-year clinical outcomes between DCB treatment for ISR and de novo disease, and identify the risk factors of adverse events after DCB intervention. Methods The study population was derived from the CAGE FREE Registry, which was a prospective, dedicated DCB treated all-comers registry in ISR and/or de novo lesions. The primary outcome was vessel-oriented composite endpoint (VoCE) at 3 years, defined as a composite of vessel-related cardiac death, vessel-related myocardial infarction (MI), and target vessel revascularization (TVR). Results A total of 2473 consecutive patients with 2804 lesions were enrolled. DCB treated in 1478 patients with 1669 de novo lesions and 995 ISR patients with 1135 lesions. The median duration of follow-up was 2.5 years (IQR 1.8-3.2) overall. At 3 years, the rate of VoCE was 12.1% (vessel-related cardiac death: 3.0%, vessel-related MI: 2.2%, and TVR: 7.8%) in the overall cohort. Patients with ISR treated with DCB had a higher rate of 3-year VoCE than those with de novo lesions (16.8% vs. 8.9%, HR: 2.00, 95%CI: 1.56-2.57, p<0.001), with the HR remaining significant after adjustment (IPTW adjusted HR: 1.79, 95%CI: 1.37-2.35). In terms of procedure-related factors, TIMI flow after PCI less than grade 3 and residual stenosis more than 25% were independent risk factors of 3-year VoCE for patients with de novo lesions. In patients with ISR, residual stenosis more than 25% had a higher risk of 3-year VoCE, whereas TIMI flow after PCI less than grade 3 only had a trend. Conclusion Patients with ISR treated with DCB had a higher rate of 3-year VoCE than those with de novo lesions. DCB appears to be an attractive alternative treatment for de novo coronary lesions. Residual stenosis ≤25% combined with TIMI flow grade 3 should be attempted after DCB angioplasty.Kaplan Meier curve for 3-year VoCE

Abstract Background The efficacy of drug-coated balloons (DCB) for treating de novo coronary stenoses in non-small lesions remains unclear. Purpose To evaluate the long-term efficacy of DCB to second-generation drug eluting stent (DES) in de novo, non-small coronary lesions. Methods Patients treated with paclitaxel-DCB were compared with patients from two second-generation drug eluting stent (DES) registries. Only patients having DES-only or DCB-only strategies were included; those with in-stent restenosis, a device diameter<2.5mm, DES bailout post-DCB treatment, or combined use of DES and DCB were excluded. The primary endpoint was a patient-oriented composite endpoint (PoCE) defined as all-cause death, any non-fatal myocardial infarction (MI), any stroke, and any revascularization at 2-year. Differences in the risk of PoCE between cohorts were compared and adjusted by inverse probability of treatment weighting (IPTW). Results The study included 6,284 patients with 5,399 treated with DES and 885 with DCB. The mean device diameters were 3.05 mm and 2.88 mm in the DES and DCB cohort, respectively. At 2-year follow-up, the primary endpoint occurred in 531 (9.8%) patients receiving DES and 92 (10.4%) patients treated with DCB (HRcrude:1.10, 95%CI:0.88-1.37, P=0.418; HRIPTW:1.08, 95%CI:0.79-1.47, P=0.639; Figure 1). All-cause death occurred in 230 (4.3%) patients in the DES group and 11 (1.2%) patients in the DCB group (HRIPTW:0.27, 95%CI: 0.12-0.57), any non-fatal MI occurred in 56 (1.0%) patients in the DES group and 13 (1.5%) patients in the DCB group (HRIPTW:0.94, 95%CI:0.39-2.25), any stroke occurred in 108 (2.0%) patients in the DES arm and 8 (0.9%) patients in the DCB group (HRIPTW:0.63, 95%CI: 0.29-1.39), and any repeat revascularization occurred in 199 (3.7%) patients in the DES arm and 69 (7.8%) patients in the DCB group (HRIPTW:2.10, 95%CI: 1.43-3.11). Conclusion We did not observe DCB to be associated with a higher rate of PoCE than DES in patients with de novo coronary lesions which were ≥2.5mm in diameter. However, DCB was associated with significantly lower mortality and significantly higher rates of repeat revascularization than DES.Figure 1

Abstract Background To compare the observed and individual predicted mortalities according to the SYNTAX score II 2020 (SSII-2020) in the all-comers SYNTAX population, and retrospectively assess the appropriateness of revascularization with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three vessel disease (3VD) and/or left main disease (LMCAD). Methods Internal and external validation of the SSII-2020 to predict 10-year all-cause death was performed in the respective randomized and registry SYNTAX populations. Differences in individual predicted mortalities following CABG or PCI were ranked and displayed with the observed mortalities. The proportions of screened patients deriving a survival benefit from CABG or PCI were determined retrospectively. Results A total of 2602 participants (as-treated population) were included in the randomized and registry cohorts. In the randomized cohort, all-cause mortality at 10 years, as an average treatment effect, was 23.8% (199/865) with CABG and 28.6% (249/901) with PCI, with a differential survival benefit of 4.6% (95% CI: 0.58% to 8.7%, log-rank p value=0.023). In the CABG and PCI registries, mortalities were 27.8% (167/644) and 55.4% (99/192), respectively. Calibration and discrimination of the SSII-2020 was helpful in CABG and PCI patients in the randomized and registry cohorts. In the PCI registry, the SSII-2020 underestimated mortality since specific comorbidities that entail high mortality are not included in the formula (C-index: 0.72, intercept: 0.38, slope: 0.66), whilst in the CABG registry, it predicted mortality with a helpful calibration and discrimination (C-index: 0.70, intercept: 0.00, slope: 0.76). The proportions of patients with a predicted survival benefit following CABG and PCI were respectively 78.3% (1383/1766) and 21.7% (383/1766) in the randomized cohort, and 82.4% (2143/2602) and 17.7% (459/2602) in the whole SYNTAX trial population. Conclusion In the randomized and registry cohort of this all-comers population with 3VD and/or LMCAD, there was reasonable agreement between the individual predicted and observed mortalities after CABG or PCI, such that the predicted 10-year survival benefit might be helpful in determining the appropriateness of each modality of revascularization. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research (Frankfurt am Main, Germany). The SYNTAX trial, during 0-5 years follow-up, was funded by Boston Scientific Corporation (Marlborough, MA, USA). 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.

Abstract Background Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow up. Objectives To investigate the impact of bifurcation lesions on observed all-cause 10-year mortality in the SYNTAX trial. Methods In the SYNTAX Extended Survival study, 10-year observed mortality was compared among four groups: (a) presence of ≥1 bifurcation lesion and treatment with PCI (n=649), (b) no bifurcation lesion and treatment with PCI (n=248), (c) presence of ≥1 bifurcation lesion and treatment with CABG (n=651), and (d) no bifurcation lesion and treatment with CABG (n=239). Results Compared to patients without bifurcations, those with bifurcation lesion(s) treated with PCI had a significantly higher risk of all-cause death (19.8% vs 30.1%; HR: 1.55, 95% CI: 1.12 to 2.14; p=0.007), whereas following CABG, mortality was similar in patients with or without bifurcation lesion(s) (23.3% vs 23.0%; HR: 0.81, 95% CI: 0.59 to 1.12; p=0.207). (Figure1) There was a significant interaction between bifurcation lesion(s) and treatment arm (p for interaction=0.006). In PCI patients, at 5-years there was no significant difference in mortality between 1- vs 2-stent techniques, whereas at 10-years, a 2-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51, 95% CI: 1.06 to 2.14; p=0.021, Figure2). Conclusions Bifurcation lesion(s) require special attention from the heart team discussion, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity may be helpful in decision-making. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research (Frankfurt am Main, Germany). The SYNTAX trial, during 0-5 years follow-up, was funded by Boston Scientific Corporation (Marlborough, MA, USA). 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.

Abstract Background Clinical presentation with STEMI is considered as a highly prothrombotic condition often associated with recurrent ischemic events. The role of aspirin as part of antiplatelet regimens in STEMI patients needs to be clarified especially in the context of new potent P2Y12 inhibitors Aim To assess the benefit and risk of 23-month ticagrelor monotherapy after one month of DAPT against the conventional 12-month DAPT with aspirin and ticagrelor followed by aspirin monotherapy among STEMI patients in the GLOBAL LEADERS trial. Methods We did a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial (2092 patients). We compared the experimental ticagrelor monotherapy group (1062 patients) with the standard 12-month DAPT group (1030 patients) in rates of GLOBAL LEADERS predefined primary (composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction (MI) and secondary end points (BARC 3 or 5 bleeding). NACE (Net Adverse Clinical Events) and POCE (Patient- Oriented Composite End points). We also compared GLOBAL LEADERS predefined end points in STEMI, UA, NSTEMI and CCS in both treatment arms. Results At two years, there were no significant differences in rates of GLOBAL LEADERS primary end points in patients who had or did not have STEMI. BARC bleeding in either treatment group didn't vary significantly among STEMI, NSTEMI and UA. Nevertheless, the experimental strategy had led to significant increase in BARC bleeding in CCS compared with STEMI at 1 and 2 years. There were similar rates of NACE and POCE in both the experimental and reference treatment groups at 1 and 2 years post PCI. Conclusions and relevance The incidence of GLOBAL LEADRER defined end points has not been impacted by STEMI presentation. Our findings suggest that an earlier cessation of DAPT at 1 month post primary PCI, with continuation of a potent P2Y12 antagonist monotherapy, could be safe and avoids additional bleeding risk in the STEMI setting. Given the post-hoc nature of the analysis, our findings should not necessitate changes in recommendations for practice by professional associations and regulatory agencies. However, all reported findings should rather be considered only as hypothesis-generating and need be replicated in dedicated large-scale randomized trials to further assess the role of Aspirin free antithrombotic strategies post PCI in STEMI. Funding Acknowledgement Type of funding sources: None.

Abstract Background Coronary artery disease is the leading cause of death among elderly men and women worldwide. The aging society worldwide will lead to increasing numbers of elderly patients with multivessel coronary artery disease. Although age is recognized as one of the most important factors in a decision-making for revascularization of multivessel coronary artery disease, the very long-term outcomes in patients undergoing revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is still unclear. Objectives The aim of the present study was to investigate the association between revascularization strategies and 10-year outcomes in elderly patients. Methods The SYNTAX Extended Survival (SYNTAXES) study (NCT 03417050) is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries, enrolling 1,800 patients with de novo three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to revascularization strategy with CABG versus PCI in the SYNTAX trial. Patients were divided into two groups according to the prespecified threshold of 70 years old; elderly patients (>70 years) and non-elderly patients (≤70 years). The primary endpoint of this study was all-cause death at 10 years. Results Out of 1,800 patients, 575 patients (31.9%) were classified as elderly (>70 years). The mean age ± standard deviation (SD) of the elderly patients and the non-elderly patients was 75.8±3.6 years and 60.1±7.4 years, respectively. Of note, elderly patients were more frequently female than non-elderly patients (33.6% vs. 17.1%, p<0.001). As expected, the elderly patients had higher prevalence of chronic kidney disease (43.4% vs. 7.9%, p<0.001), had higher anatomical SYNTAX score (30.2±11.8 vs 28.0±11.2 p<0.001) when compared to those of the non-elderly patients. Up to 10 years, all-cause death occurred in 42.7% and 18.9% in the elderly and non-elderly patients, respectively (Log-rank p<0.001). The cubic spline curve showed an exponentially increase in all-cause death at 10 years according to the increase of age both in the PCI arm and the CABG arm. At 10 years, there was no significant difference in the risk of all-cause death between CABG vs. PCI either in elderly patients (41.5% vs. 44.0%; Log-rank p=0.53) or non-elderly patients (16.6% vs. 21.1%; Log-rank p=0.051). Conclusion CABG and PCI were equipoise in terms of risk of all-cause death at 10 years in patients with de novo 3VD and/or LMCAD irrespective of their age when stratified according to the prespecified threshold of 70 years old. Kaplan-Meier curves Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Foundation of Heart Research

Abstract Background The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of the SYNTAX trial, which was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease. The SYNTAXES study is the first randomized trial that reported the complete 10-year data on all-cause death in patients with complex coronary artery disease. Purpose Patients with coronary artery disease (CAD) and concomitant diabetes mellitus (DM) or chronic kidney disease (CKD) are more susceptible to major adverse cardiovascular and cerebrovascular events. However, to date, the long-term prognosis and which revascularization strategy was associated with better clinical outcomes for patients with complex coronary artery disease and concomitant with DM and CKD have not been documented. Methods In this sub-analysis of the SYNTAXES trial, a total of 1,638 patients were classified into four subgroups according to the DM and CKD status: DM−/CKD− (n=999, 60.1%), DM+/CKD− (n=323, 19.7%), DM−/CKD+ (n=231, 14.1%), and DM+/CKD+ (n=85, 5.2%). The treatment effects of PCI and CABG were analyzed in each subgroup. The primary endpoint was all-cause death at 10 years. Results Compared with the DM−/CKD− patients, patients with DM+/CKD+ were older, more often had a history of stroke, hypertension, heart failure, and were more frequently presented with total occlusion, bifurcation lesion and three-vessel disease. At 10 years, patients with DM+/CKD+ had a 3.94-fold higher incidence of all-cause mortality compared with DM−/CKD− individuals (54.1% versus 18.9%, 95% CI [2.85–5.44]). Patients with DM−/CKD+ (38.1%, HR 2.36; 95% CI [1.83–5.44]) or DM+/CKD− (28.2%, HR 1.61; 95% CI [1.26–2.07]) had intermediate risk profile. For DM+/CKD+ patients, compared with PCI, those who underwent CABG were associated with lower incidence of all-cause mortality (64.3% versus 44.2%, adjusted HR 0.52; 95% CI [0.27–0.99], p=0.047, pinteraction=0.443). The number of needed-to-treat to reduce mortality for CABG was 12. Conclusion In the SYNTAX population, patients with DM and CKD are at markedly increased risk of long-term mortality rate compared with patients one or neither of these risk factors. For patients with both comorbidities, CABG was associated with better clinical outcome compared with PCI. These findings should be interpreted as hypothesis-generating. Figure 1. Kaplan-Meier curves showing the clinical events according to treatment and DM/CKD status. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific Corporation

Abstract Background and purpose Diabetes mellitus (DM) is associated with increased risk of cardiovascular events after percutaneous coronary intervention (PCI). To evaluate the impact of Absorb bioresorbable vascular scaffold (BVS) in patients with DM, we aimed to compare the 2-year outcomes of Absorb BVS versus 2nd generation drug eluting stents Xience (EES) by pooling diabetic patients treated with BVS or EES from two large, randomized controlled trial. Methods Patients with medically-treated DM and treated by Absorb BVS in the COMPARE-ABSORB and AIDA trial were pooled for analysis. The primary efficacy outcomes measure was target lesion failure (cardiac death, target-vessel myocardial infarction or target lesion revascularization), and the primary safety outcome measure was device thrombosis at 2-year follow-up. Results Out of a total 3515 enrolled subjects in the two trials, 913 were diabetics. Compared with the non-diabetic patients, those with DM were older, more often to have a history of hypercholesterolemia, chronic renal failure, stroke, hypertension, heart failure, peripheral vascular disease and previous PCI. At 2-years, target lesion failure occurred in 10.8% of BVS DM patients and 7.6% of EES DM patients (adjusted HR 1.43, 95% CI: 0.87–2.34, P=0.115). The 2-year rates of cardiac death (2.4% vs 1.6%, P=0.385), TV-MI (5% vs 1.6%, P=0.123) and TLR (7.8% vs 5.8%, P=0.416) showed not significant difference. The 2-year incidence of definite device thrombosis was 3.2% in Absorb BVS versus 0.7% in Xience EES (adjusted HR 4.77, 95% CI: 1.01–22.43, P=0.048). Conclusion This pooling of the diabetic patients from two large scale RCTs compared BVS versus 2nd generation DES, showed an increased rate of device thrombosis in BVS-treated patients at 2 years. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Abbott

Abstract Background Periprocedural myocardial infarction (PMI) occurs frequently after both percutaneous coronary intervention (PCI) and bypass grafting surgery (CABG) in patients with complex coronary artery disease (CAD), and PMI has been shown to have a detrimental impact on mortality. On the other hand, long-term impact of PMI on mortality has not been fully evaluated. Purpose This study aimed to assess the impact of PMI according to SCAI definition on 10-year all-cause death in patients with complex CAD. Methods The SYNTAX Extended Survival (SYNTAXES) 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 treatment with CABG or PCI in the SYNTAX trial. Blood was sampled for creatine kinase (CK) pre- and post-revascularisation, and the cardiac specific MB iso-enzyme (CK-MB) was determined only if the CK ratio ≥2 x the upper limit of normal (ULN). If the CK ratio <2 ULN, CK-MB assessment was not mandated. In this analysis, patients with at least one blood sampling within 48 hours of the procedure were included. PMI was defined as follows; peak CK-MB measured within 48 hours of the procedure ≥10 x ULN, or ≥5 x ULN with new Q-waves in 2 contiguous leads or new persistent left bundle branch block. Results Of 1800 patients, 1679 (93.2%) patients were included. Of 877 patients treated with PCI, PMI occurred in 26 patients (3.0%), whereas 14 (1.7%) PMIs were observed in 802 patients treated with CABG. Compared with patients without PMI, patients with PMI presented with unstable angina more frequently (45.0% vs. 28.7, p=0.033), and had a higher rate of bifurcation lesion (87.5% vs. 72.5, p=0.046). PMI was associated with a higher all-cause mortality at 10 years compared with no PMI (55.3% vs. 25.4%; Log-rank p<0.001, Figure), which was mainly driven by a high mortality rate within 1 year. In patients undergoing PCI, the mortality rates were significantly higher in patients with PMI not only within 1 year (Log-rank p<0.001) but also beyond one year (Log-rank p=0.016), compare to patients without PMI (Figure). On the other hand, in patients undergoing CABG, a higher mortality rate in patients with PMI was observed until 1 year (Log-rank p<0.001), but the impact of PMI on mortality beyond one year after CABG subsided (Log-rank p=0.308) (Figure 1). Conclusion PMI was associated with a poor prognosis at 10 years. The impact of PMI on mortality was strong within one year. Of note, the impact of PMI on mortality persisted beyond 1 year only in patients undergoing PCI. Patients who were treated with PCI and suffered PMI need careful follow-up beyond one year after revascularization. Figure 1 Funding Acknowledgement Type of funding source: None