Clinical Safety and Performance of GATT-Patch for Hemostasis in Minimal to Moderate Bleeding During Open Liver Surgery.

INTRODUCTION: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane. METHODS: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%. RESULTS: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred. CONCLUSIONS: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945).

NHS-POx-loaded patch versus fibrin sealant patch in a porcine robotic liver bleeding model.

BACKGROUND: The management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model. METHODS: The NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study. RESULTS: In the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001). CONCLUSIONS: In this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.

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

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

Graft flow evaluation with intraoperative transit-time flow measurement in off-pump versus on-pump coronary artery bypass grafting.

Objective: We aimed to compare transit-time flow measurement (TTFM) parameters for on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass procedures. Methods: The database of the Registry for Quality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery (REQUEST) study was retrospectively reviewed. Only single grafts were included (ie, no sequential or Y/T grafts). Primary end points were mean graft flow (MGF), pulsatility index (PI), diastolic fraction (DF), and backflow (BF). Unadjusted and propensity score-matching comparisons were performed. Results: Of 1016 patients in the REQUEST registry, 846 had at least 1 graft for which TTFM was performed. Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB procedures. Mean arterial pressure (MAP) during measurements was higher in the OPCAB group. After propensity score-matching, 312 well balanced pairs were left. In these matched patients, MGF was higher for the ONCAB versus the OPCAB group (32 vs 28 mL/min, respectively, for all grafts [P < .001]; 30 vs 27 mL/min for arterial grafts [P = .002]; and 35 vs 31 mL/min for venous grafts [P = .006], respectively). PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). Diastolic fraction was slightly lower in the ONCAB group (65% vs 67.5%; P < .001). The backflow was also lower in the ONCAB group (0.6 vs 1.3; P < .001) with trends similar to MGF and PI for venous and arterial grafts. There were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198). Conclusions: ONCAB surgery was associated with higher MGF and lower PI values, especially in venous grafts. Different TTFM cutoff values for ONCAB versus OPCAB surgery might be considered.

Ten-year all-cause mortality according to smoking status in patients with severe coronary artery disease undergoing surgical or percutaneous revascularization.

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.

Surgical Sutureless and Sutured Aortic Valve Replacement in Low-risk Patients.

BACKGROUND: Randomized clinical trials have shown that transcatheter aortic valve replacement is noninferior to surgery in low surgical risk patients. We compared outcomes in patients treated with a sutured (stented or stentless) or sutureless surgical valve from the Evolut Low Risk Trial. METHODS: The Evolut Low Risk Trial enrolled patients with severe aortic stenosis and low surgical risk. Patients were randomized to self-expanding transcatheter aortic valve replacement or surgery. Use of sutureless or sutured valves was at the surgeons' discretion. RESULTS: Six hundred eighty patients underwent surgical aortic valve implantation (205 sutureless, 475 sutured). The Valve Academic Research Consortium-2 30-day safety composite endpoint was similar in the sutureless and sutured group (10.8% vs 11.0%, P = .93). All-cause mortality between groups was similar at 30 days (0.5% vs 1.5%, P = .28) and 1 year (3.3% vs 2.6%, P = .74). Disabling stroke was also similar at 30 days (2.0% vs 1.5%, P = .65) and 1 year (2.6% vs 2.2%, P = .76). Permanent pacemaker implantation at 30 days was significantly higher in the sutureless compared with the sutured group (14.4% vs 2.9%, P < .001). Aortic valve-related hospitalizations occurred more often at 1 year with sutureless valves (9.1% vs 5.1%, P = .04). Mean gradients 1 year after sutureless and sutured aortic valve replacement were 9.9 ± 4.2 versus 11.7 ± 4.7 mm Hg (P < .001). CONCLUSIONS: Among low-risk patients, sutureless versus sutured valve use did not demonstrate a benefit in terms of 30-day complications and produced marginally better hemodynamics but with an increased rate of pacemaker implantation and valve-related hospitalizations.

Long-term survival after coronary bypass surgery with multiple versus single arterial grafts.

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.

Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease.

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.

Impact of Optimal Medical Therapy on 10-Year Mortality After Coronary Revascularization.

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).

Transit time flow measurement of coronary bypass grafts before and after protamine administration.

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.

10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease.

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; pinteraction = 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; pinteraction = 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).

Impact of stent length and diameter on 10-year mortality in the SYNTAXES trial.

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.

Impact of Body Composition Indices on Ten-year Mortality After Revascularization of Complex Coronary Artery Disease (From the Syntax Extended Survival Trial).

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/m2), 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.

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

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.

Impact of chronic obstructive pulmonary disease on 10-year mortality after percutaneous coronary intervention and bypass surgery for complex coronary artery disease: insights from the SYNTAX Extended Survival study.

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.

Mortality 10 Years After Percutaneous or Surgical Revascularization in Patients With Total Coronary Artery Occlusions.

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).

Ten-year all-cause death following percutaneous or surgical revascularization in patients with prior cerebrovascular disease: insights from the SYNTAX Extended Survival study.

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.

Impact of Peri-Procedural Myocardial Infarction on Outcomes After Revascularization.

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).

Redevelopment and validation of the SYNTAX score II to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease: secondary analysis of the multicentre randomised controlled SYNTAXES trial with external cohort validation.

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.