Understanding the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) Trial Implications for current and future clinical practice

__Abstract__ The landmark Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) Trial1-4 has aided in reducing the area of uncertainty in decision making between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with complex coronary artery disease.5-8 As part of the SYNTAX Trial, quantification of the coronary artery disease burden was undertaken with the anatomical SYNTAX Score (www.syntaxscore.com),9-11 and has since been implemented in international revascularisation guidelines.5-8 In addition, recognising the importance of quantifying coronary artery disease burden in decision-making between CABG and PCI, the US Food and Drugs Association mandates the SYNTAX Score as entry criteria in ongoing contemporary stent and structural heart disease trials. Namely, the EXCEL (Evaluation of XIENCE PRIME™ or XIENCE V® Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) Trial (ClinicalTrials.gov identifier: NCT01205776), and SURTAVI (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement) Trial (ClinicalTrials.gov identifier: NCT01586910). The SYNTAX Trial was conceived in an era when the potential benefits of drug eluting stents were first being realised between 2002-2006.12-19 After multiple prior attempts comparing CABG against PCI using older technologies – namely plain ‘old’ balloon angioplasty (POBA) and bare metal stents (BMS) – in over 20 randomised trials,20, 21 including the Bypass Angioplasty Revascularization Investigation (BARI)22 and Coronary Angioplasty versus Bypass Revascularisation Investigation (CABRI)23 trials, the time had once again come to rechallenge the cardiac surgeons in the management of complex coronary artery disease. Historically one of the major criticisms of randomised trial design comparing CABG against PCI was that the trials enrolled highly selected, “cherry-picked,” patients, with approximately 2-12% of screened subjects actually randomised in most trials, and thus being largely unrepresentative of conventional clinical practice.20, 24 At the time of the SYNTAX Trial design, one of the key requirements put forth by seven cardiac surgeons, dubbed the “magnificent seven,” and fully endorsed by the clinical and interventional cardiologists at the time, was the need for an ‘all-comers’ trial design, free from selection bias

Hierarchies of conditional beliefs and interactive epistemology in dynamic games

Digitised version produced by the EUI Library and made available online in 2020

The impact of coronary perforation in percutaneous interventions involving the left main stem coronary artery in the United Kingdom 2007-2014: Insights from the British Cardiovascular Intervention Society database

Background Percutaneous coronary intervention (PCI) is increasingly utilized for treatment of coronary disease involving the unprotected left main stem (ULMS). However, no studies to date have examined the outcomes of such interventions when complicated by coronary perforation (CP). Methods Using the British Cardiovascular Intervention society (BCIS) database, data were analyzed on all ULMS‐PCI procedures complicated by CP in England and Wales between 2007 and 2014. Multivariate logistic regressions were used to identify predictors of ULMS CP and to evaluate the association between this complication and outcomes. Results During 10,373 ULMS‐PCI procedures, CP occurred more frequently than in non‐ULMS‐PCI (0.9 vs. 0.4%, p < .001) with a stable annual incidence. Covariates associated with CP included number of stents used, female gender, use of rotational atherectomy and chronic total occlusion (CTO) intervention. Adjusted odds of adverse outcomes for ULMS‐PCI complicated by CP were higher for peri‐procedural complications including cardiogenic shock, tamponade, side‐branch loss, DC cardioversion, in‐hospital major bleeding, transfusion requirement, and peri‐procedural myocardial infarction. There were also significantly increased odds for in‐hospital major adverse cardiac events (MACCE, OR 8.961, 95% CI [4.902–16.383]) and 30‐day mortality (OR 5.301, 95% CI [2.741–10.251]). Conclusions CP is an infrequent event during ULMS‐PCI and is predicted by female gender, rotational atherectomy, CTO interventions or number of stents used. CP was associated with significantly higher odds of mortality and morbidity, but at rates similar to previously published all‐comer PCI complicated by CP

Evaluation with in vivo optical coherence tomography and histology of the vascular effects of the everolimus-eluting bioresorbable vascular scaffold at two years following implantation in a healthy porcine coronary artery model: implications of pilot results for future pre-clinical studies

To quantify with in vivo OCT and histology, the device/vessel interaction after implantation of the bioresorbable vascular scaffold (BVS). We evaluated the area and thickness of the strut voids previously occupied by the polymeric struts, and the neointimal hyperplasia (NIH) area covering the endoluminal surface of the strut voids (NIHEV), as well as the NIH area occupying the space between the strut voids (NIHBV), in healthy porcine coronary arteries at 2, 3 and 4 years after implantation of the device. Twenty-two polymeric BVS were implanted in the coronary arteries of 11 healthy Yucatan minipigs that underwent OCT at 2, 3 and 4 years after implantation, immediately followed by euthanasia. The areas and thicknesses of 60 corresponding strut voids previously occupied by the polymeric struts and the size of 60 corresponding NIHEV and 49 NIHBV were evaluated with both OCT and histology by 2 independent observers, using a single quantitative analysis software for both techniques. At 3 and 4 years after implantation, the strut voids were no longer detectable by OCT or histology due to complete polymer resorption. However, analysis performed at 2 years still provided clear delineation of these structures, by both techniques. The median [ranges] areas of these strut voids were 0.04 [0.03–0.16] and 0.02 [0.01–0.07] mm2 by histology and OCT, respectively. The mean (±SD) thickness by histology and OCT was 220 ± 40 and 120 ± 20 μm, respectively. The median [ranges] NIHEV by histology and OCT was 0.07 [0.04–0.20] and 0.03 [0.01–0.08] mm2, while the mean (±SD) NIHBV by histology and OCT was 0.13 ± 0.07 and 0.10 ± 0.06 mm2. Our study indicates that in vivo OCT of the BVS provides correlated measurements of the same order of magnitude as histomorphometry, and is reproducible for the evaluation of certain vascular and device-related characteristics. However, histology systematically gives larger values for all the measured structures compared to OCT, at 2 years post implantation

Coronary evaginations are associated with positive vessel remodelling and are nearly absent following implantation of newer-generation drug-eluting stents: an optical coherence tomography and intravascular ultrasound study

Objectives The purpose of this study was to assess the occurrence, predictors, and mechanisms of optical coherence tomography (OCT)-detected coronary evaginations following drug-eluting stent (DES) implantation. Background Angiographic ectasias and aneurysms in stented segments have been associated with a risk of late stent thrombosis. Using OCT, some stented segments show coronary evaginations reminiscent of ectasias. Methods Evaginations were defined as outward bulges in the luminal contour between struts. They were considered major evaginations (MEs) when extending ≥3 mm along the vessel length, with a depth ≥10% of the stent diameter. A total of 228 patients who had sirolimus (SES)-, paclitaxel-, biolimus-, everolimus (EES)-, or zotarolimus (ZES)-eluting stents implanted in 254 lesions, were analysed after 1, 2, or 5 years; and serial assessment using OCT and intravascular ultrasound (IVUS) was performed post-intervention and after 1 year in 42 patients. Results Major evaginations occurred frequently at all time points in SES (∼26%) and were rarely seen in EES (3%) and ZES (2%, P = 0.003). Sirolimus-eluting stent implantation was the strongest independent predictor of ME [adjusted OR (95% CI) 9.1 (1.1-77.4), P = 0.008]. Malapposed and uncovered struts were more common in lesions with vs. without ME (77 vs. 25%, P < 0.001 and 95 vs. 20%, P < 0.001, respectively) as was thrombus [49 vs. 14%, OR 7.3 (95% CI: 1.7-31.2), P = 0.007]. Post-intervention intra-stent dissection and protrusion of the vessel wall into the lumen were associated with an increased risk of evagination at follow-up [OR (95% CI): 2.9 (1.8-4.9), P < 0.001 and 3.3 (1.6-6.9), P = 0.001, respectively]. In paired IVUS analyses, lesions with ME showed a larger increase in the external elastic membrane area (20% area change) compared with lesions without ME (5% area change, P < 0.001). Conclusion Optical coherence tomography-detected MEs are a specific morphological footprint of early-generation SES and are nearly absent in newer-generation ZES and EES. Evaginations appear to be related to vessel injury at baseline; are associated with positive vessel remodelling; and correlate with uncoverage, malapposition, and thrombus at follow-u

Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score

Background The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has established itself as an important long-term prognostic factor in patients undergoing percutaneous coronary intervention (PCI). The incorporation of clinical factors may further augment the utility of the SXscore to longer-term risk stratify the individual patient for clinical outcomes. Methods and results Patient-level merged data from >6000 patients in seven contemporary coronary stent trials was used to develop a logistic regression model—the Logistic Clinical SXscore—to predict 1-year risk for all-cause death and major adverse cardiac events (MACE). A core model (composed of the SXscore, age, creatinine clearance, and left ventricular ejection fraction) and an extended model [incorporating the core model and six additional (best performing) clinical variables] were developed and validated in a cross-validation procedure. The core model demonstrated a substantial improvement in predictive ability for 1-year all-cause death compared with the SXscore in isolation [area under the receiver operator curve (AUC): core model: 0.753, SXscore: 0.660]. A minor incremental benefit of the extended model was shown (AUC: 0.791). Consequently the core model alone was retained in the final the Logistic Clinical SXscore model. Validation plots confirmed the model predictions to be well calibrated. For 1-year MACE, the addition of clinical variables did not improve the predictive ability of the SXscore, secondary to the SXscore being the predominant determinant of all-cause revascularization. Conclusion The Logistic Clinical SXscore substantially enhances the prediction of 1-year mortality after PCI compared with the SXscore, and allows for an accurate personalized assessment of patient ris