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Objectives: This study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure., Background: A cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI)., Methods: The Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score., Results: There were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score., Conclusions: This noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850)., Competing Interests: Funding Support and Author Disclosures Funding was provided by a British Heart Foundation Grant (RE/18/6134217; PG/11/2/28474) and the Chief Scientist Office. Dr Berry was supported by a Senior Fellowship from the Scottish Funding Council. The T-TIME trial was funded by the Efficacy and Mechanism Evaluation program of the National Institute for Health Research. Boehringer Ingelheim United Kingdom Ltd provided the study drugs and matched placebo. Part of this project was supported by a research agreement with Siemens Healthcare. The 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.)

Objectives: This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm)., Background: PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice., Methods: Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population., Results: At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021)., Conclusions: Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930)., Competing Interests: Funding Support and Author Disclosures The ACTIVATION trial was funded by Edwards Lifesciences and Boston Scientific. Drs Clayton and Dodd have received reimbursement from King’s College London as independent statisticians for performing statistical analysis. Dr Morice is the CEO of Cardiovascular European Research Center CTU. Dr Meneveau has received consulting fees, speaker fees, and project funding from Bayer HealthCare and BMS/Pfizer; has received speaker fees from AstraZeneca and Boehringer Ingelheim; and has received consulting fees from Abbott and Terumo. Dr Banning has received institutional grant support for an educational fellowship from Boston Scientific and has been partially funded by the NHS Oxford Biomedical Research Centre. Dr Thomas is an employee of Edwards Lifesciences. Dr Prendergast has received unrestricted educational and research grants from Edwards Lifesciences; has received speaker/consultancy fees from Edwards Lifesciences, Abbott, and Anteris. Dr Hildick-Smith has served as Proctor/Advisory to Boston Scientific, Medtronic, and Edwards. Dr Redwood has served as a proctor and received speaker fees from Edwards Lifesciences. 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.)

Nonculprit lesions are frequently observed in patients with ST-segment elevation myocardial infarction. Results from recent randomized clinical trials suggest that complete revascularization after ST-segment elevation myocardial infarction improves outcomes. In this state-of-the-art paper, the authors review these trials and consider how best to determine which nonculprit lesions require revascularization and when this should be performed., (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.)

Objectives: The aim was to establish a contemporary scoring system to predict the outcome of chronic total occlusion coronary angioplasty., Background: Interventional treatment of chronic total coronary occlusions (CTOs) is a developing subspecialty. Predictors of technical success or failure have been derived from datasets of modest size. A robust scoring tool could facilitate case selection and inform decision making., Methods: The study analyzed data from the EuroCTO registry. This prospective database was set up in 2008 and includes >20,000 cases submitted by CTO expert operators (>50 cases/year). Derivation (n = 14,882) and validation (n = 5,745) datasets were created to develop a risk score for predicting technical failure., Results: There were 14,882 patients in the derivation dataset (with 2,356 [15.5%] failures) and 5,745 in the validation dataset (with 703 [12.2%] failures). A total of 20.2% of cases were done retrogradely, and dissection re-entry was performed in 9.3% of cases. We identified 6 predictors of technical failure, collectively forming the CASTLE score (Coronary artery bypass graft history, Age (≥70 years), Stump anatomy [blunt or invisible], Tortuosity degree [severe or unseen], Length of occlusion [≥20 mm], and Extent of calcification [severe]). When each parameter was assigned a value of 1, technical failure was seen to increase from 8% with a CASTLE score of 0 to 1, to 35% with a score ≥4. The area under the curve (AUC) was similar in both the derivation (AUC: 0.66) and validation (AUC: 0.68) datasets., Conclusions: The EuroCTO (CASTLE) score is derived from the largest database of CTO cases to date and offers a useful tool for predicting procedural outcome., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography., Background: In-stent neoatherosclerosis was recently identified as a novel disease manifestation of atherosclerosis after coronary stent implantation., Methods: Angiography and intravascular optical coherence tomography were used to investigate etiologic factors of neoatherosclerosis in patients presenting with stent thrombosis >1 year after implantation (very late stent thrombosis [VLST]). Clinical data were collected according to a standardized protocol. Optical coherence tomographic acquisitions were analyzed in a core laboratory. Cox regression analysis was performed to identify factors associated with the formation of neoatherosclerosis and plaque rupture as a function of time., Results: Optical coherence tomography was performed in 134 patients presenting with VLST. A total of 58 lesions in 58 patients with neoatherosclerosis were compared with 76 lesions in 76 patients without neoatherosclerosis. Baseline characteristics were similar between groups. In-stent plaque rupture was the most frequent cause (31%) in all patients presenting with VLST. In patients with neoatherosclerosis, in-stent plaque rupture was identified as the cause of VLST in 40 cases (69%), whereas uncovered stent struts (n = 22 [29%]) was the most frequent cause in patients without neoatherosclerosis. Macrophage infiltration was significantly more frequent in optical coherence tomographic frames with plaque rupture compared with those without (50.2% vs. 22.2%; p < 0.0001), whereas calcification was more often observed in frames without plaque rupture (17.2% vs. 4%; p < 0.0001). Implantation of a drug-eluting stent was significantly associated with the formation of neoatherosclerosis (p = 0.02), whereas previous myocardial infarction on index percutaneous coronary intervention was identified as a significant risk factor for plaque rupture in patients with neoatherosclerosis (p = 0.003). No significant difference was observed in thrombus composition between patients with or without neoatherosclerosis., Conclusions: Neoatherosclerosis was frequently observed in patients with VLST. Implantation of a drug-eluting stent was significantly associated with neoatherosclerosis formation. In-stent plaque rupture was the prevailing pathological mechanism and often occurred in patients with neoatherosclerosis and previous myocardial infarction at index percutaneous coronary intervention. Increased macrophage infiltration heralded plaque vulnerability in our study and might serve as an important indicator., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to determine the extent to which the site of the left main coronary artery (LM) lesion (distal bifurcation versus ostial/shaft) influences the outcomes of revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG)., Background: Among 1,905 patients with LM disease and site-assessed SYNTAX scores of <32 randomized in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, revascularization with PCI and CABG resulted in similar rates of the composite primary endpoint of death, myocardial infarction (MI), or stroke at 3 years., Methods: Outcomes from the randomized EXCEL trial were analyzed according to the presence of angiographic core laboratory-determined diameter stenosis ≥50% involving the distal LM bifurcation (n = 1,559; 84.2%) versus disease isolated to the LM ostium or shaft (n = 293; 15.8%)., Results: At 3 years, there were no significant differences between PCI and CABG for the primary composite endpoint of death, MI, or stroke for treatment of both distal LM bifurcation disease (15.6% vs. 14.9%, odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.81 to 1.42; p = 0.61) and isolated LM ostial/shaft disease (12.4% vs. 13.5%, OR: 0.90, 95% CI: 0.45 to 1.81; p = 0.77) (p interaction  = 0.65). However, at 3 years, ischemia-driven revascularization occurred more frequently after PCI than CABG in patients with LM distal bifurcation disease (13.0% vs. 7.2%, OR: 2.00, 95% CI: 1.41 to 2.85; p = 0.0001), but were not significantly different in patients with disease only at the LM ostium or shaft (9.7% vs. 8.4%, OR: 1.18, 95% CI: 0.52 to 2.69; p = 0.68) (p interaction  = 0.25)., Conclusions: In the EXCEL trial, PCI and CABG resulted in comparable rates of death, MI, or stroke at 3 years for treatment of LM disease, including those with distal LM bifurcation disease. Repeat revascularization rates during follow-up after PCI compared with CABG were greater for lesions in the distal LM bifurcation but were similar for disease isolated to the LM ostium or shaft., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Evaluate whether PCI in combination with optimal medical therapy (OMT) will reduce all-cause death and hospitalization for HF compared to a strategy of OMT alone., Background: Ischemic cardiomyopathy (ICM) is the most common cause of heart failure (HF) and is associated with significant mortality and morbidity. Surgical revascularization has been shown to improve long-term outcomes in some patients, but surgery itself carries a major early hazard. Percutaneous coronary intervention (PCI) may allow a better balance between risk and benefit., Methods: REVIVED-BCIS2 is a prospective, multi-center, open-label, randomized controlled trial, funded by the National Institute for Health Research in the United Kingdom. Follow-up will be for at least 2 years from randomization. Secondary outcomes include left ventricular ejection fraction (LVEF), quality of life scores, appropriate implantable cardioverter defibrillator therapy and acute myocardial infarction. Patients with LVEF ≤35%, extensive coronary disease and demonstrable myocardial viability are eligible for inclusion and those with a myocardial infarction within 4 weeks, decompensated HF or sustained ventricular arrhythmias within 72 h are excluded. A trial of 700 patients has more than 85% power to detect a 30% relative reduction in hazard., Results: A total of 400 patients have been enrolled to date., Conclusions: International guidelines do not provide firm recommendations on the role of PCI in managing severe ICM, because of a lack of robust evidence. REVIVED-BCIS2 will provide the first randomized data on the efficacy and safety of PCI in ICM and has the potential to inform guidelines pertaining to both revascularization and HF. (Study of Efficacy and Safety of Percutaneous Coronary Intervention to Improve Survival in Heart Failure [REVIVED-BCIS2]; NCT01920048) (REVascularisation for Ischaemic VEntricular Dysfunction; ISRCTN45979711)., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: High platelet reactivity (HPR) was studied in patients presenting with ST-segment elevation myocardial infarction (STEMI) due to stent thrombosis (ST) undergoing immediate percutaneous coronary intervention (PCI)., Background: HPR on P2Y 12 inhibitors (HPR-ADP) is frequently observed in stable patients who have experienced ST. The HPR rates in patients presenting with ST for immediate PCI are unknown., Methods: Consecutive patients presenting with definite ST were included in a multicenter ST registry. Platelet reactivity was measured before immediate PCI with the VerifyNow P2Y 12 or Aspirin assay., Results: Platelet reactivity was measured in 129 ST patients presenting with STEMI undergoing immediate PCI. HPR-ADP was observed in 76% of the patients, and HPR on aspirin (HPR-AA) was observed in 13% of the patients. HPR rates were similar in patients who were on maintenance P2Y 12 inhibitor or aspirin since stent placement versus those without these medications. In addition, HPR-ADP was similar in patients loaded with a P2Y 12 inhibitor shortly before immediate PCI versus those who were not. In contrast, HPR-AA trended to be lower in patients loaded with aspirin as compared with those not loaded., Conclusions: Approximately 3 out of 4 ST patients with STEMI undergoing immediate PCI had HPR-ADP, and 13% had HPR-AA. Whether patients were on maintenance antiplatelet therapy while developing ST or loaded with P2Y 12 inhibitors shortly before undergoing immediate PCI had no influence on the HPR rates. This raises concerns that the majority of patients with ST have suboptimal platelet inhibition undergoing immediate PCI., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the cost-effectiveness of complete revascularization at index admission compared with infarct-related artery (IRA) treatment only, in patients with multivessel disease undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction., Methods: An economic evaluation of a multicenter randomized trial was conducted, comparing complete revascularization at index admission to IRA-only P-PCI in patients with multivessel disease (12-month follow-up). Overall hospital costs (costs for P-PCI procedure(s), hospital length of stay, and any subsequent re-admissions) were estimated. Outcomes were major adverse cardiac events (MACEs, a composite of all-cause death, recurrent myocardial infarction, heart failure, and ischemia-driven revascularization) and quality-adjusted life-years (QALYs) derived from the three-level EuroQol five-dimensional questionnaire. Multiple imputation was undertaken. The mean incremental cost and effect, with associated 95% confidence intervals, the incremental cost-effectiveness ratio, and the cost-effectiveness acceptability curve were estimated., Results: On the basis of 296 patients, the mean incremental overall hospital cost for complete revascularization was estimated to be -£215.96 (-£1390.20 to £958.29), compared with IRA-only, with a per-patient mean reduction in MACEs of 0.170 (0.044 to 0.296) and a QALY gain of 0.011 (-0.019 to 0.041). According to the cost-effectiveness acceptability curve, the probability of complete revascularization being cost-effective was estimated to be 72.0% at a willingness-to-pay threshold value of £20,000 per QALY., Conclusions: Complete revascularization at index admission was estimated to be more effective (in terms of MACEs and QALYs) and cost-effective (overall costs were estimated to be lower and complete revascularization thereby dominated IRA-only). There was, however, some uncertainty associated with this decision., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Cardiogenic shock represents a state of low cardiac output and systemic hypoperfusion resulting in insufficient end-organ perfusion and consequent multiorgan failure. The main cause of this complication in the context of acute ST-elevation myocardial infarction is left ventricular dysfunction secondary to poor myocardial perfusion. In over 50% of cardiogenic shock cases, there is evidence of significant coronary stenosis within noninfarct-related arteries. Persistent ischemia in the noninfarct territory may contribute to ongoing hypotension. Currently, ESC and ACC/AHA/SCAI guidelines advocate complete revascularization in the context of multivessel coronary artery disease in the context of cardiogenic shock, although the evidence is weak., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The study compared, by intravascular ultrasound (IVUS), acute gain (AG) at the site of the pre-procedural minimal lumen area (MLA) achieved by either the Absorb (Abbott Vascular, Santa Clara, California) scaffold or the Xience stent and identified the factors contributing to the acute performance of these devices., Background: It is warranted that the acute performance of Absorb matches that of metallic stents; however, concern exists about acute expansion and lumen gain with the use of Absorb., Methods: Of a total of 501 patients (546 lesions) in the ABSORB II (ABSORB II Randomized Controlled Trial) randomized trial, 445 patients with 480 lesions were investigated by IVUS pre- and post-procedure. Comparison of MLA pre- and post-procedure was performed at the MLA site by matching pre- and post-procedural IVUS pullbacks., Results: Lower AG on IVUS (lowest tertile) occurred more frequently in the Absorb arm than in the Xience arm (3.46 mm(2) vs. 4.27 mm(2), respectively; p < 0.001; risk ratio: 3.04; 95% confidence interval: 1.94 to 4.76). The plaque morphology at the MLA cross-section was not independently associated with IVUS acute gain. The main difference in AG in MLD by angiography was observed at the time of device implantation (Xience vs. Absorb, Δ+1.50 mm vs. Δ+1.23 mm, respectively), whereas the gain from post-dilation was similar between the 2 arms (Δ+0.16 mm vs. Δ+0.16 mm) when patients underwent post-dilation, although expected balloon diameter was smaller in the Absorb arm than in the Xience arm (p = 0.003) during post-dilation., Conclusions: At the site of the pre-procedural MLA, the increase of the lumen post-procedure was smaller in the Absorb-arm than in the Xience arm. To achieve equivalent AG to Xience, the implantation of Absorb may require more aggressive strategies at implantation, pre- and post-dilation than the technique used in the ABSORB II trial. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is a significant increase in the number of octogenarians undergoing Primary Percutaneous Intervention (PPCI) for ST elevation myocardial infarction Objective: To analyze one year all cause mortality in octogenarians who are admitted with a STEMI and received PPCI in a tertiary cardiac centre in the UK, and to observe the impact of the mode of vascular access on mortality., Methods: We reviewed registry records of consecutive STEMI patients(N=2951), admitted between 2005 and 2011.Kaplan-Meier and Cox regression analyses were used to compare mortality between OG and Age group (50-79) years., Results: Of the total population, 8.1% (n=241, Mean age: 85.3 yrs. (SD: 3.4)) were OG of whom 53.5% were male. Use of femoral arterial access (63%) was significantly higher among OG (P=0.04) compared to radial route. In univariate analysis, event free survival was significantly lower in OG (log rank test, P=0.001) compared to other age group. All cause mortality was significantly higher among patients who had femoral arterial access compared to radial route (log rank test, P=0.03) in OG. In Cox regression analysis conventional risk factors femoral access remained significantly associated with one year all cause mortality (Beta:-1.9(SE: 0.9, P=0.04)., Conclusion: In our analysis, OG who received PPCI for STEMI have disproportionately higher one year all cause mortality compared to younger age group. Use of femoral arterial access appears to be independently associated with this excess mortality. Radial access preferred to be the safer and prime option in this high risk population and warrants further investigations., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice., Methods: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044., Findings: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015)., Interpretation: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI., Funding: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc., Competing Interests: Declaration of interests SSJ has received grants from Medtronic during the conduct of the study. JAC has received grants from the Canadian Institutes of Health Research and Medtronic during the conduct of the study, and grants from Medtronic outside the submitted work. RM has received personal fees from Medtronic during the conduct of the study. AG has received personal fees and advisory board fees from AstraZeneca, and grants, meeting support, and research grants from Medronic, outside the submitted work. PGS has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Medtronic, Vivus, Janssen, Orexigen, and Regado; grants and personal fees from Sanofi and Servier; and personal fees and non-financial support from The Medicines Company, outside the submitted work. RCW has received personal fees from Medtronic; grants from Abbott Vascular and Edwards Lifesciences, grants and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Jansen and BMS/Pfizer, outside the submitted work. SVR has received personal fees from Medtronic, outside the submitted work. SP has received personal fees from Medtronic, outside the submitted work. VD has received an institutional grant to conduct the trial from the TOTAL Coordinating Centre during the conduct of the study. All other coauthors declare no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS., Background: Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES., Methods: Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months., Results: Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001)., Conclusions: DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine mortality rates among cardiogenic shock (CGS) patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome in the contemporary treatment era and to determine predictors of mortality., Background: It is unclear whether recent advances in pharmacological and interventional strategies have resulted in further improvements in short- and long-term mortality and which factors are associated with adverse outcomes in patients presenting with CGS and undergoing PCI in the setting of acute coronary syndrome., Methods: This study analyzed prospectively collected data for patients undergoing PCI in the setting of CGS as recorded in the BCIS (British Cardiovascular Intervention Society) PCI database., Results: In England and Wales, 6,489 patients underwent PCI for acute coronary syndrome in the setting of CGS. The mortality rates at 30 days, 90 days, and 1 year were 37.3%, 40.0%, and 44.3%, respectively. On multiple logistic regression analysis, age (for each 10-year increment of age: odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.51 to 1.68; p < 0.0001), diabetes mellitus (OR: 1.47, 95% CI: 1.28 to 1.70; p < 0.0001), history of renal disease (OR: 2.03, 95% CI: 1.63 to 2.53; p < 0.0001), need for artificial mechanical ventilation (OR: 2.56, 95% CI: 2.23 to 2.94; p < 0.0001), intra-aortic balloon pump use (OR: 1.57, 95% CI: 1.40 to 1.76; p < 0.0001), and need for left main stem PCI (OR: 1.90, 95% CI: 1.62 to 2.23; p < 0.0001) were associated with higher mortality at 1 year., Conclusions: In this large U.K. cohort of patients undergoing PCI in the context of CGS, mortality remains high in spite of the use of contemporary PCI strategies. The highest mortality occurs early, and this time period may be a particular target of therapeutic intervention., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In the past ten years, primary percutaneous coronary intervention (PCI) has replaced thrombolysis as the revascularisation strategy for many patients presenting with ST-segment elevation myocardial infarction (STEMI). However, delivery of primary PCI within evidence-based timeframes is challenging, and health-care provision varies substantially worldwide. Consequently, even with the ideal circumstances of rapid initial diagnosis, long transfer delays to the catheter laboratory can occur. These delays are detrimental to outcomes for patients and can be exaggerated by variations in timing of patients' presentation and diagnosis. In this Series paper we summarise the value of immediate out-of-hospital thrombolysis for STEMI, and reconsider the potential therapeutic interface with a contemporary service for primary PCI. We review recent trial data, and explore opportunities for optimisation of STEMI outcomes with a pharmacoinvasive approach., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate the relative frequency of access and nonaccess site bleeding, the association of these events with 1-year mortality, and the impact of randomized antithrombotic therapy., Background: Post-percutaneous coronary intervention (PCI) bleeding has been strongly associated with subsequent mortality. The extent to which access versus nonaccess site bleeding contributes to this poor prognosis and the role of antithrombotic therapies remains poorly understood., Methods: The incidence and impact of Thrombolysis In Myocardial Infarction (TIMI) major/minor 30-day bleeding and randomized antithrombotic therapy were examined in a combined dataset from the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events), Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials in 17,393 PCI patients., Results: The TIMI major/minor bleeding occurred in 5.3% of patients, 61.4% of which (3.3%) were nonaccess site bleeds. After multivariable adjustment, TIMI bleeding was associated with an increased risk of 1-year mortality (hazard ratio [HR]: 3.17, 95% confidence interval [CI]: 2.51 to 4.00, p < 0.0001). The HR of a nonaccess site bleed was approximately 2-fold that of an access site bleed: HR: 3.94, 95% CI: 3.07 to 5.15, p < 0.0001 versus HR: 1.82, 95% CI: 1.17 to 2.83, p = 0.008, respectively. Randomization to bivalirudin versus heparin + a glycoprotein IIb/IIIa inhibitor resulted in 38% and 43% relative reductions in TIMI major/minor and TIMI major bleeding, respectively (p < 0.0001 for both), with significant reductions in both access and nonaccess site bleeding., Conclusions: Nonaccess site bleeding after PCI is common, representing approximately two-thirds of all TIMI bleeding events, and is associated with a 4-fold increase in 1-year mortality. Use of bivalirudin rather than heparin + a glycoprotein IIb/IIIa inhibitor significantly decreases both nonaccess site as well as access site bleeding events by approximately 40%., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Thrombolysis remains the first-line therapy in a substantial proportion of patients presenting with ST elevation myocardial infarction. The optimal treatment for patients in whom there is failure of reperfusion following thrombolysis is unclear. The Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis (REACT) trial demonstrated, in 427 randomly assigned patients with failed reperfusion following thrombolysis, that event-free survival rates were significantly improved with rescue angioplasty compared with either repeat thrombolysis or conservative treatment. However, the safety and efficacy of rescue angioplasty among older patients remains uncertain., Methods and Results: We aimed to determine whether rescue angioplasty was safe and effective in an older population, by evaluating the primary and secondary clinical outcomes among the 105 patients >or=70 years of age in the REACT trial. We observed an increased overall 6-month event rate among older patients. The relative benefit of rescue angioplasty versus repeat thrombolysis or conservative treatment was maintained, and the absolute benefit actually increased in this older age group compared with the study population as a whole. There was no adverse impact of advanced age on bleeding complications. Repeat thrombolysis was no more effective than conservative therapy., Conclusions: Rescue angioplasty is the preferred management strategy for failed thrombolysis, even for patients >or=70 years of age.

Spontaneous coronary artery spasm is an important cause of morbidity both in patients with coronary artery disease and in those with variant angina. A number of pharmacological agents have been identified which can provoke coronary artery spasm in susceptible patients. The role of provocation testing in the clinical diagnosis of coronary spasm is controversial. This is reflected by variations in the clinical use of provocation testing between specialist cardiac centres. Provocation testing appears to be a sensitive method of identifying patients with variant angina and active disease but such patients can often be diagnosed clinically. The specificity is less clear. There is little evidence that altering patient therapy on the basis of a positive test modifies prognosis. There may be a role for provocation testing in rare patients with refractory disease to identify a target site for coronary stenting. A more widespread use of these tests in patients with undiagnosed chest pain syndromes would not currently be recommended.

Objective: To study variations in use of intra-aortic balloon counterpulsation (IABC) and their impact on complications by comparing aspects of its use in a Regional Cardiothoracic Centre with an international database., Methods and Results: Indications, technique and complication rate in 764 consecutive patients treated with IABC from January 1998 to November 2001 (Group I) at the Regional Cardiothoracic Centre were compared with 24,555 consecutive patients from the international ("Benchmark") database (Group II). Patients in Groups I and II were of similar mean age (65.5 vs. 65.6 years) and predominantly males (77.1% vs. 66.9%). IABC-related complications were significantly less in Group I vs. Group II (3.93% vs. 7.04%, p<0.001), probably due to the increased use of smaller French size balloons (8f in Group I: 73.3% vs. Group II: 28.8%, p<0.001) and significantly less use of femoral artery sheaths (Group I: 91.2% vs. Group II: 20.4%, p<0.001) as well as less concomitant use of potent anti-thrombotic therapy (4.2% vs. 21.7%). By comparison to the international database only a minority of our patients were transferred in specifically for insertion of IABC (Group I: 1.3% vs. Group II: 22.8%, p<0.001) suggesting under-recognition of the potential value of IABC in haemodynamically compromised patients., Conclusion: In comparison to an international database, complications were significantly less after IABC at the regional cardiothoracic centre. There were far fewer patients referred specifically for IABC use. Indications, choice of appropriate device, technique of deployment and concomitant use of anti-platelet therapy varies and perhaps needs to be standardised internationally. Regular audit of any such large database is vital to ensure dissemination of potentially important messages it contains.

Background: Vascular endothelial growth factor (VEGF) is a specific endothelial cell mitogen. It promotes re-endothelialisation of the damaged vessel surface seen after stenting. Stent thrombosis and in-stent restenosis are partly related to endothelial denudation caused by stent implantation. We propose using hydrocarbon polymer-coated stents immersed in VEGF to speed re-endothelialisation and reduce the risk of stent thrombosis and restenosis., Methods: Stents (3 x 20 mm) were immersed in VEGF solutions and maximal VEGF absorption calculated. VEGF release from these stents was measured in a perfusion circuit. Delivery of VEGF to arterial wall was measured. Sterile VEGF-loaded stents were cultured with human umbilical vein endothelial cells., Results: 18.5 +/- 4.1 microg VEGF was absorbed, 80% of which was released over 9 days; 11 +/- 6.8% of the initial VEGF loaded was delivered to the vessel wall. Cells exposed to VEGF-eluting stents showed an 11% increase in growth relative to controls., Conclusion: VEGF may be a candidate for stent-based delivery and may increase the rate of endothelialisation in vivo.

Background: Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences., Methods: We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat., Findings: Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001)., Interpretation: Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.

Expression of TNF-alpha a vascular smooth muscle cell (VSMC) mitogen, is up-regulated in injured/proliferating vessel wall. Coronary stents are tested worldwide for their use as local drug delivery devices to address vascular pathophysiology. In this study we have investigated the effect of TNF-alpha antibody eluting stents on VSMC proliferation in human saphenous vein (HSV) organ culture. The adsorption and elution characteristics of TNF-alpha antibody was assessed using stent wires. The stents adsorbed up to 0.25 microg of TNF-alpha antibody/mg of stent and showed a biexponential elution curve, with 34.4% (SD 4.4%) antibody remaining on the stent after 72 h of washing in a perfusion circuit. TNF-alpha antibody delivery from loaded stents to the vessel wall was assessed ex vivo. TNF-alpha and proliferating cell nuclear antigen (PCNA) expression in the vascular specimens was assessed by immunostaining or ELISAs. TNF-alpha ELISAs showed a significant increase in the cytokine levels from the vascular lysates prepared from proliferating tissue culture compared with fresh vein (P < 0.05). Immunohistochemical localization showed an increase in the PCNA positivity of VSMC from these cultures. PCNA staining was barely detected from the fresh tissue. However, a decrease in PCNA staining was observed from tissue sections of venous segments cultured with TNF-alpha antibody eluting stents. PCNA ELISAs demonstrated a 23.7% decline in the antigen levels from the day 7 tissue cultured with such loaded stents. In conclusion, activated VSMC in tissue culture showed an up-regulation of TNF-alpha cytokine, in association with an increase in the PCNA expression in the vessel wall. The local neutralization of this cytokine with TNF-alpha antibody eluting stents reduced VSMC proliferation in the wall. We suggest that TNF-alpha antibody eluting stents may limit restenosis in vivo, which may have important clinical benefits.