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Background: We investigated the prognostic significance of plasma N-terminal fragment of the prohormone B-type natriuretic peptide (Nt-proBNP) concentrations in addition to time to reperfusion and Thrombolysis in Myocardial Infarction (TIMI) flow before and after coronary intervention in patients with ST elevation myocardial infarction (STEMI) from the database of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial. Methods: Plasma Nt-proBNP was available in 1,037 patients with STEMI. Patients were randomized either to primary (p-PCI) or to full-dose tenecteplase before PCI (f-PCI).The study end point was the composite of death, cardiogenic shock, or congestive heart failure at 90 days. Results: According to classification tree analysis, patients with Nt-proBNP levels >694 pg/mL had the highest primary end point rates (33.8% vs 11%, P < .001). In Cox regression analysis, Nt-proBNP >694 pg/mL strongly predicted 90-day survival even among patients with short treatment delay (f-PCI < or =3 hours: hazard ratio [HR] 2.63, P = .002 and p-PCI < or =3 hours: HR 4.87, P < .001, respectively). Patients with TIMI 3 flow after coronary intervention were at significantly higher risk of the primary end point if admission Nt-proBNP exceeded 694 pg/mL (f-PCI: HR 2.88, P < .001 and p-PCI: HR 3.84, P < .001, respectively). In multivariable analysis, Nt-proBNP >694 pg/mL significantly (P = .001) predicted 90-day survival in addition to age (P < .001), TIMI flow after PCI (P < .001), body mass index (P = .026), anterior wall infarction (P = .035), and systolic blood pressure at randomization (P = .036), respectively. Conclusion: Elevated plasma concentrations of Nt-proBNP in the early phase of STEMI determine in-hospital and 90-day outcome after infarction irrespective of time to treatment and pre- or postinterventional TIMI flow. [ABSTRACT FROM AUTHOR]

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry., Methods and Results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy., Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.', Clinical Trial Registration: http://www., Clinicaltrials: gov identifier: NCT01991795., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to cancer itself or cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. The management of acute coronary syndromes and acute pericardial diseases in cancer patients was covered in part 1 of a clinical consensus document. This second part focusses on acute heart failure, acute myocardial diseases, venous thromboembolic diseases and acute arrhythmias., Competing Interests: Conflict of interest: P.L.: nothing in relation to this work. A.S.: nothing in relation to this work. G.G.: has received speaker honoraria from Novartis, Orion Pharma, AstraZeneca, and Bristol-Myers Squibb. R.A.: nothing in relation to this work. G.B.: nothing in relation to this work. S.H.: nothing in relation to this work. G.L.: nothing in relation to this work. D.F.: speaker’s honoraria or advisory board fees from Abbott Laboratories, Bayer, Boehringer Ingelheim, Leo Pharmaceuticals, Menarini, Novartis, Orion Pharma, Roche Diagnostics. S.G.: speaker’s and advisory fees (all institutional) from AstraZeneca, Daiichi-Sankyo, Boehringer. P.S.: speaker’s and advisory fees (all institutional) from AstraZeneca, Daiichi-Sankyo, Bayer, Boehringer, Pfizer, BMS, Amgen, Sanofi. P.V.D.M.: consultancy and/or Servier, Novartis, Pfizer, Pharmacosmos, Ionis. Supported by the ERC (StG 715732). A.R.L.: speaker, advisory board, or consultancy fees and/or research grants from Pfizer, Novartis, Servier, Amgen, Takeda, Roche, Janssens-Cilag Ltd., Clinigen, Eli Lily, Eisai, Bristol-Myers Squibb, Ferring Pharmaceuticals, Boehringer Ingelheim, Myocardial Solutions, iOWNA, and Heartfelt Technologies Ltd. A.O.: speaker’s and advisory fees from Seagen, Roche, Diaichi-Sankyo, and Astra Zeneca. Travel support from Lilly, Astra Zeneca, and Leo Pharmaceuticals. A.W.: honorarium, advisory board or consultancy fees: Janssen Cilag, GSK, Alexion, Caelum, Takeda, Celgene., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To assess the adherence to established quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) at the hospital-network level and its relation to outcome., Methods and Results: The data of 7774 STEMI patients admitted to 32 STEMI networks during the period 2014-18 were extracted from the Belgian STEMI database. Five QIs [primary percutaneous coronary intervention use, diagnosis-to-balloon time (DiaTB) <90 min, door-to-balloon time (DoTB) <60 min, P2Y12 inhibitor and statin prescription at discharge, and a composite QI score ranging from 0 to 10] were correlated with in-hospital mortality adjusted for differences in baseline risk profile (TIMI risk score). The median composite QI score was 6.5 [interquartile range (IQR) 6-8]. The most important gaps in quality adherence were related to time delays: the recommended DiaTB and DoTB times across the different networks were achieved in 68% (IQR 53-71) and 67% (IQR 50-78), respectively. Quality adherence was better in networks taking care of more high-risk STEMI patients. The median in-hospital mortality among the STEMI networks was 6.4% (IQR 4.1-7.9%). There was a significant independent inverse correlation between the composite QI score and in-hospital mortality (partial correlation coefficient: -0.45, P = 0.013). Stepwise regression analysis revealed that among the individual QIs, prolonged DiaTB was the most important independent outcome predictor., Conclusion: Among established STEMI networks, the time delay between diagnosis and treatment was the most variable and the most relevant prognostic QI, underscoring the importance of assessing quality of care throughout the whole network., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to the cancer itself or the cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. We summarize the most common acute CV complications of cytotoxic, targeted, and immune-based therapies. This is followed by a proposal for a multidisciplinary approach where acute cardiologists work close together with the treating oncologists, haematologists, and radiation specialists, especially in situations where immediate therapeutic decisions are needed. In this first part, we further focus on the management of acute coronary syndromes and acute pericardial diseases in patients with cancer., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium., Methods and Results: Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO 2 concentrations during lockdown (19.5 µg/m³ versus 13.2 µg/m³, p  < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74, p  = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%, p  = .04) and with longer door-to-balloon times (median of 45 versus 39 min, p  = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died., Conclusion: The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.

The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e -/- translates into significantly improved LV structural and functional remodeling at 4 weeks' follow-up. The early transcriptome of LV tissue from Clec4e -/- mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury., Competing Interests: This work was supported by a KU Leuven financing grant (C14/20/095). Ms Veltman holds a grant from the Royal Academy for Medicine in Belgium (KAGB, ZDK4478). Dr Janssens is holder of the AstraZeneca chair in Cardiology at KU Leuven. Dr Sinnaeve is co-holder of the Bayer Chair in Cardiology at KU Leuven. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk., Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels., Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL)., Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P interaction  = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P interaction  = 0.43., Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)., Competing Interests: Funding Support and Author Disclosures ODYSSEY Outcomes (NCT01663402) was funded by Sanofi and Regeneron Pharmaceuticals. Dr Schwartz has received research support to the University of Colorado from AstraZeneca, Resverlogix, Roche, Sanofi, and The Medicines Company; and is a coinventor on pending US patent 62/806,313 (“Methods for Reducing Cardiovascular Risk”) assigned in full to the University of Colorado. Dr Szarek has served as a consultant or on advisory boards (or both) for CiVi, Resverlogix, Baxter, Esperion, Lexicon, Sanofi, and Regeneron Pharmaceuticals. Dr Bittner has received grant support from Sanofi, AstraZeneca, DalCor, Esperion, Bayer, The Medicines Company, and Amgen (all paid direct to her institution); and has received personal fees from Sanofi. Dr Diaz has received research grants from Sanofi, DalCor Pharmaceuticals, the Population Health Research Institute, the Duke Clinical Research Institute, the TIMI group, Amgen, Cirius, Montreal Health Innovations Coordinating Center, and Lepetit; and has received personal fees, as a member of the executive steering committee, from Amgen and Cirius. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker and consulting honoraria (eg, advisory boards) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson & Johnson, Merck, Novartis, Novo Nordisk, Pendopharm, Pfizer, Regeneron, Sanofi, Servier, and Valeo Pharma; and has received salary support and honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, the Canadian Heart Research Centre and MD Primer, the Canadian VIGOUR Centre, the Cleveland Clinic Coordinating Centre for Clinical Research, the Duke Clinical Research Institute, the New York University Clinical Coordinating Centre, and the PERFUSE Research Institute. Dr Jukema has received research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Commission Seventh Framework Programme; and has received research support from Amgen, Astellas, AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck-Schering-Plough, Pfizer, Roche, and Sanofi. Dr Landmesser has received research grants from Novartis, Bayer, and Amgen; and has received lecture or advisory honorary fees from Amgen, Sanofi, Novartis, Bayer, Pfizer, and The Medicines Company. Dr López-Jaramillo has received honoraria for lectures from Menarini, Abbott, and Merck. Drs Manvelian and Pordy are employees of Regeneron Pharmaceuticals. Dr Scemama is an employee of Sanofi. Dr Sinnaeve has received institutional grants from the Flemish government, AstraZeneca, and Daiichi Sankyo; is a corecipient of a named chair supported by Bayer; and has received advisory and speaker fees (all institutional) from Sanofi, Amgen, Idorsia, Bristol Myers Squibb/Pfizer, AstraZeneca, and Abbott. Dr White has received grant support paid to the institution and fees for serving on a steering committee for the ODYSSEY Outcomes trial from Sanofi and Regeneron Pharmaceuticals, for the ACCELERATE study from Eli Lilly, for the STRENGTH trial from Omthera Pharmaceuticals, for the SPIRE trial from Pfizer, for the HEART-FID study from American Regent, for the CAMELLIA-TIMI study from Eisai, for the dal-GenE study from DalCor Pharma UK, for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi Australia, and for the CLEAR Outcomes study from Esperion Therapeutics. Dr White has served on advisory boards for Actelion, Sirtex, and Genentech (an affiliate of F. Hoffmann-La Roche; Lytics Post-PCI Advisory Board at the European Society of Cardiology); and has received lecture fees from AstraZeneca. Dr. Steg has received grants and nonfinancial support (cochair of the ODYSSEY Outcomes trial; as such, he received no personal fees, but his institution has received funding for the time he has devoted to trial coordination, and he has received support for travel related to trial meetings) from Sanofi; has received research grants and personal fees from Bayer (steering committee, MARINER, grant for epidemiological study), Merck (speaker fees, grant for epidemiological studies), Sanofi (cochair of the ODYSSEY Outcomes trial; cochair of the SCORED trial; consulting and speaking), Servier (chair of the CLARIFY registry; grant for epidemiological research), and Amarin (executive steering committee for the REDUCE-IT trial; consulting); and has received personal fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Idorsia, Myokardia, Novo Nordisk, Novartis, Regeneron Pharmaceuticals, and AstraZeneca. Dr Steg also has a European application number/patent number, issued on October 26, 2016 (15712241.7), for a method for reducing cardiovascular risk (all royalties assigned to Sanofi)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The treatment and early outcome of patients with acute myocardial infarction (MI) have dramatically improved the past decades, but the incidence of left ventricular (LV) dysfunction post-MI remains high. Peripheral blood RNAs reflect pathophysiological changes during acute MI and the inflammatory process. Therefore, these RNAs are promising new markers to molecularly phenotype patients and improve the early identification of patients at risk of subsequent LV dysfunction. We here discuss the coding and long non-coding RNAs that can be measured in peripheral blood of patients with acute MI and list the advantages and limitations for implementation in clinical practice. Although some studies provide preliminary evidence of their diagnostic and prognostic potential, the use of these makers has not yet been implemented in clinical practice. The added value of RNAs to improve treatment and outcome remains to be determined in larger clinical studies. International consortia are now catalyzing renewed efforts to investigate novel RNAs that may improve post-MI outcome in a precision-medicine approach. Graphical Abstract Peripheral blood RNAs reflect the inflammatory changes in acute MI. A number of studies provide preliminary evidence of their prognostic potential, although the use of these makers has not yet been assessed in clinical practice.

Objectives: Report the results at 2 years of the patients included in the SENIOR trial., Background: Patients above 75 years of age represent a fast-growing population in the cathlab. In the SENIOR trial, patients treated by percutaneous coronary intervention (PCI) with drug eluting stent (DES) and a short duration of P2Y12 inhibitor (1 and 6 months for stable and unstable coronary syndromes, respectively) compared with bare metal stents (BMS) was associated with a 29% reduction in the rate of all-cause mortality, myocardial infarction (MI), stroke, and ischaemia-driven target lesion revascularization (ID-TLR) at 1 year. The results at 2 years are reported here., Methods and Results: We randomly assigned 1,200 patients (596[50%] to the DES group and 604[50%] to the BMS group). At 2 years, the composite endpoint of all-cause mortality, MI, stroke and ID-TLR had occurred in 116 (20%) patients in the DES group and 131 (22%) patients in the BMS group (RR 0.90 [95%CI 0.72-1.13], p = .37). IDTLR occurred in 14 (2%) patients in the DES group and 41 (7%) patients in the BMS group (RR 0.35 [95%CI 0.16-0.60], p = .0002). Major bleedings (BARC 3-5) occurred in 27(5%) patients in both groups (RR 1.00, [95%CI 0.58-1.75], p = .99). Stent thrombosis rates were low and similar between DES and BMS (0.8 vs 1.3%, (RR 0.52 [95%CI 0.01-1.95], p = .27)., Conclusion: Among elderly PCI patients, a strategy combining a DES together with a short duration of DAPT is associated with a reduction in revascularization up to 2 years compared with BMS with very few late events and without any increased in bleeding complications or stent thrombosis., (© 2021 Wiley Periodicals LLC.)

Dual antiplatelet therapy (DAPT), the combination of aspirin (ASA), and a P2Y 12 inhibitor, protects against stent thrombosis and new atherothrombotic events after a stent implantation or an acute coronary syndrome, but exposes patients to an increased risk of bleeding. In most current practices, the P2Y 12 inhibitor is stopped at 6 to 12 months and ASA is continued indefinitely. The advent of safer stents, with less risk of stent thrombosis, has challenged this standard of care, however. A number of alternative strategies involving earlier de-escalation of the antiplatelet therapy have therefore been proposed. In these approaches, standard DAPT is switched to a less potent antithrombotic combination at an earlier time-point than recommended by guidelines. Three different de-escalation variations have been tested to date. The first one maintains DAPT but switches from the potent P2Y 12 inhibitors ticagrelor or prasugrel to either a lower dose or to clopidogrel, while maintaining ASA. The 2 other approaches involve changing DAPT to a single antiplatelet at some earlier time-point after the percutaneous coronary intervention procedure, by stopping either the P2Y 12 inhibitor or ASA. These strategies have all demonstrated some benefit in clinical trials so far, but especially the contribution of ASA in secondary prevention is clearly evolving as its role in increasing bleeding complications while not providing increased ischemic benefit is becoming more and more clear. In contemporary practice, the type and duration of DAPT should now be based on an individualized decision, and the de-escalation strategies, if used wisely, can be added to the existing options., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Cardiac arrest is a common complication of ST elevation myocardial infarction and is associated with high mortality. We evaluated whether vulnerability to cardiac arrest follows a circadian rhythm and whether it is related to specific patient characteristics., Methods: A total of 24,164 ST elevation myocardial infarction patients who were admitted to 60 Belgian hospitals between 2008-2017 were analysed. The proportion of patients with cardiac arrest before initiation of reperfusion therapy was calculated for different time periods (hour of the day, months, seasons) and related to patient characteristics using stepwise logistic regression analysis., Results: Cardiac arrest occurred in 10.8% of the ST elevation myocardial infarction patients at a median of 65 min (interquartile range 33-138 min) after onset of pain. ST elevation myocardial infarction patients with cardiac arrest showed a biphasic pattern with one peak in the morning and one peak in the late afternoon. Multivariate analysis identified the following independent factors associated with cardiac arrest: cardiogenic shock (odds ratio=28), left bundle branch block (odds ratio=3.7), short (<180 min) ischaemic period (odds ratio=2.2), post-meridiem daytime presentation (odds ratio=1.4), anterior infarction (odds ratio=1.3). Overall in-hospital mortality was 30% for cardiac arrest patients versus 3.7% for non-cardiac arrest patients ( p <0.0001)., Conclusion: In the present study population, cardiac arrest in ST elevation myocardial infarction showed an atypical circadian rhythm with not only a morning peak but also a second peak in the late afternoon, suggesting that cardiac arrest and ST elevation myocardial infarction triggers are, at least partially, different. In addition, specific patient characteristics, such as short ischaemic period, cardiogenic shock and left bundle branch block, increase the vulnerability to cardiac arrest.

Background: The STREAM study demonstrated that a pharmaco-invasive strategy was at least as effective as primary PCI (pPCI) in patients presenting early with ST-elevation myocardial infarction (STEMI). The current trial is a response to the finding that reduced intracranial hemorrhage (ICH) in patients ≥75 years occurred after halving the dose of tenecteplase. Additionally, a subsequent analysis of full dose tenecteplase or alteplase in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) trials demonstrated a steep increase in bleeding events beginning around the age of 60 years., Methods: STREAM-2 will compare the efficacy and safety of a novel pharmaco-invasive strategy as compared to routine pPCI in STEMI patients ≥60 years presenting within 3 hours from symptom onset. In the pharmaco-invasive arm patients will receive half-dose tenecteplase, as soon as possible before transport to a PCI center. In the pPCI arm, patients will be treated according to optimal standard of care defined by local practice. The key criteria for efficacy will be the number of patients achieving ≥50% ST-segment resolution before and after PCI in lead with maximal ST elevation at baseline and the clinical endpoints of death, congestive heart failure, shock or re-infarction, rescue PCI and aborted myocardial infarction, both singularly and as a composite at 30 days. Key safety criteria are total stroke, ICH and major non-intracranial bleeds. Approximately 600 patients will be randomized (400 to pharmaco-invasive treatment and 200 to pPCI). An interim analysis is planned after 300 patients are enrolled to consider adapting the trial to include a larger sample size aimed at undertaking a formal confirmatory trial., Discussion: The study will provide new insights aimed at establishing an effective and safer pharmaco-invasive treatment for the growing population of older STEMI patients who cannot undergo timely pPCI., Competing Interests: Disclosures The study is sponsored by Leuven Research & Development at the University of Leuven (KU Leuven) Belgium and supported by a grant from Boehringer Ingelheim GmbH to KU Leuven. The executive committee was responsible for the design and conduct of the trial. The academic authors vouch for the integrity and completeness of the data and analyses. Paul W. Armstrong has served as a consultant for Bayer and Merck. He has received research grants from CSL, Boehringer-Ingelheim, Bayer and Merck. Kris Bogaerts received consultancy fees through his institution from Boehringer Ingelheim GmbH. Robert Welsh has received research funding and honoraria from Astra Zeneca, Bayer, Boerhinger Ingelheim GmbH, and Pfizer. Peter Sinnaeve received Speaker’s and consultancy fees from Boehringer-Ingelheim. Patrick Goldstein reports travel support and lecture fees from Boehringer Ingelheim GmbH. Alain Pages is an employee of Boehringer Ingelheim GmbH. Thierry Danays is a former employee of Boehringer Ingelheim France, received consultancy fees from Boehringer Ingelheim GmbH. Frans Van de Werf received study grants to institution and lectures fees from Boehringer Ingelheim GmbH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular risk irrespective of age, but the evidence is less strong for older patients., Methods and Results: This prespecified analysis from ODYSSEY OUTCOMES compared the effect of alirocumab vs. placebo in 18 924 patients with recent acute coronary syndrome (ACS) according to age. We examined the effect of assigned treatment on occurrence of the primary study outcome, a composite of coronary heart disease death, myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization [major adverse cardiovascular event (MACE)] and all-cause death. Relative risk reductions were consistent for patients ≥65 vs. <65 years for MACE [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.68-0.91 vs. 0.89, 0.80-1.00; Pinteraction = 0.19] and all-cause death [HR 0.77, 0.62-0.95 vs. 0.94, 0.77-1.15; Pinteraction = 0.46], and consistent for MACE when dichotomizing at age 75 years (HR 0.85, 0.64-1.13 in ≥75 vs. 0.85, 0.78-0.93 in <75, Pinteraction = 0.19). When considering age as a continuous variable in regression models, advancing age increased risk of MACE, as well as the absolute reduction in MACE with alirocumab, with numbers-needed-to-treat for MACE at 3 years of 43 (25-186) at age 45 years, 26 (15-97) at age 75 years, and 12 (6-81) for those at age 85 years. Although adverse events were more frequent in older patients, there were no differences between alirocumab and placebo., Conclusion: In patients with recent ACS, alirocumab improves outcomes irrespective of age. Increasing absolute benefit but not harm with advancing age suggests that LDL-C lowering is an important preventive intervention for older patients after ACS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.

Background: Elderly patients receive bare metal stents instead of drug-eluting stents (DES) to shorten the duration of dual antiplatelet therapy (DAPT). The SENIOR trial compared outcomes between these 2 types of stents combined with a short duration of DAPT. A significant decrease in the number of patients with at least 1 major adverse cardiac and cerebrovascular event (MACCE) was noted in the DES group., Objectives: The objective of this article was to perform an economic evaluation of the SENIOR trial., Methods: This evaluation was performed separately in 5 participating countries using pooled patient-level data from all study patients and country-specific unit costs and utility values. Costs, MACCEs, and quality-adjusted life-years (QALYs) were calculated in both arms at 1 year, and an incremental cost-effectiveness ratio was estimated. Uncertainty was explored by probabilistic bootstrapping., Results: A total of 1200 patients underwent randomization. The average total cost per patient was higher in the DES group. The number of MACCEs and average QALYs were not statistically different between the 2 groups. The 1-year incremental cost-effectiveness ratio for each country of reference ranged from €13 752 to €20 511/MACCE avoided and from €42 835 to €68 231/QALY gained. The scatter plots found a wide dispersion, reflecting a large uncertainty surrounding the results. But in each country studied, 90% of the bootstrap replications indicated a higher cost for greater effectiveness for the DES group. Assuming a willingness to pay of €50 000/QALY, there was between a 40% and 50% chance that the use of DES was cost-effective in 4 countries., Conclusion: The use of DES instead of bare metal stents combined with a short duration of DAPT in elderly patients induced higher cost for greater effectiveness in each of the 5 countries studied., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction., Methods: We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole-blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction in the discovery cohort, in an external validation cohort (n=449), and in a representative porcine MI model with cardiac magnetic resonance-based measurements of infarct size and postmortem myocardial pathology (n=33)., Results: RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, IL (interleukin)-6, and NF-κB (nuclear factor-κB) signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of QSOX1 , PLBD1 , and S100A8 on admission with MI correlated with LV dysfunction at follow-up. Using quantitative polymerase chain reaction, we confirmed that QSOX1 and PLBD1 predicted LV dysfunction (odds ratio, 2.6 [95% CI, 1.1-6.1] and 3.2 [95% CI, 1.4-7.4]), whereas S100A8 did not. In the external validation cohort, we confirmed QSOX1 and PLBD1 as new independent markers of LV dysfunction (odds ratio, 1.41 [95% CI, 1.06-1.88] and 1.43 [95% CI, 1.08-1.89]). QSOX1 had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). In the porcine MI model, whole-blood levels of QSOX1 and PLBD1 related to neutrophil infiltration in the ischemic myocardium in an infarct size-independent manner., Conclusions: Peripheral blood QSOX1 and PLBD1 in acute MI are new independent markers of LV dysfunction post-MI.

Percutaneous drainage is the default strategy for evacuating a pericardial effusion. A pericardiocentesis can be necessary or required in a wide variety of clinical settings ranging from urgent tamponade to relieve in iatrogenic hemorrhagic effusions in the electrophysiology or catheterization room, to planned diagnostic procedures in patients with suspected or known malignancy or infections. With the help of several procedural improvements over the past decades, echocardiography and fluoroscopy-guided percutaneous pericardiocentesis has become the standard intervention for evacuating pericardial effusions, as well as an essential tool in the diagnostic work-up of an unexplained pericardial effusion. When performed by skilled physicians assisted by appropriate imaging it is a very safe procedure, and provided that an indwelling catheter is placed, it is also very effective with an acceptably low risk of recurrences. In this review, the indications and standard techniques for pericardiocentesis are discussed, as well as their consequences for patients with iatrogenic and malignant effusions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether hospital context influences the effect of care pathway implementation on teamwork processes and output in STEMI care., Design: A multicenter pre-post intervention study., Setting: Eleven acute hospitals., Participants: Cardiologists-in-chief, nurse managers, quality staff, quality managers and program managers reported on hospital context. Teamwork was rated by professional groups (medical doctors, nurses, allied health professionals, other) in the following departments: emergency room, catheterization lab, coronary care unit, cardiology ward and rehabilitation., Intervention: Care pathway covering in-hospital care from emergency services to rehabilitation., Main Outcome Measures: Hospital context was measured by the five dimensions of the Model for Understanding Success in Quality: microsystem, quality improvement team, quality improvement support, high-level organization, external environment. Teamwork process measures reflected teamwork between professional groups within departments and teamwork between departments. Teamwork output was measured through the level of organized care. Two-level regression analysis accounted for clustering of respondents within hospitals and assessed the influence of hospital context on the impact of care pathway implementation on teamwork., Results: Care pathway implementation significantly improved teamwork processes both between professional groups (P < 0.001) and between departments (P < 0.001). Teamwork output also improved (P < 0.001). The effect of care pathway implementation on teamwork was more pronounced when the quality improvement team and quality improvement support and capacity were more positively reported on., Conclusions: Hospitals can leverage the effect of quality improvement interventions such as care pathways by evaluating and improving aspects of hospital context., (© The Author(s) 2018. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The optimal therapeutic strategy for ST-segment elevation myocardial infarction (STEMI) patients found to have multi-vessel disease (MVD) is controversial but recent data support complete revascularisation (CR). Whether CR should be completed during the index admission or during a second staged admission remains unclear. Our main objective was to measure rates of major adverse cardiovascular events (MACEs) during the waiting period in STEMI patients selected for staged revascularisation (SR), in order to determine the safety of delaying CR. For completeness, we also describe 30-day and long-term outcomes in STEMI patients with MVD who underwent in-hospital CR., Methods: A single-centre retrospective analysis of 931 STEMI patients treated by primary percutaneous coronary intervention (PCI) identified 397 patients with MVD who were haemodynamically stable and presented within 12 hours of chest pain onset. Of these, 191 underwent multi-vessel PCI: 49 during the index admission and 142 patients undergoing a strategy of SR., Results: Our main finding was that waiting period MACE were 2% (three of 142) in patients allocated to SR (at a median of 31 days). In patients allocated to in-hospital CR, 30-day MACE rates were 10% (five of 49). During a median follow up of 39 months, all-cause mortality was 7.0% vs. 28.6%, and cardiac mortality was 2% vs. 8%, in patients allocated to SR or CR, respectively., Conclusions: Patients with STEMI and MVD who, based on clinical judgement, were allocated to a second admission SR strategy had very few adverse events during the waiting period and excellent long-term outcomes.

Background: Acute myocardial infarction (MI) invokes a large inflammatory response, which contributes to myocardial repair., Hypothesis: We investigated whether C-reactive protein (CRP) measured during MI vs at 1 month follow-up improves the prediction of left ventricular (LV) function., Methods: We prospectively enrolled 131 consecutive patients with acute MI and without non-cardiovascular causes of inflammation. We correlated admission and peak levels of CRP during hospitalization and high-sensitivity (hs) CRP at 1 month follow-up with markers of cardiac injury. Clinical follow-up and echocardiography for LV function were performed at a mean of 17 months., Results: Median CRP levels were 1.89 mg/L on admission with MI, peaked to 12.10 mg/L during hospitalization and dropped to 1.24 mg/L at 1 month. Although admission CRP levels only weakly correlated with ejection fraction in the acute phase of MI (coefficient -0.164, P = 0.094), peak CRP was significantly related to ejection fraction (coefficient -0.4, P < 0.001), hsTroponin T (0.389, P < 0.001), and white blood cell count (0.389, P < 0.001). hsCRP at 1 month was not related to the extent of acute cardiac injury. These findings were replicated in an independent cohort of 57 patients. Peak CRP predicted LV dysfunction at follow-up (OR 11.0, 3.1-39.5 per log CRP, P < 0.001), persisting after adjustment for infarct size (OR 5.1, 1.1-23.6, P = 0.037), while hsCRP at 1 month was unrelated to LV function at follow-up., Conclusions: hsCRP 1 month post-MI does not relate to acute cardiac injury or LV function at follow-up, but we confirm that peak CRP is an independent predictor of LV dysfunction at follow-up., (© 2018 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: A focus on specific priorities increases the success rate of quality improvement efforts for broad and complex-care processes. Importance-performance analysis presents a possible approach to set priorities around which to design and implement effective quality improvement initiatives. Persistent variation in hospital performance makes ST-elevation myocardial infarction care relevant to consider for importance-performance analysis., Aims: The purpose of this study was to identify quality improvement priorities in ST-elevation myocardial infarction care., Methods: Importance and performance levels of ST-elevation myocardial infarction key interventions were combined in an importance-performance analysis. Content validity indexes on 23 ST-elevation myocardial infarction key interventions of a multidisciplinary RAND Delphi Survey defined importance levels. Structured review of 300 patient records in 15 acute hospitals determined performance levels. The significance of between-hospital variation was determined by a Kruskal-Wallis test. A performance heat-map allowed for hospital-specific priority setting., Results: Seven key interventions were each rated as an overall improvement priority. Priority key interventions related to risk assessment, timely reperfusion by percutaneous coronary intervention and secondary prevention. Between-hospital performance varied significantly for the majority of key interventions. The type and number of priorities varied strongly across hospitals., Conclusions: Guideline adherence in ST-elevation myocardial infarction care is low and improvement priorities vary between hospitals. Importance-performance analysis helps clinicians and management in demarcation of the nature, number and order of improvement priorities. By offering a tailored improvement focus, this methodology makes improvement efforts more specific and achievable.

Background: Elderly patients regularly receive bare-metal stents (BMS) instead of drug-eluting stents (DES) to shorten the duration of double antiplatelet therapy (DAPT). The aim of this study was to compare outcomes between these two types of stents with a short duration of DAPT in such patients., Methods: In this randomised single-blind trial, we recruited patients from 44 centres in nine countries. Patients were eligible if they were aged 75 years or older; had stable angina, silent ischaemia, or an acute coronary syndrome; and had at least one coronary artery with a stenosis of at least 70% (≥50% for the left main stem) deemed eligible for percutaneous coronary intervention (PCI). Exclusion criteria were indication for myocardial revascularisation by coronary artery bypass grafting; inability to tolerate, obtain, or comply with DAPT; requirement for additional surgery; non-cardiac comorbidities with a life expectancy of less than 1 year; previous haemorrhagic stroke; allergy to aspirin or P2Y 12 inhibitors; contraindication to P2Y 12 inhibitors; and silent ischaemia of less than 10% of the left myocardium with a fractional flow reserve of 0·80 or higher. After the intended duration of DAPT was recorded (1 month for patients with stable presentation and 6 months for those with unstable presentation), patients were randomly allocated (1:1) by a central computer system (blocking used with randomly selected block sizes [two, four, eight, or 16]; stratified by site and antiplatelet agent) to either a DES or similar BMS in a single-blind fashion (ie, patients were masked), but those assessing outcomes were masked. The primary outcome was to compare major adverse cardiac and cerebrovascular events (ie, a composite of all-cause mortality, myocardial infarction, stroke, or ischaemia-driven target lesion revascularisation) between groups at 1 year in the intention-to-treat population, assessed at 30 days, 180 days, and 1 year. This trial is registered with ClinicalTrials.gov, number NCT02099617., Findings: Between May 21, 2014, and April 16, 2016, we randomly assigned 1200 patients (596 [50%] to the DES group and 604 [50%] to the BMS group). The primary endpoint occurred in 68 (12%) patients in the DES group and 98 (16%) in the BMS group (relative risk [RR] 0·71 [95% CI 0·52-0·94]; p=0·02). Bleeding complications (26 [5%] in the DES group vs 29 [5%] in the BMS group; RR 0·90 [0·51-1·54]; p=0·68) and stent thrombosis (three [1%] vs eight [1%]; RR 0·38 [0·00-1·48]; p=0·13) at 1 year were infrequent in both groups., Interpretation: Among elderly patients who have PCI, a DES and a short duration of DAPT are better than BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischaemia-driven target lesion revascularisation. A strategy of combination of a DES to reduce the risk of subsequent repeat revascularisations with a short BMS-like DAPT regimen to reduce the risk of bleeding event is an attractive option for elderly patients who have PCI., Funding: Boston Scientific., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To evaluate long-term clinical outcomes after treatment of complex bifurcation lesions with the AXXESS dedicated self-expanding biolimus A9-eluting bifurcation stent., Methods: Between 2004 and 2013, 123 patients with complex bifurcation lesions were treated in a single-center with the AXXESS stent in the proximal main vessel (MV) and additional drug-eluting stents in branches when required. Median follow-up was 5 years. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included MACE components (cardiac death, non-periprocedural clinical myocardial infarction [MI], target lesion revascularization [TLR] and definite/probable stent thrombosis [ST]) as well as all-cause death, target vessel revascularization (TVR) and non-TVR., Results: During follow-up, 11 (8.9%) patients experienced a MACE, of whom 2 (1.6%) suffered cardiac death, 2 (1.6%) had a non-periprocedural clinical MI requiring TLR, and 7 (5.7%) underwent elective TLR. No definite/probable ST was observed. All-cause death occurred in 9 (7.3%) patients, TVR in 11 (8.9%) and non-TVR in 11 (8.9%). Patients treated for left main (LM) bifurcation lesions were more likely to experience MACE than non-LM bifurcation lesions (25% vs. 6.5%, p = 0.04)., Conclusions: Percutaneous revascularization of complex bifurcation lesions with the AXXESS stent is safe and provides excellent long-term results, especially in non-LM lesions.

Objectives: To study the care pathway effect on the percentage of patients with ST-elevation myocardial infarction -(STEMI) receiving timely coronary reperfusion and the percentage of STEMI patients receiving optimal secondary prevention., Methods: A care pathway was implemented by the Collaborative Model for Achieving Breakthrough Improvement. One pre-intervention and 2 post-intervention audits included all adult STEMI patients admitted within 24 h after onset and eligible for reperfusion. Adjusted (hospital random intercepts and controls for transfer and out-of-office admission) differences in composite outcomes were analyzed by a multilevel logistic regression., Results: Significant improvements in intervals between the first medical contact (FMC) to percutaneous coronary intervention (PCI) and between the door to PCI were shown between post-intervention audit II and post-intervention audit I. Secondary prevention significantly deteriorated at post-intervention audit I but improved significantly between both post-intervention audits. Six out of nine outcomes were significantly poorer in the case of transfer. The interval from FMC to PCI was significantly poorer for patients admitted during out-of-office hours., Conclusions: After care pathway implementation, composite outcomes improved for in-hospital STEMI care. Collaborative efforts exploited heterogeneity in performance between hospitals. Iterative and incremental care pathway implementation maximized performance improvement., (© 2018 S. Karger AG, Basel.)

Background: Pericardial effusions can be caused by a variety of disorders. The frequency of the underlying diseases varies with patient population; therefore, previously reported series are not necessarily representative of other populations. Our purpose was to examine the etiology of pericardial effusions and the survival of patients requiring pericardiocentesis at a tertiary center., Methods and Results: We performed a retrospective observational study of 269 consecutive patients who underwent percutaneous pericardiocentesis at our university hospital between 2006 and 2016 and had prospective follow-up for up to 10 years. The most frequent etiologies were idiopathic (26%), malignancy (25%), and iatrogenicity (20%), whereas bacterial causes were very rare. The most frequent malignancies originated from the lung (53%) or breast (18%). A new cancer was diagnosed with malignant pericardial effusion as the presenting complaint for 9% of patients, whereas the pericardium was the first metastatic site of a known malignancy in 4% of patients. Survival was significantly poorer in malignancy-related versus non-malignancy-related effusions ( P <0.001) and in cytology-positive versus cytology-negative effusions in the overall cohort ( P <0.001). Among cancer-only patients, however, there was no significant difference in long-term survival between cytology-positive and -negative effusions., Conclusions: In this contemporary tertiary-center cohort, pericardial effusions often represent the primary instance of a new malignancy, underscoring the importance of cytological analyses of noniatrogenic effusions in patients without known cancer, as survival is significantly worse. In cancer patients, however, the presence of pericardial malignant cytology does not appear to affect outcome significantly., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: Identification, selection and validation of key interventions and quality indicators for improvement of in hospital quality of care for ST-elevated myocardial infarction (STEMI) patients., Methods and Results: A structured literature review was followed by a RAND Delphi Survey. A purposively selected multidisciplinary expert panel of cardiologists, nurse managers and quality managers selected and validated key interventions and quality indicators prior for quality improvement for STEMI. First, 34 experts (76% response rate) individually assessed the appropriateness of items to quality improvement on a nine point Likert scale. Twenty-seven key interventions, 16 quality indicators at patient level and 27 quality indicators at STEMI care programme level were selected. Eighteen additional items were suggested. Experts received personal feedback, benchmarking their score with group results (response rate, mean, median and content validity index). Consequently, 32 experts (71% response rate) openly discussed items with an item-content validity index above 75%. By consensus, the expert panel validated a final set of 25 key interventions, 13 quality indicators at patient level and 20 quality indicators at care programme level prior for improvement of in hospital care for STEMI., Conclusions: A structured literature review and multidisciplinary expertise was combined to validate a set of key interventions and quality indicators prior for improvement of care for STEMI. The results allow researchers and hospital staff to evaluate and support quality improvement interventions in a large cohort within the context of a health care system.

The present report describes the quality of care, including in hospital mortality for more than 22.000 STEMI patients admitted in 60 Belgian hospitals for the period 2008-2016. We found a strong increase in the use of primary PCI over time, particularly for patients that were admitted first in a non-PCI capable hospital, reaching a penetration rate of >95%. The transition of thrombolysis to transfer for pPCI in the setting of a STEMI network was, however, associated with an increase of the proportion of patients with prolonged (>120 min) diagnosis-to-balloon time (from 16 to 22%), suggesting still suboptimal interhospital transfer. The in-hospital mortality of the total study population was 6.5%. For non-cardiac arrest patients in-hospital mortality decreased from 5.1% to 3.7%, while it increased for cardiac arrest patients from 29 to 37%. The observation that quality indicators (QI's), such as modalities and timing of reperfusion therapy, were associated with lower levels of mortality, underscores the potential of QIs for STEMI to improve care and reduce unwarranted variation and premature death from STEMI.

Aims: This study is a real world, observational study evaluating the treatment persistence of oral antiplatelet (OAP) therapy during a one-year follow-up in patients after an acute coronary syndrome (ACS)., Methods and Results: Data on diagnosis, comorbidities, follow-up, OAP treatment, reasons, and decision maker for treatment discontinuation in patients who were discharged from a hospital in Belgium after an ACS between 1 July 2012 and 1 June 2013 were collected by cardiologists from 18 centres, up to 360 days from discharge. Out of the 671 patients surveyed, 295 patients were included in the persistence analysis. The remainder was excluded from the analysis due to the lack of precise information on OAP stopping date. The proportion of patients still using OAPs after 90, 180, 270, and 360 days was 92, 89, 83, and 73%, respectively. OAP persistence was higher for patients treated with prasugrel or ticagrelor. At 360 days, 79% of patients with a ST-segment elevation myocardial infarction (STEMI) and 66% of patients with a non-STEMI were still adhering to the prescribed course of treatment. Among the 79 patients with early treatment discontinuation, the mean treatment duration was 197.0 ± 125.18 days. The main decision taker in premature treatment cessation was the cardiologist (31% of cases), while the most frequently cited reasons included surgery (25%) and perceived high bleeding risk (19%)., Conclusion: Treatment persistence with OAPs after ACS in Belgium is high throughout the recommended period. Discontinuation was observed more often in patients treated with clopidogrel and was mainly initiated by the cardiologist., (© The Author 2017. Published on behalf of the European Society of Cardiology)

Background: Innate antigen-presenting cells and adaptive immune T cells have been implicated in the development of hypertension. However, the T-lymphocyte subsets involved in the pathophysiology of hypertension remain unclear. A small subset of innate-like T cells expressing the γδ T cell receptor (TCR) rather than the αβ TCR could play a role in the initiation of the immune response in hypertension. We aimed to determine whether angiotensin (Ang) II caused kinetic changes in γδ T cells; deficiency in γδ T cells blunted Ang II-induced hypertension, vascular injury, and T-cell activation; and γδ T cells are associated with human hypertension., Methods: Male C57BL/6 wild-type and Tcrδ -/- mice, which are devoid of γδ T cells, or wild-type mice injected IP with control isotype IgG or γδ T cell-depleting antibodies, were infused or not with Ang II for 3, 7, or 14 days. T-cell profiling was determined by flow cytometry, systolic blood pressure (SBP) by telemetry, and mesentery artery endothelial function by pressurized myography. TCR γ constant region gene expression levels and clinical data of a whole blood gene expression microarray study, including normotensive and hypertensive subjects, were used to demonstrate an association between γδ T cells and SBP., Results: Seven- and 14-day Ang II infusion increased γδ T-cell numbers and activation in the spleen of wild-type mice ( P <0.05). Fourteen days of Ang II infusion increased SBP ( P <0.01) and decreased mesenteric artery endothelial function ( P <0.01) in wild-type mice, both of which were abrogated in Tcrδ -/- mice ( P <0.01). Anti-TCRγδ antibody-induced γδ T-cell depletion blunted Ang II-induced SBP rise and endothelial dysfunction ( P <0.05), compared with isotype antibody-treated Ang II-infused mice. Ang II-induced T-cell activation in the spleen and perivascular adipose tissue was blunted in Tcrδ -/- mice ( P <0.01). In humans, the association between SBP and γδ T cells was demonstrated by a multiple linear regression model integrating whole blood TCR γ constant region gene expression levels and age and sex ( R 2 =0.12, P <1×10 -6 )., Conclusions: γδ T cells mediate Ang II-induced SBP elevation, vascular injury, and T-cell activation in mice. γδ T cells might contribute to the development of hypertension in humans., (© 2017 American Heart Association, Inc.)

Acute coronary syndrome patients receive DAPT up to one year after their initial event. Exceptions to the guideline-recommended one-year rule, however, are not uncommon. The reasoning behind shorter treatments, such as unacceptable bleeding risk or urgent surgery, should be well documented in the patient's charts and discharge letter. Based on recent evidence, patients at high risk for repetitive events should continue on low-dose ticagrelor without a significant interruption at one year and indefinitely in the absence of excess bleeding risk. As there is currently no reimbursement, policy makers and insurers should be made aware of the continuing risk and unmet clinical need in this patient population. Nevertheless, many unsolved questions need to be answered, both through additional analyses from recent trials such as PEGASUS-TIMI 54 or DAPT, as well as new carefully designed clinical studies.

Objectives: Emergency medical services play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates the effect of emergency medical services use on adherence to reperfusion therapy guidelines in Belgian STEMI patients and on in-hospital mortality., Methods: The mode of admission with against without emergency medical services was associated with baseline risk profile, reperfusion modalities and in-hospital mortality in 5692 consecutive STEMI patients from 2012 to 2014., Results: A total of 3896 STEMI patients (68%) were transported to the hospital by emergency medical services, and 1796 patients (32%) arrived at the hospital using their own transport (self-referral). Emergency medical services patients were older than self-referral patients (64 vs. 62 years) and more frequently presented with cardiac arrest (14% vs. 5%) and with cardiogenic shock (10% vs. 4%). Emergency medical services patients received primary percutaneous coronary intervention more often (95% vs. 91%, P<0.0001) and more frequently within 90 minutes (72% vs. 65%, P<0.001). Moreover, the time interval between symptom onset and reperfusion therapy was shorter in the emergency medical services group (median of 195 vs. 255 minutes, P<0.001). Crude in-hospital mortality was higher in the emergency medical services group (7.7% vs. 3.8%, P<0.0001) and was mainly driven by the high prevalence of cardiogenic shock and cardiac arrest in the emergency medical services group. After adjustment, the impact on mortality was no longer significantly different., Conclusion: Emergency medical services are used by two-thirds of Belgian STEMI patients and are associated with a better adherence to STEMI reperfusion guidelines. These data favour the use of emergency medical services as the preferred transfer system for patients with chest pain suspicious for STEMI., (© The European Society of Cardiology 2016.)

Background: Clinical practice variation and the subsequent burden on health care quality has been documented for patients with ST-elevated myocardial infarction (STEMI). Reduction of clinical practice variation is possible by increasing guideline adherence. Care pathway documents can increase guideline adherence by implementing evidence-based key interventions and quality indicators in daily practice., Aims: This study aims to examine guideline adherence of care pathway documents for patients with STEMI., Methods: Lay-out, size and timeframe of submitted care pathways documents were analysed. Two independent reviewers used a checklist to systematically assess the guideline adherence of care pathway documents. The checklist comprised a set of key interventions and quality indicators extracted from evidence and international guidelines. The checklist distinguished the evidence level for each item and was validated by expert consensus. Results were verified by inviting participating hospitals to provide feedback., Results: Fifteen out of 25 invited hospitals submitted care pathway documents for STEMI. The care pathway documents differed in timeframe, lay-out and size. Analysis of the care pathway documents showed important variation in formalizing adherence to evidence: between hospitals, inclusion of 24 key interventions in care pathway documents varied from 13 to 97%. Inclusion of 11 essential quality indicators varied from 0 to 40%., Conclusion: Care pathway documents for patients with STEMI differ considerably in lay-out, timeframe and size. This study showed variation in, and suboptimal inclusion of, evidence-based key interventions and quality indicators in care pathway documents. The use of these care pathway documents might result in suboptimal quality of care for STEMI patients., (© The European Society of Cardiology 2015.)

Elderly patients constitute a large and growing proportion of ST-elevation myocardial infarction (STEMI) patients, yet they have been under-represented or even excluded from reperfusion trials. Despite evidence that fibrinolysis improves outcomes irrespective of age, many elderly STEMI patients still remain undertreated or subject to major delays to primary percutaneous coronary intervention (PCI). The fear of an excessive risk of intracranial hemorrhage (ICH) in these patients can lead to avoidance of potentially life-saving reperfusion treatment, despite the fact that current STEMI guidelines do not exclude the elderly from a pharmaco-invasive strategy. Age-specific dose reductions have been succesfully made to antithrombotic drugs such as clopidogrel and enoxaparin as an adjunct to fibrinolysis, but until recently no dose adjustments for elderly patients have been applied to the fibrinolytic agents. In the pharmaco-invasive STREAM trial, halving the bolus of tenecteplase for patients aged >75 years because of an unacceptably high ICH rate in the elderly was associated with a more favorable safety/efficacy profile. Whether a pharmaco-invasive strategy including half-dose tenecteplase, age- and weight-adjusted enoxaparin, and a tailored P2Y12 inhibitor followed by routine angiography represents a safe and efficacious alternative reperfusion therapy for elderly patients remains to be prospectively assessed in a clinical trial in this age group.