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Aims: Low cholesterol efflux capacity and elevated levels of Interleukin-1ß (IL-1ß) are both associated with residual cardiovascular risk in patients with acute myocardial infarction (MI) and may be used as new biomarkers to identify patients at higher cardiovascular risk., Methods: We evaluated potential synergetic effect of cholesterol efflux capacity and IL-1ß on recurrent major adverse cardiovascular events (MACE) at one-year in 2012 patients with acute ST- segment elevation MI who underwent primary percutaneous coronary intervention. In addition, we evaluated the contribution to residual risk of HDL biological functions from 20 patients of the two extreme subgroups, focusing on cholesterol efflux capacity and anti-inflammatory properties., Results: Patients with MACE during the first year after the MI had significantly lower serum cholesterol efflux capacity as compared to those without recurrent events and higher level of IL-1ß, both associations were confirmed after multivariate analysis. We found an inverse relationship between CEC and circulating levels of the inflammatory markers IL-1ß, defining a very high risk (Low CEC/High IL-1ß) and a low risk (High CEC/Low IL-1ß) group of patients. Patients combining Low CEC/High IL-1ß exhibited the highest risk of recurrent MACE at one year showing an additive prognostic value of these biomarkers, regardless of all the other clinical or biological factors. In this very high-risk subgroup, patients exhibited reduced HDL-efflux capacity and defective ABCA1 and SR-BI with enhanced pro-inflammatory activity as a potential explanation for our clinical findings., Conclusion: Impaired cholesterol efflux capacity and elevated IL-1β synergistically increase the residual cardiovascular risk in MI patients, which could be explained by reduced HDL-efflux capacity and enhanced HDL pro-inflammatory activity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study examines the effects of levosimendan in patients refractory to dobutamine weaning., Methods: This retrospective study included patients with cardiogenic shock refractory to dobutamine weaning failure admitted between 2010 and 2022. Patients treated with another type of dobutamine alone were compared with those treated with levosimendan in combination with dobutamine. Successful inotrope withdrawal was defined as survival without catecholamine support, transplant, or definitive ventricular assist device at 30 days. Secondary outcomes included all-cause mortality at 30 and 90 days., Results: Among 349 patients with cardiogenic shock and failure to withdraw from dobutamine, levosimendan was administered in combination with dobutamine in 114 patients, and another type of dobutamine alone was administered in 235 patients. At 30 days, successful inotrope withdrawal occurred in 46 (43.4%) patients taking levosimendan plus dobutamine versus 24 (10.5%) patients in the dobutamine-only group (weighted odds ratio [OR] 4.99, 95% confidence interval [CI] 2.65-9.38; p < 0.001), with similar results at 90 days (weighted OR 6.16, 95% CI 3.22-11.78; p < 0.001). Levosimendan + dobutamine was associated with lower 30-day mortality (weighted OR 0.47, 95% CI 0.26-0.84; p = 0.01), with no difference at 90 days (weighted OR 0.67, 95% CI 0.39-1.14; p = 0.14)., Conclusion: Adding levosimendan to dobutamine may improve inotrope withdrawal success and reduce 30-day mortality in patients with initial weaning failure., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction., Methods: In a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life-5 Dimensions questionnaire., Results: A total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients' quality of life., Conclusions: In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The ACTION-SHOCK registry offers a decade-long perspective on patients admitted with cardiogenic shock (CS)., Aims: To assess trends in the management and outcomes of patients with CS over 10 years., Methods: Trends in the characteristics, management and outcomes of patients with CS admitted into the cardiac intensive care unit of Pitié-Salpêtrière hospital from 2011 to 2020 were analysed. Short-term outcomes included in-hospital mortality, heart transplantation or ventricular assist device. Long-term outcomes were all-cause death or readmission for acute heart failure at 1 year., Results: Over a 10-year period, data from 700 patients with CS (median [interquartile range] age 61 [50-72] years; 73% of men) were analysed. The proportion of CS related to acute myocardial infarction decreased (from 45% in 2011-2012 to 27% in 2019-2020) while the proportions related to chronic coronary syndrome (18% to 23%) and non-ischaemic cardiomyopathies (37 to 51%) increased (P<0.01). The use of rescue extracorporeal membrane oxygenation remained stable (19 to 14%) and intra-aortic balloon pump use decreased (22% to 7%) (P<0.01). In-hospital mortality remained stable (27 to 29%) as did the proportions of patients discharged after transplantation (17 to 14%) or with a durable ventricular assist device (2 to 4%). Among patients discharged alive, death or readmission for acute heart failure at 1 year remained high (37 to 47%)., Conclusion: CS remained associated with a poor prognosis over the last decade. There are significant unmet needs in the management strategies of patients with CS., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Whether saline-induced hyperaemia captures exercise-induced coronary flow regulation remains unknown., Aims: Through this study, we aimed to describe absolute coronary flow (Q) and microvascular resistance (Rμ) adaptation during exercise in participants with angina with non-obstructive coronary artery disease (ANOCA) and to explore the correlations between saline- and exercise-derived coronary flow reserve (CFR) and microvascular resistance reserve (MRR)., Methods: Rμ, Q, CFR and MRR were assessed in the left anterior descending artery using continuous thermodilution with saline infusion at 10 mL/min (rest), 20 mL/min (hyperaemia) and finally at a 10 mL/min infusion rate during stress testing with a dedicated supine cycling ergometer. An incremental workload of 30 watts every two minutes was applied. A saline-derived CFR (CFR saline ) cutoff <2.5 was used to identify coronary microvascular dysfunction (CMD)., Results: CFR saline -defined CMD was observed in 53.3% of the participants (16/30). While cycling, these patients less of an ability to increase Q (7 [interquartile range [IQR] 30.5-103.0] vs 21 [IQR 5.8-45.0] mL/min/30 watts; p=0.01) due to a smaller decrease of Rμ (109 {IQR 32-286} vs 202 [IQR 102-379] Wood units [WU]/30 watts; p<0.01) as compared with the group with normal CFR saline . In the overall population, CFR saline and exercise-derived CFR (CFR exercise ) were 2.70±0.90 and 2.85±1.54, respectively, with an agreement classification of 83.3%. A good correlation between saline and exercise techniques for both CFR (r=0.73; p<0.0001) and MRR (r=0.76; p<0.0001) was observed. Among participants with normal CFR saline , 28.7% (4/14) had an impaired CFR exercise <2.5 at the peak of exercise due to a moderate and late decrease of Rμ., Conclusions: Saline-induced hyperaemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate adaptation among participants with exercise-related CMD.

Background: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear., Objectives: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI., Methods: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI., Results: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment., Conclusions: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment., Competing Interests: Funding Support and Author Disclosures This trial was led by the Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION) Study Group, an Academic Research Organization based at Pitié-Salpêtrière Hospital in Paris, France. It was sponsored by Assistance Publique-Hôpitaux de Paris and was funded by an unrestricted grant from AstraZeneca. AstraZeneca was not involved in the data collection, analysis, or in the writing of the manuscript. The Steering Committee oversaw the conduct of the trial in collaboration with representatives of the study sponsor. The trial was monitored by an independent Data and Safety Monitoring Board. Data were collected and analyzed according to the predefined statistical analysis plan by academic statisticians of the ACTION group. Drs Silvain and Montalescot had full access to the data and final responsibility for the decision to submit for publication. There was no medical writing support. Dr Manzo-Silberman has received consulting fees from Bayer, Organon, and Exeltis; has received lecture fees from Bayer, BMS, Exeltis Organon, and Terumo; and has served on the adjudication board for a study for Biotronik. Dr Beygui has received consulting and lecture fees from AstraZeneca, Bristol Myers Squibb, Medtronic, Biosensors, Boston Scientific; and has received institutional research grants from Medtronic, Biosensors, Acist, and Boston Scientific. Dr Cayla has received speaker or congress fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi; and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi. Dr Rangé has received speaker and/or consulting fees from Abbott, Biotronik, and Microport. Dr Motovska has received consulting, speaker, investigator and advisory board fees from AstraZeneca, Boehringer Ingelheim, and Idorsia. Dr Zeitouni has received research grants from Federation Française de Cardiologie and Institut Servier; and has received honoraria from BMS/Pfizer, Bayer, AstraZeneca, and Novo Nordisk. Dr Vicaut has received consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards Lifesciences, Pfizer, Sanofi, and Novartis. Dr Montalescot has received consulting or speaker fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Silvain has received consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, Sanofi Aventis France, Abbott Medical France, SAS, and Zoll; and is a stockholder of 4P-Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Since the first description of takotsubo syndrome 30 years ago, only a little is known on the underlying physiopathology leading to peculiar left ventricular function alteration and myocardial damage related to acute emotional or physical stress. In the present case, we used continuous invasive thermodilution to evaluate coronary microvascular function at the acute phase of takotsubo and after recovery. The acute phase of takotsubo was characterized by a reduced coronary output and altered reserved flow with persistently high resistance during hyperaemia. At 6 weeks, we described a complete recovery of microvascular function, concomitant to LVEF recovery., Competing Interests: Disclosure of interest Dr M. Zeitouni has research grants or honorariums from Bayer, BMS Pfizer, la Fédération Française de Cardiologie, Servier, Amgen, AstraZeneca, NovoNordisk. Pr Collet has research grants or honorariums from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, COR2ED, Lead-Up, Medtronic, WebMD. The authors have nothing to disclose., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aims: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA)., Methods and Results: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling., Conclusion: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors., Competing Interests: Conflict of interest: M.Z. reports research grants, funding, or consulting fees from Fédération Française de Cardiologie, Institut Servier, BMS/Pfizer, AstraZeneca, and Amgen. M.K. reports research grants, funding, or consulting fees from Fédération Française de Cardiologie, Institut Servier Bayer, and Sanofi. J.S. reports research grants, funding, or consulting fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical France SAS, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Stockholder of Pharmaseeds, Terumo France SAS, and Zoll. G.M. reports research grants, funding, or consulting fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston-Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, and Terumo. J.-P.C. reports research grants, funding, or consulting fees from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, COR2ED, Lead-Up, Medtronic, and WebMD. G.R., E.C., P.-G.R., S.R., N.P., S.B., P.C., P.G., O.B., and A.R.: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Higher rates of thrombotic events have been reported in myocardial infarction (MI) patients requiring blood transfusion. The impact of blood transfusion strategy on thrombosis and inflammation is still unknown., Objective: To compare the impact of a liberal vs. a restrictive transfusion strategy on P2Y12 platelet reactivity and biomarkers in the multicentric randomized REALITY trial., Methods: Patients randomized to a liberal (hemoglobin ≤10 g/dL) or a restrictive (hemoglobin ≤8 g/dL) transfusion strategy had VASP-PRI platelet reactivity measured centrally in a blinded fashion and platelet reactivity unit (PRU) measured locally using encrypted VerifyNow; at baseline and after randomization. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the randomized groups., Results: A total of 100 patients randomized were included in this study (n = 50 in each group). Transfused patients received on average 2.4 ± 1.6 units of blood. We found no differences in change of the VASP PRI (difference 1.2% 95% CI (-10.3-12.7%)) or by the PRU (difference 13.0 95% CI (-21.8-47.8)) before and after randomization in both randomized groups. Similar results were found in transfused patients (n = 71) regardless of the randomized group, VASP PRI (difference 1.7%; 95% CI (-9.5-1.7%)) or PRU (difference 27.0; 95% CI (-45.0-0.0)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF, and TNF-α., Conclusion: In this study, we found no impact of a liberal vs. a restrictive transfusion strategy on platelet reactivity and biomarkers in MI patients with anemia. A conclusion that should be tempered due to missing patients with exploitable biological data that has affected our power to show a difference., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The 2018 World Symposium on Pulmonary Hypertension (WSPH) changed the definition of pulmonary hypertension (PH) with a new threshold of mean pulmonary artery pressure (mPAP) above 20 mmHg., Objective: To evaluate the profile and prognosis of patients with chronic heart failure (HF) considered for heart transplantation with the new definition of PH., Methods: Patients with chronic HF considered for heart transplantation were classified as mPAP ≤20mmHg , mPAP 20 - 25 mmHg , and mPAP ≥25mmHg . Using a multivariate Cox model, we compared the mortality of patients with mPAP 20 - 25mmHg , and mPAP ≥25mmHg versus those with mPAP ≤20mmHg ., Results: Of 693 patients with chronic HF considered for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP 20 - 25mmHg , mPAP ≥ 25mmHg and mPAP ≤20mmHg . Patients of mPAP ≥  25mmHg and mPAP 20 - 25 mmHg categories were older than mPAP ≤  20 mmHg (56 versus 55 and 52 year-old, p = 0.02) with more frequent co-morbidities. Within 2.8 years, the mPAP 20 - 25mmHg category displayed a higher risk of mortality compared with those of the mPAP ≤20mmHg category (aHR 2.75, 95% CI 1.27-5.97, p = 0.01). Overall, the new PH definition using a threshold of mPAP >20 mmHg was associated with a higher risk of death (adj HR 2.71, 95% CI 1.26-5.80) than the previous definition (mPAP >25 mmHg, aHR: 1.35 95% CI 1.00-1.83, p = 0.05)., Conclusions: One out of 8 patients with severe HF are reclassified as having PH following the 2018 WSPH. Patients with mPAP 20 - 25 evaluated for heart transplantation displayed significant co-morbidities and high mortality rates., Competing Interests: Declaration of Competing Interest Gilles Montalescot reports research grants, funding or consulting fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston-Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, Terumo; Michel Zeitouni reports research grants, funding or consulting fees from Fédération Française de Cardiologie, Institut Servier, BMS/Pfizer, AstraZeneca and Amgen; Johanne Silvain reports reports research grants, funding or consulting fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical France SAS, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Stockholder of Pharmaseeds, Terumo France SAS, Zoll; Mathieu Kerneis reports research grants, funding or consulting fees from Fédération Française de Cardiologie, du Programme PHRC N, de l'Institut Servier et des honoraires de Bayer, Sanofi, Servier; Jean Philippe Collet reports research grants, funding or consulting fees from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, COR2ED, Lead-Up, Medtronic, WebMD; Quentin Morlon, Stéphane Hatem, Nadjib Hammoudi, Claude Le Feuvre, Gérard Helft, Paul Guedeney, Guillaume Lebreton, Pascal Leprince, Shaida Varnous and Niki Procopi report no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation., Methods and Results: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism., Conclusion: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To determine if the changes in the European Society Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines improved the identification for primary prevention therapy in young adults at risk of a premature myocardial infarction., Methods: Patients admitted for a first ST-segment elevation myocardial infarction (STEMI) in the ePARIS registry (n=2757) between 2010 and 2018 were classified by age: <55, 55-65 and >65 years old. Using Systematic Coronary Risk Estimation 2, we evaluated whether patients would have been detected and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines. Eligibility for intensive proprotein convertase subtilisin/kexin type 9 (PCSK9i) in secondary prevention was also assessed., Results: Following 2021 ESC guidelines, 62.5% of individuals aged <55 years old would have been eligible for statins before their first STEMI, similarly to older age categories. In comparison, only 17% and 18% of young individuals would have been eligible for primary prevention statins prior to their first STEMI with 2016 and 2019 guidelines, compared with group 55-65 years (41% and 35%) and >65 years old (19% and 72%), p<0.01. After their first STEMI, 25% of patients <55 years would be eligible for PCSK9i, compared with 23.2% and 15% in patients aged 55-65 years and >65 years., Conclusions: The 2021 ESC guidelines allowed a much better detection of young individuals before their first STEMI than prior ESC guidelines. In secondary prevention, most of young individuals did not reach low-density lipoprotein cholesterol levels recommended, but only one quarter would be eligible for PCSK9i., Competing Interests: Competing interests: GM reports research grants, funding or consulting fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston-Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi and Terumo; MZ reports research grants, funding or consulting fees from Fédération Française de Cardiologie, Institut Servier, BMS/Pfizer and AstraZeneca; JS reports reports research grants, funding or consulting fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical France SAS, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Stockholder of Pharmaseeds, Terumo France SAS and Zoll; MK reports research grants, funding or consulting fees from Fédération Française de Cardiologie, du Programme PHRC N, de l’Institut Servier et des honoraires de Bayer, Sanofi and Servier; PS reports research grants, funding or consulting fees from Amgen, AstraZeneca, Bayer, BMS, Boehringer, Bouchara Recordati, Eli-Lilly, MSD, Novartis, Pfizer, Sanofi, Servier and Vifor; J-PC reports research grants, funding or consulting fees from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, COR2ED, Lead-Up, Medtronic and WebMD; DS, PG, OB, DB and NP report no conflict of interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Systematic prescription of beta-blockers after myocardial infarction remains an open question in the era of revascularization, especially for patients with uncomplicated myocardial infarction., Objective: To evaluate in a real-life registry the proportion of patients with uncomplicated myocardial infarction (preserved left ventricular ejection fraction and no cardiovascular event within the first 6 months), and to report their characteristics, outcomes and beta-blocker use., Methods: We included 1887 consecutive patients with ST-segment elevation myocardial infarction from the prospective ePARIS registry. Patients were divided into three groups: the "uncomplicated myocardial infarction" group (n=1060), defined by a left ventricular ejection fraction ≥ 40% and a 6-month period free from cardiovascular events; the "complicated myocardial infarction" group (n=366), defined by a left ventricular ejection fraction ≥ 40% and a recurrent cardiovascular event in the first 6 months; and the "left ventricular dysfunction" group (n=461), defined by a left ventricular ejection fraction<40%., Results: During a median follow-up of 2.7 years (interquartile range 1.0-4.9 years), the "uncomplicated myocardial infarction" group was at low mortality risk compared with the "complicated myocardial infarction" group (hazard ratio 0.38, 95% confidence interval 0.25-0.58; P<0.01) and the "left ventricular dysfunction" group (hazard ratio 0.22, 95% confidence interval 0.15-0.32; P<0.01). Beta-blockers were prescribed at discharge predominantly in the "uncomplicated myocardial infarction" group (93%) compared with 87% in the "complicated myocardial infarction" group and 81% in the "left ventricular dysfunction" group., Conclusions: Beta-blockers are less prescribed in patients who may need them the most. The benefit of beta-blockers-largely prescribed in lower-risk patients-remains to be shown beyond the first 6 months for these patients with no left ventricular dysfunction and no recurrent events., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Aims: The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention., Methods and Results: The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P &lt; 0.01), a finding observed in both men (62.3% vs. 35.0% vs. 24.9%, P &lt; 0.01) and women (60.2% vs. 50.7% vs. 19.3%, P = 0.18). Only 27% of individuals reached the LDL-C objective of 55 mg/L in secondary prevention: using the ESC stepwise approach, 61.7% were eligible for higher doses of statins, 26.2% for ezetimibe, and 12.1% for a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i). Based on expected LDL-C reductions, eligibility for a PCSK9i in secondary prevention was greater with 2021 vs. 2016 guidelines (44.5% vs. 22.5%, P &lt; 0.01)., Conclusion: The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Inhibition of the interleukin (IL)-1β innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hs-CRP)., Objectives: This study assessed the association between IL-1β level with all-cause mortality in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death., Methods: IL-1β concentration was measured in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) were analyzed., Results: IL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR]: 1.47 per 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively)., Conclusions: IL-1β measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Patients' prognostication around cardiac surgery is key to better assess risk-benefit balance. Preoperative brain natriuretic peptide (BNP) biomarker has been associated with mortality after cardiac surgery, but its added value with EuroScore 2 remains to be confirmed. In a prospective registry cohort of 4,980 patients undergoing cardiac surgery, the prognostic performance of EuroScore 2 and preoperative BNP was assessed regarding postoperative in-hospital mortality. Discrimination feature was evaluated using receiver-operator-characteristics analysis with area under curve (AUROC). Calibration feature was assessed using Hosmer-Lemeshow test. Multivariable analysis was performed to assess the association between covariates and in-hospital mortality. In-hospital mortality was 3.7%. The AUROC of EuroScore 2 was 0.82 (95% confidence interval (95%CI) 0.79-0.85, p < 0.0001). The AUROC of BNP was 0.66 (95%CI 0.62-0.70, p < 0.0001). The combined model with an AUROC of 0.67 (95%CI 0.63-0.71, p = 0.0001) did not yield better AUROC than EuroScore 2 alone (p < 0.0001 in disfavor of the combined model), nor BNP alone (p = 0.79). In multivariable analysis, EuroScore 2 remained independently associated with mortality (adj.OR of 1.12 (1.10-1.14), p < 0.0001), but BNP was not. Preoperative BNP was not an independent risk factor of postoperative mortality and did not add prognostic information, as compared to EuroScore 2 alone.Clinical trial registry Registry for the Improvement of Postoperative OutcomeS in Cardiac and Thoracic surgEry (RIPOSTE) database (NCT03209674).

Background: The long-term evolution of premature coronary artery disease (CAD) is unknown., Objectives: The objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes., Methods: Participants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke., Results: Eight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis., Conclusions: Premature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients at increased cardiovascular (CV) risk, noticeably hypertensive patients, have multiple CV risk factors which may be treatment targets. LDL-cholesterol is one of such targets. Using the SPRINT cohort, studying the cardiovascular outcomes of hypertensive patients at increased CV risk, this post-hoc study aimed to assess the association of LDL-C with CV outcomes., Methods: Clinical outcomes were those defined in SPRINT: a composite of various CV outcomes, all-cause mortality, and CV mortality. Association between LDL-C and the primary outcome was analyzed using survival regression adjusted on confounding factors (age, sex, body-mass index, active smoking status, eGFR-estimated kidney function, history of CV disease, Framingham risk score, SPRINT treatment arm (intensive or control), baseline high-density-lipoprotein-bound cholesterol, and co-treatments by aspirin and statins)., Results: LDL-C was not associated with the primary outcome in the overall cohort (n = 9631). Among patients in secondary prevention (i.e. with a previous history of CV disease) (n = 1562), LDL-C was marginally associated with the incidence of the primary outcome (adjusted hazard-ratio 1.005 (95% CI = 1.002-1.009), p = 0.005 (per 1 mg/dl increase)) however, discrimination was poor with a ROC AUC of 0.54, p = 0.087. There was no association between LDL-C and the primary outcome in other subgroup analyses (those under statin or not, and those in primary prevention)., Conclusion: This post-hoc analysis of SPRINT indicates that LDL-C levels do not influence cardiovascular events over a period of 3 years in a large cohort of hypertensive patients at increased risk of cardiovascular events but without previous history of clinical cardiovascular disease other than stroke., (Copyright © 2019 Elsevier B.V. All rights reserved.)