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Carbapenem-resistant Acinetobacter nosocomialis (CRAn) is a significant public health concern. Tigecycline non-susceptible CRAn (Tn-CRAn) isolates have emerged worldwide. Tigecycline resistance is mainly related to the overexpression of AdeABC efflux pump controlled by AdeRS two-component system (TCS). Two novel tetracycline derivatives, omadacycline and eravacycline, may present a treatment option for CRAn. This study investigated the in vitro antimicrobial activity of tigecycline, omadacycline and eravacycline against clinical CRAn isolates and the contribution of efflux pumps in their resistance. Eighty-nine clinical CRAn isolates, including 57 Tn-CRAn isolates were evaluated for minimum inhibitory concentrations (MICs) by the broth microdilution. The relationship between the antimicrobial resistance and efflux pump expression was assessed by their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). The contribution of the AdeABC efflux pump in their resistance was determined by the complementation of the AdeRS two-component system in wild-type, adeRS operon and adeB gene knockout strains. Among the 89 isolates, omadacycline and eravacycline MICs were correlated closely with those of tigecycline. They demonstrated improved potency, based on MIC90 values, by showing a 4 to 8-fold greater potency than tigecycline. The synergetic effects of tigecycline, omadacycline and eravacycline with NMP were observed in 57 (100%), 13 (22.8%), and 51 (89.5%) of Tn-CRAn isolates, respectively. Further analysis showed that the laboratory strain carrying the Type 1 adeRS operon increased the tigecycline, omadacycline and eravacycline MICs by 4–8-folds, respectively. Eravacycline demonstrated improved potency over tigecycline against populations of CRAn, including Tn-CRAn isolates. The over-expression of AdeABC efflux pumps was directly activated by the AdeRS two-component system and simultaneously reduced the susceptibilities of tigecycline, eravacycline, and omadacycline. Omadacycline and eravacycline MICs were correlated closely with those of eravacycline.

Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis.

Objectives: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii.Patients and Methods: This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments.Results: The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii.Conclusions: Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring. [ABSTRACT FROM AUTHOR]

Background: A better understanding of health-related quality of life (HRQoL) and psychological distress in cancer survivors can raise awareness, promote the development of policies in cancer survivorship care, and facilitate better targeted use of limited resources in low- and middle-income countries (LMICs). The main objectives of this paper were therefore to assess HRQoL and the prevalence of psychological distress amongst cancer survivors in Southeast Asia and identify risk factors of these outcomes.Methods: The ACTION study was a longitudinal study in eight LMICs in Southeast Asia with 5249 first time cancer survivors followed up at 1 year after diagnosis. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D. Psychological distress (anxiety and depression) was assessed using the Hospital Anxiety and Depression Scale. General linear models and multiple logistic regression were used to identify independent predictors of HRQoL and psychological distress.Results: One year after diagnosis, the mean EORTC QLQ-C30 global health score for survivors was 66.2 out of 100 (SD 22.0), the mean index score on the EQ-5D was 0.74 (SD 0.23), 37% of survivors had at least mild levels of anxiety, and 46% showed at least mild levels of depression. Poorest HRQoL and highest prevalence of anxiety and depression were seen in patients with lung cancer and lymphomas, while highest scores and least psychological distress were seen in female patients with breast and cervical cancer. The most significant predictor of poor HRQoL and psychological distress outcomes was cancer stage at diagnosis. Age, co-morbidities, treatment, and several socioeconomic factors were associated with HRQoL and psychological distress.Conclusions: Cancer survivors in LMICs in Southeast Asia have impaired HRQoL and substantial proportions have psychological distress. Patients with advanced cancer stages at diagnosis and those in a poor socioeconomic position were most at risk of such poor outcomes. Supportive interventions for cancer patients that address wider aspects of patient wellbeing are needed, as well as policies that address financial and other barriers to timely treatment. [ABSTRACT FROM AUTHOR]

Background: Contemporary data are lacking regarding the prognosis and management of left ventricular thrombus (LVT).Objectives: The purpose of this study was to quantify the effect of anticoagulation therapy on LVT evolution using sequential imaging and to determine the impact of LVT regression on the incidence of thromboembolism, bleeding, and mortality.Methods: From January 2011 to January 2018, a comprehensive computerized search of LVT was conducted using 90,065 consecutive echocardiogram reports. Only patients with a confirmed LVT were included after imaging review by 2 independent experts. Major adverse cardiovascular events (MACE), which included death, stroke, myocardial infarction, or acute peripheral artery emboli, were determined as well as major bleeding events (BARC ≥3) and all-cause mortality rates.Results: There were 159 patients with a confirmed LVT. Patients were treated with vitamin K antagonists (48.4%), parenteral heparins (27.7%), and direct oral anticoagulants (22.6%). Antiplatelet therapy was used in 67.9% of the population. A reduction of the LVT area from baseline was observed in 121 patients (76.1%), and total LVT regression occurred in 99 patients (62.3%) within a median time of 103 days (interquartile range: 32 to 392 days). The independent correlates of LVT regression were a nonischemic cardiomyopathy (hazard ratio [HR]: 2.74; 95% confidence interval [CI]: 1.43 to 5.26; p = 0.002) and a smaller baseline thrombus area (HR: 0.66; 95% CI: 0.45 to 0.96; p = 0.031). The frequency of MACE was 37.1%; mortality 18.9%; stroke 13.3%; and major bleeding 13.2% during a median follow-up of 632 days (interquartile range: 187 to 1,126 days). MACE occurred in 35.4% and 40.0% of patients with total LVT regression and those with persistent LVT (p = 0.203). A reduced risk of mortality was observed among patients with total LVT regression (HR: 0.48; 95% CI: 0.23 to 0.98; p = 0.039), whereas an increased major bleeding risk was observed among patients with persistent LVT (9.1% vs. 12%; HR 0.34; 95% CI: 0.14 to 0.82; p = 0.011). A left ventricular ejection fraction ≥35% (HR: 0.46; 95% CI: 0.23 to 0.93; p = 0.029) and anticoagulation therapy >3 months (HR: 0.42; 95% CI: 0.20 to 0.88; p = 0.021) were independently associated with less MACE.Conclusions: The presence of LVT was associated with a very high risk of MACE and mortality. Total LVT regression, obtained with different anticoagulant regimens, was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The real incidence of atrial arrhythmia (AA) after patent foramen ovale (PFO) closure and whether this complication can be prevented remain unknown. This study assessed if flecainide is effective to prevent AA during the first 3 months after PFO closure, and if 6 months treatment by flecainide is more effective than 3 months to prevent AA after PFO closure., Methods: AFLOAT is a prospective, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). Patients were randomized in a 1:1:1 ratio after PFO closure to receive flecainide (150 mg once a day in a sustained-release (SR) dose) for 3 months, flecainide (150 mg od SR dose) for 6 months, or no additional treatment (standard-of-care) for 6 months. The primary endpoint was the percentage of patients with at least one episode AA (≥30s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor (ICM). The secondary endpoint was the percentage of patients with at least one episode of AA (≥30s) recorded with ICM during the 3-6 months period after PFO closure., Results: 186 patients were included (mean age 54 years, male 68.8%) and AA (≥30s) occurred in 53 (28.5%) patients during the 6-month follow-up; 86.8% of these AA events occurred in the first month after PFO closure. The primary outcome occurred in 33/123 (26.8%) and 16/63 (25.4%) patients receiving flecainide for at least 3 months or standard of care, respectively [Risk Difference (RD) 1.4%; 95% confidence interval (CI) -12.9% to 13.8%, NS]. The secondary endpoint occurred in 3/60 (5.0%), 4/63 (6.3%), and 5/63 (7.9%) patients receiving flecainide 6 months, 3 months or standard of care, respectively [RD -2.9%; 95% CI -12.7% to 6.9%, and RD -1.6%; 95% CI -11.8% to 8.6%, respectively]., Conclusions: In the first 6 months following successful PFO closure, AA (≥30s) occurred in 28.5% of cases, mostly in the first month after the procedure. Flecainide did not prevent AA after PFO closure.

Background: Large datasets of transcatheter aortic valve implantation (TAVI) for pure aortic valve regurgitation (PAVR) are scarce., Aims: We aimed to report procedural safety and long-term clinical events (CE) in a contemporary cohort of PAVR patients treated with new-generation devices (NGD)., Methods: Patients with grade III/IV PAVR enrolled in the FRANCE-TAVI Registry were selected. The primary safety endpoint was technical success (TS) according to Valve Academic Research Consortium 3 criteria. The co-primary endpoint was defined as a composite of mortality, heart failure hospitalisation and valve reintervention at last follow-up., Results: From 2015 to 2021, 227 individuals (64.3% males, median age 81.0 [interquartile range {IQR} 73.5-85.0] years, with EuroSCORE II 6.0% [IQR 4.0-10.9]) from 41 centres underwent TAVI with NGD, using either self-expanding (55.1%) or balloon-expandable valves (44.9%; p=0.50). TS was 85.5%, with a non-significant trend towards increased TS in high-volume activity centres. A second valve implantation (SVI) was needed in 8.8% of patients, independent of valve type (p=0.82). Device size was ≥29 mm in 73.0% of patients, post-procedure grade ≥III residual aortic regurgitation was rare (1.2%), and the permanent pacemaker implantation (PPI) rate was 36.0%. At 30 days, the incidences of mortality and reintervention were 8.4% and 3.5%, respectively. The co-primary endpoint reached 41.6% (IQR 34.4-49.6) at 1 year, increased up to 61.8% (IQR 52.4-71.2) at 4 years, and was independently predicted by TS, with a hazard ratio of 0.45 (95% confidence interval: 0.27-0.76); p=0.003., Conclusions: TAVI with NGD in PAVR patients is efficient and reasonably safe. Preventing the need for an SVI embodies the major technical challenge. Larger implanted valves may have limited this complication, outweighing the increased risk of PPI. Despite successful TAVI, PAVR patients experience frequent CE at long-term follow-up.

Background: The MINT trial raised concern for harm from a restrictive versus liberal transfusion strategy in patients with acute myocardial infarction (MI) and anemia. Type 1 and type 2 MI are distinct pathophysiological entities that may respond differently to blood transfusion. This analysis sought to determine if the effects of transfusion varied among patients with a type 1 or a type 2 MI and anemia. We hypothesized that the liberal transfusion strategy would be of greater benefit in type 2 than in type 1 MI., Methods: We compared rates of death or MI at 30 days in patients with type 1 (n=1460) and type 2 (n=1955) MI and anemia who were randomly allocated to a restrictive (threshold of 7 to 8 g/dL) or a liberal (threshold of 10 g/dL) transfusion strategy., Results: The primary outcome of death or MI was observed in 16% of type 1 MI and 15.4% of type 2 MI patients. The rate of death or MI was higher in patients with type 1 MI randomized to a restrictive (18.2%) versus liberal (13.2%) transfusion strategy (RR 1.32, 95% CI 1.04 - 1.67) with no difference observed between the restrictive (15.8% ) and liberal (15.1% ) transfusion strategies in patients with type 2 MI (RR 1.05 95% CI 0.85-1.29). The test for a differential effect of transfusion strategy by MI type was not statistically significant (P- interaction = 0.16)., Conclusions: The concern for harm with a restrictive transfusion strategy in patients with acute MI and anemia raised in the MINT primary outcome manuscript may be more apparent in patients with type 1 than type 2 MI., Clinical Trial Registration: ClinicalTrials.gov number, NCT02981407.

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: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly., Aims: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events., Methods: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted., Results: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF., Conclusions: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Background: Patients treated with left atrial appendage occlusion (LAAO) are at high bleeding risk. Intensive antithrombotic treatment is recommended after the procedure to prevent device-related thrombosis., Objectives: This study sought to evaluate the incidence, consequences, and predictors of early nonprocedural bleeding after LAAO., Methods: This was a multicenter study including 1,649 patients undergoing LAAO in 9 centers. Early nonprocedural bleeding was defined as bleeding unrelated to the procedure occurring within 3 months after device implantation. The severity of bleeding was defined by the Valve Academic Research Consortium-2 classification. A sensitivity analysis was performed at 45 days., Results: A total of 121 (7.3%) patients experienced early nonprocedural bleeding events, and 69 (57.0%) were classified as major bleeding (4.2% of patients). Independent predictors of early nonprocedural bleeding were dual antiplatelet therapy (DAPT) at discharge (adjusted HR [aHR]: 1.61; 95% CI: 1.12-2.33; P = 0.01), prior gastrointestinal bleeding (aHR: 2.15; 95% CI: 1.38-3.35; P < 0.001), and multiple locations of prior bleeding (aHR: 2.33; 95% CI: 1.34-4.05; P < 0.001). DAPT at discharge was predictive of both all and major nonprocedural bleeding at 3 months and 45 days. After a median follow-up of 2.3 years (Q1-Q3: 1.1-4.1 years), early nonprocedural bleeding was independently associated with an increased risk of all-cause death (aHR: 1.53; 95% CI: 1.15-2.06; P < 0.001). This heightened mortality risk was similar at 45 days., Conclusions: Early nonprocedural bleeding after LAAO occurred in ∼7% of patients within 3 months, with more than one-half being classified as major bleeding. Regardless of severity, early nonprocedural bleeding was associated with increased mortality. DAPT at discharge determined an increased risk of early nonprocedural bleeding after LAAO. These results emphasize the importance of bleeding risk for determining antithrombotic strategies after LAAO., Competing Interests: Funding Support and Author Disclosures Dr Cruz-González is proctor for Boston Scientific, Abbott, and Lifetech. Dr Nombela-Franco is proctor for Abbott. Dr Rodés-Cabau holds the research chair “fondation famille Jacques Larivière” for the development of structural heart interventions (Laval University), and has received institutional research grants from Boston Scientific. 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.)

Introduction and Objectives: Percutaneous left atrial appendage closure (LAAC) has emerged as a nonpharmacological alternative for thromboembolic event prevention in patients with nonvalvular atrial fibrillation. However, there are few data on readmissions after LACC. The aim of this study was to determine the rate of early (≤ 30 days) and late (31-365 days) readmission after LAAC, and to assess the predictors and clinical impact of rehospitalization., Methods: This multicenter study included 1419 consecutive patients who underwent LAAC. The median follow-up was 33 [17-55] months, and follow-up was complete in all but 54 (3.8%) patients. The primary endpoint was readmissions for any cause. Logistic regression and Cox regression analysis were performed to determine the predictors of readmission and its clinical impact., Results: A total of 257 (18.1%) patients were readmitted within the first year after LAAC (3.2% early, 14.9% late). The most common causes of readmission were bleeding (24.5%) and heart failure (20.6%). A previous gastrointestinal bleeding event was associated with a higher risk of early readmission (OR, 2.65; 95%CI, 1.23-5.71). The factors associated with a higher risk of late readmission were a lower body mass index (HR, 0.96-95%CI, 0.93-0.99), diabetes (HR, 1.38-95%CI, 1.02-1.86), chronic kidney disease (HR, 1.60; 95%CI, 1.21-2.13), and previous heart failure (HR, 1.69; 95%CI, 1.26-2.27). Both early (HR, 2.12-95%CI, 1.22-3.70) and late (HR, 1.75; 95%CI, 1.41-2.17) readmissions were associated with a higher risk of 2-year mortality., Conclusions: Readmissions within the first year after LAAC (primary endpoint) were common (18.1%), were mainly related to bleeding and heart failure events, and were associated with the patients' comorbidity burden. Readmission after LAAC confers a higher risk of mortality during the first 2 years after the procedure., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches., Areas Covered: This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF., Expert Opinion: The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

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.)

Aims: Women are less likely to receive lipid-lowering therapy (LLT) after acute myocardial infarction (AMI). We analysed whether this under-prescription currently persists and has an impact on long-term outcomes., Methods and Results: The FAST-MI programme consists of nationwide registries including all patients admitted for AMI ≤ 48 h from onset over a 1 month period in 2005, 2010, and 2015, with long-term follow-up. This analysis focused on high-intensity LLT (atorvastatin ≥ 40 mg or equivalent, or any combination of statin and ezetimibe) in women and men. Women accounted for 28% (N = 3547) of the 12 659 patients. At discharge, high-intensity LLT was significantly less prescribed in women [54 vs. 68% in men, P < 0.001, adjusted odds ratio (OR) 0.78(95% confidence interval (CI) 0.71-0.87)], a trend that did not improve over time: 2005, 25 vs. 35% (P = 0.14); 2010, 66 vs. 79% (P < 0.001); 2015, 67 vs. 79.5% (P = 0.001). In contrast, female sex was not associated with a lack of other recommended treatments at discharge: beta-blockers [adjusted OR 0.98(95% CI 0.88-1.10), P = 0.78], or renin-angiotensin blockers [adjusted OR 0.94(95% CI 0.85-1.03), P = 0.18]. High-intensity LLT at discharge was significantly associated with improved 5 year survival and infarct- and stroke-free survival in women [adjusted hazard ratios (HR) 0.74(95% CI 0.64-0.86), P < 0.001 and adjusted HR: 0.81(95% CI: 0.74-0.89); P < 0.001, respectively]. Similar results were found using a propensity score-matched analysis [HR for 5 year survival in women with high-intensity LLT: 0.82(95% CI 0.70-0.98), P = 0.03]., Conclusion: Women suffer from a bias regarding the prescription of high-intensity LLT after AMI, which did not attenuate between 2005 and 2015, with potential consequences on both survival and risk of cardiovascular events., Competing Interests: Conflict of interest: N.D. has received personal fees and non-financial support from Amgen, AstraZeneca, Bayer, BMS, Sanofi, personal fees from Boehringer Ingelheim, Intercept, MSD, Novo Nordisk, Pfizer, Servier, UCB Pharmaceuticals, and Vifor, all outside the submitted work. E.P. reports fees for lectures and/or consulting: Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boehringer Ingelheim, Daiichi Sankyo, Lilly, MSD, The Medicine Company, Sanofi, Saint Jude Medical, Servier, Siemens. J.F. reports speaking fees for Amgen, Sanofi, Servier and MSD. F.S. reports personal fees from Amgen, AstraZeneca, Bayer, BMS, MSD, Pfizer, and Sanofi, outside the submitted work. T.S. reports grants from AstraZeneca, Daiichi Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi, and personal fees for board membership and/or consultancy and/or lectures from AstraZeneca, BMS, Sanofi, and Novartis. J.-L.G. reports personal fees for lectures and/or consulting: Amgen, MSD, Novartis, and Sanofi-Winthrop France., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted., Methods and Results: This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC., Conclusion: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

Purpose: Despite systemic thrombolysis, a few patients with high-risk pulmonary embolism (PE) remain hemodynamically unstable. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a considerable lifesaving therapy but systemic thrombolysis before cannulation could carry a high risk of hemorrhage and alter the prognosis., Methods: Between June 2012 and June 2023, we retrospectively analyzed from three intensive care units in Sorbonne University, ECMO-related complications and 90-day mortality for high-risk PE patients who received ECMO without previous systemic thrombolysis compared to those cannulated after systemic thrombolysis failure. Hospital discharge survivors were assessed for long-term health-related quality of life and echocardiographic evaluations., Results: 72 high-risk PE patients [median age 48 (37-61) years, Simplified Acute Physiology Score II (SAPS II) 74 (60-85)] were placed on VA-ECMO for 5 (5-7) days. 31 (43%) patients underwent pre-ECMO thrombolysis (thrombolysis ECMO group, T +) compared to 41 patients (57%, no thrombolysis ECMO group, T-). There was more pre-ECMO cardiac arrest in the thrombolysis ECMO group (94% vs. 67%, p = 0.02). Ninety-day survival was not different between groups (39% vs 46%, log-rank test, p = 0.31). There was no difference in severe hemorrhages (61% vs 59%, p = 1). Twenty-five over 28 patients attended follow-up at a median time of 69 (52-95) months. Long-term quality of life was acceptable and none of them experienced chronic thromboembolic pulmonary hypertension., Conclusions: Ninety-day survival and bleeding events rates did not differ in patients treated with VA-ECMO after systemic thrombolysis compared to those who were not. Recent systemic thrombolysis, as a single parameter, should not be considered as a contraindication for VA-ECMO in high-risk PE., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial., Objectives: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS., Methods: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016., Results: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes., Conclusion: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038., Competing Interests: Declaration of competing interest Manzo-Silberman S has received consulting fees from Bayer, Organon, Exeltis, lecture fees from Bayer, BMS, Exeltis and Organon, has served in the adjudication board for a study for Biotronik. Martin AC has received consulting fees from Alliance BMS-Pfizer, Bayer, grants from Alliance BMS-Pfizer, lecture fees from Alliance BMS-Pfizer, Abbott, Bayer, Novartis. Boissier.F has received travel and accomodation fees from AOP Orphan. Leurent.G reports proctoring activity, lecture and consultant fees from Abbott. Combaret N has received lecture fees from Pfizer and Medtronic. Gerbaud E has received consulting fees from Terumo, Abbott and Vifor phama. Delmas C has received consulting fees from Abiomed, Abbott and Moderna; lecture fees from Abiomed, Abott, Astrazeneca, Bayer, Orion and Servier. All the other authors have nothing to disclaimed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m 2 ( P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m 2 , P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg -1 ( P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index. NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.

Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF)., Methods and Results: We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper., Conclusions: The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.)

Background: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up., Methods: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577)., Results: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P =0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively., Conclusions: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954., Competing Interests: Disclosures None.

Aims: Inherited cardiomyopathies are relatively rare but carry a high risk of cardiac maternal morbidity and mortality during pregnancy and postpartum. However, data for risk stratification are scarce. The new CARPREG II score improves prediction of prognosis in pregnancies associated with heart disease, though its role in inherited cardiomyopathies is unclear. We aim to describe characteristics and cardiac maternal outcomes in patients with inherited cardiomyopathy during pregnancy, and to evaluate the interest of the CARPREG II risk score in this population., Methods and Results: In this retrospective single-centre study, 90 consecutive pregnancies in 74 patients were included (mean age 32 ± 5 years), including 28 cases of dilated cardiomyopathy (DCM), 46 of hypertrophic cardiomyopathy, 11 of arrhythmogenic right ventricular cardiomyopathy and 5 of left ventricular noncompaction, excluding peripartum cardiomyopathy. The discriminatory power of several risk scores was assessed by the area under the receiver-operating characteristic curve (AUC). Median CARPREG II score was 2 [0;3] and was higher in the DCM subgroup. A severe cardiac maternal complication was observed in 18 (20%) pregnancies, mainly driven by arrhythmia and heart failure (each event in 10 pregnancies), with 3 cardiovascular deaths. Forty-three pregnancies (48%) presented foetal/neonatal complications (18 premature delivery, 3 foetal/neonatal death). CARPREG II was significantly associated with cardiac maternal complications (P < 0.05 for all) and showed a higher AUC (0.782) than CARPREG (0.755), mWHO (0.697) and ZAHARA (0.604)., Conclusions: Pregnancy in women with inherited cardiomyopathy carries a high risk of maternal cardiovascular complications. CARPREG II is the most efficient predictor of cardiovascular complications in this population., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

Aims: Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study., Methods and Results: From 7-22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4-54.6)., Conclusion: In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia., Trial Registration: URL: https://clinicaltrials.gov/ct2/show/NCT05063097., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry., Methods and Results: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0%. 54.2% of the patients had cardiac arrest before admission. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-vessel CAD (38.6%), respectively. Mechanical complications were rare (21/1008; 2.1%) but associated with a high mortality of 66.7% after 1 year., Conclusion: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown., Methods/design: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study., Conclusion: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure., Clinical Trial Registration: NCT05213104 (clinicaltrials.gov)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice., Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days., Results: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83])., Conclusions: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180., Competing Interests: Disclosures Dr Yan was funded by grants from the National Natural Science Foundation of China (82100260) and Beijing Hospitals Authority Youth Program (QML20210605). Dr X. Wang was funded by grants from National Key Research & Development Program of China (2022YFC2505600), Beijing Nova Program (Z201100006820087), Interdisciplinary Cooperation Project of Beijing Nova Program (Z211100002121165), and Natural Science Foundation of Beijing, China (7222046). Dr Ma reports honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, Bayer, and AstraZeneca for giving lectures. Dr Vicaut reports consulting fees from Abbott and Bristol-Myers Squibb. Dr Montalescot reports research grants to the institution or consulting or lecture fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Boston-Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Nie was funded by Beijing Hospitals Authority Clinical Medicine Development of Special Funding support (grant ZLRK202318), National Natural Science Foundation of China (grant 82270258), and Beijing Municipal Science & Technology Commission, China (grant Z221100003522027), and reports research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui Pharmaceuticals, China Resources Sanjiu Medical & Pharmaceuticals, and East China Pharmaceuticals. The other authors have no conflicts of interest to declare.

Background: Primary ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) are potentially lethal complications in patients suffering from acute myocardial infarction (MI). In contrast with the profound data regarding the incidence and prognostic value of ventricular arrhythmias in ST elevation myocardial infarction (STEMI) patients, data regarding contemporary non-ST elevation myocardial infarction (NSTEMI) patients with ventricular arrhythmias is scarce. The aim of the current study was to investigate the incidence of VF/VT complicating NSTEMI among patients admitted to an intensive coronary care unit (ICCU). Methods: Prospective, single-center study of patients diagnosed with NSTEMI admitted to ICCU between June 2019 and December 2022. Data including demographics, presenting symptoms, comorbid conditions, and physical examination, as well as laboratory and imaging data, were analyzed. Patients were continuously monitored for arrhythmias during their admission. The study endpoint was the development of VF/sustained VT during admission. Results: A total of 732 patients were admitted to ICCU with a diagnosis of NSTEMI. Of them, six (0.8%) patients developed VF/VT during their admission. Nevertheless, three were excluded after they were misdiagnosed with NSTEMI instead of posterior ST elevation myocardial infarction (STEMI). Hence, only three (0.4%) NSTEMI patients had VF/VT during admission. None of the patients died during 1-year follow-up. Conclusions: VF/VT in NSTEMI patients treated according to contemporary guidelines including early invasive strategy is rare, suggesting these patients may not need routine monitoring and ICCU setup.

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.)

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population., (© 2024. The Author(s).)

Background and Aims: The length of stay (LOS) after transcatheter aortic valve implantation (TAVI) remains extremely variable whereas early discharge has been shown to be feasible and safe. The study objective was to evaluate the efficacy and safety of an intervention aimed at reducing LOS after transfemoral TAVI., Methods: FAST-TAVI II is a prospective, multicentre, cluster, randomized, controlled study including patients with severe symptomatic aortic stenosis, who had transfemoral TAVI. The intervention consisted in a dedicated training programme to implement 10 quality of care measures to reduce LOS with an implementation phase of eight weeks. The primary endpoint was the proportion of patients discharged early within 3 days. Secondary endpoints included: LOS, 30-day mortality and 30-day incidence of readmission for cardiovascular events., Results: During the study period, 969 patients were enrolled in the intervention group and 860 patients in the control group. Mean age was 81.9 ± 6.6 years and mean EuroSCORE II was 4.4 ± 4.5%. Early discharge was achieved in 563 (58.1%) patients in the intervention group vs. 364 (42.3%) patients in the control group (P < .0001). Median LOS was significantly reduced in the intervention group compared to the control group [3 (IQR: 3) vs. 4 days (IQR: 3), P < .0001]. Thirty-day mortality was low and similar in the two groups (0.5% vs. 0.9%, P = .30), as were 30-day readmissions (4.6% vs. 2.8%, P = .28)., Conclusions: The intervention was simple and fast to implement, and was effective and safe to reduce LOS and increase the proportion of patients discharged early after TAVI (NCT04503655)., (© The Author(s) 2024. 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.)

Competing Interests: Declaration of interests We declare no competing interests.

Background: The influence of permanent pacemaker implantation upon outcomes after transcatheter aortic valve implantation (TAVI) remains controversial., Aims: To evaluate the impact of permanent pacemaker implantation after TAVI on short- and long-term mortality, and on the risk of hospitalization for heart failure., Methods: Data from the large FRANCE-TAVI registry, linked to the French national health single-payer claims database, were analysed to compare 30-day and long-term mortality rates and hospitalization for heart failure rates among patients with versus without permanent pacemaker implantation after TAVI. Multivariable regressions were performed to adjust for confounders., Results: A total of 36,549 patients (mean age 82.6years; 51.6% female) who underwent TAVI from 2013 to 2019 were included in the present analysis. Among them, 6999 (19.1%) received permanent pacemaker implantation during the index hospitalization, whereas 232 (0.6%) underwent permanent pacemaker implantation between hospital discharge and 30days after TAVI, at a median of 11 (interquartile range: 7-18) days. In-hospital permanent pacemaker implantation was not associated with an increased risk of death between discharge and 30days (adjusted odds ratio: 0.91, 95% confidence interval: 0.64-1.29). At 5years, the incidence of all-cause death was higher among patients with versus without permanent pacemaker implantation within 30days of the procedure (adjusted hazard ratio: 1.13, 95% confidence interval: 1.07-1.19). Permanent pacemaker implantation within 30days of TAVI was also associated with a higher 5-year rate of hospitalization for heart failure (adjusted subhazard ratio: 1.17, 95% confidence interval: 1.11-1.23)., Conclusions: Permanent pacemaker implantation after TAVI is associated with an increased risk of long-term hospitalization for heart failure and all-cause mortality. Further research to mitigate the risk of postprocedural permanent pacemaker implantation is needed as TAVI indications expand to lower-risk patients., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI)., Methods: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days., Results: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (P interaction  = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11)., Conclusions: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF., Clinical Trial Registration: NCT02648113., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Re-POT (proximal optimization technique (POT)) is a simple provisional sequential technique for percutaneous coronary bifurcation revascularization with better arterial geometry respect compared to classical techniques. Re-POT has demonstrated excellent mechanical and short-term clinical results. The multicenter CABRIOLET registry (NCT03550196) evaluate the long-term clinical benefit of the re-POT sequence in non-selected patients., Methods: All consecutive patients presenting a coronary bifurcation lesion for which provisional stenting was indicated were included in 5 european centers. Re-POT strategy was systematically attempted. The primary endpoint was target lesion failure (TLF), comprising cardiac death, myocardial infarction, stent thrombosis and target lesion revascularization (TLR) at 12 months' follow-up. The secondary endpoints were the individual components of the primary endpoint, all-cause death, target vessel failure (TVF) and target vessel revascularization (TVR). Complex bifurcation was defined as Medina 0.1.1 or 1.1.1., Results: A total of 500 patients aged 67.7 ± 11.7 years, 78.4% male, were included from 2015 to 2019, 174 of whom (34.8%) were considered having complex bifurcation lesions. Bifurcations involved the left main in 35.2% of cases. The full re-POT sequence was systematically performed in all cases. At 1 year, TLF was 2.0% (1.7% in complex vs. 2.1% in non-complex bifurcation; p = NS), and TLR was 1.6%, (1.1% vs. 1.8% respectively; p = NS). TVF and TVR rates were 3.2% and 2.8%. On multivariate analysis, only multivessel disease was predictive of TLF at 1 year (OR = 1.66 (1.09-2.53), p = 0.02)., Conclusions: In this large prospective all-comer registry, provisional stenting with re-POT technique appeared safe and effective at 1 year, without anatomical bifurcation restriction., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown., Objectives: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial., Methods: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel., Results: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (P interaction  = 0.47) nor the secondary endpoints., Conclusions: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel., Competing Interests: Funding Support and Author Disclosures The ALPHEUS trial was led by the ACTION Study Group, an academic research organization based at the Pitié-Salpêtrière Hospital (Paris, France). The study was sponsored by Assistance Publique-Hopitaux de Paris and was funded by an unrestricted grant from AstraZeneca. The present work was supported by a grant of the French Federation of Cardiology. Prof Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi Sankyo, Fédération Française de Cardiologie, and the Institute of CardioMetabolism and Nutrition; consulting fees from Daiichi Sankyo and Eli Lilly; and lecture fees from AstraZeneca, Medtronic, and Novartis. Prof Cayla has received consulting fees from Edwards Lifesciences, Medtronic, and Microport CRM; and lecture fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport, Medtronic, Pfizer, and Sanofi. Prof Ducrocq has received speaker and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Novo Nordisk, and Sanofi; has served on steering committees for Amgen, Novo Nordisk, and Janssen; and has been a proctor for Boston Scientific. Dr Laredo has received speaker or consulting fees from Abbott and Biotronik. Dr Kala has received consulting fees from Boston Scientific; and lecture fees from AstraZeneca, Edwards Lifesciences, Novartis, Servier, and Terumo. Prof Varenne has received research grants from Abbott and Boston Scientific; and lecture fees from Abbott, AstraZeneca, Boston Scientific, and Servier. Prof Spaulding has received consulting fees from Edwards Lifesciences, Medtronic, Sonivie, Techwald, and Valcare; has received speaker fees from Amgen and Edwards Lifesciences; and is stock shareholder of Techwald and Valcare. Prof Beygui has received consulting and lecture fees from Medtronic, Novartis, and Pfizer; and research grants from Biosensors and Medtronic. Dr Rangé has received speaker or consulting fees from Abbott and Microport. Prof Vicaut has received consulting or speaker fees from Abbott, Amgen, Bristol Myers Squibb, Celgene, LFB, Pfizer, and Sanofi. Prof Collet has received consulting and lecture fees from AstraZeneca, Boston Scientific, Bristol Myers Squibb, COR2ED, Lead-Up, Medtronic, and WebMD. Prof Montalescot has received research grants and consulting or speaker fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Prof Silvain has received research grants and consulting or speaker fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, and Sanofi France; and is stock Shareholder of Pharmaseeds, Terumo, and Zoll. 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.)

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.)