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Tino Severinsen,1,2 Helga Lillian Gudmundsdottir,1,2 Anna Axelsson Raja,2,3 Emil Loldrup Fosbøl,2,3 Henning Bundgaard,2,3 Jens Jakob Thune1,2 1Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 3Department of Cardiology, The Heart Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, DenmarkCorrespondence: Jens Jakob Thune, Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Nordre Fasanvej 57, Frederiksberg, 2000, Denmark, Tel +45 50470723, Email Jens.Jakob.thune@regionh.dkPurpose: To assess the positive predictive value (PPV) of the diagnostic codes for hypertrophic cardiomyopathy (HCM) in the Danish National Patient Register (DNPR) and identify factors affecting the PPV.Patients and Methods: We randomly sampled 200 patients registered in DNPR with the diagnostic codes DI421 (obstructive) or DI422 (non-obstructive) HCM, from Eastern Denmark, between December 1st, 2017, and September 16th, 2021. We assessed patients’ medical records and classified whether the diagnosis of HCM was correct, incorrect, or uncertain according to the European Society of Cardiology (ESC) guidelines. Overall PPVs were estimated for all hospitals irrespective of specialty and for dedicated centers for inherited cardiac diseases.Results: Of the 200 patients, seven were excluded; six were younger than 18 years when initially diagnosed and one adult patient had requested that their medical records be unavailable for research purposes. Of the 193 patients (median age 61 years, Interquartile range (IQR) 50– 70, 40% female) with medical records available for assessment, 148 (77%) patients were registered correctly, 41 (21%) were incorrectly registered and for four (2%) patients there was insufficient data to determine if the diagnosis was correct. The overall PPV was 0.77 (95% confidence interval (CI) 0.70– 0.82). The PPV for patients diagnosed in dedicated centers for inherited cardiac diseases was 0.91 (95% CI 0.84– 0.95). For patients diagnosed in a dedicated center for inherited cardiac diseases with more than one clinical visit, the PPV increased to 0.99 (95% CI 0.93– 1), however with the risk of a reduced sensitivity as these patients constituted only 52% of the correctly registered patients.Conclusion: The overall PPV of the HCM diagnostic codes in the DNPR was 0.77 (95% CI 0.70– 0.82). The validity of the diagnosis was higher at dedicated centers for inherited cardiac diseases. These findings may prove useful for future register-based research.Keywords: Register, hypertrophic cardiomyopathy, Denmark, sample filters

Christian Madelaire,1,2 Thomas Gerds,3,4 Lars Køber,5 Finn Gustafsson,5 Charlotte Andersson,1,6 Søren Lund Kristensen,5 Jawad Haider Butt,1 Deewa Zahir Anjum,1 Ann Banke,2 Emil Loldrup Fosbøl,5 Gunnar Gislason,1,4 Christian Torp-Pedersen,7 Morten Schou1 1Department of Cardiology, Herlev and Gentofte Hospital, Hellerup, Denmark; 2Department of Cardiology, Odense University Hospital, Odense, Denmark; 3Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4The Danish Heart Foundation, Copenhagen, Denmark; 5Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 6Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University, Boston, MA, USA; 7Department of Clinical Research and Cardiology, Nordsjællands Hospital, Hillerød, DenmarkCorrespondence: Christian Madelaire, Email Christian.madelaire@rsyd.dkBackground: Heart failure (HF) is associated with increased risk of death and a hospitalization, but for patients initiating guideline directed medical therapy, it is unknown how high these risks are compared to the general population – and how this may vary depending on age and comorbidity.Methods: In this retrospective cohort study, we identified patients diagnosed with HF in the period 2011– 2017, surviving the initial 120 days after diagnosis. Patients who were on angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) and beta-blocker were included and matched to 5 non-HF individuals from the background population each based on age and sex. We assessed the 5-year risk of all-cause death, HF and non-HF hospitalization according to sex and age and baseline comorbidity.Results: We included 35,367 patients with HF and 176,835 matched non-HF individuals. Patients with HF had a five-year excess risk (absolute risk difference) of death of 13% (31% [for HF] – 18% [for non-HF]), of HF hospitalization of 17% and of non-HF hospitalization of 24%. Excess risk of death increased with increasing age, whereas the relative risk decreased - for women in their twenties, the excess risk was 7%, risk ratio 7.2, while the excess risk was 18%, risk ratio 1.5 for women in their eighties. Having HF as a 60-year old man was associated with a five-year risk of death similar to a 75-year old man without HF. Further, HF was associated with an excess risk of non-HF hospitalization, ranging from 8% for patients > 85 years to 30% for patients < 30 years.Conclusion: Regardless of age, sex and comorbidity, HF was associated with excess risk of mortality and non-HF hospitalizations, but the relative risk ratio diminishes sharply with advancing age, which may influence allocation of resources for medical care across populations.Keywords: heart failure, excess risk, mortality, hospitalization

Rasmus Rørth,1 Emil L Fosbøl,1 Kristian Kragholm,2 Ulrik M Mogensen,1,3 Pardeep S Jhund,3 Mark C Petrie,3 Christian Torp-Pedersen,4 Gunnar H Gislason,5 John JV McMurray,3 Lars Køber,1 Søren L Kristensen1,3 1Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Department of Anesthesiology and Intensive Care Medicine, Cardiovascular Research Centre, Aalborg University Hospital, Aalborg, Denmark; 3BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; 4Department of Health, Science and Technology, Aalborg University, Aalborg, Denmark; 5Department of Cardiology, Gentofte/Herlev University Hospital, Copenhagen, Denmark Background: Heart failure (HF) has a major impact on a patient’s quality of life and functional status. This impact may be sufficiently profound to prevent independent living although how often this is the case is unknown. We examined the need for domiciliary assistance and admission to a nursing home following first HF hospitalization. Methods: In nationwide Danish registries, we identified a cohort of patients discharged alive after a first-time HF hospitalization in the period 2008–2014 who were matched 1:5 with comparison subjects based on age and sex and followed for 5 years. Results: We included 37,547 patients (69% men) discharged after a first-time HF-hospitalization and 187,735 comparison subjects. The 5-year incidence of initiation of domiciliary care was 24.1% [23.7%–24.6%] among HF patients and 9.2% [9.1%–9.4%] among the comparison cohort and yielded a corresponding adjusted HR of 2.02 [1.96–2.09]. Covariates associated with initiation of domiciliary support included older age (HR 1.08 [1.07–1.08] per 1 year increase in age), living alone (HR 2.09 [2.04–2.15]) and comorbidities. The 5-year incidence of nursing home admission was 3.9% [3.7%–4.0%] among HF patients and 1.7% [1.7%–1.8%] among the comparison cohort and this resulted in an adjusted HR of 1.91 [1.77–2.06]. Covariates associated with nursing home admission included older age (HR 1.10 [1.10–1.11]), living alone (HR 2.15 [2.02–2.28]) and history of stroke (HR 2.71 [2.53–2.90]). Conclusion: Hospitalization for HF is associated with increased need for domiciliary support and nursing home admissions. Older age, living alone, and comorbidities were associated with higher risk of both outcomes. Keywords: domiciliary care, nursing home admission, heart failure, epidemiology

BACKGROUND: The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. METHODS AND RESULTS: We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). CONCLUSIONS: The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI. [ABSTRACT FROM AUTHOR]

Background: The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI.Methods: Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.Results: The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).Conclusions: We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain. [ABSTRACT FROM AUTHOR]

Background: Hospitalizations are a major burden for both patients and society but are potentially preventable. We examined the one-year hospitalization burden in patients undergoing transcatheter aortic valve replacement (TAVR) and compared hospitalization rates and patterns with those undergoing isolated surgical aortic valve replacement (SAVR)., Methods: Using Danish nationwide registries, we identified patients who underwent first-time TAVR and isolated SAVR (2008-2019), respectively. Subsequent hospitalizations were classified as cardiovascular or noncardiovascular according to discharge diagnosis codes., Results: Patients undergoing TAVR (N = 4,921) were older and had more comorbidities than those undergoing SAVR (N = 5,220). There were 5,725 and 4,426 hospitalizations within the first year after discharge in the TAVR and SAVR group, respectively. During the one-year follow-up period post-TAVR, 46.6% were not admitted, 25.4% were admitted once, 12.6% twice, and 15.4% 3 times or more. The corresponding proportions in patients undergoing SAVR were 55.3%, 25.1%, 10.0%, and 9.5%, respectively. Among patients with ≥1 hospitalization following TAVR, 50.3% had a total length of all hospital stays between 1 and 7days, 19.0% 8-14days, 18.0% 15-30days, 9.9% 31-60days, and 2.8% ≥61days. The corresponding proportions for patients undergoing SAVR were 58.6%, 17.2%, 13.1%, 7.4%, and 3.7%, respectively. Compared with patients undergoing SAVR, those undergoing TAVR had a lower early (day0-30: HR 0.89 [95% CI, 0.80-0.98]), but a higher late hospitalization rate (day 31-365: 1.46 [1.32-1.60])., Conclusions: The 1-year hospitalization burden following TAVR is substantial. Compared with patients undergoing isolated SAVR, those undergoing TAVR had a lower early, but a higher late hospitalization rate - a difference that likely reflects unmeasured differences in the patient cohorts., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Pre-eclampsia (PE), a pregnancy-induced hypertensive disorder, affects 4-5% of pregnancies worldwide. It is well known that hypertension is associated with an increased risk of arrhythmias; however, data on the association between PE and arrhythmias are sparse., Methods and Results: In this observational cohort study, we identified all primiparous women who gave birth in Denmark (1997-2016) using Danish nationwide registries. The women were stratified on whether they developed PE during primiparous pregnancy and followed from primiparous pregnancy to incident arrhythmia, emigration, death, or end of study (31 December 2018). A total of 523 271 primiparous women with a median age of 28 years were included, and 23 367 (4.5%) were diagnosed with PE. During a median follow-up of 10.1 years, women with and without PE were associated with a higher incidence of arrhythmias (1.42 vs. 1.02%): (i) composite of cardiac arrest, ventricular tachycardia/fibrillation, or implantable cardioverter defibrillator implantation [adjusted hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.14-2.24], (ii) composite of advanced second- or third-degree atrioventricular block, sinoatrial dysfunction, or pacemaker implantation [adjusted HR 1.48 (95% CI 0.97-2.23)], (iii) composite of supraventricular tachyarrhythmias or extra systoles [adjusted HR 1.34 (95% CI 1.19-1.51)], and (iv) composite of all the above-mentioned arrhythmias [adjusted HR 1.37 (95% CI 1.23-1.54)]., Conclusion: Pre-eclamptic women were associated with a significantly and at hitherto unknown long-term increased rate of arrhythmias. This finding suggests that women with PE may benefit from cardiovascular risk assessment, screening, and preventive education., 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.)

Background: As more patients with congenital heart disease (CHD) survive into adulthood, the population of adults with CHD is expanding. This trend is accompanied by an increasing incidence of complications, including arrhythmias. However, the long-term risk of arrhythmias remains sparsely investigated., Methods: In this observational cohort study, all Danish patients with CHD born from 1977 to 2024 were identified using registries and followed from date of birth until the occurrence of arrhythmia, emigration, death, or end of follow-up (March 2024). The risk of arrhythmias was assessed among patients with CHD and compared to age- and sex-matched controls from the background population., Results: A total of 45,820 patients with CHD (50.9% men) were identified and matched with 183,280 controls from the background population. During a median follow-up of 21.5 years, 2.6% of patients with CHD and 0.2% of controls developed arrhythmias-corresponding to incidence rates (IR) of 1.2 (95% CI 1.2-1.3) and 0.1 (95% CI 0.1-0.1) per 1,000 PY, respectively, and a hazard ratio (HR) of 16.4 (95% CI 14.4-18.7). The most common arrhythmias in patients with CHD were advanced atrioventricular block (IR 0.4 [95% CI 0.4-0.4] per 1,000 PY) and atrial flutter/fibrillation (IR 0.5 [95% CI 0.5-0.6] per 1,000 PY). Patients with malformations of the heart chambers, transposition of the great arteries, tetralogy of Fallot, and atrioventricular septal defect were at the highest risk of arrhythmias. Moreover, the risk of arrhythmias among those with ASD was not negligible. In patients with CHD, arrhythmia was associated with a significantly higher risk of death (HR of 6.9 [95% CI 5.9-8.1])., Conclusions: Patients with CHD are at significantly higher risk of arrhythmias than the background population, and those with complex CHD are at particularly high risk. In patients with CHD, arrhythmia is associated with an increased risk of death. Additional studies are warranted to investigate how we can improve the diagnosis and management of arrhythmias in CHD., Competing Interests: Disclosures None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap., Methods: Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality., Results: In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96])., Conclusions: Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings., (© 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 and Aims: Patients with congenital heart disease (CHD) form a high-risk subgroup for infective endocarditis (IE), necessitating tailored prevention and treatment strategies. However, comprehensive nationwide data comparing IE characteristics and outcomes in patients with and without CHD, including children, are sparse. This study aims to address this gap in knowledge., Methods: Using Danish nationwide registries, all patients with IE from 1977 to 2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e. in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups., Results: In total, 14 040 patients with IE were identified, including 895 (6.4%) with CHD. Patients with vs. without CHD were younger at the time of IE diagnosis (median age 38.8 vs. 70.7 years), less comorbid, and more frequently underwent cardiac surgery during admission (35.7% vs. 23.0%, P < .001). Notably, 76% of patients with IE < 18 years of age had CHD. The IE-related bacteraemia differed between groups: Streptococci (29.9%) were the most common in patients with CHD, and Staphylococcus aureus (29.9%) in patients without CHD. Patients with CHD had a significantly lower cumulative incidence of in-hospital mortality (5.7% vs. 17.0%, P < .001) and 1-year mortality (9.9% vs. 31.8%, P < .001) compared with those without CHD. The 10-year cumulative incidence of IE recurrence was similar between groups (13.0% and 13.9%, P = .61)., Conclusions: Patients with CHD who develop IE exhibit distinct characteristics and improved long-term outcomes compared with patients without CHD. Notably, the majority of children and adolescents with IE have underlying CHD., (© 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.)

Objectives: To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education., Methods: Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis., Results: A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again., Conclusions: A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment., Competing Interests: C.T.P. has received grants for studies from Novo Nordisk and Bayer without relation to the current study. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Diabetes mellitus (DM) and multiple sclerosis (MS) are two common diseases known to worsen the trajectory of each other, yet it is unknown whether MS is associated with incident DM., Methods: Using Danish nationwide registries, we identified all patients aged 18-99 with a first-time primary or secondary discharge diagnosis with MS between 2000 and 2018, with no known DM. These patients were matched with control subjects from the background population in a 1:5 ratio based on age and sex, to assess their risk of DM., Results: A total of 13,376 patients with MS and 66,880 matched control subjects were included (33 % men; median age, 42 years [25th-75th percentile, 33-51]). During a median follow-up of 8.3 years (25th-75th percentile, 4.0-13.3), 467 (3.5 %) patients with MS and 2397 (3.6 %) control subjects were diagnosed with DM. The cumulative incidence of DM was similar among patients with MS and control subjects (95 % confidence interval [CI] 6.5 % [5.7-7.2 %] vs. 7.3 % [95 % CI 6.9-7.9 %], respectively), and adjusted analysis yielded a hazard ratio (HR) of 0.98 [95 % CI 0.89-1.09]). The overall risk of incident type 1 diabetes was low and yielded a HR of 1.60 [95 % CI 0.98-1.40] in patients with MS compared with control subject (P = 0.07)., Conclusion: This study demonstrated that patients with MS had a similar risk of incident DM as compared to age- and sex matched controls from the background population., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [ 64 Cu]Cu-DOTATATE ([ 64 Cu]Cu-[1,4,7,10-tetraazacyclododecane- N , N ', N ″, N ‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate)., Case Summary: An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [ 64 Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [ 64 Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis., Discussion: In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [ 64 Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake., Competing Interests: Conflict of interest: K.H.-T., M.Ø.F., P.H., and R.S.R.: none declared. A.K.: inventor/holds IPR on a patent covering [64Cu]Cu-DOTATATE for use in neuroendocrine tumours. L.K. has received lecture fees from Astra Zeneca, Bayer, Boehringer, Novartis, and Novo, unrelated to this manuscript. E.F. has received independent research grant related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association, unrelated to this manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This report aimed to examine temporal changes in the number of recommendations on management of infective endocarditis in the European and American guidelines. The number of recommendations has increased since 2004 without an increment in evidence base in the European iteration. American guidelines have reduced the number of recommendations with a main evidence base of level B., Competing Interests: Conflict of interest Lauge Østergaard: Independent research grant from the Novo Nordisk Foundation for the research of mitral valve regurgitation. Lars Køber: Speakers honorarium from Novo, Novartis, AstraZeneca, Boehringer and Bayer Emil Loldrup Fosbøl: Novo Nordisk Foundation and the Danish Heart Association: Independent research grant related to valvular heart disease and endocarditis. Sofie Truong, Eva Havers-Borgersen and Jeppe Petersen: None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Major emergency abdominal surgery is associated with postoperative complications and high mortality. Long-term outcomes in patients with perioperative atrial fibrillation (POAF) have recently received increased attention, especially POAF in non-thoracic surgery., Purpose: This study aimed to compare long-term AF related hospitalization and stroke in patients with POAF in relation to major emergency abdominal surgery and in patients with non-perioperative AF., Methods: We crosslinked data from Danish nationwide registries and identified all patients who underwent major emergency abdominal surgery (2000-2018) and were diagnosed with POAF, and patients who developed AF in a non-perioperative setting. Patients with POAF were matched in a 1:5 ratio on age, sex, year of AF diagnosis and oral anticoagulation (OAC) status at the beginning of follow-up with patients with non-perioperative AF. From discharge, we examined adjusted hazard ratios (HR) of stroke using multivariable Cox regression analysis., Results: The study population comprised 1,041 (out of 42,021 who underwent major emergency abdominal surgery) patients with POAF and 5,205 patients with non-perioperative AF. The median age was 78 years [interquartile range: 71-84] for those initiated on OAC therapy and 78 years [interquartile range: 71-85] for those not initiated on OAC therapy. During the first year of follow up, POAF was associated with similar rates of stroke as non-perioperative AF (patients initiated on OAC: HR 0.96 (95% confidence interval (CI) 0.52-1.77) and patients not initiated on OAC: HR 0.69 (95% CI 0.41-1.15)., Conclusion: POAF in relation to major emergency abdominal surgery was associated with similar rates of stroke as non-perioperative AF. These results suggest that POAF not only carry an acute burden but also a long-term burden in patients undergoing major emergency abdominal surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Infective endocarditis (IE) is a dangerous and lethal illness with high mortality rates. One of the main indications for surgery according to the guidelines is prevention of embolic events. However, uncertainty remains concerning the timing of surgery and the effect of early surgery in combination with antibiotic therapy versus antibiotic therapy alone in IE patients with a vegetation size > 10 mm., Methods: We conducted a comprehensive review by searching the PubMed, MEDLINE, and EMbase databases. Titles and abstracts were screened, and studies of interest were selected for full-text assessment. Studies were selected for review if they met the criteria of comparing surgical treatment + antibiotic therapy to antibiotic therapy alone in patients with vegetations > 10 mm., Results: We found 1,503 studies through our database search; nine of these were eligible for review, with a total number of 3,565 patients. Median age was 66 years (range: 17-80) and the median percentage of male patients was 65.6% (range: 61.8 - 71.4%). There was one randomised controlled trial, one prospective study, and seven retrospective studies. Seven studies found surgery + antibiotic therapy to be associated with better outcomes in patients with IE and vegetations > 10 mm, one of them being the randomised trial [hazard ratio = 0.10; 95% confidence interval 0.01-0.82]. Two studies found surgery + antibiotic therapy was associated with poorer outcomes compared with antibiotic therapy alone., Conclusion: Overall, data vary in quality due to low numbers and selection bias. Evidence is conflicting, yet suggest that surgery + antibiotic therapy is associated with better outcomes in patients with IE and vegetations > 10 mm for prevention of emboli. Properly powered randomised trials are warranted., (© 2024. The Author(s).)

Background: First-time detected atrial fibrillation (AF) is associated with aggravated prognosis in patients admitted with acute coronary syndrome (ACS). Yet, among patients surviving beyond one year after ACS, it remains unclear how the recurrence of AF within the initial year after ACS affects the risk of stroke., Methods: With Danish nationwide data from 2000 to 2021, we identified all patients with first-time ACS who were alive one year after discharge (index date). Patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without a recurrent hospital contact with AF (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent hospital contact with AF (recurrent AF). From index date, two-year rates of ischemic stroke were compared using multivariable adjusted Cox regression analysis. Treatment with antithrombotic therapy was assessed as filled prescriptions between 12 and 15 months following ACS discharge., Results: We included 139,137 patients surviving one year post ACS discharge: 132,944 (95.6%) without AF, 3920 (2.8%) with transient AF, and 2273 (1.6%) with recurrent AF. Compared to those without AF, the adjusted two-year hazard ratios of ischemic stroke were 1.45 (95% CI, 1.22-1.71) for patients with transient AF and 1.47 (95% CI: 1.17-1.85) for patients with recurrent AF. Prescription rates of oral anticoagulation increased over calendar time, reaching 68.3% and 78.7% for transient and recurrent AF, respectively, from 2019 to 2021., Conclusion: In patients surviving one year after ACS with first-time detected AF, recurrent and transient AF were associated with a similarly increased long-term rate of ischemic stroke., Competing Interests: Declaration of competing interest Jeppe Kofoed Petersen: None. Jawad Haider Butt: Advisory board honoraria from Bayer. Adelina Yafasova: None. Christian Torp-Pedersen: Grants for studies from Bayer and Novo Nordisk. Rikke Sørensen: None. Christina Kruuse: Independent research grant from Novo Nordisk Foundation. Local PI in trials from Bayer and Bristol-Myers Squibb. Naja Emborg Vinding: None. Anna Gundlund: None. Lars Køber: Speakers honorarium from Novo, Novartis, AstraZeneca and Boehringer. Emil Loldrup Fosbøl: Independent research grant from Novo Nordisk foundation. Lauge Østergaard: Independent research grant from Novo Nordisk foundation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: While the proportion of drug-use-associated infective endocarditis (DU-IE) has been increasing during the opioid crisis in the United States, it is unknown whether this is seen in Denmark, where several preventive means have been implemented. We aimed to assess the temporal proportion of DU-IE and examine the rate of IE recurrence and mortality., Methods: This nationwide cohort study identified all patients with first-time infective endocarditis in 1999-2018. Drug use was defined using ICD-8/10 codes or prescription filling of medication for opioid use disorder. Long-term mortality was examined with a Kaplan-Meier estimator and a multivariate Cox model. The recurrence of IE was examined with the Aalen-Johansen method and a multivariate cause-specific hazard model., Results: We included 8,843 patients with IE: 407 with DU-IE (60.7% male, median age 43.8 years) and 8,436 with non-DU-IE (65.8% male, median age 71.5 years). The proportion of DU-IE decreased from 5.9% to 3.8% during our study period. The one-year cumulative incidence of all-cause mortality was 16.9% (CI 12.9%-20.8%) for patients with DU-IE and 17.3% (CI 16.4%-18.2%) for patients with non-DU-IE. Drug use was associated with higher one-year mortality (adjusted HR 1.64 (CI 1.23%-2.21%)). The 1-year cumulative incidence of IE recurrence was 12.8% (CI 9.3%-16.3%) in patients with DU-IE and 4.3% (CI 3.8%-4.8%) in patients with non-DU-IE. Drug use was associated with a higher 1-year recurrence of IE (adjusted HR 3.39 (CI 2.35-4.88))., Conclusion: In Denmark, the proportion of patients with DU-IE fell by one-third from 1999 to 2018. DU-IE was associated with higher mortality and recurrence rates than non-DU-IE., Competing Interests: Conflict of interest Jeppe Kofoed Petersen: None. Lucas Grove Vejlstrup Bager: None. Lauge Østergaard: None. Peter Laursen Graversen: None. Kasper Iversen: None. Henning Bundgaard: None. Lars Køber: Speakers honorarium from Novo, Novartis, AstraZeneca, and Boehringer. Emil Loldrup Fosbøl: Independent research grant from Novo Nordisk foundation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse., Research Question: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population?, Study Design and Methods: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE., Results: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15)., Interpretation: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. Y. reports a grant from the Foundation of Rigshospitalet. E. L. F. reports independent and unrelated research funding from the Danish Heart Association and the Novo Nordisk Foundation. F. G. reports being an advisor for Abbott, Fineheart, AdjuCor, Bayer, Ionis, Alnylam, AstraZeneca, and Pfizer; and a speaker for Novartis, all outside the submitted work. S. L. K. reports being on the advisory board for Bayer, outside the submitted work. M. S. reports lecture fees from Novo Nordisk, Bohringer, Astra Zeneca, and Novartis, outside the submitted work. K. R. reports being an advisory board member for Abbott, Novo Nordisk, and Boehringer-Ingelheim; and speaking fees from AstraZeneca, Boehringer-Ingelheim, Abbott, and MSD, all outside the submitted work. L. K. reports compensation from Novartis, Novo Nordisk, and AstraZeneca for other services, outside the submitted work. J. H. B. reports advisory board honoraria from AstraZeneca and Bayer, consultant honoraria from Novartis and AstraZeneca, and travel grants from AstraZeneca, all outside the submitted work. None declared (S. B. K., J. K. P., G. S., S. N. D.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Patients with atrial fibrillation (AF) are at increased risks of cardiovascular diseases and mortality, but risks according to age at diagnosis have not been reported. This study investigated age-specific risks of outcomes among patients with AF and the background population., Methods: This nationwide population-based cohort study included patients with AF and controls without outcomes by the application of exposure density matching on the basis of sex, year of birth, and index date. The absolute risks and hazard rates were stratified by age groups and assessed using competing risk survival analyses and Cox regression models, respectively. The expected differences in residual life years among participants were estimated., Results: The study included 216 579 AF patients from year 2000 to 2020 and 866 316 controls. The mean follow-up time was 7.9 years. Comparing AF patients with matched controls, the hazard ratios among individuals ≤50 years was 8.90 [95% confidence interval (CI), 7.17-11.0] for cardiomyopathy, 8.64 (95% CI, 7.74-9.64) for heart failure, 2.18 (95% CI, 1.89-2.52) for ischaemic stroke, and 2.74 (95% CI, 2.53-2.96) for mortality. The expected average loss of life years among individuals ≤50 years was 9.2 years (95% CI, 9.0-9.3) years. The estimates decreased with older age., Conclusions: The findings show that earlier diagnosis of AF is associated with a higher hazard ratio of subsequent myocardial disease and shorter life expectancy. Further studies are needed to determine causality and whether AF could be used as a risk marker among particularly younger patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety., Objectives: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes., Methods: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above., Results: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%])., Conclusions: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation., Competing Interests: Funding Support and Author Disclosures This study has been funded by external, independent grants from “IMK Almene Fond” (J. nr. 30206-383), “Helsefonden” (20-B-0035) “Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond” (J 167/1), “Marie og M.B. Richters Fond” (J. nr. 2020-0379), and “Dagmar Marshalls Fond.” Dr Fosbøl has received grants from the Novo Nordisk Foundation for research in valvular heart disease, unrelated to this study. Dr Køber has received speaker fees from Novo, AstraZeneca, Novartis, and Boehringer, unrelated to this study. Dr Torp-Pedersen has received grants from Novo and Bayer, unrelated to this study. Dr Schou has received speaker fees from Novartis, Boehringer Ingelheim, Bayer, Novo, and AstraZeneca, unrelated to this study. Dr Lamberts has received grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; has received speaker fees from BMS/Pfizer, Bayer, AstraZeneca, MSD, and Merck; and has had advisory board positions with BMS/Pfizer, Bayer, and Mundipharma, unrelated to this study. 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: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups., Methods: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years)., Findings: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8])., Interpretation: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure., Funding: None., Translation: For the Danish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests MS reports lecture fees from Boehringer, Novo AstraZeneca, and Novartis. MCP reports grants from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos, and lecture and consultant fees from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. JJVM reports lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J B Chemicals & Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart. Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy, and consultant fees from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. LK reports speaker's honorarium from AstraZeneca, Bayer, Boehringer, Novartis and Novo. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Infective endocarditis (IE) is a deadly disease, constituting both diagnostic and treatment challenges. A positive outcome requires rapid and accurate diagnosis, and for that, echocardiography unequivocally remains the cornerstone. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have complementary roles and have been markedly improved during the last decades. The transthoracic modality is the recommended first-line approach but may only be sufficient in patients where the probability of IE is low and/or with clear acoustic windows, especially in patients with right-sided IE. The transesophageal modality is superior to TTE in most aspects and is recommended for all other patients. Both TTE and TEE may delineate vegetation location and size, assess for paravalvular extension of infection, and have the added advantage of defining the hemodynamic effects of valvular or device infection. However, echocardiography still has significant limitations, and novel imaging techniques are increasingly being exploited to improve diagnostic potential. Cardiac computed tomography (CT) performs better than TEE in the detection of abscess or pseudoaneurysm, while magnetic resonance imaging (MRI) has limited value in the diagnostic phase of IE but adds knowledge to the evaluation of extracardiac events. Nuclear molecular techniques are evolving as key supplementary methods in difficult-to-diagnose cases. Although newer imaging modalities are undergoing preliminary evaluation and multimodal imaging will play an increasing role in IE, echocardiography will continue to be pivotal in patients with IE for the foreseeable future., Competing Interests: Conflict of interestJeppe Kofoed Petersen: None Lauge Østergaard: Independent research grant from Novo Nordisk Foundation Emil Fosbøl: Independent research grant from Novo Nordisk Foundation, (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: Vegetation size assessed by transoesophageal echocardiography (TOE) is a decisive metric in guiding surgical intervention and prognosis in patients with definite infective endocarditis (IE). The aim of this study was to assess the impact of echocardiographic experience on the reliability and reproducibility of TOE measurements of vegetations in patients with IE., Methods and Results: Twenty-nine raters from a cardiac department at a tertiary centre were divided into three groups according to echocardiographic experience: experts, cardiologists, and novices. All raters were instructed to measure the maximum length of vegetations in 20 different TOE exams. Interrater agreement was evaluated using intraclass correlation coefficient (ICC), one-way analysis of variance, Kruskal-Wallis test, and Bland-Altmann plots. Reliability was assessed by minimal detectable change (MDC). All measurements were compared with the measured size agreed on by the multi-disciplinary IE team.There was an overall significant interrater variance between the three groups ( P < 0.001). The variance was 10.1, 14.8, and 21.7 for the experts, cardiologists, and novices, respectively. ICC was excellent for experts (96.3%) and cardiologists (93.7%) and good for novices (84.6%). The three groups tended to measure smaller than the endocarditis team. MDC was 2.6 mm for experts, 3.3 mm for cardiologists, and 3.6 mm for novices., Conclusion: The study showed good to excellent intraclass correlation but high dispersion in all groups. Variance decreased with higher experience. Our findings support current recommendations that complicated cases should be cared for by the multi-disciplinary endocarditis team and underline the importance of echocardiographic expertise when evaluating and measuring vegetations in patients with IE., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Sex differences in infective endocarditis (IE) are reported, but patient characteristics are sparse and conflicting findings on the association between sex and short-term outcomes demand further research. We aimed to characterize sex differences in IE in terms of patient characteristics, frailty, microbiology, socioeconomic status, management and outcome on a nationwide scale., Methods: Between 2010 and 2020, we used Danish national registries to characterize patients with IE according to sex using ICD codes and microbiological lab reports. Frailty was assessed with the Hospital Frailty Risk Score. Mortality was reported with Kaplan-Meier estimates. Logistic regression and Cox regression were used for adjusted analyses., Results: We included 6259 patients with IE with 2047 (32.7%) female patients and 4212 (67.3%) male patients. Female patients were older (median age 75.0 years (64.3-82.2) vs. 71.7 (61.7-78.9)) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%). Staphylococcus aureus-IE were most common in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus-IE (10.5% vs. 18.1%). Female patients were less surgically treated (14.0% vs. 21.2%). Female sex was associated with increased in-hospital mortality (adj. OR 1.33, 95% CI 1.16-1.52), but no statistically significant difference in associated 1- and 5-year mortality from hospital discharge were identified (adj. HR 1.09, 95% CI 0.95-1.24 and 1.02, 95% CI 0.92-1.12, respectively)., Conclusion: Female sex is associated with increased in-hospital mortality, but not in long-term mortality as compared with male patients. Female patients have a lower prevalence of Enterococcus-IE and rates of surgery. Further research is needed to understand these differences., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs., Methods: Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs., Results: In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05)., Conclusions: Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals., (© 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: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS)., Methods and Results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%)., Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—advisory board: AstraZeneca, Janssen-Cilag, and Novo Nordisk; grant support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number CPD5Y-2022004-HF); and speaker honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; speaker engagements with Novartis and Roche Diagnostics; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. C.B. discloses the following relationships—speaker honorarium: Bayer. T.B.-S. discloses the following relationships—steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare and Sanofi Pasteur. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. C.P.M. is supported by a grant from the National Institutes of Health (K23HL167659) and has received consulting fees/honorarium from Roche Diagnostics and Abbott Laboratories. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott and Shockwave. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no relevant disclosures., (© 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: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time., Methods and Results: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016)., Conclusions: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Background: Prevention and management of childhood overweight involves the entire family. We aimed to investigate purchase patterns in households with at least one member with overweight in childhood by describing expenditure on different food groups., Methods: This Danish register-based cohort study included households where at least one member donated receipts concerning consumers purchases in 2019-2021 and at least one member had their Body mass index (BMI) measured in childhood within ten years prior to first purchase. A probability index model was used to evaluate differences in proportion expenditure spent on specific food groups., Results: We identified 737 households that included a member who had a BMI measurement in childhood, 220 with overweight and 517 with underweight or normal weight (reference households). Adjusting for education, income, family type, and urbanization, households with a member who had a BMI classified as overweight in childhood had statistically significant higher probability of spending a larger proportion of expenditure on ready meals 56.29% (95% CI: 51.70;60.78) and sugary drinks 55.98% (95% CI: 51.63;60.23). Conversely, they had a statistically significant lower probability of spending a larger proportion expenditure on vegetables 38.44% (95% CI: 34.09;42.99), compared to the reference households., Conclusion: Households with a member with BMI classified as overweight in childhood spent more on unhealthy foods and less on vegetables, compared to the reference households. This study highlights the need for household/family-oriented nutrition education and intervention., Competing Interests: CTP reports grants for studies from Bayer and Novo Nordisk unrelated to the current study. All other authors declare no competing interests., (Copyright: © 2024 Sørensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease., Methods: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10 th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources., Conclusions and Perspectives: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed., Competing Interests: Disclosures Peter L. Graversen: None Katra Hadji-Turdeghal: None Jacob Eifer Møller: Institutional research grant from Novo Nordic Foundation, Danish Hear Foundation and Abiomed outside submitted work. Unrelated to this study. Niels Eske Bruun: has received investigator initiated grants from: The Novo Nordisk Foundation, The Augustinus Foundation, The Kaj Hansen Foundation, and Health Insurance Denmark, unrelated to this study. Hicham Laghmoch: None Andreas Dalsgaard Jensen: None Jeppe K. Petersen: None Henning Bundgaard: has received lecture fees from Amgen, BMS, MSD and Sanofi, unrelated to this study. Kasper Iversen: None Jonas A Povlsen: None Claus Moser: has received an independent research grant from the Novo Nordisk Foundation in translational research grant number (NNF17OC0025074). Unrelated to this study. Morten Smerup: None Hanne Sortsøe Jensen: None Peter Søgaard: None Jannik Helweg-Larsen: None Daniel Faurholt-Jepsen: None Lauge Østergaard: has received an independent research grant from the Novo Nordisk Foundation (NNF23OC0081668) related to mitral valve regurgitation. Unrelated to this study. Lars Køber speakers fee from AstraZeneca, Baer, Boehringer, Novartis and Novo, unrelated to this study Emil L. Fosbøl: has received independent research grants related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Severe, symptomatic aortic stenosis may cause heart failure, acute myocardial infarction, or syncope; limited data exist on the occurrence of such events before transcatheter aortic valve replacement (TAVR) and their impact on subsequent outcomes. Thus, we investigated the association between a preceding event and outcomes after TAVR., Methods: From 2014 to 2021 all Danish patients who underwent TAVR were included. Preceding events up to 180 days before TAVR were identified. A preceding event was defined as a hospitalization for heart failure, acute myocardial infarction, or syncope. The 1-year risk of all-cause death, and cardiovascular or all-cause hospitalization was compared for patients with versus without a preceding event using Kaplan-Meier, Aalen-Johansen, and in Cox regression analyses adjusted for patient characteristics., Results: Of 5,851 patients included, 759 (13.0%) had a preceding event. The median age was 81 years in both groups. Male sex and frailty were more prevalent in patients with a preceding event (males: 64.7% vs 55.2%, frailty: 49.6% vs 40.6%). The most common type of preceding event was a hospitalization for heart failure (n = 524). For patients with a preceding event, the 1-year risk of death was 11.7% (95% CI: 9.4%-14.1%) versus 8.0% (95% CI: 7.2%-8.7%) for patients without. The corresponding adjusted hazard ratio (aHR) was 1.29 (95%CI: 1.01-1.64). Mortality was highest for patients with a preceding event of a heart failure admission (1-year risk: 13.5% [95%CI: 10.5%-16.5%]). Comparing patients with a preceding event to those without, the 1-year risk for cardiovascular rehospitalization was 15.0% versus 8.2% (aHR 1.60 [95%CI: 1.29-1.99]) and 57.6% versus 50.6% for all-cause rehospitalization (aHR 1.08 [95%CI: 0.87-1.20])., Conclusions: A hospitalization for heart failure, myocardial infarction, or syncope prior to TAVR was associated with a poorer prognosis and could represent a group to focus resource management on. Interventions to prevent preceding events and improvements in pre- and post-TAVR optimization of these patients are warranted., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In patients undergoing transcatheter aortic valve replacement (TAVR), the impact of acute kidney injury (AKI) on the prognosis and especially on future kidney function has been sparsely examined, and data from large cohorts are warranted., Methods and Results: With Danish nationwide registries, we identified all patients undergoing TAVR from 2014 to 2021 with no previous dialysis treatment. According to 2 plasma creatinine samples, we identified those suffering a postprocedural AKI within 21 days after TAVR. With 1 year of follow-up, we compared the associated rates of dialysis treatment and death between patients with and without an AKI using multivariable Cox analysis. Finally, according to the lowest recorded creatinine sample, we assessed the kidney function among AKI survivors between 90 and 180 days after the index date. We identified 4091 TAVRs: 193 (4.7%) with AKI (55.4% men; median age, 82 years) and 3898 (95.3%) without AKI (57.0% men; median age, 81 years). Compared with those without AKI, patients with AKI showed increased associated 1-year rates of dialysis treatment (hazard ratio [HR], 7.20 [95% CI, 4.10-12.66]) and death (HR, 2.39 [95% CI, 1.59-3.58]). After 6 months, 74% of AKI survivors had complete kidney recovery, 14.7% had incomplete kidney recovery, 6.3% failed to recover, and 5.1% were on dialysis treatment., Conclusions: We identified that AKI after TAVR was associated with an increased rate of future dialysis treatment and all-cause death. Among survivors, 74% had complete kidney recovery within 6 months.

Background: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is associated with high mortality and surgery is rarely performed. Thus, to inform on preventive measures and treatment strategies, we investigated patient characteristics and microbiology of IE after TAVI., Methods: Using Danish nationwide registries, we identified patients with IE after TAVI, IE after non-TAVI prosthetic valve (nTPV), and native valve IE. Patient characteristics; overall, early (≤12 m), and late IE (>12 m) microbiology; and unadjusted and adjusted mortality were compared., Results: We identified 273, 1022, and 5376 cases of IE after TAVI, IE after nTPV, and native valve IE. Age and frailty were highest among TAVI IE (4.8%; median age: 82 y; 61.9% frail). Enterococcus spp. were common for IE after TAVI (27.1%) and IE after nTPV (21.2%) compared with native valve IE (11.4%). Blood culture-negative IE was rare in IE after TAVI (5.5%) compared with IE after nTPV (15.2%) and native valve IE (13.5%). The unadjusted 90-day mortality was comparable, but the 5-year mortality was highest for IE after TAVI (75.2% vs 57.2% vs 53.6%). In Cox models adjusted for patient characteristics and bacterial etiology for 1-90 days and 91-365 days, there was no significant difference in mortality rates., Conclusions: Patients with IE after TAVI are older and frailer, enterococci and streptococci are often the etiologic agents, and are rarely blood culture negative compared with other IE patients. Future studies regarding antibiotic prophylaxis strategies covering enterococci should be considered in this setting., Competing Interests: Potential conflicts of interest. L. K.: Lecture fees from AstraZeneca, Bayer, Boehringer, Novartis, and Novo. H. B.: Lecture fees from Amgen, MSD, Bristol-Myers Squibb, and Sanofi. M. V.: Lecture fees from MyLab Oy. J. B. O.: Speaker’s honoraria or consultancy fees from Bayer, Bristol-Myers Squibb, and Pfizer. E. L. F.: Independent research grant from Novo Nordisk Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose. Transthyretin is produced in the retina and approximately one quarter of patients with variant transthyretin amyloidosis (ATTRv) develop ocular involvement. Glaucoma is the most important ocular manifestation, leading to rapid loss of vision. The usefulness of glaucoma as a red flag for cardiac amyloidosis is unknown. Materials and Methods. On a national scale, we investigated the association between glaucoma and development of amyloidosis, compared to an age- and sex-matched population from the general population. Results. The study population included 365,496 subjects (1:1 ratio). Adjusted Cox-models showed no significant association between glaucoma and future diagnosis of amyloidosis (hazard ratio: 1.16 [0.80-1.70], p  = .44). Conclusion. We conclude that while ocular involvement is a possible early manifestation of ATTRv, nationwide data suggest that glaucoma is probably not useful as a red flag for cardiac amyloidosis.

Aims: Previous small-scale studies have indicated a short-term stroke incidence of 1.0-1.3% following Takotsubo (syndrome). In this nationwide register-based study, we investigated the 90-day risk of ischemic stroke (IS) or transient ischemia attack (TIA) and mortality of patients with Takotsubo., Methods and Results: Patients with incident Takotsubo between January 1st 2009 to September 30th 2018 were identified from Danish nationwide registries. Takotsubo patients were age- and sex-matched with background-, atrial fibrillation/flutter- (AF) and myocardial infarction (MI) cohorts. Cumulative incidences and Cox proportional-hazard regression models were used to analyze the following outcomes: 1) composite of IS/TIA and 2) all-cause mortality. A total of 890 patients with Takotsubo were followed for 90 days. The cumulative 90-day incidence of IS/TIA in the Takotsubo-, background-, AF- and MI cohort, was 2.1% (n = 19), 0.1% (n = 4), 1.1% (n = 47) and 1.5% (n = 66), respectively. The cumulative 90-day mortality in the Takotsubo-, background-, AF- and MI cohort was 5.1% (n = 45), 0.3% (n = 13), 1.7% (n = 75) and 5.6% (n = 230), respectively. The adjusted hazard ratio (HR) for 90-day IS/TIA was when compared to the background-, AF- and MI cohort, 26.43 (95% CI: 8.82-79.24), 1.91 (95% CI: 1.09-3.35) and 2.06 (95% CI: 1.12-3.79), respectively. The adjusted HR for 90-day mortality was when compared to the background-, AF- and MI cohort, 14.19 (95% CI: 7.43-27.09), 0.73 (95% CI: 0.52-1.02) and 1.96 (95% CI: 1.25-3.07), respectively., Conclusion: Patients with Takotsubo had an increased 90-day hazard for IS/TIA when compared to age- and sex-matched background-, AF- and MI cohorts., Competing Interests: Declaration of Competing Interest No authors have any conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci., Objectives: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated., Patients and Methods: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination., Results: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively., Conclusions: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE., Methods: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE., Results: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species., Conclusion: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species., (© 2023. The Author(s).)

The prevalence and impact of perioperative atrial fibrillation (AF) during an admission for major emergency abdominal surgery are sparsely examined. Therefore, this study aimed to compare the 30-day and 1-year outcomes (AF-related hospitalization, stroke, and all-cause mortality) in patients with and without perioperative AF to their major emergency abdominal surgery. All patients without a history of AF who underwent major emergency abdominal surgery from 2000 to 2019 and discharged alive were identified using Danish nationwide registries. Patients with and without perioperative AF (defined as new-onset AF during the index hospitalization) were matched 1:4 on age, gender, year of surgery, and type of surgery. The cumulative incidences and hazard ratios of outcomes were assessed using a multivariable Cox regression analysis comparing patients with and without perioperative AF. A total of 2% of patients were diagnosed with perioperative AF. The matched cohort comprised 792 and 3,168 patients with and without perioperative AF, respectively (median age 78 years [twenty-fifth to seventy-fifth percentile 70 to 83 years]; 43% men). Cumulative incidences of AF-related hospitalizations, stroke, and mortality 1 year after discharge were 30% versus 3.4%, 3.4% versus 2.7%, and 35% versus 22% in patients with and without perioperative AF, respectively. The 30-day outcomes were similarly elevated among patients with perioperative AF. Perioperative AF during an admission for major emergency abdominal surgery was associated with higher 30-day and 1-year rates of AF-related hospitalization and mortality and similar rates of stroke. These findings suggest that perioperative AF is a prognostic marker of increased morbidity and mortality in relation to major emergency abdominal surgery and warrants further investigation., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Methylphenidate, a sympathomimetic drug prescribed to treat attention-deficit/hyperactivity disorder (ADHD), is associated with cardiovascular events, but few studies have explored the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether methylphenidate use is associated with OHCA in the general population., Methods and Results: Using Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the odds ratio (OR) of OHCA by comparing methylphenidate use with no use of methylphenidate.The study population consisted of 46 578 OHCA cases [median: 72 years (interquartile range: 62-81), 68.8% men] and 232 890 matched controls. Methylphenidate was used by 80 cases and 166 controls, and was associated with an increased OR of OHCA compared with non-users {OR: 1.78 [95% confidence interval (CI): 1.32-2.40]}. The OR was highest in recent starters (OR≤180 days: 2.59, 95% CI: 1.28-5.23). The OR of OHCA associated with methylphenidate use did not vary significantly by age (P-value interaction: 0.37), sex (P-value interaction: 0.94), and pre-existing cardiovascular disease (P-value interaction: 0.27). Furthermore, the ORs remained elevated when we repeated the analyses in individuals without registered hospital-based ADHD (OR: 1.85, 95% CI: 1.34-2.55), without severe psychiatric disorders (OR: 1.98, 95% CI: 1.46-2.67), without depression (OR: 1.93, 95% CI: 1.40-2.65), or in non-users of QT-prolonging drugs (OR: 1.79, 95% CI: 1.27-2.54)., Conclusion: Methylphenidate use is associated with an increased risk of OHCA in the general population. This increased risk applies to both sexes and is independent of age and the presence of cardiovascular disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)