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Optical interconnects (OIs) based on vertical-cavity surface-emitting lasers (VCSELs) are the main workhorse within data centers, supercomputers, and even vehicles, providing low-cost, high-rate connectivity. VCSELs must operate under extremely harsh and time-varying conditions, thus requiring adaptive and flexible designs of the communication chain. Such designs can be built based on mathematical models (model-based design) or learned from data (machine learning (ML) based design). Various ML techniques have recently come to the forefront, replacing individual components in the transmitters and receivers with deep neural networks. Beyond such component-wise learning, end-to-end (E2E) autoencoder approaches can reach the ultimate performance through co-optimizing entire parameterized transmitters and receivers. This tutorial paper aims to provide an overview of ML for VCSEL-based OIs, with a focus on E2E approaches, dealing specifically with the unique challenges facing VCSELs, such as the wide temperature variations and complex models.

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.

Background: Materials extracted from atherosclerotic arteries can disclose data about the molecular pathology of cardiovascular disease, but obtaining such samples is complex and requires invasive surgery. To overcome this barrier, this study investigated whether angioplasty balloons inflated during standard percutaneous coronary interventions retain proteins from treated (dilated) atherosclerotic lesions and whether proteomic analysis of this material could provide data on lesion protein profiles and distinguish between patients with stable and unstable coronary artery disease. Methods: Patients with ST-segment–elevation myocardial infarction and stable angina pectoris were subjected to routine percutaneous coronary interventions. All angioplasty balloons inflated in a coronary artery were collected. Proteins retained on the balloons were extracted and analyzed using shotgun proteomic analysis. Results: Proteomics identified and quantified 1365 unique proteins captured on percutaneous coronary intervention balloons. Control balloons inflated in the ascending aorta showed minimal nonspecific protein binding, indicating specificity to the luminal region of atherosclerotic lesions of the diseased artery wall. Clustering and principal component analyses showed that ST-segment–elevation myocardial infarction and stable angina pectoris subjects could be separated by variations in protein content and abundance. We identified 206 proteins as differentially abundant between ST-segment–elevation myocardial infarction and stable angina pectoris subjects. Pathway analysis indicated several enriched processes in the ST-segment–elevation myocardial infarction group involved in neutrophil-mediated immunity and platelet activation. Conclusions: Disease-related proteins from coronary artery lesions adhere to angioplasty balloons and constitute a source of material for proteomic analysis. This approach can identify proteins and processes occurring in unstable coronary atherosclerotic lesions and suggest novel therapeutic approaches.

Background and purpose: Reperfusion therapy is the mainstay of treatment for acute ischaemic stroke (AIS); however, little is known about the use of reperfusion therapy and time delay amongst immigrants. Methods: This is a Danish nationwide register-based cohort study of patients with AIS aged ≥18 years (n = 49,817) recruited from 2009 to 2018. Use of reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) and time delay between immigrants and Danish-born residents were compared using multivariable logistics and quantile regression. Results: Overall, 10,649 (39.8%) Danish-born residents and 452 (39.0%) immigrants with AIS were treated with reperfusion therapy in patients arriving

BackgroundThere are no methods for classifying patients with ischemic heart disease (IHD) based on the entire spectrum of pre-existing diseases. Such methods might be clinically useful due to the marked differences in presentation and course of disease.MethodsA population-based cohort study from a Danish secondary care setting of patients with IHD (2004-2016) and subjected to a coronary angiography (CAG) or coronary computed tomography angiography (CCTA). Data sources were The Danish National Patient Registry, in-hospital laboratory data, and genetic data from Copenhagen Hospital Biobank. Comorbidities included diagnoses assigned prior to presentation of IHD. Patients were clustered by means of the Markov Clustering Algorithm using the entire spectrum of registered multimorbidity. The two prespecified outcomes were: New ischemic events (including death from IHD causes) and death from non-IHD causes. Patients were followed from date of CAG/CCTA until one of the two outcomes occurred or end of follow-up, whichever came first. Biological and clinical appropriateness of clusters was assessed by comparing risks (estimated from Cox proportional hazard models) in clusters and by phenotypic and genetic enrichment analyses, respectively.FindingsIn a cohort of 72,249 patients with IHD (mean age 63.9 years, 63.1% males), 31 distinct clusters (C1-31, 67,136 patients) were identified. Comparing each cluster to the 30 others, seven clusters (9,590 patients) had statistically significantly higher or lower risk of new ischemic events (five and two clusters, respectively). 18 clusters (35,982 patients) had a higher or lower risk of death from non-IHD causes (12 and six clusters, respectively). All clusters at increased risk of new ischemic events, associated with risk of death from non-IHD causes as well. Cardiovascular or inflammatory diseases were commonly enriched in clusters (13), and distributions for 24 laboratory test results differed significantly across clusters. Clusters enriched for cerebrovascular diseases were generally not at increased risk of the two outcomes. Polygenic risk scores were increased in a total of 15 clusters (48.4%).ConclusionsClustering of patients with IHD based on pre-existing comorbidities identified subgroups of patients with significantly different clinical outcomes and presented a tool to rank pre-existing comorbidities based on their association with clinical outcomes. This novel method may support better classification of patients and thereby differentiation of treatment intensity depending on expected outcomes in subgroups.

Background To quantify the potential decline in dynamic lung volumes following coronavirus disease 2019 (COVID-19) in the general population. Methods A prospective matched cohort study of adult Copenhagen General Population Study (CGPS) participants with a prepandemic spirometry available. CGPS individuals with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test performed repeat spirometry, a questionnaire regarding respiratory symptoms, and diffusing capacity test for carbon monoxide. A matched uninfected CGPS control sample was used, and simple regression and linear mixed effect models were computed to study lung function decline. Results A total of 606 individuals were included; 92/107 (85.9%) with positive SARS-CoV-2 PCR test experienced coronavirus disease 2019 (COVID-19) symptoms and 12 (11.2%) were hospitalized. Spirometry was performed at median 5.6 months (interquartile range, 3.9–12.8) after positive SARS-CoV-2 PCR test. COVID-19 was associated with adjusted 7.3 mL (95% confidence interval [CI], .3–14.3) and 22.6 mL (95% CI, 13.1–32.0) steeper decline in annual forced expiratory volume in first second (FEV1) and FVC or total 113.8 and 301.3 mL lower FEV1 and FVC from baseline to follow-up. Results were robust in analyses restricted to individuals not requiring hospitalization. Conclusions COVID-19–related declines of dynamic lung volume in the general population not requiring hospitalization were small but measurable.

Receiving evidence-based stroke care processes is associated with good clinical outcome. However, data on early stroke care among immigrants are scarce.We investigated whether guideline-recommended acute stroke care and associated factors differ between immigrants and Danish-born residents.Patients admitted with ischemic and hemorrhagic stroke diagnoses (n=129,724) between 2005 and 2018 were identified from the Danish Stroke Registry.We included 123,928 Danish-born residents and 5796 immigrants with stroke. Compared with Danish-born residents, immigrants were less likely to be admitted to a stroke unit within 24 hours after stroke onset (81.5% vs. 83.9%, P0.001) and had lower odds of early stroke care including dysphagia screening, physiotherapy, occupational therapy, and nutritional assessment. After adjustment for age, sex, clinical, and sociodemographic factors, immigrants had lower odds of early stroke unit admission (odds ratio [OR]: 0.97; 95% CI, 0.94-0.99), early dysphagia screening (OR: 0.96; 95% CI, 0.93-0.98), early physiotherapy (OR: 0.96; 95% CI, 0.94-0.99), and early occupational therapy (OR: 0.96; 95% CI, 0.93-0.98) than Danish-born residents. Small absolute differences in overall quality of stroke care were found when comparing immigrants and Danish-born residents. Significant factors associated with greater likelihood of stroke care included high income, high education, and cohabitation.Immigrants had lower chances of early stroke unit admission and received fewer individual early stroke care processes such as dysphagia screening, physiotherapy and occupational therapy than Danish-born residents. However, the absolute disparities were in general minor and largely influenced by socioeconomic status and cohabitation.

AIM: To explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I-EWS) are used and how they support nurses' patient risk assessment practice.DESIGN: A qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019.METHODS: Data were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts.RESULTS: NEWS and I-EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I-EWS had the effect of enhancing nurse autonomy and responsibility for decision-making in relation to patient care.CONCLUSIONS: EWS systems support nurses' patient risk assessment practice, providing useful information. I-EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses.IMPACT: The findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person-centred nursing care.

ImportancePsychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions.ObjectivesTo determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population.Design, Setting, and ParticipantsINTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress.ExposuresPsychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work.Main Outcomes and MeasuresThe association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control.ResultsAmong 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years; that of controls, 61.3 (13.3) years; 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58]; P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98]; P < .001 for interaction) for acute stroke.Conclusions and RelevancePsychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.

Introduction: The objective of the study was to assess use and persistence of secondary preventive treatment after ischemic stroke comparing immigrants and Danish-born residents. Patients and methods: A cohort of patients discharged with ischemic stroke (IS) diagnosis ( n = 106,224) by immigration status was identified from the Danish Stroke Registry between 2005 and 2018. We investigated use (claiming at least one prescription in 180 days post-discharge according to information from the Register of Medicinal Products Statistics) and persistence of treatment within 180 days thereafter using multivariable logistic regression and Fine and Gray models. Results: Overall, 82,078 Danish-born residents (80.6%) and 3589 (80.7%) immigrants with IS used at least one of the recommended preventive medications post-discharge. Immigrants had lower odds of use of anticoagulants and angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB) (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.53–0.82 and OR, 0.87; 95% CI, 0.75–0.98, respectively) but had higher odds of use of beta-blockers (OR, 1.25; 95% CI, 1.02–1.53) than Danish-born residents after adjustment for age at stroke, sex, sociodemographic factors, duration of residence, stroke severity, and comorbidities. The odds were most evident among immigrants originating from non-Western countries. Persistence of medication use did not differ between immigrants and Danish-born residents after adjustment for sociodemographic factors and comorbidities. Conclusion: Modest disparities in use of standard guideline recommended secondary preventive medications were observed when comparing immigrants and Danish-born residents with ischemic stroke. Furthermore, no differences in persistence of medication therapy were observed.

Supplemental Digital Content is available in the text., Background and Purpose: Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure. Methods: We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up. Results: At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24–0.81], P=0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P=0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P=0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts. Conclusions: The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00738894.

Introduction Human body functions exhibit a circadian rhythm generated in peripheral cells and synchronized by the suprachiasmatic nucleus (SCN), which mostly is entrained by the daily light/dark cycles. Activity, meals and posture are capable of interfering with the endogenous circadian rhythm of coagulation parameters. An increasing number of human disorders show a circadian component, and epidemiological studies find cardiovascular events to peak in the morning hours. The aim was to review the circadian rhythms impact on fibrinolysis and coagulation in healthy individuals and cardiovascular patients. Materials and methods A total number of 25 studies were identified where 8 enrolled cardiovascular patients with or without healthy individuals. Using a MeSH-search in MEDLINE PubMed. Only original peer-reviewed papers were included. Results Results showed substantial variance with respect to exhibition of circadian rhythms and/or peak/trough times. Circadian rhythms of fibrinolysis were less pronounced in cardiovascular patients than in healthy individuals with decreased levels in the morning hours compared to healthy inducing higher risk of blood clotting. Conclusions Because of small studied group sizes and failure to control for entraining factors, larger studies are needed to fully establish the effects of the circadian rhythm on especially coagulation. The findings of chronobiologic rhythms in coagulation and fibrinolysis could suggest a need for a chrono-pharmacological approach when treating/preventing cardiovascular diseases.

Sleep-disordered breathing (SDB) occurs frequently after stroke and is associated with poor functional outcome and increased mortality. The purpose of this study was to detect changes in SDB over time after acute ischemic stroke and investigate relationships between SDB and stroke etiologies with focus on cerebral small vessel disease. From May 2015 to August 2016, we conducted an observational study of 99 patients with mild to moderate stroke (median age: 68 years, range 36–88; 56% men). Polysomnography was performed within 7 days of stroke onset (n = 91) and after 6 months (n = 52). The strokes were classified using the etiological TOAST classification. Total small vessel disease (SVD) scores were calculated based on MRIs. SDB, defined as an apnea–hypopnea index (AHI) ≥ 15, was found in 56% of patients in the acute state and in 44% at follow-up. AHI decreased over time (median change 4.7, 95% confidence interval [95% CI] 0.5–8.9; p = 0.03). Patients with AHI ≥ 15 in both the acute state and at follow-up had higher SVD score at follow-up (p = 0.003). AHI was not associated with ischemic stroke subgroups according to the TOAST classification. In conclusion, 6 months after stroke, AHI decreased, but 44% still had AHI ≥ 15. Persistent SDB in both the acute state and at follow-up was associated with a higher SVD score, but not to the TOAST subgroups. SDB evaluation should be offered to stroke patients, and the effect of SDB on cerebral small vessel disease needs to be further investigated using the well-defined SVD score. clinicaltrials.gov NCT02111408, April 11, 2014

Introduction Maternal factors such as smoking during pregnancy, advanced age, and obesity are associated with increased risk of complex congenital heart defects in the offspring. It is unknown whether maternal risk factors may also cause subtle abnormalities in cardiac structure and function. Purpose To investigate whether the following maternal factors: advanced age, high body mass index (BMI), and smoking during pregnancy are associated with changes in left ventricle (LV) dimensions and systolic function in the newborn child. Methods Data was obtained as part of a population-based cohort study with prenatal inclusion and postnatal transthoracic echocardiography (TTE) of newborns within 60 days of birth. The TTE protocol included measurements of: Interventricular septal thickness at end-diastole (IVSd), LV posterior wall thickness at end-diastole (LVPWd), LV internal diameter at end-diastole (LVIDd) and LV internal diameter at end-systole (LVIDs). Fractional shortening (FS) was calculated by use of Teicholz's formula. Children of mothers with data available on age, BMI, and smoking status, respectively, were divided into the following groups depending on whether their mothers were: of young age Associations between different groups with each maternal risk factor and newborn LV parameters were analysed using a multiple linear regression model. Results Children of mothers with advanced age at the time of childbirth (n=1,411) had significantly smaller LVIDd and LVIDs (Table 1) compared to children of mothers in their early thirties (n=10,045). Children of preobese (n=4,707) and obese mothers (n=2,138) had significantly smaller LVIDd and LVIDs than children of mothers in the normal BMI range (n=17,654). Children of mothers who smoked during pregnancy (n=808) had significantly larger LVPWd than children of non-smoking mothers (n=24,072). A significant difference in FS was only seen in children of obese mothers. Subanalyses of the quantity of maternal smoking (available data in n=548 [67.8%] of mothers who smoked during pregnancy) showed that children of heavy smoking mothers (≥15 cigarettes/day, n=101), had significantly thicker IVSd and LVPWd compared with children of nonsmoking mothers, whereas no significant effect was identified in newborns of mothers smoking less than 15 cigarettes per day (Table 2). Conclusions Systematic population-based echocardiography of newborns showed that an increased maternal BMI and maternal age above 40 years were associated with smaller LV cavity dimensions in the offspring and that heavy smoking during pregnancy was associated with increased LV myocardial thickness. FS was only affected in children of obese mothers. The long-term effects of these novel findings are unknown. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Herlev-Gentofte Hospital Internal Funding for Cardiological Research andThe Novo Nordisk Foundation

Background Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 0.8% of new-borns. BAV is associated with valve dysfunction, as well as an increased risk of aortopathy. The prevalence of BAV in first-degree relatives of symptomatic BAV patients, is reported to be 5–10%. First-degree relatives also have an increased risk of aortic dilatation, independently of aortic valve morphology. Purpose The purpose of the study was to determine the prevalence of BAV, associated valve dysfunction and aortopathy in first-degree relatives to children diagnosed with BAV neonatally in a population-based study. Methods Between April 2016 and October 2018 all expecting parents at three major maternity centres were offered inclusion in a large-scale population study with focus on congenital heart disease (N≥25,000). A total of 197 children, in 196 families, were diagnosed with BAV. All first-degree relatives, including half-siblings, were offered inclusion in the follow-up study with standardized transthoracic echocardiography. Adults were also examined with transoesophageal echocardiography. Aorta diameters were measured at the AV annulus, sinuses of Valsalva, sino-tubolare junction and in the proximal ascending aorta. Aortic dilatation in children were defined as any aortic root or ascending aorta diameter ≥2 standard deviations (SD) from the expected mean, calculated as z-score using formulas from the Paediatric Heart Network Echocardiogram Database. In adults, aortic dilatation was defined as aortic root and/or ascending aorta diameters indexed to body surface area (BSA) exceeding normal reference values established by the European Association of Cardiovascular Imaging. Results In total, 352 first-degree relatives (242 adults [35.3 years SD 5.5] and 110 children [4.5 years, SD 3.5] were included. BAV was diagnosed in 24 relatives (6.8%). BAV could not be conclusively ruled out in 52 relatives (14.8%), who are awaiting further examination with transoesophageal echocardiography. Dilatation of the aortic root was observed in 8 adult relatives and in 17 children (7.1%). Aortic valve regurgitation was observed in 23 relatives (6.5%). In total 58 relatives (16.2%) were diagnosed with either BAV, dilated aorta, or aortic regurgitation. Conclusion One in fifteen first-degree relatives to children diagnosed with BAV neonatally, also had BAV, corresponding to >8 fold increase in prevalence compared with the background population. One in six relatives had BAV, dilated aorta, or aortic regurgitation. These findings are of importance for family-screening programs of BAV. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Children's Heart Association

Introduction Patency of the oval foramen (PFO) and atrial septal defects (ASDs), i.e. interatrial communications, have been reported to be present in 24–92% of newborns. For isolated ASDs, the reported prevalence varies from 0.3–2.4 per 1000 livebirths. This broad range partly reflects the absence of a clear and universal clinical classification of interatrial communications. On this basis we have recently proposed a clinically applicable echocardiographic algorithm for classification of interatrial communications (figure 1), which proved superior to standard assessment by experts in terms of inter- and intraobserver agreement. Purpose To determine the prevalence of interatrial communications in newborns. Methods Echocardiograms (TTEs) from newborns (0–30 days) included in a population study (N>25,000) were assessed/analyzed for interatrial communications according to the new algorithm and categorized into three PFO subtypes and three ASD subtypes. Results TTEs from 16,420 newborns were analyzed; 3,694 (22.5%) were excluded due to suboptimal image quality and 9 ( Conclusion An interatrial communication was present in almost 4 out of 5 newborns. ASD was diagnosed in 6% of the newborns and the prevalence of PFO was 12 times higher than the prevalence of ASD. Follow-up studies of these children are expected to provide clinically useful information on the long term structural and hemodynamic impact of these well categorized ASD and PFO subtypes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Candy's Foundation, The Danish Children's Heart Foundation

Background The incidence of infective endocarditis (IE) is increasing in the adult population, as is the insertion of prosthetic heart valves. Patients with prosthetic heart valves are considered at high risk of IE – a complication with a high mortality. However, data on temporal changes in the incidence of IE among patients with prosthetic heart valves from unselected cohorts are sparse Purpose We aimed to examine nationwide temporal trends in the incidence of IE in patients with an implanted prosthetic heart valve in Denmark from 1999 to 2018. Methods Using Danish nationwide health-care registries we identified all patients, who underwent heart valve implantation between 1996–2018. Crude annual incidence rates per 1,000 person years (PY) of IE were computed and presented in two year intervals. Analyses were stratified by sex and age groups (80 years). Results We identified 26,604 patients with first time prosthetic valve implantation with a median age of 72.7 years at the time of implantation, 63.1% were men with a median follow-up of 6.5 years. We found 1,442 cases of first time IE. The IE incidence rate ranged from 5.4 /1,000 PY (95% CI 3.9–7.4) in calendar period 2001–2002 to 10.0/1,000 PY (95% 8.84–11.11) in calendar period 2017–2018 with an unadjusted increasing trend during the study period (ptrend Conclusion The incidence of IE following prosthetic heart valve implantation has increased slightly over the last 20 years in Denmark. Funding Acknowledgement Type of funding sources: None.

Background Diastolic dysfunction (DD) in heart failure (HF) is associated with increased myocardial cytosolic calcium, and calcium-efflux via the sodium-calcium-exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR)-agonist lowers cytosolic sodium and has been shown to reverse organ congestion. Purpose To assess whether β3-AR-agonist treatment improves DD. Methods In a first-in-man randomized controlled, double-blind trial, we assigned 70 patients with HF with reduced ejection fraction (HFrEF) (NYHA II–III) and LVEF Results Baseline and follow-up echocardiographic data were available in 57 patients (59±11 years, 88% male, 49% ischemic heart disease). Baseline LVEF was 34%±8%. No significant change in DD grade was found between the groups at follow-up, p=0.72. Neither was there any clinical differences in any singular diastolic parameters within or between groups by echocardiography (E/e' placebo: 13.3±6.9 to 12.6±5.1, p=0.19 vs. mirabegron: 12.0±5.7 to 12.8±7.9, p=0.67, mean difference 1.12 [95% CI −1.68 to 4.3], p=0.37), or CCT (left atrial max volume index: between group mean difference 0.2 [95% CI −6.2 to 5.6] ml/m2, p=0.91). Conclusions In patients with HFrEF, no improvement nor worsening in DD gradings or singular diastolic parameters after β3-AR stimulation compared to placebo were identified. The findings add to previous literature questioning the role of impaired Na+-Ca2+ mediated Ca2+ export as a major culprit in DD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Heart Centre Research Foundation, RigshospitaletThe Novo Nordic Foundation

Background and introduction Maternal pre-existing and gestational diabetes affect approximately 6% of all pregnancies in Denmark and are well known risk factors for congenital heart disease (CHD). Worldwide, CHD is the most common congenital defect and a leading cause of infant death. The association between maternal diabetes, and CHD in the offspring has previously been studied, however, these studies have been limited by small study cohorts and/or registry studies without systematic transthoracic echocardiography (TTE) of the children. Purpose To assess the prevalence of atrial and ventricular septal defects (ASD and VSD) in children born to mothers with pre-existing or gestational diabetes by systematic TTE, in a large, population-based cohort of neonates. Method Systematic, standardized TTE was performed in neonates included in a population-based cohort study between 2016 and 2018. For the present study, the prevalence of VSD in cases and controls was assessed in the entire cohort of neonates who underwent TTE within 30 days of birth, and in whom information regarding maternal diabetes was available (n=24,921). The prevalence of ASD was assessed in a sub-cohort of neonates (n=12,682) with the same inclusion criteria and in whom an interatrial communication had been classified as ASD or patent oval foramen according to a validated algorithm. ASD was defined as an interatrial communication with a defect size ≥4mm, a location in the inferior 1/3 of septum, or multiple communications. VSD was defined as flow across the interventricular septum in colour Doppler mode in one or more views. VSDs were classified as either muscular, perimembranous, or subarterial. Information about maternal pre-existing and gestational diabetes was collected from review of the mother's medical records and from an Obstetrical Database maintained by the participating hospitals. Cases were compared with controls, which here consists of the full cohort for VSD and sub-cohort for ASD, respectively, after excluding cases. Results The median age at examination of the entire cohort was 11 days [interquartile range (IQR) 7; 14] and 48% were female. The prevalence of VSD in children with maternal diabetes was 3.1% compared with 3.3% among children of mothers without maternal diabetes, RR 1.00 (95% CI 0.99–1.01, p=0.771). There was no difference between cases and controls when comparing the prevalence of subtypes of VSD (table 1). In the sub-cohort of 12,682 neonates assessed for ASD (median age at examination 12 days [IQR, 8; 15], 48% female), the presence of an ASD was found in 7.3% of cases compared to 5.9% among controls, RR 0.81 (95% CI 0.59–1.13, p=0.214). Conclusion In a large population-based cohort of infants, we did not find an increased risk for ASD or VSD, nor any of the subtypes of VSD, among children born to mothers with pre-existing or gestational diabetes as compared to controls. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): The Capital Region of Denmarks Research Fund.The Research Council of Herlev and Gentofte Hospital.

Background Our knowledge of changes in vegetation size throughout the course of infective endocarditis (IE) and the impact of persistent vegetations on mortality or embolization after completed antibiotic treatment is sparse. No study has previously investigated the prevalence or clinical impact of persistent vegetations on transthoracic echocardiography (TTE) at 6-months follow-up after ended IE treatment. Purpose To investigate the association between persistent vegetations at the 6-months TTE after treatment for IE and long-term prognosis as assessed in the POET trial. Methods The POET trial was a nationwide, multicenter RCT, randomizing 400 patients to either partial oral or intravenous (IV) antibiotic treatment of left-sided IE, after initial stabilization of infection using conventional IV therapy. A persistent vegetation was defined as a vegetation seen on 6-months follow-up TTE (4–7 months) after ended antibiotic treatment for IE. In the POET trial, primary outcome was defined as 1) all-cause mortality, 2) unplanned cardiac surgery, 3) embolic events or 4) relapse of bacteremia, in the 5-year follow-up period. Patients without TTE due to death or lack of available TTE were excluded. Results Out of 400 patients, 20 were excluded due to death during 6-months follow-up, and 201 were excluded due to unavailable TTE, leaving 179 TTEs for analysis. At 6-months follow-up, a persistent vegetation was seen in 30 patients (16.7%, 21 males (70%), mean age 69.6 years (SD 7.7)) (Table 1). Seventeen patients (56.7%) had a persistent vegetation on the aortic valve and 13 patients (43.3%) on the mitral valve. More patients without a persistent vegetation had undergone initial surgical treatment of IE than those with a vegetation (57.7 vs 23.3%, p=0.001). In all surgically treated patients with persistent vegetation at 6-months follow-up, the vegetation was found on another valve than the operated valve. The composite primary outcome from 6-months follow-up and until 5-year follow-up occurred in 8 patients (26.7%) with a persistent vegetation, compared to 38 patients (25.5%) (p=1.00) without. (Table 2) In patients randomized for peroral treatment, no significant difference in prevalence of persistent vegetation was found (15 patients (50%) with persistent vegetations vs. 74 patients (49.7%) without, p=1.00). Conclusion The occurrence of persistent vegetations at 6 months follow-up was 16.7%. There was no association between persistent vegetations at 6-months follow-up and the occurrence of the primary outcome after 5 years follow-up, suggesting that the risk associated with residual vegetations after end of antibiotic treatment is negligible after 6-months. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation

Background Myocardial development is still incomplete by the time of birth making the cardiomyocyte vulnerable in the perinatal period. However, little is known on whether perinatal factors affect the neonatal electrocardiogram, and if so, to what degree these effects persist in the neonatal period. Purpose To investigate the impact of maternal and perinatal factors on the neonatal electrocardiogram in a large unselected cohort of neonates. Methods In a multicentre, prospective, population-based cohort study, neonates underwent cardiac evaluation during the first month of life. Electrocardiograms and echocardiograms were obtained and systematically analysed. Medical and demographic information on the parents, pregnancy, and birth-related factors were registered, and the following perinatal risk factors were evaluated: maternal comorbidities, maternal BMI ≥25, use of assisted reproduction technology, parity, (preterm) premature rupture of membranes, placental disorders, abnormal foetus presentation, induction of labour with synthetic hormone, instrumental induction, administration of nitrous oxide, epidural/spinal administration, labour ≥24h, pushing stage ≥1h, Caesarean section, and instrumental delivery. Results A total of 15,928 singletons with normal echocardiograms were included (52% boys; median age at examination 11 days). The neonates were divided into groups by accumulated number of perinatal risk factors: 0 (n=1,587), 1 (n=3,718), 2 (n=4,026), 3–4 (n=4,998), and ≥5 (n=1,197), and differences in ECG parameters between the groups were analysed. Heart rate, QRS axis, uncorrected QT interval, QTcBazett, QTcFridericia, and maximum amplitudes in R-V1 and R-V6 differed across the five subgroups (all p Conclusion We observed a cumulative effect of perinatal risk factors including a significantly more left-shifted QRS axis, increased values of the QT interval, and higher amplitudes in R-V1 and R-V6 in the subgroup with ≥5 perinatal risk factors. These findings suggest a relatively lower right ventricular dominance pattern, discrete prolongation of the QT interval and increased myocardial mass of the right ventricle in neonates exposed to multiple perinatal risk factors. However, the absolute differences in ECG parameters were relatively small. These findings may be useful for identification of neonates with increased cardiovascular risk. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Department of Cardiology, Herlev-Gentofte Hospital, Internal Funding