Gentofte University Hospital Research Articles

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP

IntroductionThe primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer.Methods...

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study

Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. Department of Cardiology, Herlev and Gentofte University Hospital. For the Danish translation of the abstract see Supplementary Materials section.

Bleeding risk in female patients undergoing intravesical injection of onabotulinumtoxinA for overactive bladder: a Danish retrospective cohort study

Introduction and hypothesisWe aimed to examine the risk of bleeding in female patients undergoing intravesical onabotulinumtoxinA (BTX-A) treatments and provide clinical recommendations for the perioperative management of patients on antithrombotic therapy prior to BTX-A treatments.MethodsThis was a retrospective cohort of Danish female patients, who had their first BTX-A treatment because of an overactive bladder at the Department of Gynecology and Obstetrics, Herlev and Gentofte University Hospital, between January 2015 and December 2020. Data extraction was from an electronic medical journal system. BTX-A, Botox® Allergan was injected in the detrusor at 10–20 sites. Significant bleeding during or after a BTX-A treatment was defined as persistent macroscopic hematuria. Bleeding reporting was based on information obtained from journal notes.ResultsWe included 400 female patients, who had a total of 1,059 BTX-A treatments. Median age at first BTX-A treatment was 70 years (IQR 21), and median number of BTX-A treatments was 2 (range 1–11). In total, 27.8% (n=111) received antithrombotic therapy. Within this group, 30.6% and 69.4% were on anticoagulant and antiplatelet therapy. No cases of hematuria were reported in our cohort. We found that no patients stopped their antithrombotic therapy, were bridged, or monitored by International Normalized Ration (INR) levels.ConclusionsWe suggest that BTX-A treatments might be classified as low-risk procedures. Discontinuation of antithrombotic therapy is not required in the perioperative management of this patient group.

Discontinuation and reinitiation of SGLT-2 inhibitors and GLP-1R agonists in patients with type 2 diabetes: a nationwide study from 2013 to 2021.

Small observational studies have observed poor persistency to sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucacon-like-peptide-1-receptor agonists (GLP1-RA), contrary to what has been reported in clinical trials. Therefore, we investigated the risk of discontinuing SGLT2-is and GLP1-RAs in patients with type 2 diabetes (T2D) in a nationwide population. From Danish nationwide registers, all first-time users of SGLT2-is and GLP1-RAs from 2013 to 2021 were identified. Adherence over the first year of therapy, the five-year risk of discontinuing therapy for the first time and the subsequent one-year probability of reinitiating therapy, was assessed. The Aalen-Johansen estimator was used to account for censoring and competing risks and multivariable Cox regression models were used to identify covariates associated with discontinuation. A total of 77,745 first-time users of SGLT2-is (64% male, median age 64 [interquartile range 56-72]) and 56,037 first-time users of GLP1-RAs (56% male, median age 61 [53-70]) were included. The absolute five-year risk of discontinuing therapy was 56% (95% CI: 55-57) and 45% (45-46) for SGLT2-i- and GLP1-RA users, respectively, with a significantly decreased risk over the period studied. The subsequent one-year probability of reinitiating therapy was 24% (95% CI: 24-25) for initial SGLT2-i users and 26% (25-27) for GLP1-RA users. Approximately half of the users of SGLT2-is and GLP1-RAs discontinued therapy within five years, respectively. However, a large proportion of these patients reinitiated therapy during the following year. Further insight into the reasons for discontinuation and initiatives to reduce the time to reinitiation in eligible patients are warranted. The work was funded by an unrestricted research grant from 'Department of Cardiology, Herlev and Gentofte University Hospital'.

The prognostic value of the ratio of early transmitral filling velocity to early diastolic strain rate in a large general population cohort

Abstract Background The ratio of early transmitral filling velocity (E) to early diastolic strain rate (e'sr) (E/e'sr) has recently been proposed as a novel non-invasive measure of early LV filling pressure. Using two-dimensional speckle tracking derived e'sr instead of Doppler-derived e' circumvents several of the limitations known to the Doppler-based method including angle-dependency and the high susceptibility to sampling location. The prognostic value of E/e'sr in relation to cardiovascular morbidity and mortality has previously been demonstrated in a range of specific patient populations including patients with type 2 diabetes, heart failure, atrial fibrillation, and a smaller general population study. Purpose To investigate the prognostic value of E/e'sr in relation to major adverse cardiovascular events (MACE) in a large low-risk general population. Methods A total of 3,782 participants were included in the present study. All participants had a comprehensive echocardiographic examination performed and analyzed. Two-dimensional speckle tracking analysis was performed to determine e'sr. Additionally, participants answered a questionnaire and underwent a general health examination. The outcome was MACE defined as a composite of incident heart failure, acute myocardial infarction, and cardiovascular death. Cox proportional hazards regression models were used to assess the relationship between E/e'sr and MACE. Results The mean age of the study population was 56±17 years and 57.2% were female. Mean E/e'sr was 63.4±19.6cm, mean E/e' was 7.6±2.8, and mean left ventricular ejection fraction was 56.8±5.9%. During follow-up (median: 3.5 years, IQR: 2.6, 4.3) a total of 133 (3.5%) met the composite outcome. Increasing E/e'sr was significantly associated with MACE in a univariable model (Figure 1) with a Harrel's C-statistic of 0.73. Increasing E/e'sr remained significantly associated with MACE in a multivariable model adjusted for age, sex, smoking status, hypercholesterolemia, hemoglobin, diabetes, history of ischemic heart disease, hypertension, heart rate, LVEF &amp;lt;50%, systolic blood pressure, and left atrial volume index (HR=1.09 [95% CI: 1.03; 1.16], p=0.002, per 10cm increase). A total of 824 participants had an E/e' in the indeterminate zone (E/e' between 9 and 14). In this subgroup, E/e'sr remained significantly associated with MACE (HR=1.14 [95% CI: 1.01; 1.29], p=0.038, per 10cm increase). This was also the case in all participants with a E/e &amp;lt;14 (n=3,649) (HR=1.12 [95% CI: 1.02; 1.23], p=0.018, per 10cm increase). Conclusion In this large general population sample, E/e'sr provides independent prognostic information in relation to MACE. This was even the case in participants with normal E/e'. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital

Increased risk of out-of-hospital cardiac arrest in patients with congenital heart disease: a nationwide study

Abstract Background The last four decades witnessed substantial improvements in treatment of congenital heart disease (CHD) leading to most children surviving into adulthood. Currently, the number of adults with CHD surpasses that of children. The shift in the CHD population's age composition necessitates focusing on long-term problems. A significant, but not well-investigated, issue is the risk of out-of-hospital cardiac arrest (OHCA) in adults with CHD. Purpose To investigate overall and temporal changes in the rate of OHCA associated with CHD compared with the general population. Method We conducted a nested case-control study matching all adult patients with OHCA of presumed cardiac cause between 2001 and 2015 with up to five controls from the entire Danish population on age, sex, date of OHCA and cardiac comorbidities status (at least one among ischemic heart disease, heart failure and presence of implantable cardioverter-defibrillator). Patients with CHD were identified using in- and out-patient hospital diagnoses any time prior to OHCA and divided into two mutually exclusive subgroups, either non-severe or severe CHD. The subclassification of CHD is based on a hierarchical approach previously used, where at least one severe CHD diagnosis is required to be classified as severe. We used Cox regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI) of OHCA. We stratified on CHD status (non-severe, severe or control), sex and OHCA year group (2001–2008 vs 2009–2015). Results We included 35,005 OHCA cases and 175,025 controls: the median age was 72 years, 66.9% were male and 34.6% had cardiac comorbidities. In total, among cases, we identified 103 patients with non-severe CHD and 51 with severe CHD, while, among controls, 247 with non-severe CHD and 69 with severe CHD. Both non-severe and severe CHD were overall associated with higher rates of OHCA compared with the general population: HR 2.11 (95% CI, 1.68–2.66) and HR 3.93 (95% CI, 2.71–5.69), respectively (Figure A). We found similar results when we stratified the analyses according to the presence of cardiac comorbidities at date of OHCA (Figure B) and sex. When stratified by OHCA year group, we observed stable rates of OHCA associated with non-severe CHD: from HR 2.03 (95% CI, 1.36–3.03) in the period 2001–2008 to HR 2.15 (95% CI, 1.62–2.86) in the period 2009–2015. Conversely, we observed a trend towards decreasing rates of OHCA associated with severe CHD: from HR 5.04 (95% CI, 2.79–9.11) in the period 2001–2008 to HR 3.10 (95% CI, 1.80–5.19) in the period 2009–2015 Conclusions Non-severe and severe CHD were both associated with higher rates of OHCA compared with the general population. While we observed decreasing rates of OHCA over calendar year for severe CHD, they remained stable for non-severe CHD. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital, Hellerup, Denmark

Risk of acute myocardial infarction, stroke and thromboembolism following COVID-19 vaccination compared to testing positive for COVID-19 infection: a nationwide cohort study of 4.6 mio individuals

Abstract Background Large randomized controlled trials (RCT) have shown that COVID-19 vaccines are effective at preventing severe COVID-19. However, the RCT's are not powered to detect rare adverse events. It has been reported that the new mRNA based COVID-19 vaccines may increase the risk of thromboembolic and ischemic events. Likewise, thromboembolic and ischemic events are also known complications to infection with SARS-CoV-19. Currently, less is known about the risk-reward relationship of receiving an mRNA-based COVID-19 vaccine versus contracting COVID-19 infection with respect to thromboembolic and ischemic outcomes. Purpose To compare the risk of thromboembolic and ischemic events following COVID-19 vaccination to the risk following infection with SARS-CoV-19. Methods The study period was from March 2020 to August 2021. All individuals were &amp;gt;18 years old. The population was stratified into two different groups. The vaccinated group consisted of recipients of the first dose of either Moderna (mRNA-1273, n=488,220) or Pfizer-BioNTech (BNT162b2 mRNA, n=3,186,164) vaccines. Individuals who had previously tested positive for SARS-CoV-19 were excluded. The other group consisted of individuals who had tested positive for SARS-CoV-19 in the same period who had not yet received their first vaccination dose (n=233,926). The exposure period for both groups was set to 28 days following vaccination/testing positive for SARS-CoV-19 (Figure 1). Patient level data were obtained on all included individuals using nationwide registries. Primary outcomes were acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism (PE), and deep venous thrombosis (DVT). Odds ratios were obtained from logistic regression models with the vaccinated group acting as reference. Multivariable models were adjusted for demographics and comorbidities. Results In the vaccinated group, mean age was 53±19 years and 50.3% were female. In the group of participants testing positive for SARS-CoV-19, mean age was 42.1±17.4 years and 50.2% were female. In total, 773 suffered a stroke, 472 suffered a PE, 500 suffered an AMI, and 484 suffered a DVT during the 28-day exposure period. We observed an increased absolute risk of all outcomes for participants testing positive for SARS-CoV-19 as compared to participants being vaccinated (stroke: 0.049% vs 0.019%, p&amp;lt;0.001), (PE: 0.91% vs 0.0072%, p&amp;lt;0.001), (AMI: 0.021 vs 0.013, p=0.0004), and (DVT: 0.037% vs 0.011%, p&amp;lt;0.001). In multivariable models, participants testing positive for SARS-CoV-19 had a significantly increased risk of all outcomes compared to participants being vaccinated: (stroke: OR: 4.0, 95% CI: [2.9–5.6], p&amp;lt;0.001), (PE: OR: 38.6 95% CI: [30.3–48.5], p&amp;lt;0.001), (AMI: OR: 3.3, 95% CI: [2.1–5.00], p&amp;lt;0.001), and (DVT: OR: 5.3, 95% CI: [3.8–7.5], p&amp;lt;0.001) (Figure 2). Conclusion The risks of thromboembolic and ischemic events were substantially higher after SARS-CoV-19 infection than after vaccination in the Danish population. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital

Case of the Month from Herlev and Gentofte University Hospital, Herlev, Denmark: Ablation of spermatogenesis due to acute spinal cord injury: a case report

Case of the Month from Herlev and Gentofte University Hospital, Herlev, Denmark: Ablation of spermatogenesis due to acute spinal cord injury: a case report

MP48-05 CHANGES IN PITUITARY–GONADAL HORMONES AFTER ENZALUTAMIDE OR ABIRATERONE PLUS PREDNISONE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER (HEAT): RESULTS FROM A RANDOMISED CLINICAL TRIAL

You have accessJournal of UrologyCME1 May 2022MP48-05 CHANGES IN PITUITARY–GONADAL HORMONES AFTER ENZALUTAMIDE OR ABIRATERONE PLUS PREDNISONE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER (HEAT): RESULTS FROM A RANDOMISED CLINICAL TRIAL Klara Ternov, Jens Sønksen, Mikkel Fode, Henriette Lindberg, Caroline Kistorp, Rasmus Bisbjerg, Jens Faber, Ganesh Palapattu, and Peter Busch Østergren Klara TernovKlara Ternov More articles by this author , Jens SønksenJens Sønksen More articles by this author , Mikkel FodeMikkel Fode More articles by this author , Henriette LindbergHenriette Lindberg More articles by this author , Caroline KistorpCaroline Kistorp More articles by this author , Rasmus BisbjergRasmus Bisbjerg More articles by this author , Jens FaberJens Faber More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , and Peter Busch ØstergrenPeter Busch Østergren More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Enzalutamide (ENZ) and abiraterone acetate plus prednisone (AAP) are both androgen receptor targeting treatments for metastatic castration-resistant prostate cancer (mCRPC). AAP inhibits the androgen production, whereas ENZ blocks the androgen receptor signalling. Herein, we compare treatment changes between ENZ and AAP in hormones of the pituitary–gonadal axis. METHODS: First-line ENZ (160 mg/day) and AAP (1000 mg abiraterone acetate and 10 mg prednisone/day) for mCRPC were compared in this randomised (1:1) phase IV trial. Eligible patients had progressive metastatic prostate cancer castrate levels of testosterone (<1.7 nmol/L). Fasting serum hormones, including testosterone, free-testosterone, sexual hormone binding globulin (SHGB), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), were measured by the gold standard assay liquid chromatography – tandem mass spectrometry before 11 am at baseline and at 12-week post-intervention. The treatment difference in changed hormones was compared with logarithmic mixed models analysis, and the within-subject change for each treatment group was analysed with logarithmic paired samples t-test. RESULTS: From June 2017 to September 2019, 170 participants were randomized to receive ENZ (n=84 analysed) or AAP (n=85 analysed). A 19.9% higher increase in FSH was found for ENZ than AAP. A larger decline in testosterone and SHGB was found for AAP than ENZ. More patients had lower than detectable levels of free-testosterone in the AAP group (83/85) than the ENZ group (6/84) (chi-square test p <0.001). CONCLUSIONS: In men with castrate-levels of testosterone, ENZ and AAP both inhibit the androgen stimulation of prostate cancer, but by different mechanism of action resulting in different pituitary–gonadal hormonal profiles. Source of Funding: Herlev and Gentofte University Hospital © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e821 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Klara Ternov More articles by this author Jens Sønksen More articles by this author Mikkel Fode More articles by this author Henriette Lindberg More articles by this author Caroline Kistorp More articles by this author Rasmus Bisbjerg More articles by this author Jens Faber More articles by this author Ganesh Palapattu More articles by this author Peter Busch Østergren More articles by this author Expand All Advertisement PDF DownloadLoading ...

Prognostic value of layer-specific global longitudinal strain in patients undergoing coronary artery bypass grafting

Abstract Background Recent improvements in speckle tracking echocardiography have made sectionalized quantification of layer-specific global longitudinal strain (GLS) possible. Prior studies have reported prognostic value of GLS in several cardiac diseases, however, the use of layer-specific strain has not been investigated in patients undergoing coronary artery bypass grafting (CABG). Purpose To determine the prognostic value of layer-specific GLS for predicting all-cause mortality after CABG. Methods In this retrospective cohort study, consecutive patients undergoing isolated CABG between 2006 and 2011 were included. The patients were followed through nation-wide registries for the endpoint of all-cause mortality. Multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics were used to assess the association between layer-specific GLS and all-cause mortality. Cumulative survival was stratified by clinical age and gender-dependent cut-off values for the layer-specific GLS, which was obtained from a large healthy population study. Results Of 641 patients included (mean age 67 years, 84% male), 70 (10.9%) died during follow-up (median 3.8 years [IQR: 2.7; 4.9 years]). Patients who died during follow-up were significantly older (71 years vs. 67 years, P = &amp;lt;0.001) and had a lower LVEF (46% vs. 51% P = &amp;lt;0.001). Endocardial GLS (GLSendo) (−14.2% vs. −16.3%, P&amp;lt;0.001), whole wall GLS (−12.1% vs. −13.9%, P&amp;lt;0.001), and epicardial GLS (GLSepi) (−10.6% vs. −12.2%, P&amp;lt;0.001) were all reduced in patients who died during follow-up, and patients with GLS below cut-off had a more than two-fold increased risk of all-cause mortality (Figure 1). The risk of dying increased linearly with decreasing absolute GLS for all layers (p&amp;lt;0.0002 for all layers), (Figure 2). In multivariable models, all layer-specific strain parameters remained significantly associated with all-cause mortality; GLSepi: HR=1.14 (1.05–1.23), p=0.002; GLS: HR=1.12 (1.04–1.20), p=0.002; GLSendo: HR=1.09 (1.03–1.16), p=0.003, per 1% absolute decrease. However, only GLSepi remained significantly associated with mortality when also adjusting for echocardiographic parameters (GLSepi: HR=1.12 (1.00–1.25), p=0.049, per 1% absolute decrease) and separately also after adjusting for the EuroScore II (GLSepi: HR=1.09 (1.00–1.18), p=0.043, per 1% absolute decrease). Conclusion Layer-specific GLS is an independent prognosticator of all-cause mortality after CABG. In multivariable models, GLSepi provided significant prognostic value after adjusting for echocardiographic parameters and EuroScore II. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Research grant from Herlev &amp; Gentofte University Hospital's internal research funds. Figure 1. Kaplan-Meier survival estimatesFigure 2. Incidence rate of all-cause mortality

Effects of Empagliflozin on Extracellular Volume, Plasma Volume, and Measured Glomerular Filtration Rate in Patients with Heart Failure: A Double-Blind, Randomised, and Placebo-Controlled Trial (Empire HF Renal)

Background: Sodium-glucose co-transporter-2 inhibitors are a promising new treatment option for patients with heart failure and reduced ejection fraction (HFrEF) with and without type 2 diabetes. We investigated the effects of empagliflozin on estimated extracellular volume (ECV), estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with HFrEF. Methods: Empire HF Renal was an investigator-initiated, double-blind, placebo-controlled, randomised trial with recruitment from four hospitals in Denmark. Patients in New York Heart Association class I-III, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or placebo once daily for 12 weeks. The co-primary renal outcomes were the between-group difference in the change of estimated ECV, estimated plasma volume, and measured GFR from baseline to 12 weeks. The trial is registered at ClinicalTrials.gov (NCT03198585). Findings: Between June 29, 2017, and July 15, 2019, 391 patients were screened and 120 (31%) were assigned to empagliflozin or placebo; 59 (98%) in the empagliflozin group and 58 (97%) in the placebo group were included in the analyses. Significant reductions in estimated ECV, estimated plasma volume, and measured GFR with empagliflozin versus placebo were observed [estimated ECV; adjusted mean difference of change empagliflozin versus placebo -0·12 L; 95% confidence interval (CI) -0·18 to -0·05, P=0·0006. Estimated plasma volume; -7·3%; 95% CI -10·3 to -4·3, P<0·0001. Measured GFR; -7·5 mL/min; 95% CI -11·2 to -3·8, P=0·0001]. These findings were consistent across important clinical heart failure subgroups. In the empagliflozin group, five patients (8·3%) had one or more serious adverse events, versus three patients (5·0%) in the placebo group. Interpretation: In patients with HFrEF, empagliflozin reduced estimated ECV, estimated plasma volume, and measured GFR after 12 weeks. Trial Registration Number: The trial is registered with ClinicalTrials.gov (number NCT03198585) and EudraCT (number 2017-001341-27). Funding: This work was supported by the Research Council at Herlev and Gentofte University Hospital, Herlev, Denmark [institutional research grant]; the Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark [institutional research grant]; the Capital Region of Denmark, Copenhagen, Denmark [grant number A6058]; the Danish Heart Foundation, Copenhagen, Denmark [grant numbers 17-R116-A7714-22076, 18 R124-A8573-22107]; the A.P. Moller Foundation for the Advancement of Medical Science, Copenhagen, Denmark [grant number 17-L-0002]. Conflict of Interest: JJ reports grants from the Research Council at Herlev and Gentofte University Hospital, Denmark, grants from the Research and Innovation Foundation of the Department of Cardiology ((FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Denmark, and grants from the A.P. Moller Foundation for the Advancement of Medical Science, Denmark, during the conduct of the study. MO reports grants from The Steno Diabetes Center Odense, Denmark, during the conduct of the study. CK reports personal fees from scientific advisory panel and speaker fees from Boehringer Ingelheim, Merck, Sharp & Dohme, AstraZeneca, Amgen, Novartis,Novo Nordisk, and Shire, outside the submitted work. CT has nothing to disclose. IG has nothing to disclose. LK reports personal fees from speaker honorarium from Novartis, AstraZeneca, Novo Nordisk, and Boehringer Ingelheim, outside the submitted work. FG reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Orion Pharma Abbott, Bayer, AstraZeneca, and Carmat, outside the submitted work. JF has nothing to disclose. MEM has nothing to disclose. ELF has nothing to disclose. NEB has nothing to disclose. JLF has nothing to disclose. LTJ has nothing to disclose. JEM reports grants and personal fees from Abiomed, personal fees from Novartis, and Orion Pharma, outside the submitted work. MS reports grant from The Capital Region of Denmark, and grants from The Danish Heart Foundation, during the conduct of the study; personal fees and non-financial support from AstraZeneca, personal fees from Novo Nordisk and Boehringer Ingelheim, outside the submitted work. Ethical Approval: The trial was approved by the local ethics committee, and all patients provided written informed consent (Danish National Committee on Health Research Ethics, number H-17010756).

Maintaining control: A qualitative study of being a patient in need of specialized palliative care during the COVID-19 pandemic

Being a patient in need of specialized palliative during the COVID-19 pandemic is challenging. Governments around the world have reduced the available health care services as well as restricted in-person meetings between patients, health care professionals, and relatives. The aim of this study was to explore the experiences of patients with specialized palliative care needs during the period of restrictions requiring social distancing due to the COVID-19 pandemic. The analysis of this qualitative study was guided by a grounded theory approach. The participants were patients living in their own homes who were being treated by the outpatient clinic palliative care unit at the Herlev and Gentofte University Hospital in Denmark. Participants’ main concern was maintaining control during the pandemic. They achieved this by aiming to secure a meaningful life by remaining occupied during the day, balancing social contact, contemplating the reopening of society, and seeking help from health care professionals. Participants were concerned about losing control and this concern increased with the reopening of society. Health care professionals must ensure that they provide support and care for patients with specialized palliative care needs when societal restrictions change.

Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial

SGLT2 inhibitors are a promising treatment option in patients with heart failure and reduced ejection fraction. We aimed to investigate the effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with heart failure and reduced ejection fraction. Empire HF Renal was a prespecified substudy of the investigator-initiated, double-blind, randomised, placebo-controlled Empire HF trial. The study was done at Herlev and Gentofte University Hospital (Herlev, Denmark), with patients recruited from four Danish heart failure outpatient clinics. Patients with New York Heart Association class I-III symptoms, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or matched placebo once daily for 12 weeks. The allocation sequence was computer-generated. Patients and study investigators were masked to treatment allocation. The coprimary prespecified renal outcomes were the between-group difference in the changes in estimated extracellular volume, estimated plasma volume, and measured GFR from baseline to 12 weeks. All analyses were done in the intention-to-treat population (apart from safety analyses, which were done in patients who received at least one dose of study drug), with no interim analyses done during the trial. The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585, and EudraCT, 2017-001341-27. Between June 29, 2017, and July 15, 2019, we assessed 391 patients for eligibility, of whom 120 (31%) were randomly assigned to empagliflozin or placebo, including 105 (88%) without diabetes. In intention-to-treat analyses, 60 (100%) patients in the empagliflozin group and 59 (98%) patients in the placebo group were included for estimated extracellular volume and estimated plasma volume, and 59 (98%) patients in the empagliflozin group and 58 (97%) patients in the placebo group were included for measured GFR. Empagliflozin treatment resulted in reductions in estimated extracellular volume (adjusted mean difference -0·12 L, 95% CI -0·18 to -0·05; p=0·00056), estimated plasma volume (-7·3%, -10·3 to -4·3; p<0·0001), and measured GFR (-7·5 mL/min, -11·2 to -3·8; p=0·00010) compared with placebo. Five (8%) of 60 patients in the empagliflozin group and three (5%) of 60 patients in the placebo group had one or more serious adverse events. In patients with heart failure and reduced ejection fraction, empagliflozin reduced estimated extracellular volume, estimated plasma volume, and measured GFR after 12 weeks. Fluid volume changes might be an important mechanism underlying the beneficial clinical effects of SGLT2 inhibitors. Research Council at Herlev and Gentofte University Hospital, Research and Innovation Foundation of the Department of Cardiology at Herlev and Gentofte University Hospital, Capital Region of Denmark, Danish Heart Foundation, and AP Møller Foundation for the Advancement of Medical Science.

P2442Myocardial performance index predicts mortality in people with obstructive lung function from the general population

Abstract Background Forced expiratory volume in one second (FEV1) is a significant predictor of mortality in patients with obstructive lung function (OL). Whether echocardiography can be used to identify patients at high risk, and whether it provides incremental prognostic information on mortality in patients with OL, remains unknown. Methods In a large, low-risk general population study, 1873 participants underwent a health examination with spirometry and echocardiography, including tissue Doppler imaging (TDI). The myocardial performance index (MPI) was calculated as the sum of the isovolumic contraction time (IVCT) and the isovolumic relaxation time (IVRT) divided by the left ventricle ejection time (LVET). Spirometry included measurements of (FEV1) and the forced vital capacity (FVC). OL was defined as FEV1/FVC &lt;0.70. The primary endpoint was all-cause mortality. Results The mean age was 59±16 years, 57% were women, 43% had hypertension, 11% had diabetes, and 6% had ischemic heart disease. Of the 1873 included participants, 288 (15%) were classified as having OL at baseline. During follow up (median 13.7 years (IQR 13.2–16.2)), 584 (31%) persons died, hereof 178 (62%) in the subgroup of participants with OL and 406 (26%) in the subgroup of participants with normal lung function. OL was associated with presence of left ventricular hypertrophy (higher left ventricular mass index), impaired diastolic function (lower E, higher A, lower E/A ratio, longer deceleration time, lower e' and higher E/e'), lower global longitudinal strain, and higher MPI. In unadjusted analysis, higher MPI was associated with all-cause mortality for participants with OL (HR=1.18 (1.11–1.26), p&lt;0.001, per 0.1 increase) and for participants with normal lung function (HR=1.42 (1.34–1.50), p&lt;0.001, per 0.1 increase). The predictive value of MPI was significantly modified by the presence of obstructive lung function (p&lt;0.001). After multivariable adjustment for age, sex, FEV1/FVC, heart rate, systolic blood pressure, smoking status, body mass index (BMI), hypertension, diabetes, ischemic heart disease, ischemic stroke and heart failure at baseline, MPI remained an independent predictor of all-cause mortality (HR=1.19 (1.06–1.34), p=0.004, per 0.1 increase) for participants with OL but not for participants with normal lung function (HR=1.02 (0.94–1.11), p=0.598, per 0.1 increase). When adding the MPI to the updated Age, Dyspnea and Obstruction (ADO) index, MPI provided incremental prognostic information beyond the updated ADO index, as determined from a significant increase in the Harrell's C-statistics (0.785 to 0.792, p=0.003). Conclusion Presence of OL is associated with subtle impairment of left ventricular systolic function, impaired left ventricular diastolic function, and higher MPI. MPI is an independent predictor of mortality in people with OL and provides incremental prognostic information regarding all-cause mortality in this population. Acknowledgement/Funding Herlev &amp; Gentofte University Hospital PhD fund

1347The flu vaccine and mortality in hypertension. A Danish nationwide cohort study

Abstract Background Influenza infection is associated with an increased risk of acute myocardial infarction (AMI) and stroke. It is currently unknown whether influenza vaccination may reduce mortality in patients with hypertension. Purpose To determine whether influenza vaccination is associated with lower risks of death in hypertensive patients without significant cardiovascular or other chronic disease. Methods Using nationwide registers, we identified all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007–2016 who were treated with at least 2 different classes of antihypertensive medication (beta-blockers, diuretics, calcium antagonists or renin-angiotensin system inhibitors). Patients who were not 18–100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Prior to each influenza season we assessed the exposure to influenza vaccination. End-points were death from all causes, from AMI or stroke, or cardiovascular death. For each season, patients were followed from December 1 until April 1 the next year, spanning the period of high influenza activity in Denmark. Results A total of 608,452 Patients were followed for a median of 5 seasons (interquartile-range: 2–8 seasons), with total follow-up time of 975,902 person-years. The vaccine coverage during study seasons ranged from 26% to 36%. During follow-up, 21,571 patients died of all-causes (3.5%), 12,270 patients died of cardiovascular causes (2.0%) and 3,846 patients died of AMI/stroke (0.6%). Vaccination was associated with older age, Diabetes Mellitus, atrial fibrillation, lower educational level, lower income and higher medication use. In unadjusted analysis considering all seasons, vaccination was significantly associated with increased risk of all-cause death, cardiovascular death and death from AMI/stroke. However, following adjustment for season, age, sex, comorbidities, medications, income, education, and more, vaccination was significantly associated with reduced risks of all-cause death, cardiovascular death and death from AMI/stroke (Figure). PY, person-years. Conclusion In a nationwide study spanning 9 consecutive influenza seasons including more than 600,000 hypertensive patients without significant cardiovascular disease identified through medication use, influenza vaccination was significantly associated with a reduced risk of death from all-causes, cardiovascular causes and AMI/stroke. Influenza vaccination may improve patient outcome in hypertension. Acknowledgement/Funding Daniel Modin was supported by the Herlev &amp; Gentofte University Hospital Internal Research Fund and by the Novo Nordisk Foundation.

Factors Associated with Long-Term Outcome in 191 Patients with Ilio-Femoral DVT Treated With Catheter-Directed Thrombolysis

To identify factors associated with long-term treatment success after catheter-directed thrombolysis (CDT) for acute deep venous thrombosis (DVT) involving the ilio-femoral vein. This was a non-randomised observational cohort study. From 1999 to 2013, 191 consecutive patients (203 limbs) attending a tertiary vascular centre at Gentofte University Hospital, Denmark underwent CDT. All patients had ultrasonically verified acute ilio-femoral DVT with open distal popliteal vein and calf veins. Patients were seen in the outpatient clinic 6 weeks, 3, 6, and 12 months, and annually thereafter following the DVT. Successful outcome was defined as patent deep veins without reflux on Duplex ultrasound scanning (DUS). Data were collected prospectively as per protocol and analysed retrospectively. Median age was 27 years (range 14-74 years) and overall median lysis time was 56 h (range 22-146 h). A stent was placed in 106 limbs (52%). Six patients had major bleeding. The median follow-up was 5 years (range 1 month-14.3 years). The cumulative rate of patients with deep patent veins without reflux at 7 years was 79%. Multivariate Cox regression analyses showed that symptom duration >2 weeks (hazard ratio (HR) 2.78, 95% CI 1.14-6.73) and chronic post-thrombotic lesions (HR 19.3, 95% CI 7.29-51.2) were significantly associated with poorer outcome, while the pulse-spray technique (HR 0.15, 95% CI 0.05-0.48) was associated with better outcome. Age, gender, side, IVC atresia, stenting, and lysis duration did not affect outcome. In this observational study of CDT for ilio-femoral DVT it was demonstrated that symptom duration less than 2 weeks, absence of chronic post-thrombotic lesions and use of the pulse-spray technique for CDT resulted in better primary patency including normal valve function in the long term.

Editor's Choice – Factors Associated with Long-Term Outcome in 191 Patients with Ilio-Femoral DVT Treated With Catheter-Directed Thrombolysis

To identify factors associated with long-term treatment success after catheter-directed thrombolysis (CDT) for acute deep venous thrombosis (DVT) involving the ilio-femoral vein. This was a non-randomised observational cohort study. From 1999 to 2013, 191 consecutive patients (203 limbs) attending a tertiary vascular centre at Gentofte University Hospital, Denmark underwent CDT. All patients had ultrasonically verified acute ilio-femoral DVT with open distal popliteal vein and calf veins. Patients were seen in the outpatient clinic 6 weeks, 3, 6, and 12 months, and annually thereafter following the DVT. Successful outcome was defined as patent deep veins without reflux on Duplex ultrasound scanning (DUS). Data were collected prospectively as per protocol and analysed retrospectively. Median age was 27 years (range 14-74 years) and overall median lysis time was 56h (range 22-146h). A stent was placed in 106 limbs (52%). Six patients had major bleeding. The median follow-up was 5 years (range 1 month-14.3 years). The cumulative rate of patients with deep patent veins without reflux at 7 years was 79%. Multivariate Cox regression analyses showed that symptom duration >2 weeks (hazard ratio (HR) 2.78, 95% CI 1.14-6.73) and chronic post-thrombotic lesions (HR 19.3, 95% CI 7.29-51.2) were significantly associated with poorer outcome, while the pulse-spray technique (HR 0.15, 95% CI 0.05-0.48) was associated with better outcome. Age, gender, side, IVC atresia, stenting, and lysis duration did not affect outcome. In this observational study of CDT for ilio-femoral DVT it was demonstrated that symptom duration less than 2 weeks, absence of chronic post-thrombotic lesions and use of the pulse-spray technique for CDT resulted in better primary patency including normal valve function in the long term.

Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial

Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of thisanalysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin. In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24-week depot injections. Androgen status was measured by liquid chromatography-tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression. Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2-41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups. The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.

Contact allergy to chlorhexidine in a tertiary dermatology clinic in Denmark.

Chlorhexidine is a widely used disinfectant in the healthcare setting and in cosmetic products. A high prevalence of chlorhexidine contact allergy was reported in Denmark in the 1980s (2.0-5.4% of patients patch tested). It is unknown whether the prevalence is still high, which products cause the contact allergy, and whether accidental re-exposure occurs in some patients. To estimate the prevalence of chlorhexidine contact allergy in a tertiary dermatology clinic in Denmark; to investigate whether patch testing with both chlorhexidine diacetate and chlorhexidine digluconate is necessary; to investigate how many patients have combined immediate-type allergy and contact allergy; and to identify which products cause chlorhexidine contact allergy, and whether patients are accidentally re-exposed. This was a retrospective study including all patients patch tested with chlorhexidine during 2003-2013 at the Department of Dermato-Allergology at Copenhagen University Hospital Gentofte (n = 8497). All patients with a positive patch test reaction to chlorhexidine were sent a questionnaire comprising questions about the cause of the allergy and re-exposure. Overall, 1.0% (n = 82) of all patients patch tested with chlorhexidine were positive. A decrease in the prevalence was observed over time, most likely because of lowering of the test concentration from 1.0 to 0.5% in 2008. Of the 82 patients, 28 (0.3%) had positive test reactions to both chlorhexidine salts, 43 (0.5%) had a positive test reaction only to chlorhexidine diacetate, and 11 (0.1%) had a positive test reaction to chlorhexidine digluconate. Three patients were both patch test-positive and prick test-positive. A known cause of the allergy was reported by 19 patients (40%) in the questionnaire: the products used in the healthcare setting were mainly reported, but some reported cosmetic products. Accidental re-exposure was reported by 15 patients (32%), of whom 13 reported symptoms. The prevalence of chlorhexidine contact allergy does not seem to be higher in Denmark than in other European countries. Patch testing with both chlorhexidine diacetate and chlorhexidine digluconate may be beneficial. Testing for immediate-type allergy in patients with a positive patch test reaction to chlorhexidine is recommended. Chlorhexidine-containing products used in the healthcare setting and in cosmetics are potential causes of sensitization and allergy. Re-exposure is common, highlighting the fact that patients and healthcare personnel need to be well informed about possible sources of exposure.

Effectiveness of an Early Versus a Conservative Invasive Treatment Strategy in Acute Coronary Syndromes

Randomized clinical trials have found that early invasive strategies reduce mortality, myocardial infarction (MI), and rehospitalization compared with a conservative invasive approach in acute coronary syndromes (ACSs), but the effectiveness of such strategies in real-world settings is unknown. To investigate adverse cardiovascular outcomes of an early versus a conservative invasive strategy in a national cohort of patients with ACSs. Retrospective cohort study. Administrative health care data on hospitalizations, procedures, and outcomes abstracted from the Danish national registries and covering all acute invasive procedures in patients presenting with an ACS. 19704 propensity score-matched patients hospitalized with a first ACS between 1 January 2005 and 31 December 2011. Risk for cardiac death or rehospitalization for MI within 60 days of hospitalization. Compared with a conservative approach, early invasive strategies were associated with a lower risk for cardiac death (cumulative incidence, 5.9% vs. 7.6%; adjusted hazard ratio [HR], 0.75 [95% CI, 0.66 to 0.84]; P< 0.001). Similar results were found for rehospitalization for MI (cumulative incidence, 3.4% vs. 5.0%; adjusted odds ratio, 0.67 [CI, 0.58 to 0.77]; P< 0.001) and all-cause death (cumulative incidence, 7.3% vs. 10.6%; adjusted HR, 0.65 [CI, 0.59 to 0.72]; P< 0.001). Potential residual confounding due to lack of core clinical variables. In this real-world cohort of patients with a first hospitalization for an ACS, the use of an early invasive treatment strategy was associated with a lower risk for cardiac death and rehospitalization for MI compared with a conservative invasive approach. Department of Cardiology, University Hospital Gentofte.