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IntroductionSince 2007, transcatheter aortic valve implantation (TAVI) has emerged as another treatment strategy for severe symptomatic aortic stenosis (AS) compared with surgical aortic valve replacement (SAVR). The objectives were to compare annual rates of aortic valve replacement (AVR) procedures performed in Denmark in the era of TAVI and to assess proportion of AVRs stratified by age with use of age recommendations presented in current guidelines.MethodsUsing Danish nationwide registries, we identified first-time AVRs between 2008 and 2020. Patients who were not diagnosed with AS prior to AVR were excludedResultsThe rate of AVRs increased by 39% per million inhabitants from 2008 to 2020. TAVI has steadily increased since 2008, accounting for 64.2% of all AVRs and 72.5% of isolated AVRs by 2020. Number of isolated SAVRs decreased from 2014 and onwards. The proportion of TAVI increased significantly across age groups (<75 and ≥75 years of age, ptrend<0.001), and TAVI accounted for 91.5% of isolated AVR procedures in elderly patients (aged ≥75 years). Length of hospital stay were significantly reduced for all AVRs during the study period (ptrend all<0.001).ConclusionsThe number of AVRs increased from 2008 to 2020 due to adaptation of TAVI, which represented 2/3 of AVRs and more than 70% of isolated AVRs. In elderly patients, the increased use of AVR procedures was driven by TAVI, in agreement with the age recommendations in current guidelines; however, TAVI was used more frequently in patients aged <75 years, accompanied by a flattening use of SAVR.

•What is already known:•Much of the previous studies on infective endocarditis(IE) is often based on cohorts from tertiary hospitals or retrospective registry studies, which may not represent the whole IE population, creating a need for nationwide characterization.•What this study adds:•The NIDUS registry is a validated national cohort encompassing all IE cases in Denmark from 2016 to 2021, including 3,557 patients (79.6% classified as definite IE and 20.4% as possible IE).•It provides comprehensive insights into IE demographics, clinical features, comorbidities, and outcomes from a contemporary nationwide cohort: most patients presented with fever (61.1%), followed by dyspnea (33.0%) and myalgias (27.0%). Sepsis was identified in 828 (23.3%) patients, and 378 (10.6%) exhibited signs of embolization at admission.•In the NIDUS registry, in-hospital mortality was 17.3%, 1-year mortality reached 31.3%, 19.4% of the patients underwent surgical treatment during hospitalization, and Staphylococcus aureus was the most common pathogen. Most knowledge on infective endocarditis (IE) comes from large IE cohorts that include patients from tertiary hospitals, leading to referral bias and retrospective population-based studies. This highlights the need for a more detailed characterization of IE in unselected patient cohorts. In the National Danish Endocarditis Studies (NIDUS) registry, all hospitalizations in Denmark from 2016 to 2021 with an IE diagnosis were reviewed and validated using electronic medical records (EMR) by healthcare professionals under the supervision of IE experts. Episodes meeting the European Society of Cardiology 2015 modified diagnostic criteria for possible or definite IE were included. We screened 4390 unique patients, of whom 3557 (81%) were included in the NIDUS registry. Of the 3557 unique patients, 2832 (79.6%) were classified as definite IE and 725 (20.4%) as possible IE. The age was 73.7 years, and most patients were men (68.3%). In total, 689 (19.4%) underwent surgery during hospitalization. The most frequent comorbidities were diabetes (23.7%), heart failure (18.7%), and chronic kidney disease (17.4%). Most patients presented with fever (61.1%), followed by dyspnea (33.0%) and myalgias (27.0%). Sepsis was found in 828 (23.3%) patients, while 378 (10.6%) had signs of embolization at admission. Positive blood cultures were identified in 3191 (89.7%) patients, and the most frequent microbiological etiology was Staphylococcus aureus (31.9%). The in-hospital mortality was 17.3%, and the 1-year mortality rate was 31.3%. The NatIonal Danish endocarditis studies (NIDUS) registry provides comprehensive, granular, and nationwide data on a cohort of patients with infective endocarditis, revealing that when selection is not restricted to tertiary hospitals or voluntary registries, some important differences emerge. Patients with IE are on average older, have a similar burden of comorbidities, and less often undergo surgery. Minimizing selection bias with the use of a national registry provides a clearer picture of IE as it occurs in real-world clinical settings. [Display omitted]

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. 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. 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)). 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.

BackgroundBacteraemia and infective endocarditis (IE) are rare but severe complications of transcatheter aortic valve implantation (TAVI). Limited data exist on the incidence and microbiological profile of early bacteraemia in this population. This study aimed to evaluate the 6-month incidence of bacteraemia, IE and associated mortality following TAVI.MethodsUsing Danish nationwide registries, all patients who underwent TAVI from 2012 to 2021 were identified and matched 1:1 by age, sex and index year with patients who underwent elective coronary angiography (CAG). Outcomes were assessed with cumulative incidence functions and adjusted HRs.ResultsAmong 5990 patients with first-time TAVI (57% male, mean age 80 years, SD 6.9), bacteraemia occurred in 4.2% within 6 months, compared with 2.6% in the CAG group (adjusted HR 1.57, 95% CI 1.26 to 1.96). Common pathogens post-TAVI included Streptococci (20%), Coagulase-negative staphylococci (19%) and Enterococci (18%), differing from the CAG group, where Coagulase-negative staphylococci (22%) and Staphylococcus aureus (16%) predominated. IE developed in 1.1% of patients with TAVI versus 0.1% of patients with CAG (adjusted HR 20.01, 95% CI 5.97 to 67.48).ConclusionBacteraemia and IE rates are substantially elevated within 6 months following TAVI compared with elective CAG. The bacterial profile post-TAVI suggests that current prophylactic antibiotic regimens may not provide adequate coverage.

Abstract Aims Little is known about the mortality for patients with infective endocarditis (IE) on a nationwide scale, and previous studies have been conducted in selected cohorts from tertiary centers. We aimed to investigate temporal trends in mortality using nationwide Danish registries. Methods and results We identified patients with first-time IE between 1999–2018, and they were grouped by calendar periods (1999–2003, 2004–2008, 2009–2013, 2014–2018). One-year mortality was estimated using Kaplan–Meier estimates. For calendar periods, odds ratios (ORs) and hazard ratios (HRs) were computed using multivariable adjusted logistic regression and Cox proportional Hazards analyses for in-hospital and one-year mortality, respectively. We identified 8804 patients with IE. Age and proportions of men were: 66.7 (25th–75th percentile: 53.4–76.7) years and 59.9% in 1999–2003 and 72.8 (25th–75th percentile: 63.4–80.3) and 65.8% in 2014–2018. In-hospital mortality was 1999–2003: 24.5%, 2004–2008: 22.8%, 2009–2013: 18.8%, and 2014–2018: 18.3%. Relative to 1999–2003, adjusted likelihoods of in-hospital mortality were: OR = 0.81 (95% CI: 0.69–0.96) in 2004–2008, OR = 0.59 (95% CI: 0.50–0.69) in 2009–2013, and OR = 0.51 (95% CI: 0.43–0.60) in 2014–2018. By calendar periods, crude risks of one-year mortality were: 34.4% (95% CI: 32.0–36.8%), 33.5% (95% CI: 31.5–35.6%), 32.1% (95% CI: 30.2–34.0%), and 33.1% (95% CI: 31.3–34.8%). Relative to 1999–2003, adjusted rates of one-year mortality were: HR = 0.88 (95% CI 0.79–0.99) in 2004–2008, HR = 0.76 (95% CI: 0.68–0.86) in 2009–2013, and HR = 0.72 (95% CI: 0.64–0.81) in 2014–2018. Conclusion In this nationwide study of patients with first-time IE between 1999–2018, both short- and long-term survival has improved over time when accounting for changes in patient characteristics. One-sentence Summary When accounting for patient characteristics, both short- and long-term mortality have improved in patients with first-time infective endocarditis.

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.

BackgroundValvular surgery for infective endocarditis (IE) can improve survival but carries substantial risk. Limited data exist on long-term outcomes for patients who survive surgery compared with a background population. We aim to compare long-term mortality and morbidity in patients with IE, who survive 90-days following valvular surgery to a matched Danish background population.MethodsUsing Danish registries, we identified patients who survived >90 days post-valvular surgery for first-time IE (2010–2023). Each patient was matched 1:3 with controls from the background population by age, sex and selected comorbidities. All-cause mortality was assessed at 5 and 10 years using the Kaplan-Meier estimator and the multivariate Cox model. Further, we examined the time spent in hospital during the first year following the index date.ResultsWe identified 1050 patients (77.5% male, median age 65.8 years) surgically treated for IE and 3150 controls. The most common pathogens were: Viridans group streptococci (44.6%), Staphylococcus aureus (23.1%), Enterococci (17.9%). Patients with IE had higher absolute 5-year (20.1% vs 12.9%, p=0.001) and 10-year (38.5% vs 27.9%, p<0.001) mortality compared with controls. Adjusted 5-year and 10-year mortality rates were also higher in patients with IE (5-year HR=1.49 (95% CI 1.24 to 1.79) and 10-year HR 1.38 (95% CI 1.19 to 1.60)). Patients with IE experienced more frequent and longer hospitalisations within the first year postsurgery, as 36.8% patients with IE were hospitalised within the first year following index compared with 17.5% in the matched controls. 9.3% of patients with IE were hospitalised for >14 days compared with 3.0% in matched controls. 60 patients with IE (5.7%) died within the first year following index compared with 51 (1.6%) in the matched controls.ConclusionPatients with IE who underwent valve surgery had a higher crude mortality than their controls from the background population. After adjusting for confounders, 5-year and 10-year mortality rates remained higher in the IE patient population.

Background: Prosthetic valve endocarditis (PVE) is considered a serious complication of valve replacement, and worse outcomes have been reported for PVE versus native valve endocarditis (NVE). Comprehensive data on clinical presentation and practice patterns are lacking. Methods: The Danish NatIonal enDocarditis stUdieS (NIDUS) registry was used to obtain data on all patients with left-sided PVE or NVE from 2016–2021 in Denmark. Patients were classified as having a PVE or NVE according to the modified Duke criteria One-year mortality rates for PVE and NVE were assessed using the reversed Kaplan–Maier estimator and adjusted Cox’s regression models. Results: In total, 3017 patients were included, of which 791 (26.2%) had PVE and 2226 (73.8%) had NVE. In the PVE group, the median age was 76 years [IQR 70–82], and 74% were males. In the NVE group, the median age was 73 years [IQR 63–80], and 65% were males. The comorbidity burden was similar between groups. The median length of hospital stay was 44 days [IQR 28–52] for PVE and 34 days [IQR 24–45] for NVE. In the PVE group, 567 (74.8%) had definite IE vs. 1863 (82.5%) in the NVE group. At admission, the proportion of patients who presented with embolism (PVE 10.1% vs. NVE 12.5%) and sepsis (PVE 24.4% vs. NVE 23.2%) were comparable. The most common microbiological etiologies for PVE vs. NVE were Streptococcus spp. (30.2% vs. 33.8%), S. aureus (21.6% vs. 33.4%), and Enterococcus spp. (24.5% vs. 14.3%). Surgery during admission was performed in 23.4% of patients with PVE vs. 20.7% with NVE. The absolute risk of one-year mortality in patients with PVE was 30% [95% CI: 27–33], and for NVE, it was 35% [95% CI 33–37] (p = 0.0036), with an adjusted hazard ratio (HR) of 0.79 [95% CI 0.68–0.92], with p = 0.002. This difference between groups was mainly driven by those above the age of 70 years. Conclusions: This nationwide study showed that patients with PVE were older, had similar comorbidity burden, and had a longer length of hospital stay compared to patients with NVE. The PVE group had a numerically higher prevalence of Enterococcus spp. Although PVE is a severe condition, our findings indicate that the associated outcomes are more comparable to or even better than NVE than previously assumed, probably related to the unselected and nationwide nature of these data.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen–Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan–Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, “other microbiological etiologies”, and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Purpose Surgery is required in 20–50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). Methods We identified all IE patients who underwent surgery during admission (2010–2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores (< 5 points) and frail patients (≥ 5 points). We analyzed time hospitalized after discharge and all-cause mortality from the date of surgery with a one-year follow-up. Statistical analyses utilized the Kaplan–Meier estimator, Aalen–Johansen estimator, and the Cox regression model. Results We identified 1282 patients who underwent surgery during admission, of whom 967 (75.4%) had low frailty scores, and 315 (24.6%) were frail. Frail patients were characterized by advanced age, a lower proportion of males, and a higher burden of comorbidities. Frail patients were more hospitalized (> 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09–1.71]). Conclusion Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.