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.

Objective The incidence of infective endocarditis (IE) is increasing, as is the insertion of prosthetic heart valves. We aimed to examine nationwide temporal trends in the incidence of IE in patients with a prosthetic heart valve in Denmark from 1999 to 2018. Methods Using the Danish nationwide registries, we identified patients who underwent heart valve implantation (for other reasons than IE) between 1999 and 2018. Crude incidence rates of IE per 1000 person-years (PY) were computed in 2-year intervals. IE incidences were compared using sex-adjusted and age-adjusted incidence rate ratios (IRR) using Poisson regression across calendar periods (1999–2003, 2004–2008, 2009–2013, and 2014–2018). Results We identified 26 604 patients with first-time prosthetic valve implantation (median age 71.7 years (IQR 62.7–78.0), 63% males). The median follow-up time was 5.4 years (IQR 2.4–9.6). Patients in the time period 2014–2018 were older (median age of 73.9 years (66.2:80.3)), and with a higher burden of comorbidities compared with the time period 1999–2003 (median age of 67.9 years (58.3:74.5)) at the time of implantation. A total of 1442 (5.4%) patients developed IE. The lowest IE incidence rate was 5.4/1000 PY (95% CI 3.9 to 7.4) in 2001–2002, and the highest incidence rate was 10.0/1000 PY (95% CI 8.8 to 11.1) in 2017–2018 with an unadjusted increase during the study period (p=0.003). We found an adjusted IRR of 1.04 (95% CI 1.02 to 1.06) (p<0.0007) per two calendar-years increments. Age-adjusted IRR for men were 1.04 (95% CI 1.01 to 1.07) (p=0.002) per two calendar years increment, and for women 1.03 (95% CI 0.99 to 1.07) (p=0.12), with p=0.32 for interaction. Conclusion In Denmark, the incidence of IE increased during the last 20 years in patients with prosthetic heart valves.

BACKGROUND: Surgery is an essential treatment for selected patients with infective endocarditis (IE). Despite indications for surgery, not all patients undergo surgery. Most previous IE cohorts have examined a selected group of patients from primary tertiary centers. Thus, the aims of this study were to describe the use of surgery by indication and to assess mortality in a nationwide cohort of patients with left-sided IE. METHODS: This study was an observational cohort study including patients with left-sided IE from the National Danish Endocarditis Studies (2016-2021). Patients were categorized according to the presence of surgical indications defined as a Class I indication for surgery according to the 2015 European guidelines or a vegetation ≥10 mm on the diagnostic echocardiography and whether surgery was performed. One-year mortality was assessed with the 1-Kaplan-Meier estimator and multivariable Cox regression models. RESULTS: Among 3017 patients, 662 (21.9%; median age, 66.9 years) underwent surgery, 655 (21.6%; median age, 75.9 years) had surgical indications but received conservative treatment, and 1700 (56.5%; median age, 76.0 years) had no surgical indications. Patients who underwent surgery had fewer comorbidities and more streptococci, whereas conservatively treated patients had more comorbidities and Staphylococcus aureus . Patients with surgical indications who did not undergo surgery had the highest in-hospital (31.8% versus 12.5% versus 15.7%; P <0.001) and 1-year (50.5% versus 17.0% versus 33.5%, P <0.001) mortality compared with patients who underwent surgery and those without indications for surgery. Multivariable Cox models confirmed these findings. High surgical risk (22.8%) was the most reported reason for withholding surgery. CONCLUSIONS: In a nationwide consecutive cohort of patients with left-sided IE, 40% had indications for surgery according to guidelines, but only half of these underwent surgery. Surgically treated patients had the highest survival but were a decade younger, had fewer comorbidities, and had less frequent IE caused by S aureus. Thus, confounding by indication remains a limitation, and more studies are warranted to explore the management of patients at high surgical risk.

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.

Aims: Recent advancements in transcatheter aortic valve implantation (TAVI) and patient selection have significantly improved the outcomes of TAVI. Yet it is unknown whether patients undergoing TAVI in the modern era have comparable mortality as the general population. Methods and results: All patients undergoing TAVI in Denmark (2015–23) were matched on age and sex with controls from the general population (1:4). Patients were followed from 30-day post-TAVI until death or end of study (12/23). The 5-year all-cause mortality was examined by cumulative incidence functions and Cox-regression analyses. The 5-year all-cause hospitalization burden was analysed among those alive at 5-year post-index. The study included 7250 patients undergoing TAVI [median age 81.2 years (IQR 77.0–84.9), 57.3% men] and 29 000 controls. The absolute risk of death was 39.6% [95% confidence interval (CI) 38.1–41.2] in the TAVI group, compared to 32.2% (95% CI 31.5–32.9) among controls. The associated all-cause mortality was similar between patients undergoing TAVI and controls [adjusted hazard ratio 0.95 (95% CI 0.90–1.01)]. Stratification by age revealed a higher risk of death among the TAVI group aged <80 years compared with controls, while patients aged ≥80 years showed a lower risk of death. Patients undergoing TAVI experienced longer and more frequent hospitalizations compared with controls, while the relative difference decreased over time. Conclusion: Our findings suggest that TAVI was associated with long-term mortality and hospitalization rates comparable to the general population. Stratified by age, mortality was higher among TAVI patients <80 years and lower among those ≥80 years. These findings support patient selection, safety, and long-term outcomes of TAVI.

In patients undergoing heart valve surgery, subsequent bacteremia and infective endocarditis are feared events. Data on the incidence and bacterial microbiological etiology following left-sided heart valve surgery are sparse. Between 2010–2021, all patients undergoing left-sided valve surgery were identified using Danish nationwide registries. Incidence and type bacteremia within one-year post-surgery was analyzed. Secondary outcome of interest was infective endocarditis. Cumulative incidence curves were stratified for bacterial species and for subgroups of interest: type of valve surgery, age, and sex. A total of 14 935 patients were included, of which 69% were male and the median age was 70.4 years (25^th-75^th percentile 62.4–76.2 years). The one-year cumulative incidence of bacteremia was 6.1% (95% CI 5.7–6.5%), and the most frequent bacteremia was coagulase-negative staphylococci (27%). More than half of the bacteremia with coagulase-negative staphylococci occurred within 30 days of follow-up. Patients developing bacteremia had a significantly higher Charlson comorbidity score at baseline, more often underwent CABG concomitant to valve surgery, and more often had surgery on both valves. The one-year cumulative incidence of infective endocarditis was 1.5% (95% CI 1.3–1.7), of which 23% were caused by Enterococci, and 22% were blood culture negative. The median time from surgery to infective endocarditis was 109 days. Bacteremia and infective endocarditis following left-sided heart valve surgery occurred in 6.1% and 1.5% of patients, respectively. The most frequent bacteremia was coagulase-negative staphylococci, and more than half of these occurred within 30 days of surgery. Optimization of prophylactic strategies are warranted.