NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

Temporal trends in the incidence of infective endocarditis in patients with a prosthetic heart valve.

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.

Long-Term Cause of Death in Patients Who Underwent Transcatheter Aortic Valve Implantation.

As our knowledge on treatment with transcatheter aortic valve implantation (TAVI) increases and more implantations are conducted, we need knowledge on how TAVI affects the end of life. Long-term causes of death remain sparsely described. The aim of the study was to examine differences in the cause of death according to time from TAVI. All patients who underwent TAVI in Denmark from 2008 to 2017 were matched on gender, age, and calendar year with controls from the background population (1:4). Mortality and the proportion of cardiovascular and noncardiovascular death was assessed at 1-year time points during follow-up. A total of 3,434 patients receiving TAVI and 13,672 controls were identified. The median follow-up was 2.67 years for patients receiving TAVI and 2.90 years for controls. Among patients receiving TAVI, 1,254 deaths (36.5%) were recorded, with 46.7% being from cardiovascular causes. The corresponding numbers for controls were 3,338 deaths (24.4%) and 27.2% being from cardiovascular causes. The proportion of cardiovascular deaths decreased from 53.8% in the first year after TAVI to 32.7% among those who died >7 years from TAVI (p = 0.008 for trend). For controls, no difference was seen in the proportion of cardiovascular death regardless of follow-up time. In conclusion, with data from nationwide registries, we provide results reassuring that patients with long-term survival from TAVI resemble the general public regarding the cause of death.

Changes in aortic valve replacement procedures in Denmark from 2008 to 2020.

INTRODUCTION: Since 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. METHODS: Using Danish nationwide registries, we identified first-time AVRs between 2008 and 2020. Patients who were not diagnosed with AS prior to AVR were excluded RESULTS: The 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). CONCLUSIONS: The 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.

Prevalence and Mortality of Infective Endocarditis in Community-Acquired and Healthcare-Associated Staphylococcus aureus Bacteremia: A Danish Nationwide Registry-Based Cohort Study.

Background: Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods: First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results: We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86-2.41]). No difference in mortality was observed with 0-40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83-1.37]), while with 41-365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53-.95]). Conclusions: Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

Surgical treatment of patients with infective endocarditis: changes in temporal use, patient characteristics, and mortality-a nationwide study.

BACKGROUND: Valve surgery guidelines for infective endocarditis (IE) are unchanged over decades and nationwide data about the use of valve surgery do not exist. METHODS: We included patients with first-time IE (1999-2018) using Danish nationwide registries. Proportions of valve surgery were reported for calendar periods (1999-2003, 2004-2008, 2009-2013, 2014-2018). Comparing calendar periods in multivariable analyses, we computed likelihoods of valve surgery with logistic regression and rates of 30 day postoperative mortality with Cox regression. RESULTS: We included 8804 patients with first-time IE; 1981 (22.5%) underwent surgery during admission, decreasing by calendar periods (N = 360 [24.4%], N = 483 [24.0%], N = 553 [23.5%], N = 585 [19.7%], P = < 0.001 for trend). For patients undergoing valve surgery, median age increased from 59.7 to 66.9 years (P ≤ 0.001) and the proportion of males increased from 67.8% to 72.6% (P = 0.008) from 1999-2003 to 2014-2018. Compared with 1999-2003, associated likelihoods of valve surgery were: Odds ratio (OR) = 1.14 (95% CI: 0.96-1.35), OR = 1.20 (95% CI: 1.02-1.42), and OR = 1.10 (95% CI: 0.93-1.29) in 2004-2008, 2009-2013, and 2014-2018, respectively. 30 day postoperative mortalities were: 12.7%, 12.8%, 6.9%, and 9.7% by calendar periods. Compared with 1999-2003, associated mortality rates were: Hazard ratio (HR) = 0.96 (95% CI: 0.65-1.41), HR = 0.43 (95% CI: 0.28-0.67), and HR = 0.55 (95% CI 0.37-0.83) in 2004-2008, 2009-2013, and 2014-2018, respectively. CONCLUSIONS: On a nationwide scale, 22.5% of patients with IE underwent valve surgery. Patient characteristics changed considerably and use of valve surgery decreased over time. The adjusted likelihood of valve surgery was similar between calendar periods with a trend towards an increase while rates of 30 day postoperative mortality decreased.

Temporal trends of mortality in patients with infective endocarditis: a nationwide study.

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.

Temporal changes in the incidence of infective endocarditis in Denmark 1997-2017: A nationwide study.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease, yet substantial variation in reported incidences of the disease exist. We aimed to conduct a contemporary, nationwide study of the temporal changes in incidence of IE. METHODS: We included all Danish cases of first-time IE (1997-2017) using nationwide registries. Patients were grouped into three seven-year intervals (1997-2003, 2004-2010, 2011-2017). Crude annual incidence rates (IR) per 100,000 person-years (PY) were examined overall and per subgroups: age, sex, patients without prior prosthetic heart valve or a cardiac implantable electronic device (CIED). Incidence rate ratios (IRR) were calculated adjusting for age-group, sex and diabetes. RESULTS: We identified 8675 patients with IE. Over time, patients were older at diagnosis with a median age of 66.2 years (interquartile range, IQR: 51.5-76.5) and 72.2 years (IQR 62.2-79.9) in 1997-2003 and 2011-2017, respectively. The overall IR increased from 5.0/100,000 PY (95% CI: 4.4-5.6) to 10.5/100,000 PY (95% CI: 9.6-11.3) from 1997 to 2017. IR for patients without prior prosthetic heart valve or a CIED increased from 4.9/100,000 PY (95% CI: 4.3-5.5) to 6.4/100,000 PY (95% CI: 5.8-7.1) (P ≤ 0.0001 for interaction). The IR in males increased from 5.6/100,000 PY (95% CI: 4.7-6.5) to 14.2/100,000 PY (95% CI: 12.9-15.6). The IR in females increased from 4.3/100,000 PY (95% CI: 3.6-5.2) to 6.7/100,000 PY (95% CI: 5.8-7.7). IRR (adjusted for age-groups, sex and diabetes) increased over time (IRR = 1.60 (1.39-1.85) in 2017 vs 1997). CONCLUSION: The incidence of IE more than doubled during the study period. The increase was mainly seen among men and elderly patients only partly explained by the increase in patients with prior heart valve prosthesis or a CIED.

Outcome of Dialysis-Requiring Acute Kidney Injury in Patients With Infective Endocarditis: A Nationwide Study.

BACKGROUND: Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. METHODS: Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis-naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed 1 year postdischarge. Multivariable adjusted Cox proportional hazard analysis was used to examine 1-year mortality for patients surviving IE according to use of dialysis. RESULTS: We included 7307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with nondialysis patients (47.4% vs 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n = 197), 153 (77.7%) initiated dialysis on or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (P < .0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within 1 year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased 1-year mortality from IE discharge, hazard ratio = 1.64 (95% confidence interval, 1.21-2.23). CONCLUSION: In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximate 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.

Differences in mortality in patients undergoing surgery for infective endocarditis according to age and valvular surgery.

BACKGROUND: Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE. METHODS: By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000-2017. Patients were grouped by age < 60 years, 60-75 years, and ≥ 75 years. Multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality. RESULTS: We included 1767 patients with IE undergoing surgery, 735 patients < 60 years (24.1% female), 766 patients 60-75 years (25.8% female), and 266 patients ≥75 years (36.1% female). The proportions of patients undergoing surgery were 35.3, 26.9, and 9.1% for patients < 60 years, 60-75 years, and > 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p < 0.001) for three age groups. In adjusted analyses, patients 60-75 years and patients ≥75 years were associated with a higher mortality, HR = 1.84 (95% CI: 1.48-2.29) and HR = 2.47 (95% CI: 1.88-3.24) as compared with patients < 60 years. Factors associated with 90-day mortality were: mitral valve surgery, a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, age, diabetes, and prosthetic heart valve implantation prior to IE admission. CONCLUSIONS: In patients undergoing surgery for IE, mortality increased significantly with age and 1 in 5 died above age 75 years. Mitral valve surgery as well as multiple valve interventions augmented mortality further.