Long-Term Incidence of Ischemic Stroke After Transient Ischemic Attack: A Nationwide Study From 2014 to 2020.

BACKGROUND: The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies. METHODS: Patients with first-time TIA (index date) in the Danish Stroke Registry (January 2014-December 2020) were included and matched 1:4 with individuals from the background population and 1:1 with patients with a first-time ischemic stroke on the basis of age, sex, and calendar year. The incidences of ischemic stroke and mortality from index date were estimated by Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups using multivariable Cox regression. RESULTS: We included 21 500 patients with TIA, 86 000 patients from the background population, and 21 500 patients with ischemic stroke (median age, 70.8 years [25th-75th percentile, 60.8-78.7]; 53.1% males). Patients with TIA had more comorbidities than the background population, yet less than the control stroke population. The 5-year incidence of ischemic stroke after TIA (6.1% [95% CI, 5.7-6.5]) was higher than the background population (1.5% [95% CI, 1.4-1.6], P<0.01; hazard ratio, 5.14 [95% CI, 4.65-5.69]) but lower than the control stroke population (8.9% [95% CI, 8.4-9.4], P<0.01; hazard ratio, 0.58 [95% CI, 0.53-0.64]). The 5-year mortality for patients with TIA (18.6% [95% CI, 17.9-19.3]) was higher than the background population (14.8% [95% CI, 14.5-15.1], P<0.01; hazard ratio, 1.26 [95% CI, 1.20-1.32]) but lower than the control stroke population (30.1% [95% CI, 29.3-30.9], P<0.01; hazard ratio, 0.41 [95% CI, 0.39-0.44]). CONCLUSIONS: Patients with first-time TIA had an ischemic stroke incidence of 6.1% during the 5-year follow-up period. After adjustment for relevant comorbidities, this incidence was approximately 5-fold higher than what was found for controls in the background population and 40% lower than for patients with recurrent ischemic stroke.

Patient characteristics, treatment patterns, and prognosis in drug-use-associated infective endocarditis in Denmark from 1999 to 2018.

BACKGROUND: 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. METHODS: 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. RESULTS: 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)). CONCLUSION: 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.

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.

Surgery in patients with infective endocarditis and prognostic importance of patient frailty.

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.

Recurrence of bacteremia and infective endocarditis according to bacterial species of index endocarditis episode.

PURPOSE: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE. METHODS: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE. RESULTS: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species. CONCLUSION: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species.

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.

Influence of socioeconomic status on rates of advanced heart failure therapies.

BACKGROUND: Socioeconomic deprivation is associated with a lower likelihood of referral for advanced heart failure (HF) evaluation, but it is not known whether it influences rates of advanced HF therapies independently of key hemodynamic measures and comorbidity following advanced HF evaluation in a universal healthcare system. METHODS: We linked data from a single-center Danish clinical registry of consecutive patients evaluated for advanced HF with patient-level information on socioeconomic status. Patients were divided into groups based on the level of education (low, medium, and high), combined degree of socioeconomic deprivation (low, medium, and high), and household income quartiles. Rates of the combined outcome of left ventricular assist device implantation or heart transplantation (advanced HF therapy) with death as a competing risk were estimated with cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, central venous pressure, cardiac index, and comorbidities. RESULTS: We included 629 patients, median age 53 years, of whom 77% were men. During a median follow-up of 5 years, 179 (28%) underwent advanced HF therapy. The highest level of education was associated with higher rates (high vs low, adjusted HR 1.81 95% CI 1.14-2.89, p = 0.01), whereas household income quartile groups (Q4 vs Q1, adjusted HR 1.37 95% CI 0.76-2.47, p = 0.30) or groups of combined socioeconomic deprivation (high vs low degree of deprivation, adjusted HR 0.86 95% CI 0.50-1.46, p = 0.56) were not significantly associated with rates of advanced HF therapy. CONCLUSIONS: Patients with a lower level of education might be disfavored for advanced HF therapies and could require specific attention in the advanced HF care center.

Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020.

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.

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.

Frailty and Recurrent Hospitalization After Transcatheter Aortic Valve Replacement.

Background For frail patients with limited life expectancy, time in hospital following transcatheter aortic valve replacement is an important measure of quality of life; however, data remain scarce. Thus, we aimed to investigate frailty and its relation to time in hospital during the first year after transcatheter aortic valve replacement. Methods and Results From 2008 to 2020, all Danish patients who underwent transcatheter aortic valve replacement and were alive at discharge were included. Using the validated Hospital Frailty Risk Score, patients were categorized in the low, intermediate, and high frailty groups. Time in hospital and mortality up to 1 year are reported according to frailty groups. In total, 3437 (57.6%), 2277 (38.1%), and 257 (4.3%) were categorized in the low, intermediate, and high frailty groups, respectively. Median age was ≈81 years. Female sex and comorbidity burden were incrementally higher across frailty groups (low frailty: heart failure, 24.1%; stroke, 7.2%; and chronic kidney disease, 4.5%; versus high frailty: heart failure, 42.8%; stroke, 34.2%; and chronic kidney disease, 29.2%). In the low frailty group, 50.5% survived 1 year without a hospital admission, 10.8% were hospitalized >15 days, and 5.8% of patients died. By contrast, 26.1% of patients in the high frailty group survived 1 year without a hospital admission, 26.4% were hospitalized >15 days, and 15.6% died within 1 year. Differences persisted in models adjusted for sex, age, frailty, and comorbidity burden (excluding overlapping comorbidities). Conclusions Among patients undergoing transcatheter aortic valve replacement, frailty is strongly associated with time in hospital and mortality. Prevention strategies for frail patients to reduce hospitalization burden could be beneficial.

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.

Cardiovascular risk prediction: Can Systematic Coronary Risk Evaluation (SCORE) be improved by adding simple risk markers? Results from the Copenhagen City Heart Study.

AIM: European society of cardiology (ESC) guidelines recommend that cardiovascular disease (CVD) risk stratification in asymptomatic individuals is based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, which estimates individual 10-year risk of death from CVD. We assessed the potential improvement in CVD risk stratification of 19 easily available risk markers by adding them to the SCORE algorithm. METHODS AND RESULTS: We followed 8476 individuals without prior CVD or diabetes from the Copenhagen City Heart study. The 19 risk markers were: major and minor electrocardiographic (ECG) abnormalities, heart rate, family history (of ischaemic heart disease), body mass index (BMI), waist-hip ratio, walking duration and pace, leisure time physical activity, forced expiratory volume (FEV)1%pred, household income, education, vital exhaustion, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), high-sensitive C-reactive protein (hsCRP) and fibrinogen. With the exception of family history, BMI, triglycerides and minor ECG changes, all risk markers remained significantly associated with CVD mortality after adjustment for SCORE variables. However, the addition of the remaining 15 risk markers resulted in only small changes in discrimination calculated by area under the curve (AUC) and integrated discrimination improvement (IDI) and no improvement in net reclassification improvement (NRI). HsCRP improved AUC by 0.006 (p = 0.015) and IDI by 0.012 (p = 0.002); FEV1%pred improved AUC by 0.006 (p = 0.032) and IDI by 0.006 (p = 0.029). In the intermediate risk group FEV1%pred, education, vital exhaustion and ApoA1 all improved NRI but FEV1%pred was the only risk marker to significantly improve both IDI, AUC and NRI. CONCLUSION: The SCORE algorithm predicted CVD mortality in a Danish cohort well. Despite strong association with CVD mortality, the individual addition of 19 easily available risk makers to the SCORE model resulted in small risk stratification improvements.