Treatment intensity level as a proxy for severity of chronic obstructive pulmonary disease: A risk stratification tool.

BACKGROUND: Increasing severity of chronic obstructive pulmonary disease (COPD) is associated with increasing risk of poor outcomes. Using health registry data, we aimed to assess the association between treatment intensity levels (TIL), as a proxy for underlying COPD severity, and long-term outcomes. METHODS: Using Danish nationwide registries, we identified patients diagnosed with COPD during 2001-2016, who were alive at index date of 1 January 2017. We stratified patients into exclusive TILs from least to most severe: no use, short term therapy, mono-, dual-, triple therapy, oral corticosteroid (OCS), and long-term oxygen treatment (LTOT). Survival analyses were used to assess 5-year outcomes by TIL. RESULTS: We identified 53,803 patients with COPD in the study period (median age: 72 years [inter quartile range, 64‒80], 48% male). The three most severe TILs were associated with a significant incremental increase in all-cause mortality with an adjusted hazard ratio (aHR) for triple therapy, OCS and LTOT of 1.44 (95% CI: 1.38‒1.51), 1.67 (95% CI: 1.59‒1.75), and 2.91 (95% CI: 2.76‒3.07) compared with those receiving no therapy as reference. The same pattern was evident for the composite outcome of 5-year mortality or COPD-related hospitalization with an aHR for triple therapy, OCS and LTOT of 2.30 (95% CI: 2.22‒2.38), 2.85 (95% CI: 2.74‒2.96), and 4.00 (95% CI: 3.81‒4.20), respectively. CONCLUSION: Increasing TILs were associated with increasing five-year mortality and risk of COPD-related hospitalization. TILs may be used as a proxy for underlying COPD severity in epidemiological studies.

Comparative Rates of Stroke and Rehospitalization of Atrial Fibrillation in Patients with Perioperative Atrial Fibrillation Following Major Emergency Abdominal Surgery and Patients with Non-perioperative Atrial Fibrillation.

BACKGROUND: Major emergency abdominal surgery is associated with postoperative complications and high mortality. Long-term outcomes in patients with perioperative atrial fibrillation (POAF) have recently received increased attention, especially POAF in non-thoracic surgery. PURPOSE: This study aimed to compare long-term AF related hospitalization and stroke in patients with POAF in relation to major emergency abdominal surgery and in patients with non-perioperative AF. METHODS: We crosslinked data from Danish nationwide registries and identified all patients who underwent major emergency abdominal surgery (2000-2018) and were diagnosed with POAF, and patients who developed AF in a non-perioperative setting. Patients with POAF were matched in a 1:5 ratio on age, sex, year of AF diagnosis and oral anticoagulation (OAC) status at the beginning of follow-up with patients with non-perioperative AF. From discharge, we examined adjusted hazard ratios (HR) of stroke using multivariable Cox regression analysis. RESULTS: The study population comprised 1,041 (out of 42,021 who underwent major emergency abdominal surgery) patients with POAF and 5,205 patients with non-perioperative AF. The median age was 78 years [interquartile range: 71-84] for those initiated on OAC therapy and 78 years [interquartile range: 71-85] for those not initiated on OAC therapy. During the first year of follow up, POAF was associated with similar rates of stroke as non-perioperative AF (patients initiated on OAC: HR 0.96 (95% confidence interval (CI) 0.52-1.77) and patients not initiated on OAC: HR 0.69 (95% CI 0.41-1.15). CONCLUSION: POAF in relation to major emergency abdominal surgery was associated with similar rates of stroke as non-perioperative AF. These results suggest that POAF not only carry an acute burden but also a long-term burden in patients undergoing major emergency abdominal surgery.

Early surgery to prevent embolic events in patients with infective endocarditis: a comprehensive review.

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.

Prognostic Impact of Anemia in Patients Undergoing Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: Patients undergoing aortic valve replacement (AVR) have high readmission rates. Several risk factors have been proposed as potential modifiable targets, including anemia. We examined the association between anemia at discharge and subsequent outcomes in these patients. METHODS: Using Danish nationwide registries, we identified all patients who underwent AVR between 2015-2021, were alive at discharge (index date), and had an available hemoglobin (Hb) measurement taken between procedure and discharge. Patients were categorized as having i) moderate/severe anemia (Hb<6.2 mmol/L) or ii) no/mild anemia (Hb≥6.2 mmol). The one-year rates of all-cause mortality, all-cause hospital admission, heart failure (HF) admission, and atrial fibrillation (AF) admission were compared using multivariable Cox regression models. RESULTS: 8,614 patients were identified; 2,847 (33.1%) had moderate/severe anemia (60.2% male, median age 74) and 5,767 (66.9%) had no/mild anemia (68.0% male, median age 76). For these two groups, respectively, the cumulative one-year incidences of the outcomes were: i) all-cause mortality: 5.1% vs. 4.3%; ii) all-cause admission: 53.8% vs. 47.5%; iii) AF admission: 14.0% vs. 11.6%); iv) HF admission: 6.8% vs. 6.2%. In adjusted analysis, moderate/severe anemia, compared with no/mild anemia, was associated with higher rates of all-cause mortality (hazard ratio (HR) 1.27 [95%CI 1.02-1.58]), all-cause admission (HR 1.22 [95%CI 1.14-1.30]), and AF admission (HR 1.23 [95%CI 1.08-1.40]), but not HF admission (HR 1.09 [95%CI 0.91-1.31]). CONCLUSION: In patients undergoing AVR, moderate/severe anemia at discharge, compared with no/mild anemia, was associated with increased all-cause mortality, all-cause hospital admission, and AF admission, but not HF admission, at one-year post-discharge.

Temporal trends in mortality, heart failure hospitalisation, and stroke in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018 on 152,059 patients.

AIMS: We aimed to investigate temporal trends in all-cause mortality, heart failure (HF) hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and atrial fibrillation (AF). METHODS AND RESULTS: From Danish nationwide registers, we identified 152 059 patients with new-onset HF between 1997 and 2018. Patients were grouped according to year of new-onset HF and AF-status: Prevalent AF (n = 34 734), New-onset AF (n = 12 691), and No AF (n = 104 634). Median age decreased from 76 to 73 years between 1997 and 2018. The proportion of patients with prevalent or new-onset AF increased from 24.7% (n = 9256) to 35.8% (n = 14 970). Five-year risk of all-cause mortality went from 69.1% (CI: 67.9%-70.2%) to 51.3% (CI: 49.9%-52.7%), 62.3% (CI: 60.5%-64.4%) to 43.0% (CI: 40.5%-45.5%), and 61.9% (CI: 61.3%-62.4%) to 36.7% (CI: 35.9%-37.6%) for the Prevalent AF, New-onset AF and No AF-group, respectively. Minimal changes were observed in the risk of HF-hospitalisation. Five-year stroke risk decreased from 8.5% (CI: 7.8%-9.1%) to 5.0% (CI: 4.4%-5.5%) for the prevalent AF group, 8.2% (CI: 7.2%-9.2%) to 4.6% (CI: 3.7%-5.5%) for new-onset AF, and 6.3% (CI: 6.1%-6.6%) to 4.9% (CI: 4.6%-5.3%) for the No AF group. Simultaneously, anticoagulant therapy increased for patients with prevalent (from 42.7% to 93.1%) and new-onset AF (from 41.9% to 92.5%). CONCLUSION: From 1997 to 2018, we observed an increase in patients with HF and co-existing AF. Mortality decreased for all patients, regardless of AF-status. Anticoagulation therapy increased, and stroke risk for patients with AF was reduced to a similar level as patients without AF in 2013-2018.

Incidence of clinical outcomes in heart failure patients with and without advanced chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is a well-established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 have been systematically excluded from clinical trials. This study investigated the incidence of HF and kidney outcomes in HF patients with and without advanced CKD, that is, eGFR < 30. METHODS: From nationwide registries, HF patients were identified from 2014 to 2018 and categorized into three groups according to baseline eGFR (eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30). The incidence of primary outcomes (all-cause mortality, HF hospitalization, end-stage kidney disease and sustained 50% eGFR decline) was estimated using cumulative incidence functions. RESULTS: Of the 21 959 HF patients included, the median age was 73.9 years, and 30% of patients had an eGFR between 30 and 60 and 7% had an eGFR < 30. The 4 year incidence of all-cause mortality was highest for patients with eGFR < 30 (28.3% for patients with eGFR ≥ 60, 51.6% for patients with 60 > eGFR ≥ 30 and 72.2% for patients with eGFR < 30). The 4 year incidence of HF hospitalization was comparable between the groups (25.8%, 29.8% and 26.1% for patients with eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30, respectively). For patients with eGFR < 30, kidney outcomes were four times more often the first event than patients with eGFR > 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR < 30). CONCLUSIONS: Patients with advanced CKD had a higher incidence of mortality and poorer kidney outcomes than those without advanced CKD, but a similar incidence of HF hospitalizations.

Burden of Hospitalization During the First Year Following Transcatheter and Surgical Aortic Valve Replacement.

BACKGROUND: Hospitalizations are a major burden for both patients and society but are potentially preventable. We examined the one-year hospitalization burden in patients undergoing transcatheter aortic valve replacement (TAVR) and compared hospitalization rates and patterns with those undergoing isolated surgical aortic valve replacement (SAVR). METHODS: Using Danish nationwide registries, we identified patients who underwent first-time TAVR and isolated SAVR (2008-2019), respectively. Subsequent hospitalizations were classified as cardiovascular or non-cardiovascular according to discharge diagnosis codes. RESULTS: Patients undergoing TAVR (N=4,921) were older and had more comorbidities than those undergoing SAVR (N=5,220). There were 5,725 and 4,426 hospitalizations within the first year after discharge in the TAVR and SAVR group, respectively. During the one-year follow-up period post-TAVR, 46.6% were not admitted, 25.4% were admitted once, 12.6% twice, and 15.4% three times or more. The corresponding proportions in patients undergoing SAVR were 55.3%, 25.1%, 10.0%, and 9.5%, respectively. Among patients with ≥1 hospitalization following TAVR, 50.3% had a total length of all hospital stays between 1-7days, 19.0% 8-14days, 18.0% 15-30days, 9.9% 31-60days, and 2.8% ≥61days. The corresponding proportions for patients undergoing SAVR were 58.6%, 17.2%, 13.1%, 7.4%, and 3.7%, respectively. Compared with patients undergoing SAVR, those undergoing TAVR had a lower early (day0-30: HR 0.89 [95%CI,0.80-0.98]), but a higher late hospitalization rate (day31-365: 1.46 [1.32-1.60]). CONCLUSIONS: The one-year hospitalization burden following TAVR is substantial. Compared with patients undergoing isolated SAVR, those undergoing TAVR had a lower early, but a higher late hospitalization rate - a difference that likely reflects unmeasured differences in the patient cohorts.

Importance of experience in transoesophageal echocardiographic evaluation of vegetation size in patients with infective endocarditis: a reliability study.

Aims: Vegetation size assessed by transoesophageal echocardiography (TOE) is a decisive metric in guiding surgical intervention and prognosis in patients with definite infective endocarditis (IE). The aim of this study was to assess the impact of echocardiographic experience on the reliability and reproducibility of TOE measurements of vegetations in patients with IE. Methods and results: Twenty-nine raters from a cardiac department at a tertiary centre were divided into three groups according to echocardiographic experience: experts, cardiologists, and novices. All raters were instructed to measure the maximum length of vegetations in 20 different TOE exams. Interrater agreement was evaluated using intraclass correlation coefficient (ICC), one-way analysis of variance, Kruskal-Wallis test, and Bland-Altmann plots. Reliability was assessed by minimal detectable change (MDC). All measurements were compared with the measured size agreed on by the multi-disciplinary IE team.There was an overall significant interrater variance between the three groups (P < 0.001). The variance was 10.1, 14.8, and 21.7 for the experts, cardiologists, and novices, respectively. ICC was excellent for experts (96.3%) and cardiologists (93.7%) and good for novices (84.6%). The three groups tended to measure smaller than the endocarditis team. MDC was 2.6 mm for experts, 3.3 mm for cardiologists, and 3.6 mm for novices. Conclusion: The study showed good to excellent intraclass correlation but high dispersion in all groups. Variance decreased with higher experience. Our findings support current recommendations that complicated cases should be cared for by the multi-disciplinary endocarditis team and underline the importance of echocardiographic expertise when evaluating and measuring vegetations in patients with IE.

Education and Age in Return to Work After Ischemic Stroke: A Danish Nationwide Registry-based Cohort Study.

OBJECTIVES: To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education. METHODS: Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again. CONCLUSIONS: A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment.

Role of echocardiography in the diagnosis and clinical management of infective endocarditis.

Infective endocarditis (IE) is a deadly disease, constituting both diagnostic and treatment challenges. A positive outcome requires rapid and accurate diagnosis, and for that, echocardiography unequivocally remains the cornerstone. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have complementary roles and have been markedly improved during the last decades. The transthoracic modality is the recommended first-line approach but may only be sufficient in patients where the probability of IE is low and/or with clear acoustic windows, especially in patients with right-sided IE. The transesophageal modality is superior to TTE in most aspects and is recommended for all other patients. Both TTE and TEE may delineate vegetation location and size, assess for paravalvular extension of infection, and have the added advantage of defining the hemodynamic effects of valvular or device infection. However, echocardiography still has significant limitations, and novel imaging techniques are increasingly being exploited to improve diagnostic potential. Cardiac computed tomography (CT) performs better than TEE in the detection of abscess or pseudoaneurysm, while magnetic resonance imaging (MRI) has limited value in the diagnostic phase of IE but adds knowledge to the evaluation of extracardiac events. Nuclear molecular techniques are evolving as key supplementary methods in difficult-to-diagnose cases. Although newer imaging modalities are undergoing preliminary evaluation and multimodal imaging will play an increasing role in IE, echocardiography will continue to be pivotal in patients with IE for the foreseeable future.

Temporal changes in the number of European and American guideline recommendations and underlying evidence base for the management of infective: An update of previous published data.

This report aimed to examine temporal changes in the number of recommendations on management of infective endocarditis in the European and American guidelines. The number of recommendations has increased since 2004 without an increment in evidence base in the European iteration. American guidelines have reduced the number of recommendations with a main evidence base of level B.

Association of multiple sclerosis with incident diabetes: A nationwide cohort study.

AIM: Diabetes mellitus (DM) and multiple sclerosis (MS) are two common diseases known to worsen the trajectory of each other, yet it is unknown whether MS is associated with incident DM. METHODS: Using Danish nationwide registries, we identified all patients aged 18-99 with a first-time primary or secondary discharge diagnosis with MS between 2000 and 2018, with no known DM. These patients were matched with control subjects from the background population in a 1:5 ratio based on age and sex, to assess their risk of DM. RESULTS: A total of 13,376 patients with MS and 66,880 matched control subjects were included (33 % men; median age, 42 years [25th-75th percentile, 33-51]). During a median follow-up of 8.3 years (25th-75th percentile, 4.0-13.3), 467 (3.5 %) patients with MS and 2397 (3.6 %) control subjects were diagnosed with DM. The cumulative incidence of DM was similar among patients with MS and control subjects (95 % confidence interval [CI] 6.5 % [5.7-7.2 %] vs. 7.3 % [95 % CI 6.9-7.9 %], respectively), and adjusted analysis yielded a hazard ratio (HR) of 0.98 [95 % CI 0.89-1.09]). The overall risk of incident type 1 diabetes was low and yielded a HR of 1.60 [95 % CI 0.98-1.40] in patients with MS compared with control subject (P = 0.07). CONCLUSION: This study demonstrated that patients with MS had a similar risk of incident DM as compared to age- and sex matched controls from the background population.

N-terminal pro-B-type natriuretic peptide levels pre-transcatheter aortic valve implantation and relationship with long-term outcomes.

Background: Blood levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been suggested as a future guidance tool for the selection of patients for aortic valve replacement. This study aimed to examine how levels of NT-proBNP pre-transcatheter aortic valve implantation (TAVI) is associated with one-year rates of heart failure (HF) admission and mortality following TAVI. Methods: With Danish nationwide registries, we identified all patients undergoing TAVI from 2014 to 2021 who had at least one recorded NT-pro-BNP measurement within one year before TAVI. Patients were compared by quartiles of pre-TAVI NT-proBNP: quartile 4 (high NT-proBNP group) vs quartile 1-3 (low NT-proBNP group). Comparisons of all-cause mortality and HF-admissions were conducted using Kaplan-Meier analysis, cumulative incidence, and Cox analysis, as appropriate. Results: We identified 1,140 patients undergoing first-time TAVI with a recorded NT-pro-BNP; 846 (74.2 %) with a low NT-proBNP (<420 pmol/L) (55.0 % male, median age 81 year) and 294 (25.8 %) with a high NT-proBNP (≥420 pmol/L) (53.1 % male, median age 82 year). A high versus low NT-proBNP was associated with increased one-year cumulative incidence of HF-admissions (9.1 % vs. 23.1 %, adjusted HR 2.00 [95 % CI, 1.40-2.85]) and all-cause mortality (6.0 % vs. 14.6 %, adjusted HR 1.95 [95 % CI: 1.24-3.07]). A high NT-proBNP was associated with higher rates of outcomes irrespective of previously known atrial fibrillation, HF, chronic kidney disease, and hypertension. Conclusion: In patients undergoing TAVI, a baseline NT-proBNP ≥ 420 pmol/L was associated with increased one-year rates of HF-admission and mortality post-TAVI and may be utilized to identify a high-risk population.

Glucagon-like-peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes in diabetes in relation to achieved glycemic control. A Danish nationwide study.

AIM: To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c). METHODS: We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users. RESULTS: The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5-65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6-71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6-5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2-12.3) versus 24.3% (22.7-25.8); HbA1c > 53 mmol/mol: 16.0% (14.3-17.6) versus 21.1% (20.3-21.9); missing HbA1c: 17.1% (15.7-18.5) versus 25.6% (24.9-26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52-0.80); HbA1c > 53 mmol/mol: 0.92 (0.83-1.03); missing HbA1c: 0.92 (0.84-1.02) (p value for interaction <.001). CONCLUSION: GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.

Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Association between Preeclampsia and Long-term Risk of Arrhythmias.

BACKGROUND: Preeclampsia (PE), a pregnancy-induced hypertensive disorder, affects 4-5% of pregnancies worldwide. It is well known that hypertension is associated with an increased risk of arrhythmias; however, data on the association between PE and arrhythmias are sparse. METHODS: In this observational cohort study, we identified all primiparous women who gave birth in Denmark (1997-2016) using Danish nationwide registries. The women were stratified on whether they developed PE during primiparous pregnancy, and followed from primiparous pregnancy to incident arrhythmia, emigration, death, or end of study (December 31, 2018). RESULTS: A total of 523,271 primiparous women with a median age of 28 years were included and 23,367 (4.5%) were diagnosed with PE. During a median follow-up of 10.1 years, women with vs without PE were associated with a higher incidence of arrhythmias (1.42% vs 1.02%): 1) Composite of cardiac arrest, ventricular tachycardia/fibrillation, or ICD implantation (adjusted HR 1.60 [95% CI 1.14-2.24]), 2) Composite of advanced 2nd degree or 3rd degree atrioventricular block, sinoatrial dysfunction, or pacemaker implantation (adjusted HR 1.48 [95% CI 0.97-2.23]), 3) Composite of supraventricular tachyarrhythmias or extra systoles (adjusted HR 1.34 [95% CI 1.19-1.51]), 4) Composite of all the above-mentioned arrhythmias (adjusted HR 1.37 [95% CI 1.23-1.54]). CONCLUSION: Preeclamptic women were associated with a significantly and at hitherto unknown long-term increased rate of arrhythmias. This finding suggests that women with PE may benefit from cardiovascular risk assessment, screening, and preventive education.

This study examined whether preeclampsia, a condition that can occur during pregnancy and cause high blood-pressure, was linked to heart rhythm problems in first-time mothers. Women who had preeclampsia in their first pregnancy were more likely to develop heart rhythm problems later in life.This suggests that women with a history of preeclampsia might need extra attention to prevent future problems.

Use of medical therapy and risk of clinical events according to frailty in heart failure patients - A real-life cohort study.

AIMS: Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. METHODS AND RESULTS: Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively). CONCLUSION: In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization.

Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study.

BACKGROUND: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups. METHODS: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years). FINDINGS: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8]). INTERPRETATION: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Infective native aneurysms of the infrapopliteal arteries - A systematic literature review and report of two cases.

Infective native aneurysms (INA) of the infrapopliteal arteries are rare and have previously been poorly described. This systematic review aims to provide an overview of the literature of this entity. Furthermore, two case reports of our own clinical experience are presented. PubMed, ScienceDirect, Cochrane, Ovid Embase, Ovid MEDLINE, and Web of Science were searched for articles on INAs of the infrapopliteal segment from January 1990 to September 2023. Article screening and selection were performed adhering to PRISMA guidelines. A total of 98 articles were screened and 20 were eligible for inclusion, of which all were case reports. In total, 22 patients with 28 infrapopliteal INAs were identified. The majority of INAs were located in the tibioperoneal trunk (n = 10, 36%) followed by the posterior tibial artery (n = 7, 25%). A current, or history of, infective endocarditis (IE) was described in 18 out of 22 patients (82%). Two patients died during hospitalization and one patient required a transfemoral amputation. A conservative antibiotic-only approach was chosen in three out of 28 INAs, two of which were the case reports described in this article; surgical or endovascular intervention was performed in 19 out of 28 aneurysms. No complications occurred in the conservative group, but one complication (transfemoral amputation) occurred in the interventional group. Infrapopliteal INA is a rare entity, and most described cases are precipitated by IE. Surgery or endovascular treatment might be indicated, but more research is warranted to define which patient would benefit and by what surgical approach.

An Unusual Presentation of an Enterococcus faecalis Endocarditis With Wrist and Forearm Infection: A Case Report.

In this case, an unusual presentation of Enterococcus faecalis (E.faecalis) endocarditis and clinical signs of wrist and forearm infection are reported. Before the patient was diagnosed with E.faecalis endocarditis, the patient managed to be treated with both prednisolone, various antibiotics, and colchicine on suspicion of gout, erysipelas, and deep tissue infection. Growth of E.faecalis in blood cultures raised the suspicion of endocarditis, and transesophageal echocardiography revealed vegetations on the aortic and the mitral valves with a perforation of the anterior mitral leaflet. Since the patient responded well to antibiotic treatment and there was no progression of the size of the vegetations or the perforation, it was decided by the endocarditis team to refrain from surgery. E. faecalis endocarditis can be difficult to diagnose because the patients are often elderly, and symptoms may be subtle and misleading. In the present case, the diagnostic process was based on the Danish IE guidelines, which state that E. faecalis is a typical IE bacterium. Accepting E. faecalis as a typical infective endocarditis bacterium may lead to an earlier diagnosis and treatment.