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Aims: Patients with heart failure (HF) often experience delayed identification of palliative care needs. While communication with HF patients and their caregivers is increasingly stressed, systematic conversations about end-of-life care wishes remain a gap. This study explores a dyad experience of Advance Care Planning (ACP) conversations in an HF outpatient clinic., Methods and Results: A qualitative interview study with 15 patients diagnosed with end-stage HF and 14 caregivers. Through qualitative content analysis and investigator triangulation, three subthemes emerged: 'ACP as a harsh reality', 'ACP as a catalyst for crucial conversations', and 'ACP conversations help appreciating life's small moments and adjusting hope'. Despite significant symptom burden, many patients lacked awareness of their end-stage HF prognosis. Following an initial 'reality shock', ACP conversations facilitated open discussions about end-of-life care wishes. Especially spousal caregivers experienced a significant caregiving load, generating complex emotions for both patients and their families. Notably, patients prioritized self-care, daily activities, and social interaction for maintaining quality of life., Conclusion: This study highlights a gap between patients with end-stage HF disease status and their comprehension of disease severity. Early integration of ACP may address knowledge gaps, enable informed decision-making, and alleviate caregiver burden. The study also emphasizes the patient-and family-centred care to support self-care, daily life activities, and social connections for improved quality of life throughout the disease trajectory., Registration: ClinicalTrials.gov: NCT05269875., Competing Interests: Conflict of interest: The authors declare no conflict of interest with respect to the research, authorship, and/or publication of this article and that they all agree with the final versions of this manuscript., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Heart failure (HF) is considered a multifaceted and life-threatening syndrome characterized by high symptom-burden and significant mortality., Objectives: To describe the symptom-burden in patients with HF and identify their palliative care needs. In this respect, symptom burden related to sex, age and classification of HF using New York Heart Association Functional Classification (NYHA) were analyzed., Methods: A cross-sectional questionnaire survey included adult HF patients according to NYHA II, III, and IV. Palliative care needs were assessed using validated patient reported outcomes measures; SF-36v1, HeartQoL, EORTC- QLQ-C15-PAL, MFI-20 and HADS. Patients were recruited from the Department of Cardiology, North Zealand Hospital, Denmark., Results: In total, 314 patients (79%) completed the questionnaire (233 men). Mean age = 74 years (range 35-94 years). In all, 42% had NYHA III or IV and 53% self-rated their health to be fair or poor. In all, 19% NYHA II and 67% NYHA III/IV patients had ≥4 severe palliative symptoms according to EORTC-QLQ-C15-PAL. In addition, NYHA III/IV had a mean of 8.9 symptoms and a mean of 5.4 severe symptoms. Women, older patients, and those with NYHA III/IV had worse outcomes regarding health-related quality of life, functional capacity, and symptom burden., Conclusions: Patients with HF have a high prevalence of symptoms and, thus, potential palliative care needs. Predominantly, women, older patients, and those with higher severity of disease have the highest symptom burden. PROMs can help cardiologists address the palliative care needs and systematic assessment may be a prerequisite to integrate symptom-modifying and palliative care interventions., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci., Objectives: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated., Patients and Methods: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination., Results: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively., Conclusions: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs)., Methods: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated., Results: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics., Conclusions: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis., Competing Interests: Potential conflicts of interest. C. T. P. reports a grant from Bayer for a randomized study, and a grant from Novo Nordisk for an epidemiological study. L. K. reports payment for speaking engagements from AstraZeneca, Bayer, Boehringer, and Novartis. C. M. reports payment for speaking engagements from AstraZeneca, GSK, MSD, and Pfizer; co-authorship of the Danish Treatment Guidelines for Infective Endocarditis and of the ESCMID guidelines for prevention, treatment and diagnosis of biofilm infections; and service as a board member of the European Society for Clinical Microbiology Study Group (ESCMID) for Biofilms (ESGB). E. L. F. reports grants from Novo Nordisk Foundation and the Danish Heart Association. N. E. B. reports grants from Novo Nordisk Foundation, Health Insurance Denmark, and Augustinus Foundation (all unrelated to this study). F. S. R. reports unpaid positions on the Danish Ministry of Health's National expert advisory board on antimicrobial stewardship, the Region of Southern Denmark's Regional working group on antimicrobial stewardship, and chairman on the Steering committee and working group at Odense University Hospital for rational use of antimicrobial drugs. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P =0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Purpose: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis., Methods: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model., Results: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01)., Conclusion: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257., Trial Registry: POET ClinicalTrials.gov number, NCT01375257., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE)., Methods: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores)., Results: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses., Conclusion: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating., Gov Id: NCT04377035., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Background: β3-AR (β3-adrenergic receptor) stimulation improved systolic function in a sheep model of systolic heart failure (heart failure with reduced ejection fraction [HFrEF]). Exploratory findings in patients with New York Heart Association functional class II HFrEF treated with the β3-AR-agonist mirabegron supported this observation. Here, we measured the hemodynamic response to mirabegron in patients with severe HFrEF., Methods: In this randomized, double-blind, placebo-controlled trial we assigned patients with New York Heart Association functional class III-IV HFrEF, left ventricular ejection fraction <35% and increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels to receive mirabegron (300 mg daily) or placebo orally for a week, as add on to recommended HF therapy. Invasive hemodynamic measurements during rest and submaximal exercise at baseline, 3 hours after first study dose and repeated after 1 week's treatment were obtained. Predefined parameters for analyses were changes in cardiac- and stroke volume index, pulmonary and systemic vascular resistance, heart rate, and blood pressure., Results: We randomized 22 patients (age 66±11 years, 18 men, 16, New York Heart Association functional class III), left ventricular ejection fraction 20±7%, median NT-proBNP 1953 ng/L. No significant changes were seen after 3 hours, but after 1 week, there was a significantly larger increase in cardiac index in the mirabegron group compared with the placebo group (mean difference, 0.41 [CI, 0.07-0.75] L/min/BSA; P =0.039). Pulmonary vascular resistance decreased significantly more in the mirabegron group compared with the placebo group (-1.6 [CI, -0.4 to -2.8] Wood units; P =0.02). No significant differences were seen during exercise. There were no differences in changes in heart rate, systemic vascular resistance, blood pressure, or renal function between groups. Mirabegron was well-tolerated., Conclusions: Oral treatment with the β3-AR-agonist mirabegron for 1 week increased cardiac index and decreased pulmonary vascular resistance in patients with moderate to severe HFrEF. Mirabegron may be useful in patients with worsening or terminal HF., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: 2016-002367-34.

Objective: To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality., Methods: In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia., Results: Out of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment., Conclusion: Moderate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome., Competing Interests: Competing interests: LK received speaker’s honorarium from Novo, Novartis, AstraZeneca and Boehringer, unrelated to this study. NEB received investigator-initiated grant from the Novo Nordisk Foundation and from the Region of Zealand, not related to this study. ELF has received independent research grant from Novo Nordisk Foundation, unrelated to this study. The other authors have nothing to declare., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression., Methods: Patients completed the Hospital Anxiety and Depression Scale (HADS) at randomization, at antibiotic completion, and after month 3 and month 6. Changes in anxiety and depression (each subdimension 0-21, high scores indicating worse) were calculated using a repeated measure analysis of covariance model with primary assessment after 6 months. Change in score of 1.7 represented a minimal clinical important difference (MCID)., Results: Among the 400 patients enrolled in the POET trial, 263 (66%) completed HADS at randomization with reassessment rates of 86-87% at the three subsequent timepoints. Patients in the partial-oral group and the intravenous group had similar improvements after 6 months in levels of anxiety (-1.8 versus -1.6, P = 0.62) and depression (-2.1 versus -1.9, P = 0.63), although patients in the partial-oral group had numerically lower levels of anxiety and depression throughout. An improvement in MCID scores after 6 months was reported by 47% versus 45% (p = 0.80) patients for anxiety and by 51% versus 54% (p = 0.70) for depression., Conclusion: Patients with endocarditis receiving partial-oral outpatient treatment reported similar significant improvements in anxiety and depression at 6 months, as compared to conventionally treated, but numerically lower levels throughout. These findings support the usefulness of partial-oral treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Infective endocarditis (IE) is a serious complication of bacteremia and is most often caused by Gram positive cocci. We investigated the prevalence of IE in patients where echocardiography was encouraged when bacteremia with Gram positive cocci was present., Methods: The study included patients with Gram positive cocci bacteremia hospitalized at two Danish hospitals between March and December 2016. Information concerning echocardiography, demographics and bacterial species was collected from the patients' medical files. Patients without echocardiography were followed for 6 months in order to confirm or reject possible IE., Results: The study included 585 patients with Gram positive cocci bacteremia, and echocardiography was performed in 414 (71%) of them. The prevalence of IE in patients with high risk bacteremia, i.e. Staphylococcus aureus, non-beta-hemolytic streptococci, Enterococcus faecalis, and coagulase-negative staphylococci was 16%. Patients with Enterococcus faecalis had the highest prevalence of IE (33%) followed by non-beta-hemolytic streptococci (23%) and Staphylococcus aureus (12%). Among low risk bacteremia the prevalence of IE was 1%. The mean age of patients with IE was 74 years (SD 12.9) and 71% were male., Conclusion: These findings strongly support routine echocardiography in patients with high risk bacteremia and non-performance of echocardiography in patients with low risk bacteremia.

Aims: The present study had two aims: (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death., Methods and Results: In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by pre-determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow-up (median: 40 days), 25 COVID-19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07-1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07-1.35], P = 0.002, per 1% decrease) were significantly associated with COVID-19-related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease., Conclusions: RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF. Methods: This prospective study included 399 outpatients. Inclusion criteria were: age ≥ 60 years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed. Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction ( N  = 12 LVEF ≤ 40%, N  = 7 LVEF > 40% to ≤50%, N  = 46 LVEF > 50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16-2.72; p  = 0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22-1.82; p  < 0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC = 0.886; p  < 0.001) and NT-proBNP (AUC = 0.910; p  < 0.001) compared to patient-reported symptoms of HF (AUC = 0.830), but NT-proBNP added more diagnostic information compared to MR-proANP ( p  = 0.022). Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.

The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.

Objective: This study evaluated the associations between the natriuretic peptide activity and the neurohormonal response in non-obese and obese outpatients with and without heart failure (HF)., Background: Obesity-related HF may be a distinct subtype of HF. Obesity is associated with lower plasma concentrations of natriuretic peptides. The associations between obesity and neurohormonal activation estimated by mid-regional pro-adrenomedullin (MR-proADM) and copeptin in patients with HF is not elucidated., Methods: This prospective cohort-study included 392 outpatients ≥60years, plus ≥1 risk-factor(-s) for HF (hypertension, ischemic heart disease, atrial fibrillation, diabetes, chronic kidney disease), and without known HF. Patients were categorized 'non-obese' BMI = 18.5-29.9 kg/m 2 (n = 273) and 'obese' BMI ≥ 30 kg/m 2 (n = 119). The diagnosis of HF required signs, symptoms, and abnormal echocardiography. NT-proBNP, MR-proANP, MR-proADM, and copeptin were analyzed., Results: Obese patients were younger, had a higher prevalence of diabetes and chronic kidney disease, but a lower prevalence of atrial fibrillation. A total of 39 (14.3%) non-obese and 26 (21.8%) obese patients were diagnosed with HF. In obese patients, HF was not associated with higher plasma concentrations of NT-proBNP (Estimate: 0.063; 95%CI: -0.037-1.300; P = 0.064), MR-proANP (Estimate: 0.207; 95%CI: -0.101-0.515; P = 0.187), MR-proADM (Estimate: 0.112; 95%CI: -0.047-0.271; P = 0.168), or copeptin (Estimate: 0.093; 95%CI: -0.333-0.518; P = 0.669). Additionally, obese patients with HF had lower plasma concentrations of NT-proBNP (Estimate: -0.998; 95%CI: -1.778-0.218; P = 0.012), and MR-proANP (Estimate: -0.488; 95%CI: -0.845-0.132; P = 0.007) compared to non-obese patients with HF, whereas plasma concentrations of MR-proADM (Estimate: 0.066; 95%CI: -0.119-0.250; P = 0.484) and copeptin (Estimate: 0.140; 95%CI: -0.354-0.633; P = 0.578) were comparable., Conclusions: Patients with obesity-related HF have natriuretic peptide deficiency and lack of increased plasma concentrations of MR-proADM and copeptin suggesting that patients with obesity-related HF have a blunted overall neurohormonal activity., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Aims: To describe the prevalence of heart failure (HF) stages in elderly outpatients with risk factors for HF but without known HF, and characterise the clinical, biochemical and echocardiographic findings in each stage., Background: Early stages of HF are underdiagnosed; nevertheless, they are associated with an increased risk of hospitalisation and increased mortality. The prevalence of HF stages in elderly high-risk patients is unknown., Methods: A total of 400 patients were consecutively included: ≥60 years old, ≥1 risk factor for HF (diabetes, chronic kidney disease, cardiovascular disease, atrial fibrillation, hypertension), and without known or suspected HF. HF stages were defined as the following: stage A (risk factor for HF, normal echocardiography), stage B (abnormal echocardiography, without symptoms of HF) and stage C (abnormal echocardiography, symptoms of HF, clinical signs/increased plasma aminoterminal pro-B-type natriuretic peptide [NT-proBNP] concentrations)., Results: After thorough examination 44.25% of patients were categorised as HF stage A, 37.5% were HF stage B and 18.25% HF stage C. Those with higher stages of HF were older (p<0.001) and more often had atrial fibrillation (p=0.006). The median plasma NT-proBNP concentrations (pg/mL) were 132.5 for HF stage A, 275.5 for HF stage B and 400.0 for HF stage C (p<0.001). Detectable plasma troponin-I was more frequent with abnormal echocardiography: HF stage A 9.7%, HF stage B 27.3% and HF stage C 30.1% (p<0.001). HF stage C reported higher score on the Minnesota Living with Heart Failure Questionnaire (p<0.001)., Conclusions: In an elderly high-risk population without known or suspected HF, more than half were HF stage B or C. Higher stages of HF had increased plasma concentrations of NT-proBNP and troponin-I, besides a reduced quality of life. Focus on symptoms and signs of HF in this population are warranted., Competing Interests: Competing interests: None declared.

Background: The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography., Methods: 1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies., Results: Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively., Conclusions: Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown., Methods: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed., Results: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria., Conclusions: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).