Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study.

BACKGROUND AND AIMS: In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven clinical implementation of the oral step-down POET regimen was examined. METHODS: Patients with IE, caused by Staphylococcus aureus, Enterococcus faecalis, Streptococcus spp. or coagulase-negative staphylococci diagnosed between May 2019 and December 2020 were possible candidates for initiation of oral step-down antibiotic therapy, at the discretion of the treating physician. The composite primary outcome in patients finalizing antibiotic treatment consisted of embolic events, unplanned cardiac surgery, relapse of bacteraemia and all-cause mortality within 6 months. RESULTS: A total of 562 patients [median age 74 years (IQR, interquartile range, 65-80), 70% males] with IE were possible candidates; PO was given to 240 (43%) patients and IV to 322 (57%) patients. More patients in the IV group had IE caused by S. aureus, or had an intra-cardiac abscess, or a pacemaker and more were surgically treated. The primary outcome occurred in 30 (13%) patients in the PO group and in 59 (18%) patients in the IV group (P = .051); in the PO group, 20 (8%) patients died vs. 46 (14%) patients in the IV group (P = .024). PO-treated patients had a shorter median length of stay [PO 24 days (IQR 17-36) vs. IV 43 days (IQR 32-51), P < .001]. CONCLUSIONS: After clinical implementation of the POET regimen almost half of the possible candidates with IE received oral step-down antibiotic therapy. Patients in the IV group had more serious risk factors for negative outcomes. At 6-month follow-up, there was a numerically but not statistically significant difference towards a lower incidence of the primary outcome, a lower incidence of all-cause mortality and a reduced length of stay in the PO group. Due to the observational design of the study, the lower mortality may to some extent reflect selection bias and unmeasured confounding. Clinical implementation of PO regimens seemed feasible and safe.

Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial.

BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).

Left-sided heart disease and risk of death in patients with end-stage kidney disease receiving haemodialysis: an observational study.

BACKGROUND: Cardiovascular disease is the most common cause of death in patients with end-stage kidney disease on haemodialysis. The potential clinical consequence of systematic echocardiographic assessment is however not clear. In an unselected, contemporary population of patients on maintenance haemodialysis we aimed to assess: the prevalence of structural and functional heart disease, the potential therapeutic consequences of echocardiographic screening and whether left-sided heart disease is associated with prognosis. METHODS: Adult chronic haemodialysis patients in two large dialysis centres had transthoracic echocardiography performed prior to dialysis and were followed prospectively. Significant left-sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%. RESULTS: Among the 247 included patients (mean 66 years of age [95%CI 64-67], 68% male), 54 (22%) had significant left-sided heart disease. An LVEF ≤40% was observed in 31 patients (13%) and severe or moderate valve disease in 27 (11%) patients. The findings were not previously recognized in more than half of the patients (56%) prior to the study. Diagnosis had a potential impact on management in 31 (13%) patients including for 18 (7%) who would benefit from initiation of evidence-based heart failure therapy. After 2.8 years of follow-up, all-cause mortality among patients with and without left-sided heart disease was 52 and 32% respectively (hazard ratio [HR] 1.95 (95%CI 1.25-3.06). A multivariable adjusted Cox proportional hazard analysis showed that left-sided heart disease was an independent predictor of mortality with a HR of 1.60 (95%CI 1.01-2.55) along with age (HR per year 1.05 [95%CI 1.03-1.07]). CONCLUSION: Left ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage kidney failure on haemodialysis and are associated with a higher risk of death. For more than 10% of the included patients, systematic echocardiographic assessment had a potential clinical consequence.

YKL-40 in patients with end-stage renal disease receiving haemodialysis.

PURPOSE: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40. METHODS: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment. RESULTS: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL-1 (IQR: 193-291 µgL-1) before HD treatment and 198 µgL-1 (IQR: 147-258 µgL-1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment. CONCLUSION: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.

Effects of liraglutide and ischemic postconditioning on myocardial salvage after I/R injury in pigs.

OBJECTIVES: Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45 min coronary occlusion of left anterior descending artery (LAD). DESIGN: Fifty-eight non-diabetic female Danish Landrace pigs (60 ± 10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45 min. Group 1 (n = 14) was treated with i.v. liraglutide after 15 min of ischemia. Group 2 (n = 17) received liraglutide treatment concomitant with ischemic postconditioning, after 45 min of ischemia. Group 3 (n = 15) recieved ischemic postconditioning and group 4 (n = 12) was kept as controls. RESULTS: No intergroup differences in relative infarct size were detected (overall mean 57 ± 3%; p = 0.68). Overall mortality was 34% (CI 25-41%) including 26% post-intervention, with no intergroup differences (p = 0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25-80%) including 39% postintervention with no intergroup differences (p = 0.65). CONCLUSIONS: In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.

Prevalence of airflow obstruction in patients with stable systolic heart failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in heart failure (HF). However, routine use of spirometry in outpatient HF clinics is not implemented. The aim of the present study was to determine the prevalence of both airflow obstruction and non obstructive lung function impairment in patients with HF and to examine the effect of optimal medical treatment for HF on lung function parameters. METHODS: Consecutive patients with HF (ejection fraction (EF) < 45%) and New York Heart Association (NYHA) functional class II-IV at 10 different outpatient heart failure clinics were examined with spirometry at their first visit and after optimal medical treatment for HF was achieved. airflow obstruction was classified and graded according to the GOLD 2011 revision. RESULTS: Baseline spirometry was performed in 593 included patients and 71 (12%) had a clinical diagnosis of COPD. Mean age was 69 ± 11 years and mean EF was 30 ± 9%. Thirty-two % of the patients were active smokers and 53% were previous smokers. Mean FEV1 and FVC was 77.9 ± 1.7% and 85.4 ± 1.5% of predicted respectively. Obstructive pattern was observed in 233 (39%) of the patients. Of these, 53 patients (9%) had mild disease (GOLD I) and 180 (30%) patients had moderate to very severe disease (GOLD II-IV). No difference in spirometric variables was observed following up titration of medication. CONCLUSION: In stable patients with HF airflow obstruction is frequent and severely underdiagnosed. Spirometry should be considered in all patients with HF in order to improve diagnosis and treatment for concomitant pulmonary disease.

Iron Deficiency in COPD Associates with Increased Pulmonary Artery Pressure Estimated by Echocardiography.

OBJECTIVES: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients. METHODS: Non-anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin<100µg/L. Pulmonary artery pressure was estimated from the tricuspid regurgitation maximum velocity (TR Vmax). Tricuspid regurgitation Vmax indicative of pulmonary hypertension was considered present for values ≥ 2.9 m/s. RESULTS: In a total of 75 included patients, 31 (41%) had ID. These patients had a significantly higher TR Vmax (3.02 vs. 2.77 m/s, p=0.01) and lower diffusion capacity of carbon monoxide (40% vs. 50% of predicted, p<0.01), though similar in age, sex, pack years, FEV1 and high-sensitive CRP (p>0.05). Ferritin inversely correlated with TR Vmax in ID patients (-0.37 (p=0.04)). The prevalence of TR Vmax ≥ 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID (compared to no ID) was 3.3 (95% CI 1.3-8.6, p=0.015). CONCLUSION: Iron deficiency in non-anaemic COPD patients was associated with a modest increase in systolic pulmonary artery pressure and limitation of diffusion capacity.

Influence of acute glycaemic level on measures of myocardial infarction in non-diabetic pigs.

OBJECTIVE: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model. DESIGN: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk. RESULTS: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups. CONCLUSION: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.

Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

BACKGROUND AND PURPOSE: There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. METHODS: Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years and female sex (CHA2DS2-VASc) scores. RESULTS: One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4-7.2, all P≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0; P<0.001). CONCLUSIONS: In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Risk stratification in emergency patients by copeptin.

BACKGROUND: Rapid risk stratification is a core task in emergency medicine. Identifying patients at high and low risk shortly after admission could help clinical decision-making regarding treatment, level of observation, allocation of resources and post discharge follow-up. The purpose of the present study was to determine short-, mid- and long-term mortality by plasma measurement of copeptin in unselected admitted patients. METHOD: Consecutive patients >40-years-old admitted to an inner-city hospital were included. Within the first 24 hours after admission, a structured medical interview was conducted and self-reported medical history was recorded. All patients underwent a clinical examination, an echocardiographic evaluation and collection of blood for later measurement of risk markers. RESULTS: Plasma for copeptin measurement was available from 1,320 patients (average age 70.5 years, 59.4% women). Median follow-up time was 11.5 years (range 11.0 to 12.0 years). Copeptin was elevated (that is, above the 97.5 percentile in healthy individuals).Mortality within the first week was 2.7% (17/627) for patients with elevated copeptin (above the 97.5 percentile, that is, >11.3 pmol/L) compared to 0.1% (1/693) for patients with normal copeptin concentrations (that is, ≤11.3 pmol/L) (P <0.01). Three-month mortality was 14.5% (91/627) for patients with elevated copeptin compared to 3.2% (22/693) for patients with normal copeptin. Similar figures for one-year mortality and for the entire observation period were 27.6% (173/627) versus 8.7% (60/693) and 82.9% (520/527) versus 57.5% (398/693) (P <0.01 for both), respectively.Using multivariable Cox regression analyses shows that elevated copeptin was significantly and independently related to short-, mid- and long-term mortality. Adjusted hazard ratios were 2.4 for three-month mortality, 1.9 for one-year mortality and 1.4 for mortality in the entire observation period. CONCLUSIONS: In patients admitted to an inner-city hospital, copeptin was strongly associated with short-, mid- and long-term mortality. The results suggest that rapid copeptin measurement could be a useful tool for both disposition in an emergency department and for mid- and long-term risk assessment.