Changes and Prognostic Implications of Myocardial Work in Aortic Stenosis Subtypes Undergoing Transcatheter Valve Implantation.

Background: Evaluation of left ventricle (LV) systolic function in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) is challenging, as LV ejection fraction (LVEF) and global longitudinal strain are afterload dependent. LV global work indices (GWIs) estimate the afterload corrected systolic function. Objectives: The purpose of this study was to evaluate changes in and prognostic implications of GWIs in subtypes of AS patients before and 1 month after TAVI. Methods: We included 473 patients undergoing TAVI. GWI was estimated using strain imaging and by adding the aortic valve mean gradient to the systolic blood pressure. The primary endpoint was all-cause mortality, evaluated by Cox proportional hazards and Kaplan-Meier curves. Results: High gradient, low flow/low gradient, and normal flow/low gradient AS was found in 48%, 27%, and 25%. In patients with LVEF ≥50% delta GWI decreased from preoperative assessment to 1-month follow-up across all subtypes; high gradient (-353 ± 589 mm Hg%, P < 0.01), low flow/low gradient (-151 ± 652 mm Hg%, P = 0.13), and normal flow/low gradient (-348 ± 606 mm Hg%, P < 0.01). For patients with LVEF <50% delta GWI increased; high gradient 127 ± 491 mm Hg%, P = 0.05; low flow/low gradient 106 ± 510 mm Hg%, P = 0.06; normal flow/low gradient 107 ± 550 mm Hg%, P < 0.27. The median follow-up time was 60 months (IQR: 45-69 months). Each step of 100 mm Hg% higher GWI at pre-TAVI assessment was associated with a reduction in all-cause mortality in multivariable analysis (HR: 0.96 [95% CI: 0.92-1.00], P = 0.033). Conclusions: GWI increases in patients with reduced LVEF after TAVI across AS subtypes whereas GWI decreases in patients with preserved LVEF. Assessment of GWI offers additional prognostic implications beyond LVEF and global longitudinal strain.

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.

Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study.

Background: Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. Methods: In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Findings: Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4-2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8-2.3) and 1.5% (0.8-2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8-9.2) vs. 4.7% (3.2-6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Interpretation: Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI. Funding: The funder had no role in the study design, data management, or writing.

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

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

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

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.

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.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

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.

Prognostic implications of residual left ventricular hypertrophy and systolic dysfunction in aortic stenosis following transcatheter aortic valve replacement.

The impact of left ventricle (LV) hypertrophy (LVH) regression on contractility-associated measures, the extent of residual cardiac dysfunction and prognostic implications after the initial remodeling process after transcatheter aortic valve replacement (TAVR) has not been investigated. We aimed to assess whether greater LV mass regression from pre-TAVR to 12-months after TAVR was associated with increased systolic function; and assess the prognostic value of residual LVH, systolic function and contractility-associated measures 12-months after TAVR. A total of 439 symptomatic patients were included and examined by echocardiography. LVH regression was assessed as percentage change in LV mass index (LVMi) from baseline to 12-months after TAVR. Midwall fractional shortening (mFS) and stress-corrected (SC-mFS) were used as contractility-associated measures. Primary outcome was all-cause mortality. SC-mFS increased from 0.94 (0.7) at baseline (BS) to 1.22 (0.7) (p < 0.05) 12-months after TAVR for patients with the most LVH regression, compared to patients with no LV regression (BS 1.06 (0.7) to 1.04 (0.5), NS). At 12-months after TAVR, multivariate analysis showed independent prognostic value of LVEF < 50% or GLS < 15% (HR 1.59, p = 0.049) and mFS < 14% (HR 1.99, p = 0.002) for future all cause death. LVH regression in AS after TAVR is associated with significant improvements of LV systolic function in contrast to patients without LV regression. Residual LVH and subsequent LV systolic dysfunction is substantial 12 months after TAVR and are associated with reduced survival. Impaired mFS and the combination of abnormal LVEF or GLS independently predicted all-cause mortality beyond 12 months after TAVR.

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

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

Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial.

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.

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis.

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.

Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts.

A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.

Distribution and prognostic value of left ventricular global longitudinal strain in elderly patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival. METHODS: We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available. RESULTS: Mean age was 80.1 ± 7.1 years and aortic valve area (AVA) index 0.4 ± 0.1 cm2. 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50 ± 13% and mean LVGLS was - 14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS > - 18% was seen in 75% of the patients. Previous myocardial infarction, LVEF < 50%, LVGLS > - 14%, low gradient AS (< 4.0 m/s), tricuspid regurgitant gradient > 30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS > - 14% (HR 1.79 [1.02-3.14], p = 0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS > - 14% in the total population (p < 0.002) but also in patients with high AS gradient with preserved LVEF. LVGLS provided incremental prognostic value with respect to clinical characteristics, AVA and LVEF (χ2 19.9, p = 0.006). CONCLUSIONS: In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS > - 14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS > - 14%.

Prevalence and Prognostic Implications of Increased Apical-to-Basal Strain Ratio in Patients with Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: The aim of this study was to investigate the preoperative prevalence, relation to symptoms, and prognostic implications of elevated left ventricular (LV) apical-to-basal strain ratio (ABr) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement. METHODS: A total of 499 contemporary consecutive patients with AS treated with transcatheter aortic valve replacement were retrospectively included. Patients were included if they underwent preoperative echocardiography with adequate image quality for assessment of LV global longitudinal strain. Baseline clinical and echocardiographic data were collected and analyzed in ABr subgroups. From two-dimensional echocardiographic apical images, ABr was calculated as mean longitudinal strain of the five LV apical segments divided by the mean of the six basal segments. RESULTS: Median follow-up time was 743 days. Mean age was 79.8 ± 7 years. The prevalence of severely increased ABr ≥4 was 16% (n = 78). Patients with ABr ≥4 had higher preoperative New York Heart Association functional class; 77% of those with ABr ≥4 were in New York Heart Association functional class III or IV compared with 59% of those with ABr of 0 to 1.9 (P < .01). Median preoperative N-terminal pro-brain natriuretic peptide level in patients with ABr ≥4 was 1,781 pmol/L, compared with 876 pmol/L in those with ABr of 0 to 1.9 (P = .003). N-terminal pro-brain natriuretic peptide levels at 3-month follow-up remained considerably elevated in patients with ABr ≥4 (the median in patients with ABr ≥4 was 1,262 pmol/L vs 645 pmol/L in those with ABr of 0 to 1.9, P < .01). AS severity was comparable across ABr subgroup levels. Overall, increased ABr ≥4 was associated with poor survival, as overall 3-year survival was 67% among patients with ABr ≥4 compared with 83% in those with ABr of 2 to 3.9 and 86% in those with ABr of 0 to 1.9 (P = .04). CONCLUSION: Among patients with increased ABr ≥4, pre- and postoperative New York Heart Association functional class, serum N-terminal pro-brain natriuretic peptide level, and mortality were significantly increased, and ABr may thus serve as a new echocardiographic marker of high mortality risk among patients with AS treated with transcatheter aortic valve replacement.

Accelerated treatment of endocarditis-The POET II trial: Rationale and design of a randomized controlled trial.

BACKGROUND: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. OBJECTIVE: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. METHODS: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. CONCLUSIONS: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.

Major Differences in the Use of Protocols for Dispatcher-Assisted Cardiopulmonary Resuscitation Among ILCOR Member Countries.

INTRODUCTION AND PURPOSE: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) increases the rate of bystander cardiopulmonary resuscitation (CPR). DA-CPR is recommended by resuscitation councils globally and it has been shown that the general public expects to receive pre-arrival instructions while waiting for help. A scientific advisory from the American Heart Association identifies standardized and structured DA-CPR protocols as important to increase bystander CPR rates. This study aims to investigate whether different International Liaison Committee on Resuscitation (ILCOR) member countries use DA-CPR protocols and to compare protocol contents between countries. METHODS: All resuscitation councils forming ILCOR were inquired by email to provide a copy of their DA-CPR protocol, and to state whether this protocol was used by all emergency dispatch centers in their country. The collected protocols were translated into English, and content was compared. RESULTS: A total of 60 countries were contacted (response rate: 83%). Of these, 46% stated to have a nationwide protocol, 30% reported to use local protocols, and 24% did not use a protocol. Overall, 54% provided a copy of their protocol. All translated protocols asked the rescuer to check for responsiveness and breathing, 35% to activate phone speaker function, half contained notes about agonal breathing and 59% included notes about integrating an automated external defibrillator. CONCLUSION: Almost one quarter of ILCOR member countries did not use a protocol for DA-CPR. Half of the protocols included notes about agonal breathing. Activation of phone speaker function and protocolled encouragements during CPR were rarely included.

Diagnostic delay in wild type transthyretin cardiac amyloidosis - A clinical challenge.

AIM: To determine the diagnostic delay in patients with wild-type transthyretin cardiac amyloiodosis (ATTRwt). To determine the clinical and echocardiogtraphic characteristics of patients with an early and a late diagnosis and to study the suspected diagnoses and identification of diagnostic "red flags" before the ATTRwt diagnosis was established. METHODS: In 50 consecutive patients with ATTRwt diagnosed from 2017 to 2019, clinical and echocardiographic patient characteristics were investigated based on electronic patient charts and echocardiographic database review at Aarhus University Hospital, Denmark. RESULTS: The median diagnostic delay was 13 months (2-47 months) and a diagnostic delay above 3 months was associated with more advanced symptoms and left ventricular (LV) diastolic dysfunction at the time of the diagnosis. Thirty patients (60%) were investigated for at least two non-ATTRwt diagnoses during the time period from the first cardiac examination to the time of the confirmed diagnosis. ATTR red flags were significantly less used in patients with the longest diagnostic delay (p < 0.001). Abormal LV global longitudinal strain (LV-GLS < 18%) and apical sparring ratio (APSR ≥ 1.5) were present in 96% and 94% of the ATTRwt patients, respectively. CONCLUSION: The diagnostic delay in ATTRwt was substantial and a prolonged diagnostic delay was associated with more advanced symptoms and LV diastolic dysfunction at the time of the diagnosis. Established ATTR red flags are poorly utilized in the diagnostic process. Echocardiographic analysis of LV-GLS and APSR contributes significantly to the evaluation of LV myocardial performance and helps raise the suspicion of ATTRwt.

Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study.

AIMS: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. METHODS AND RESULTS: By crosslinking nationwide registries from 2010 to 2017, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. In total 69 021, distributed with 15 350, 16 726, 19 251, and 17 694 BSIs were identified in the periods of 2010-2011, 2012-2013, 2014-2015, and 2016-2017, respectively. Patients with E. faecalis had the highest prevalence of IE (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis and Streptococcus spp. increased significantly (P = 0.0005 and P = 0.03, respectively). Male patients had a higher prevalence of IE for E. faecalis, Streptococcus spp., and CoNS compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. CONCLUSION: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI.

Type 2 diabetes mellitus worsens neurological injury following cardiac arrest: an animal experimental study.

BACKGROUND: Cardiac arrest carries a poor prognosis. The typical cardiac arrest patient is comorbid, and studies have shown that diabetes mellitus is an independent risk factor for increased mortality after cardiac arrest. Despite this, animal studies lack to investigate cardiac arrest in the setting of diabetes mellitus. We hypothesize that type 2 diabetes mellitus in a rat model of cardiac arrest is associated with increased organ dysfunction when compared with non-diabetic rats. METHODS: Zucker diabetic fatty (ZDF) rats (n = 13), non-diabetic Zucker lean control (ZLC) rats (n = 15), and non-diabetic Sprague Dawley (SprD) rats (n = 8), underwent asphyxia-induced cardiac arrest. Animals were resuscitated and monitored for 180 min after return of spontaneous circulation (ROSC). Blood levels of neuron-specific enolase were measured to assess neurological injury. Cardiac function was evaluated by echocardiography. RESULTS: No differences in cardiac output or neuron-specific enolase existed between the groups at baseline. Median levels of neuron-specific enolase 180 min after ROSC was 10.8 µg/L (Q25;Q75-7.6;11.3) in the ZDF group, which was significantly higher compared to the ZLC group at 2.0 µg/L (Q25;Q75-1.7;2.3, p < 0.05) and the SprD group at 2.8 µg/L (Q25;Q75-2.3;3.4, p < 0.05). At 180 min after ROSC, cardiac output was 129 mL/min/kg (SD 45) in the ZDF group, which was not different from 106 mL/min/kg (SD 31) in the ZLC group or 123 mL/min/kg (SD 26, p = 0.72) in the SprD group. CONCLUSIONS: In a cardiac arrest model, neuronal injury is increased in type 2 diabetes mellitus animals compared with non-diabetic controls. Although this study lacks to uncover the specific mechanisms causing increased neuronal injury, the establishment of a cardiac arrest model of type 2 diabetes mellitus lays the important foundation for further experimental investigations within this field.