Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.

Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF stress trial.

BACKGROUND: With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests. METHODS: The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e' > 8) who underwent simultaneous rest and exercise-stress echocardiography and right heart catheterisation (RHC). HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15 mmHg stress: ≥25 mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e'). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH). RESULTS: The final study population included 68 patients (HFpEF n = 34 and NCD n = 34) of which 23 reached the clinical endpoint, 1 patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p < 0.001) compared to patients with a score ≤ 4. LA compliance at rest outperformed E/e' (AUC 0.78 vs 0.87, p = 0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p = 0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p < 0.001) irrespective of concomitant atrial fibrillation. CONCLUSIONS: LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.

Repurposing the ß3-Adrenergic Receptor Agonist Mirabegron in Patients With Structural Cardiac Disease: The Beta3-LVH Phase 2b Randomized Clinical Trial.

Importance: Left ventricular (LV) hypertrophy contributes to the onset and progression of heart failure (HF), particularly for patients with pre-HF (stage B) for whom no treatment has yet proven effective to prevent transition to overt HF (stage C). The ß3-adrenergic receptors (ß3ARs) may represent a new target, as their activation attenuates LV remodeling. Objective: To determine whether activation of ß3ARs by repurposing a ß3AR agonist, mirabegron, is safe and effective in preventing progression of LV hypertrophy and diastolic dysfunction among patients with pre- or mild HF. Design, Setting, and Participants: The Beta3-LVH prospective, triple-blind, placebo-controlled phase 2b randomized clinical trial enrolled patients between September 12, 2016, and February 26, 2021, with a follow-up of 12 months. The trial was conducted at 10 academic hospitals in 8 countries across Europe (Germany, Poland, France, Belgium, Italy, Portugal, Greece, and the UK). Patients aged 18 years or older with or without HF symptoms (maximum New York Heart Association class II) were screened for the presence of LV hypertrophy (increased LV mass index [LVMI] of ≥95 g/m2 for women or ≥115 g/m2 for men) or maximum wall thickness of 13 mm or greater using echocardiography. Data analysis was performed in August 2022. Intervention: Participants were randomly assigned (1:1) to mirabegron (50 mg/d) or placebo, stratified by the presence of atrial fibrillation and/or type 2 diabetes, for 12 months. Main Outcomes and Measures: The primary end points were LVMI determined using cardiac magnetic resonance imaging and LV diastolic function (early diastolic tissue Doppler velocity [E/e'] ratio assessed using Doppler echocardiography) at 12 months. Patients with at least 1 valid measurement of either primary end point were included in the primary analysis. Safety was assessed for all patients who received at least 1 dose of study medication. Results: Of the 380 patients screened, 296 were enrolled in the trial. There were 147 patients randomized to mirabegron (116 men [79%]; mean [SD] age, 64.0 [10.2] years) and 149 to placebo (112 men [75%]; mean [SD] age, 62.2 [10.9] years). All patients were included in the primary intention-to-treat analysis. At 12 months, the baseline and covariate-adjusted differences between groups included a 1.3-g/m2 increase in LVMI (95% CI, -0.15 to 2.74; P = .08) and a -0.15 decrease in E/e' (95% CI, -0.69 to 0.4; P = .60). A total of 213 adverse events (AEs) occurred in 82 mirabegron-treated patients (including 31 serious AEs in 19 patients) and 215 AEs occurred in 88 placebo-treated patients (including 30 serious AEs in 22 patients). No deaths occurred during the trial. Conclusions: In this study, mirabegron therapy had a neutral effect on LV mass or diastolic function over 12 months among patients who had structural heart disease with no or mild HF symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02599480.

Concomitant latent pulmonary vascular disease leads to impaired global cardiac performance in heart failure with preserved ejection fraction.

AIMS: The REDUCE-LAP II trial demonstrated adverse outcomes after interatrial shunt device (IASD) placement in heart failure with preserved ejection fraction (HFpEF) attributed to latent pulmonary vascular disease (PVD). We hypothesized that exercise stress cardiovascular magnetic resonance (CMR) imaging could provide non-invasive characterization of cardiac and pulmonary physiology for improved patient selection. METHODS AND RESULTS: The HFpEF-Stress trial prospectively enrolled 75 patients with exertional dyspnoea and diastolic dysfunction. Patients underwent rest and exercise stress right heart catheterization, echocardiography and CMR imaging. Pulmonary artery and capillary wedge pressures, cardiac index (CI) and pulmonary vascular resistance (PVR) were calculated. Latent PVD was defined as increased PVR ≥ 1.74 Wood units during exercise stress. CMR assessed long-axis strains (LAS) and filling volumes of all cardiac chambers. Right ventricular (RV) function was further quantified by stroke and peak flow volumes. Patients with latent PVD (n = 24) showed lower RV function (rest tricuspid annular plane systolic excursion, p = 0.010; stress RV LAS, p < 0.001) compared to patients without (n = 43). During exercise stress, RV stroke and peak flow volumes (p < 0.001) were reduced and led to impaired left atrial filling (p = 0.040) with a strong statistical trend to impaired ventricular (LV) filling (p = 0.098). This subsequently resulted in reduced LV-CI (p < 0.001) despite preserved LV systolic function (LV LAS p ≥ 0.255). The degree of RV dysfunction during exercise stress best predicted latent PVD (RV peak flow, area under the curve at rest 0.73 vs. stress 0.89, p = 0.004). CONCLUSIONS: Latent PVD is a feature of HFpEF and is associated with impaired RV functional reserve, global diastolic filling and LV-CI. This can be quantified by CMR and used to identify patients likely to benefit from IASD implantation.

[Management of chronic heart failure: state of the art according to the 2021 guideline]. / Therapie der chronischen Herzinsuffizienz ­ State of the Art nach den europäischen Leitlinien von 2021.

Treatment of heart failure with reduced ejection fraction (HFrEF) requires four drug classes that should be initiated simultaneously and up-titrated rapidly. All four have received class I recommendations. Sacubitril/valsartan can be considered in initial treatment, even for patients in whom no previous treatment with an angiotensin converting enzyme inhibitor has been given. Treatment with dapagliflozin and empagliflozin is started irrespective of diabetes mellitus to reduce mortality and hospitalization rates for heart failure. Most drug treatment recommendations for HFrEF can be extrapolated to heart failure with mildly-reduced ejection fraction, even though the evidence base is not as robust as in HFrEF. Treatment individualization considers co-morbidities such as atrial fibrillation, valvular disease and iron deficiency as well as advanced heart failure. Following cardiac decompensation, verciguat is now available as an additional treatment option.

Structured, Harmonized, and Interoperable Integration of Clinical Routine Data to Compute Heart Failure Risk Scores.

Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.

Pharmacological treatment options for heart failure with reduced ejection fraction: A 2022 update.

INTRODUCTION: Despite considerable advances in the treatment of heart failure with reduced ejection fraction (HFrEF) over the last 60 years, mortality and morbidity remains high. Fortunately, in the last years, further developments expanded the toolbox for HF treatment. AREAS COVERED: The authors provide an overview of recent developments in HF treatment and bring the recommendations in the HF guidelines of the European Society of Cardiology into perspective. EXPERT OPINION: Nowadays, basic pharmacological treatment of patients with HFrEF consists of a combination of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA), and the SGLT2 inhibitors dapagliflozin or empagliflozin. Treatment initiation of all four drug classes should be fast and simultaneous. In some cases, the ARNI sacubitril/valsartan may be initiated even in ACE inhibitor-naïve patients. Further HF treatment has to be individualized. Another important point is that both SGLT2 inhibitors and vericiguat can be used in patients with severely reduced kidney function. Finally, an important piece in the HF management puzzle is the treatment of its comorbidities. For instance, patients hospitalized for acute HF decompensation should be systematically screened for iron deficiency, since HF patients with proven iron deficiency benefit from intravenous ferric carboxymaltose.

Travelling with heart failure: risk assessment and practical recommendations.

Patients with heart failure are at a higher risk of cardiovascular events compared with the general population, particularly during domestic or international travel. Patients with heart failure should adhere to specific recommendations during travel to lower their risk of developing heart failure symptoms. In this Review, we aim to provide clinicians with a set of guidelines for patients with heart failure embarking on national or international travel. Considerations when choosing a travel destination include travel distance and time, the season upon arrival, air pollution levels, jet lag and altitude level because all these factors can increase the risk of symptom development in patients with heart failure. In particular, volume depletion is of major concern while travelling given that it can contribute to worsening heart failure symptoms. Pre-travel risk assessment should be performed by a clinician 4-6 weeks before departure, and patients should receive advice on potential travel-related illness and on strategies to prevent volume depletion. Oxygen supplementation might be useful for patients who are very symptomatic. Upon arrival at the destination, potential drug-induced photosensitivity (particularly in tropical destinations) and risks associated with the local cuisine require consideration. Special recommendations are needed for patients with cardiac implantable electronic devices or left ventricular assist devices as well as for those who have undergone major cardiac surgery.

Exercise Stress Real-Time Cardiac Magnetic Resonance Imaging for Noninvasive Characterization of Heart Failure With Preserved Ejection Fraction: The HFpEF-Stress Trial.

BACKGROUND: Right heart catheterization using exercise stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiac magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary noninvasive alternative for diagnosing HFpEF. METHODS: The HFpEF-Stress trial (CMR Exercise Stress Testing in HFpEF; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association class ≥II) to undergo echocardiography, right heart catheterization, and RT-CMR at rest and during exercise stress. HFpEF was defined according to pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular filling, left atrial (LA) emptying, and left ventricular/LA long axis strain. RESULTS: Patients with HFpEF (n=34; median pulmonary capillary wedge pressure at rest, 13 mm Hg; at stress, 27 mm Hg) had higher E/e' (12.5 versus 9.15), NT-proBNP (N-terminal pro-B-type natriuretic peptide; 255 versus 75 ng/L), and LA volume index (43.8 versus 36.2 mL/m2) compared with patients with noncardiac dyspnea (n=34; rest, 8 mm Hg; stress, 18 mm Hg; P≤0.001 for all). Seven patients were excluded because of the presence of non-HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR left ventricular total and early diastolic filling at rest and during exercise stress (P≥0.164) between patients with HFpEF and noncardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (P<0.001) diastolic emptying in patients with HFpEF during exercise stress. RT-CMR exercise stress LA long axis strain was independently associated with HFpEF (adjusted odds ratio, 0.657 [95% CI, 0.516-0.838]; P=0.001) after adjustment for clinical and imaging measures and emerged as the best predictor for HFpEF (area under the curve at rest 0.82 versus exercise stress 0.93; P=0.029). CONCLUSIONS: RT-CMR allows highly accurate identification of HFpEF during physiologic exercise and qualifies as a suitable noninvasive diagnostic alternative. These results will need to be confirmed in multicenter prospective research studies to establish widespread routine clinical use. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17.

A machine learning approach for the prediction of pulmonary hypertension.

BACKGROUND: Machine learning (ML) is a powerful tool for identifying and structuring several informative variables for predictive tasks. Here, we investigated how ML algorithms may assist in echocardiographic pulmonary hypertension (PH) prediction, where current guidelines recommend integrating several echocardiographic parameters. METHODS: In our database of 90 patients with invasively determined pulmonary artery pressure (PAP) with corresponding echocardiographic estimations of PAP obtained within 24 hours, we trained and applied five ML algorithms (random forest of classification trees, random forest of regression trees, lasso penalized logistic regression, boosted classification trees, support vector machines) using a 10 times 3-fold cross-validation (CV) scheme. RESULTS: ML algorithms achieved high prediction accuracies: support vector machines (AUC 0.83; 95% CI 0.73-0.93), boosted classification trees (AUC 0.80; 95% CI 0.68-0.92), lasso penalized logistic regression (AUC 0.78; 95% CI 0.67-0.89), random forest of classification trees (AUC 0.85; 95% CI 0.75-0.95), random forest of regression trees (AUC 0.87; 95% CI 0.78-0.96). In contrast to the best of several conventional formulae (by Aduen et al.), this ML algorithm is based on several echocardiographic signs and feature selection, with estimated right atrial pressure (RAP) being of minor importance. CONCLUSIONS: Using ML, we were able to predict pulmonary hypertension based on a broader set of echocardiographic data with little reliance on estimated RAP compared to an existing formula with non-inferior performance. With the conceptual advantages of a broader and unbiased selection and weighting of data our ML approach is suited for high level assistance in PH prediction.

Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study.

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a post hoc analysis of 843 normotensive PE patients prospectively included in three European cohorts.Within the first 30 days, 21 patients (2.5%, 95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to PE. Patients with copeptin ≥24 pmol·L-1 had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3-25.6, p=0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248 intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95% CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at higher risk was even better when copeptin was measured on top of the 2014 ESC algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6-27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest risk group versus all other risk groups). This identified 85 patients (10.1%) with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4-16.2) at risk of PE-related deaths.Copeptin improves risk stratification of normotensive PE patients, especially when identifying patients with an increased risk of an adverse outcome.

Echocardiographic Estimation of Mean Pulmonary Artery Pressure: A Comparison of Different Approaches to Assign the Likelihood of Pulmonary Hypertension.

BACKGROUND: Current guidelines advise using echocardiography for noninvasive estimation of the likelihood that a patient has pulmonary hypertension (PH). To estimate the echocardiographic probability of PH, the maximal tricuspid regurgitation velocity (TR Vmax) is recommended as the main parameter to use over more complex algorithms that provide an estimation of pulmonary artery pressure. This preference is based on concerns about inaccuracies and amplification of measurement errors that can occur from using derived variables. However, this has not been examined systematically. METHODS: A retrospective database analysis was performed of invasively determined measurements of right heart pressure in 90 patients, corresponding echocardiographic estimations of pulmonary artery pressure, and additional parameters obtained within 24 hours. Several algorithms were compared for their correlations and accuracy parameters. RESULTS: Although a Bland-Altman analysis demonstrated that all examined algorithms exhibited inaccuracies that could be clinically relevant in individuals, algorithms estimating mean pulmonary artery pressure (PAPm) on the basis of tricuspid regurgitation generally exhibited stronger correlations with invasively determined PAPm and more accurate identification of PH than did TR Vmax. Echocardiographic estimation of right atrial pressure >15 mm Hg exhibited the highest odds ratio for invasively confirmed PH, suggesting that this parameter is of additional diagnostic value. Indeed, algorithms that also considered right atrial pressure performed best, whereas empirical algorithms, TR Vmax, and methods relying on pulmonary acceleration time exhibited weaker performance. CONCLUSIONS: Although all methods are associated with inaccuracies, echocardiographically determined PAPm was superior to the current guideline recommendation of using TR Vmax with regard to its correlation with invasively determined PAPm and the presence of PH. PAPm may be considered as an alternative to TR Vmax for evaluating the echocardiographic probability of PH.

Mid- to long-term outcome of patients treated with everolimus-eluting bioresorbable vascular scaffolds: Data of the BVS registry Göttingen predominantly from ACS patients.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) are widely used in routine clinical practice. While previous studies reported acceptable short- to midterm outcome after BVS implantation, data on longer-term outcome are rare. METHODS: Patients treated with at least one Absorb®-BVS were consecutively enrolled. Follow-up data were assessed after 834.0 [769.0-1026.0] days. The primary device-oriented composite endpoint (DOCE) was defined as cardiovascular death, myocardial infarction (MI) and/or target lesion revascularization (TLR). RESULTS: Between 2012 and 2014, 195 patients were included into study analysis. Overall, 244 BVS were implanted. Mean patient age was 64.0[54.3-74.0] years. Three-quarter of patients had an ACS; of those 42.9% had ST-elevation-MI and 40.8% had non-ST-elevation-MI. DOCE occurred in 3.1%, 6.7%, 11.8% and 15.4% of patients during hospital stay, within 6-months, 18-months or during the complete follow-up period, respectively. In those patients, median time until DOCE was 211.5[43.25-567.25] days. In 11 (36.7%) patients DOCE occurred after >12months. Using univariable analysis, bifurcation stenting was associated with a hazard ratio (HR) of 11.8[2.38-58.57] for TLR (p=0.002) and 2.1[1.02-4.49] for DOCE (p=0.045). Similarly, in ACS patients, bifurcation stenting was associated with an increased risk for TLR (HR=10.4[2.01-53.56]; p=0.005) and for DOCE (HR=2.4[1.09-5.32]; p=0.029) and in multivariable analysis, it remained an independent predictor of DOCE (HR=3.0; p=0.018). CONCLUSIONS: Although, the rates of (potentially) device-related complications following BVS implantation are acceptable, they are nonetheless not negligible. Interestingly, they did not decline over time. Bifurcation stenting could be found as relevant procedure-related predictor of DOCE, especially in ACS patients. Randomized trials are warranted to confirm these findings.

Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival.

TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity.

Early pneumonia and timing of antibiotic therapy in patients after nontraumatic out-of-hospital cardiac arrest.

BACKGROUND: While early pneumonia is common in patients after out-of-hospital cardiac arrest (OHCA), little is known about the impact of pneumonia and the optimal timing of antibiotic therapy after OHCA. METHODS: We conducted a 5-year retrospective cohort study, including patients who suffered from OHCA and were treated with therapeutic hypothermia. ICU treatment was strictly standardized with defined treatment goals and procedures. Medical records, chest radiographic images and microbiological findings were reviewed. RESULTS: Within the study period, 442 patients were admitted to our medical ICU after successfully resuscitated cardiac arrest. Of those, 174 patients fulfilled all inclusion and no exclusion criteria and were included into final analysis. Pneumonia within the first week could be confirmed in 39 patients (22.4%) and was confirmed or probable in 100 patients (57.5%), without a difference between survivors and non-survivors (37.8% vs. 23.1% confirmed pneumonia, p = 0.125). In patients with confirmed pneumonia a tracheotomy was performed more frequently (28.2 vs. 12.6%, p = 0.026) compared to patients without confirmed pneumonia. Importantly, patients with confirmed pneumonia had a longer ICU- (14.0 [8.5-20.0] vs. 8.0 [5.0-14.0] days, p < 0.001) and hospital stay (23.0 [11.5-29.0] vs. 15.0 [6.5-25.0] days, p = 0.016). A positive end expiratory pressure (PEEP) > =10.5 mbar on day 1 of the hospital stay was identified as early predictor of confirmed pneumonia (odds ratio 2.898, p = 0.006). No other reliable predictor could be identified. Median time to antibiotic therapy was 8.7 [5.4-22.8] hours, without a difference between patients with or without confirmed pneumonia (p = 0.381) and without a difference between survivors and non-survivors (p = 0.264). Patients receiving antibiotics within 12 hours after admission had a shorter ICU- (8.0 [4.0-14.0] vs. 10.5 [6.0-16.0] vs. 13.5 [8.0-20.0] days, p = 0.004) and hospital-stay (14.0 [6.0-25.0] vs. 16.5 [11.0-27.0] vs. 21.0 [17.0-28.0] days, p = 0.007) compared to patients receiving antibiotics after 12 to 36 or more than 36 hours, respectively. CONCLUSIONS: Early pneumonia may extend length of ICU- and hospital-stay after OHCA and its occurrence is difficult to predict. A delayed initiation of antibiotic therapy in OHCA patients may increase the duration of the ICU- and hospital-stay.

Comparison of risk assessment strategies for not-high-risk pulmonary embolism.

We compared the prognostic performance of the 2014 European Society of Cardiology (ESC) risk stratification algorithm with the previous 2008 ESC algorithm, the Bova score and the modified FAST score (based on a positive heart-type fatty acid-binding protein (H-FABP) test, syncope and tachycardia, modified using high-sensitivity troponin T instead of H-FABP) in 388 normotensive pulmonary embolism patients included in a single-centre cohort study.Overall, 25 patients (6.4%) had an adverse 30-day outcome. Regardless of the score or algorithm used, the rate of an adverse outcome was highest in the intermediate-high-risk classes, while all patients classified as low-risk had a favourable outcome (no pulmonary embolism-related deaths, 0-1.4% adverse outcome). The area under the curve for predicting an adverse outcome was higher for the 2014 ESC algorithm (0.76, 95% CI 0.68-0.84) compared with the 2008 ESC algorithm (0.65, 95% CI 0.56-0.73) and highest for the modified FAST score (0.82, 95% CI 0.75-0.89). Patients classified as intermediate-high-risk by the 2014 ESC algorithm had a 8.9-fold increased risk for an adverse outcome (3.2-24.2, p<0.001 compared with intermediate-low- and low-risk patients), while the highest OR was observed for a modified FAST score ≥3 points (OR 15.9, 95% CI 5.3-47.6, p<0.001).The 2014 ESC algorithm improves risk stratification of not-high-risk pulmonary embolism compared with the 2008 ESC algorithm. All scores and algorithms accurately identified low-risk patients, while the modified FAST score appears more suitable to identify intermediate-high-risk patients.

Risk stratification of normotensive pulmonary embolism: prognostic impact of copeptin.

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (high-sensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)).We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study.Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6-90.8) versus 13.2 (5.9-39.3) pmol·L(-1); p=0.020). Patients with copeptin levels above the calculated optimal cut-off value of 24 pmol·L(-1) had a 5.4-fold increased risk for an adverse outcome (95% CI 1.68-17.58; p=0.005). We developed a strategy for risk stratification based on biomarkers. None of 141 patients (52.6%) with hsTnT <14 pg·mL(-1) or NT-proBNP <600 pg·mL(-1) had an adverse outcome (low risk). Copeptin ≥24 pmol·L(-1) stratified patients with elevated hsTnT and NT-proBNP as intermediate-low and intermediate-high risk (5.6% and 20.0% adverse outcome, respectively). Compared to the algorithm proposed by the 2014 European Society of Cardiology guideline, more patients were classified as low risk (52.8% versus 17.5%, p<0.001) and more patients in the intermediate-high risk group had an adverse outcome (20.0% versus 11.6%).Copeptin might be helpful for risk stratification of normotensive patients with pulmonary embolism, especially if integrated into a biomarker-based algorithm.