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Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients. [ABSTRACT FROM AUTHOR]

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure. [ABSTRACT FROM AUTHOR]

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. [ABSTRACT FROM AUTHOR]

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. [ABSTRACT FROM AUTHOR]

Objective: Correct assessment of patient urgency is critical to ensuring patient safety in emergency departments (EDs). Although significant time and effort have been devoted to developing triage systems, less attention has been paid to the development of quality control. The aim of this study is to introduce and test observation technique, which enables identifying of patient groups at risk of erroneous assessment in triage. The introduced technique is aimed to be less laborious to use than existing triage quality control methods.Design: The study developed an observation technique for identifying patients with possible erroneous assessments in triage. Data sample for the observation technique is carried out with survey form filled in by nurse.Setting: Hospital ED with ~74 000 patient visits annually.Participants: Consecutive adult patients in an ED for baseline study period of 14 days (1774 patients) in 2010 and control study period of 4 days (541 patients) in 2012.Intervention: Triage observation technique for continuous improvement of triage performance.Main Outcome Measures: Primary measures of triage improvement were triage accuracy and nurses' ability to predict patient admissions.Results: With the observation technique the ED staff was able to identify patient groups at risk for erroneous triage. Under-triage related mostly to patients with chest pain, shortness of breath, collapse, stomach pain and infections. Instead injures and muscular skeletal symptoms were seldom undertriaged even though they are common.Conclusions: EDs can control triage quality with simple observation technique. The usability of observation technique and triage quality improvement process were good. [ABSTRACT FROM AUTHOR]

Background: We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE).Methods: Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58±19 years) and without (n=31, age 55±16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission.Results: The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months.Conclusions: Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD. [ABSTRACT FROM AUTHOR]

Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. Methods and results The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome ( ACS) or non- ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2 mmol/L despite fluid resuscitation ( n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non- ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% ( n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85). Conclusion Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials. Trial registration NCT01374867. [ABSTRACT FROM AUTHOR]

In our study the time of onset of RRT was recorded in 17/22 patients and only 7 patients (5% of all patients included in our study) had RRT performed within 24 h of study baseline. Abbreviations P-PENK: Plasma proenkephalin P-NGAL: Plasma neutrophil gelatinase-associated lipocalin RRT: Renal replacement therapy Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reply to: High levels of plasma biomarkers at 24 h were found to be strong predictors of 90-day mortality: beware of some potential confounders!. [Extracted from the article]

Aims: Acute heart failure (AHF) has a poor prognosis. We evaluated 3- and 12-month mortality in different clinical classes of AHF patients from 30 European countries who were included in the EuroHeart Failure Survey (EHFS) II. [ABSTRACT FROM PUBLISHER]

Background: Although weakly supported by scientific evidence, according to guidelines the use of inotropes in acute heart failure is indicated in the presence of hypoperfusion refractory to fluid resuscitation. Aims: We examined the characteristics of the inotrope-treated patients, as well as, their in-hospital mortality. The frequency and dosing of inotropic infusions in patients admitted with acute heart failure was assessed in detail. Methods: We included 620 consecutive patients with acute heart failure who were admitted to hospital during three months during spring 2004 in an observational multi-centre study. Results: Of the patients 84 (14%) were treated with inotropes. Dopamine was used in 46 (7%), dobutamine 22 (4%), epinephrine 5 (1%), norepinephrine in 33 (5%), and levosimendan in 44 (7%) cases. The in-hospital mortality was 21% in the inotrope-treated group, and 5% in the control group. The mortality was 7% if only one inotrope was used. The mortality increased in proportion to the number of inotropes used. Lower blood pressure at admission, low ejection fraction, elevated C-reactive protein and cardiac markers correlated with the inotrope administration. Conclusion: Inotrope administration is a marker of increased mortality in patients with acute heart failure. Still, the use of a single inotrope during hospital stay seems rather safe. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This analysis evaluates the gender differences in patients hospitalised for acute heart failure (AHF) in the EuroHeart Failure Survey II (EHFS). Results: Of the 3580 patients included in EHFS II, 1384 (39%) were women, mean age 73 years. 2196 (61%) were men, mean age 68 years. Women more frequently had new-onset AHF, hypertension and valvular disease and less frequently coronary heart disease or dilated cardiomyopathy compared with men. Smoking, chronic obstructive pulmonary disease, peripheral arterial disease and renal failure were less common, but diabetes and anaemia significantly more frequent in women. Atrial fibrillation and preserved left ventricular function were more common in women. Men were more often non-compliant with medication. After adjustment for indications and age, there were no significant gender differences in prescription of HF medication. All-cause readmission rate during the one-year follow-up was lower in women. However, the proportion of HF hospitalisation and one-year mortality after discharge (20%) were similar in both genders. Conclusion: Women frequently present with new-onset AHF. A significant gender difference exists in aetiology, ventricular function and co-morbidities. Women''s use of HF medication has improved. These findings emphasize the importance of individualised management and need for more comprehensive recruitment of women in clinical trials. [Copyright &y& Elsevier]

Abstract: Backround: The myosin heavy chain (MHC) is altered in chronic heart failure (CHF), but the effect of exercise on MHC expression in CHF patients is not understood. The aim of the present study was to show the effect of aerobic exercise on MHC distribution in patients with CHF. Methods: Patients (n =17) with stable NYHA class I–III CHF were randomised into training and control groups. For a period of three months, the training group cycled on an ergometric cycle 3 times a week for 30 min, the control group continued as they did previously. Both a baseline and a final 3 month graded maximal exercise test and exercise endurance test with constant submaximal work load were performed. Muscle samples, obtained from vastus lateralis muscle at baseline and after 3 months from the 8 patients in the training group and the 9 in the control group, were analysed for MHC distribution using SDS-polyacrylamide gel electrophoresis. Results: Baseline MHC distributions were similar in both groups and training did not alter the MHC distribution. Exercise duration, at constant submaximal work load, improved from 14.9±7.1 to 26.9±9.6 min (p <0.01 for the change between the groups). Training did not improve peak oxygen consumption. Conclusion: No correlation between the change in exercise capacity and MHC distribution appeared despite the significant improvement of exercise duration. [Copyright &y& Elsevier]

Heart failure (HF) has emerged as a major public health issue and is among the most significant causes of morbidity and mortality for older adults in Western countries. Acute HF syndromes (AHFS) encompass many important etiologies and comorbidities. There are several different clinical definitions and classifications of AHFS that are based on their clinical picture and pathophysiology. These definitions and classifications should, at best, serve to individually tailor diagnostics and therapy. Another important application of these definitions and classifications is to help guide future clinical trials in AHFS. The epidemiology of AHFS has been studied in large and small registries and surveys in both North America and Europe. The properties of the population of patients with acute HF are discussed in light of these data. [Copyright &y& Elsevier]

Abstract: Aims: Acute heart failure (HF) is a common but ill-defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an unfavourable outcome. Methods and results: We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty-eight percent had de-novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV-EF was &#60;35%, 35–50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU-treatment was necessary in 39% of the patients. Thirty-day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve-month all-cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age. Conclusions: This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high. [Copyright &y& Elsevier]

Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST‐segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI‐patients. Methods: STEMI‐patients (n = 49), with (CS, n = 25) and without CS (non‐CS, n = 24) fulfilling inclusion criteria were included from HSCSP‐cohort (Derivation‐cohort). CS‐miRNAs were analysed by Affymetrix‐microarray and RT‐PCR. Results were validated in a second cohort of CS‐patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. Results: Of the 5‐miRNA signature obtained from microarray analysis, miR‐619‐5p showed higher levels in CS than in Non‐CS patients (p =.003) and discriminating power for CS by ROC (AUC:.752, p =.003). miR‐619‐5p directly associated with risk scores [GRACE, p =.001; CardShock, p <.001]. Furthermore, miR‐619‐5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP‐cohort (p =.02; AUC:.78 ±.095) and the Validation CardShock‐cohort (p =.017; AUC:.737 ±.086) By in silico analysis, miR‐619‐5p target genes and TNF‐alpha were involved in the regulation of inflammation. miR‐619‐5p and TNF‐alpha levels discriminated mortality outcome in CS‐patients during 30‐day follow‐up (Validation‐Cohort: ROC:.812, p =.002; HR: 9.99, p =.003). Conclusions: Up‐regulation of miR‐619‐5p is found in the plasma of STEMI‐patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI. [ABSTRACT FROM AUTHOR]

Levosimendan, a new calcium sensitizer, was administered orally to 10 patients with severe congestive heart failure (CHF), who had a mean baseline pulmonary capillary wedge pressure (PCWP) of 22 mm Hg and a left ventricular ejection fraction of 23%. Each patient received 3 escalating doses of 1 mg, 2 mg, and 4 mg of levosimendan within 18-24 hours in an open-label pilot study. After administration of a 1-mg dose of levosimendan, PCWP decreased by 18% (p = 0.002) and cardiac output increased by 22% (p = 0.005). Diastolic blood pressure was decreased by about 5 mm Hg. Plasma catecholamine levels were unaffected. Plasma concentrations of levosimendan were unexpectedly Iow after administration of the 2-mg dose, and responses were weak. This was probably due to delayed drug absorption and altered baseline hemodynamics caused by ingestion of a meal before drug intake. The 4-mg dose of levosimendan was associated with a 27% increase in cardiac output (p = 0.009). PCWP showed only a small decrease, probably a result of relatively Iow baseline values (carryover from previous doses). Right atrial pressure decreased substantially by 40%. Heart rate increased by only 1-8 beats/min after administration of the 1- and 4-mg doses of levosimendan. It is concluded that oral levosimendan has favorable cardiac and hemodynamic effects in patients with severe CHF, and that these effects are similar to those seen after intravenous dosing with levosimendan in this patient group. [ABSTRACT FROM AUTHOR]

The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Abstract: Background: The costs of different classes of acute HF (AHF) are not known. Methods: AHF patients (N =620) were divided in a national, prospective, observational study into five clinical classes: cardiogenic shock, pulmonary oedema, congestive HF, hypertensive HF, and right HF. Index episode and 6-month readmissions were assessed and hospitalization costs were evaluated. Results: The length of index episode, ICU/CCU stay and costs of index episode and cumulative 6-month costs differed significantly between the clinical classes. The highest cumulative 6-month hospitalization costs, 25,963 (15,053–44778) € (mean, 95% confidence interval) incurred in cardiogenic shock, followed by pulmonary oedema, 12,912 (11,006–15,148) €, and congestive HF, 9475 (8550–10,500) €. Conclusions: AHF leads to significant need for hospital care and high costs which differ significantly between clinical classes of AHF. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p < 0.001) and 5.2 (95% CI 2.8–9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. Trial registration: NCT01374867 at www.clinicaltrials.gov, registered 16 Jun 2011—retrospectively registered [ABSTRACT FROM AUTHOR]

Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non-specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point-of-care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short-term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre- and post-discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure. [ABSTRACT FROM AUTHOR]

Aims: Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice.Methods and Results: cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling.Conclusion: Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown. Materials and methods: P-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality. Results: Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5–4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1–3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2–5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2–7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome. Conclusions: Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock. Trial registration: at ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence‐based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear‐cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF. [ABSTRACT FROM AUTHOR]

Aims: To investigate the incidence, haemodynamic alterations and 90‐day mortality of acute kidney injury (AKI) in patients with cardiogenic shock. We assessed the utility of creatinine, urine output (UO) and cystatin C (CysC) definitions of AKI in prognostication. Methods and results: Cardiogenic shock patients with serial plasma samples (n = 154) from the prospective multicenter CardShock study were included in the analysis. Acute kidney injury was defined and staged according to the KDIGO criteria by creatinine (AKIcrea) and/or UO (AKIUO). CysC‐based AKI (AKICysC) was defined similarly to AKIcrea. Changes in haemodynamic parameters were assessed over time from baseline until 96 h. Mean age of the study population was 66 ± 12 years and 74% were men. Median baseline creatinine was 1.12 [interquartile range (IQR) 0.87–1.54] mg/dL and CysC 1.19 (IQR 0.90–1.69) mg/L. The 90‐day mortality was 38%. The incidences for AKI were: AKIcrea 31%, AKIUO 50%, and AKICysc 33%. AKIcrea [odds ratio (OR) 12.2, 95% confidence interval (CI) 4.1–36.0] and AKICysC (OR 2.5, 95% CI 1.1–6.1), but not AKIUO, were independent predictors of mortality. However, a stricter UO cut‐off of <0.3 mL/kg/h for 6 h was independently associated with 90‐day mortality (OR 3.6, 95% CI 1.4–9.3). Development of AKI was associated with persistently elevated central venous pressure and decreased cardiac index and mean arterial pressure. Conclusions: Acute kidney injury is frequent in patients with cardiogenic shock and especially AKIcrea predicts poor outcome. The KDIGO UO criterion seems, however, rather liberal and a stricter AKI definition of UO <0.3 mL/kg/h for at least 6 h seems more useful for mortality risk prediction. Haemodynamic alterations reflecting venous congestion and hypoperfusion were associated with AKI. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators, inotropes and/or vasopressors-in acute heart failure (AHF).Methods and Results: The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592-1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031-2.572 vs. no inotropes).Conclusions: Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF. [ABSTRACT FROM AUTHOR]

Aims: The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group.Methods and Results: The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF <40% (HFrEF)], mid-range EF [EF 40-50% (HFmrEF)] and preserved EF [EF >50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients.Conclusions: Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals. [ABSTRACT FROM AUTHOR]

Aims: To identify differences in clinical epidemiology, in-hospital management and 1-year outcomes among patients hospitalized for acute heart failure (AHF) and enrolled in the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) Registry, stratified by clinical profile at admission.Methods and Results: The ESC-HF-LT Registry is a prospective, observational study collecting hospitalization and 1-year follow-up data from 6629 AHF patients. Among AHF patients enrolled in the registry, 13.2% presented with pulmonary oedema (PO), 2.9% with cardiogenic shock (CS), 61.1% with decompensated heart failure (DHF), 4.8% with hypertensive heart failure (HT-HF), 3.5% with right heart failure (RHF) and 14.4% with AHF and associated acute coronary syndromes (ACS-HF). The 1-year mortality rate was 28.1% in PO, 54.0% in CS, 27.2% in DHF, 12.8% in HT-HF, 34.0% in RHF and 20.6% in ACS-HF patients. When patients were classified by systolic blood pressure (SBP) at initial presentation, 1-year mortality was 34.8% in patients with SBP <85 mmHg, 29.0% in those with SBP 85-110 mmHg, 21.2% in patients with SBP 110-140 mmHg and 17.4% in those with SBP >140 mmHg. These differences tended to diminish in the months post-discharge, and 1-year mortality for the patients who survived at least 6 months post-discharge did not vary significantly by either clinical profile or SBP classification.Conclusion: Rates of adverse outcomes in AHF remain high, and substantial differences have been found when patients were stratified by clinical profile or SBP. However, patients who survived at least 6 months post-discharge represent a more homogeneous group and their 1-year outcome is less influenced by clinical profile or SBP at admission. [ABSTRACT FROM AUTHOR]

Aims: To identify differences in clinical epidemiology, in-hospital management and 1-year outcomes among patients hospitalized for acute heart failure (AHF) and enrolled in the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) Registry, stratified by clinical profile at admission. Methods and results: The ESC-HF-LT Registry is a prospective, observational study collecting hospitalization and 1-year follow-up data from 6629 AHF patients. Among AHF patients enrolled in the registry, 13.2% presented with pulmonary oedema (PO), 2.9% with cardiogenic shock (CS), 61.1% with decompensated heart failure (DHF), 4.8% with hypertensive heart failure (HT-HF), 3.5% with right heart failure (RHF) and 14.4% with AHF and associated acute coronary syndromes (ACS-HF). The 1-year mortality rate was 28.1% in PO, 54.0% in CS, 27.2% in DHF, 12.8% in HT-HF, 34.0% in RHF and 20.6% in ACS-HF patients. When patients were classified by systolic blood pressure (SBP) at initial presentation, 1-year mortality was 34.8% in patients with SBP <85 mmHg, 29.0% in those with SBP 85-110 mmHg, 21.2% in patients with SBP 110-140 mmHg and 17.4% in those with SBP >140 mmHg. These differences tended to diminish in the months post-discharge, and 1-year mortality for the patients who survived at least 6 months post-discharge did not vary significantly by either clinical profile or SBP classification. Conclusion Rates of adverse outcomes in AHF remain high, and substantial differences have been found when patients were stratified by clinical profile or SBP. However, patients who survived at least 6 months post-discharge represent a more homogeneous group and their 1-year outcome is less influenced by clinical profile or SBP at admission. [ABSTRACT FROM AUTHOR]

Background: The red cell distribution width (RDW) reflects the degree of heterogeneity of red blood cells. Elevated RDW is associated both with frailty and with increased mortality in hospital-admitted patients. In this study we evaluate whether high RDW values are associated with mortality in older emergency department (ED) patients with frailty, and if the association is independent of the degree of frailty. Methods: We included ED patients with the following criteria: ≥ 75 years of age, Clinical Frailty Scale (CFS) score of 4 to 8, and RDW % measured within 48 h of ED admission. Patients were allocated to six classes by their RDW value: ≤ 13%, 14%, 15%, 16%, 17%, and ≥ 18%. The outcome was death within 30 days of ED admission. Crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for a one-class increase in RDW for 30-day mortality were calculated via binary logistic regression analysis. Age, gender and CFS score were considered as potential confounders. Results: A total of 1407 patients (61.2% female), were included. The median age was 85 with an inter-quartile range (IQR) of 80–89, median CFS score 6 (IQR: 5–7), and median RDW 14 (IQR: 13–16). Of the included patients, 71.9% were admitted to hospital wards. A total of 85 patients (6.0%) died during the 30-day follow-up. Mortality rate was associated with RDW increase (p for trend <.001). Crude OR for a one-class increase in RDW for 30-day mortality was 1.32 (95% CI: 1.17–1.50, p <.001). When adjusted for age, gender and CFS-score, OR of mortality for one-class RDW increase was still 1.32 (95% CI: 1.16–1.50, p <.001). Conclusion: Higher RDW values had a significant association with increased 30-day mortality risk in frail older adults in the ED, and this risk was independent of degree of frailty. RDW is a readily available biomarker for most ED patients. It might be beneficial to include it in risk stratification of older frail ED patients to identify those who could benefit from further diagnostic assessment, targeted interventions, and care planning. [ABSTRACT FROM AUTHOR]

Discusses the abstract of the article "Levosimendan in Chronic Heart Failure," by Harjola Veli-Pekka submitted at the 27th Congress of The Scandinavian Society of Anesthesiology and Intensive Care Medicine.

Objective: Emergency medicine (EM) was established as a specialty in Finland at the beginning of 2013. The training period of six years conforms to the principles of the European Curriculum for EM. In this study, we evaluated the first-year experience of training in the Kanta-Häme Central Hospital, Finland.. Material and Methods: We studied both qualitatively and quantitatively the typical structure of the working week of EM residents. A qualitative analysis of a weekly learning day was carried out with regards to the programme, learning methods and themes. A quantitative analysis was carried out by pre/post setting of the topics offered in weekly clinical lectures and the numbers of attending physicians. Results: Since the initiation of EM specialty, the lectures became more comprehensive (p<0.001).The proportion of topics of conservative specialties decreased from 77.0% to 46.7% while those of operative specialties increased from 5.9% to 36.7%. The mean (±standard error of mean) number of attending doctors increased from 14.0±0.4 to 22.7±0.9 (p<0.001).The working group sessions, lectures and ultrasound training increased after establishment of EM specialty. Conclusion: According to these preliminary results, a successful training programme of EM is achievable by systematic planning of practical training. [ABSTRACT FROM AUTHOR]

Background: Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes.Methods: This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression.Results: Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p < 0.001), more often female (56.4% vs. 42.1%, p = 0.002) and had more dementia (18.7% vs. 7.2%, p < 0.001). On admission, EMS patients had more often confusion (14.2% vs. 2.1%, p < 0.001) and higher respiratory rate (24/min vs. 21/min, p = 0.014; respiratory rate > 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027).Conclusion: Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality. [ABSTRACT FROM AUTHOR]

Objectives. Oral levosimendan improves ventricular function in short-term clinical trials. The effects of long-term treatment with oral levosimendan were investigated on echocardiographic parameters of left ventricular function in patients with chronic heart failure. Design. Twenty-nine patients with NYHA III-IV congestive chronic HF were prospectively enrolled in a randomised, double-blind, placebo controlled study. Oral levosimendan was administered on top of existing medication over a treatment period of at least 180 days. Echocardiographic measurements estimating pulmonary capillary wedge pressure (PCWP) and tissue Doppler mitral basal myocardial velocities (Sm, Em) were performed at baseline and 90 and 180 days after randomisation. Results. Estimated PCWP at baseline was elevated in both groups and decreased by 13% in the levosimendan group compared to an increase of 9% in the placebo group (p == 0.035). Sm was decreased in both groups at baseline and improved by 0.9 cm/s in the levosimendan group and decreased by 0.1 cm/s in the placebo group (p == 0.035). Levosimendan did not significantly alter heart rate or systolic blood pressure. Conclusions. Oral levosimendan improved hemodynamic function in chronic heart failure patients and the effect was sustained over the 180-day follow-up period. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF). Aim: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF. Methods: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-α), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated. Results: Elevated levels of IL-6 and TNF-α were strongly associated with increased 12-month mortality (P <0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P <0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years'' increase and TNF-α were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome. Conclusions: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients. [Copyright &y& Elsevier]

• Elevated venous lactate predicts adverse outcomes in normotensive pulmonary embolism. • Optimal prognostic performance was observed for venous lactate ≥3.3 mmol/l. • Adding venous lactate to the 2019 ESC algorithm may improve risk stratification. • The established threshold for arterial lactate has limited specificity in venous samples. Arterial lactate is an established risk marker in patients with pulmonary embolism (PE). However, its clinical applicability is limited by the need of an arterial puncture. In contrast, venous lactate can easily be measured from blood samples obtained via routine peripheral venepuncture. We investigated the prognostic value of venous lactate with regard to in-hospital adverse outcomes and mortality in 419 consecutive PE patients enrolled in a single-center registry between 09/2008 and 09/2017. An optimised venous lactate cut-off value of 3.3 mmol/l predicted both, in-hospital adverse outcome (OR 11.0 [95% CI 4.6–26.3]) and all-cause mortality (OR 3.8 [95%CI 1.3–11.3]). The established cut-off value for arterial lactate (2.0 mmol/l) and the upper limit of normal for venous lactate (2.3 mmol/l) had lower prognostic value for adverse outcomes (OR 3.6 [95% CI 1.5–8.7] and 5.7 [95% CI 2.4–13.6], respectively) and did not predict mortality. If added to the 2019 European Society of Cardiology (ESC) algorithm, venous lactate <2.3 mmol/l was associated with a high negative predictive value (0.99 [95% CI 0.97–1.00]) for adverse outcomes in intermediate-low-risk patients, whereas levels ≥3.3 mmol/l predicted adverse outcomes in the intermediate-high-risk group (OR 5.2 [95% CI 1.8–15.0]). Venous lactate above the upper limit of normal was associated with increased risk for adverse outcomes and an optimised cut-off value of 3.3 mmol/l predicted adverse outcome and mortality. Adding venous lactate to the 2019 ESC algorithm may improve risk stratification. Importantly, the established cut-off value for arterial lactate has limited specificity in venous samples and should not be used. [ABSTRACT FROM AUTHOR]

Objective: Lower respiratory tract infection (LRTI) is a frequent cause of dyspnoea in EDs, and is associated with considerable morbidity and mortality. We described and compared the management of this disease in Europe and Oceania/South‐East Asia (SEA) cohorts. Methods: We conducted a prospective cohort study with three time points in Europe and Oceania/SEA. We included in this manuscript patients presenting to EDs with dyspnoea and a diagnosis of LRTI in ED. We collected comorbidities, chronic medication, clinical signs at arrival, laboratory parameters, ED management and patient outcomes. Results: A total of 1389 patients were included, 773 in Europe and 616 in SEA. The European cohort had more comorbidities including chronic heart failure, obesity, chronic obstructive pulmonary disease and smoking. Levels of inflammatory markers were higher in Europe. There were more patients with inflammatory markers in Europe and more hypercapnia in Oceania/SEA. The use of antibiotics was higher in SEA (72.2% vs 61.8%, P < 0.001) whereas intravenous diuretics, non‐invasive and invasive ventilation were higher in Europe. Intensive care unit admission rate was 9.9% in Europe cohort and 3.4% in Oceania/SEA cohort. ED mortality was 1% and overall in‐hospital mortality was 8.7% with no differences between regions. Conclusions: More patients with LRTI in Europe presented with cardio‐respiratory comorbidities, they received more adjunct therapies and had a higher intensive care unit admission rate than patients from Oceania/SEA, although mortality was similar between the two cohorts. [ABSTRACT FROM AUTHOR]

Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0−120 h) from 183 patients in the CardShock study. The study population was dichotomized by PCT max ≥ and < 0.5 μg/L, and IL-6 and CRP max above/below median. PCT peaked already at 24 h [median PCT max 0.71 μg/L (IQR 0.24–3.4)], whereas CRP peaked later between 48 and 72 h [median CRP max 137 mg/L (59–247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCT max ≥ 0.5 μg/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRP max. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCT max ≥ 0.5 μg/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRP max showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. • Inflammatory marker levels are considerably elevated during the first days of CS. • PCT peaks early at 24 h, while CRP continues to rise until 48 to 72 h in CS. • High levels of PCT and IL-6 are strongly associated with systemic hypoperfusion in CS. • High inflammatory marker levels are associated with increased mortality in CS. [ABSTRACT FROM AUTHOR]

Background: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high inhospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). Methods: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. Results: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices (P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. Conclusions: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score. [ABSTRACT FROM AUTHOR]

Background: The aim of the emergency department (ED) triage is to recognize critically ill patients and to allocate resources. No strong evidence for accuracy of the current triage instruments, especially for the older adults, exists. We evaluated the National Early Warning Score 2 (NEWS2) and a 3-level triage assessment as risk predictors for frail older adults visiting the ED.Methods: This prospective, observational study was performed in a Finnish ED. The data were collected in a six-month period and included were ≥ 75-year-old residents with Clinical Frailty Scale score of at least four. We analyzed the predictive values of NEWS2 and the three-level triage scale for 30-day mortality, hospital admission, high dependency unit (HDU) and intensive care unit (ICU) admissions, a count of 72-h and 30-day revisits, and ED length-of-stay (LOS).Results: A total of 1711 ED visits were included. Median for age, CFS, LOS and NEWS2 were 85 years, 6 points, 6.2 h and 1 point, respectively. 30-day mortality was 96/1711. At triage, 69, 356 and 1278 of patients were assessed as red, yellow and green, respectively. There were 1103 admissions, of them 31 to an HDU facility, none to ICU. With NEWS2 and triage score, AUCs for 30-day mortality prediction were 0.70 (0.64-0.76) and 0.62 (0.56-0.68); for hospital admission prediction 0.62 (0.60-0.65) and 0.55 (0.52-0.56), and for HDU admission 0.72 (0.61-0.83) and 0.80 (0.70-0.90), respectively. The NEWS2 divided into risk groups of low, medium and high did not predict the ED LOS (p = 0.095). There was a difference in ED LOS between the red/yellow and as red/green patient groups (p < 0.001) but not between the yellow/green groups (p = 0.59). There were 48 and 351 revisits within 72 h and 30 days, respectively. With NEWS2 AUCs for 72-h and 30-day revisit prediction were 0.48 (95% CI 0.40-0.56) and 0.47 (0.44-0.51), respectively; with triage score 0.48 (0.40-0.56) and 0.49 (0.46-0.52), respectively.Conclusions: The NEWS2 and a local 3-level triage scale are statistically significant, but poor in accuracy, in predicting 30-day mortality, and HDU admission but not ED LOS or revisit rates for frail older adults. NEWS2 also seems to predict hospital admission. [ABSTRACT FROM AUTHOR]

Background/aim: To describe seasonal variations in epidemiology, management, and short-term outcomes of patients in Europe presenting to an emergency department (ED) with a main complaint of dyspnea. Materials and methods: An observational prospective cohort study was performed in 66 European EDs which included consecutive patients presenting to EDs with dyspnea as the main complaint during 3 72-h study periods. Data were collected on demographics, comorbidities, chronic treatment, prehospital treatment, mode of arrival of patient to ED, clinical signs at admission, treatment in the ED, ED diagnosis, discharge from ED, and in-hospital outcome. Results: The study included 2524 patients with a median age of 69 (53-80) years old. Of the patients presented, 991 (39.3%) were in autumn, 849 (33.6%) were in spring, and 48 (27.1%) were in winter. The winter population was significantly older (P < 0.001) and had a lower rate of ambulance arrival to ED (P < 0.001). In the winter period, there was a higher rate for lower respiratory tract infection (35.1%), and patients were more hypertensive, more hypoxic, and more hyper/hypothermic compared to other seasons. The ED mortality was about 1% and, in hospital, mortality for admitted patients was 7.4%. Conclusion: The analytic method and the outcome of this study may help to guide the allocation of ED resources more efficiently and to recommend seasonal ED management protocols based on the seasonal trend of dyspneic patients. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management. [ABSTRACT FROM AUTHOR]

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non‐invasive ventilation (NIV) for patients with respiratory acidosis. Aim: To determine compliance with guideline recommendations for patients treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. Methods: In each region, an observational prospective cohort study was performed that included patients presenting to ED with the main complaint of dyspnoea during three 72‐h periods. This planned sub‐study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in‐hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. Results: A total of 801 patients was included from 122 ED (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44 and 60.6% of patients with pH <7.3 received NIV. The proportion administered systemic corticosteroids was higher in SEA (EUR vs SEA for all comparisons; 52 vs 66%, P < 0.001) as was administration of antibiotics (40 vs 49%, P = 0.02). Rates of NIV and mechanical ventilation were similar. Overall in‐hospital mortality was 4.2% (SEA 3.9% vs EUR 4.5%, P = 0.77). Conclusion: Compliance with guideline recommended treatments, in particular administration of corticosteroids and NIV, was sub‐optimal in both regions. Improved compliance has the potential to improve patient outcome. [ABSTRACT FROM AUTHOR]

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. • Inotropes increase cardiac output mainly by enhancing cardiac contractility. • Inotropes indicated for heart failure are beta-agonists, milrinone, levosimendan. • Inotropes should only be used in low-output acute or advanced heart failure. • Identifying patients with low-output heart failure is often challenging. • Inotrope selection should be individually tailored. [ABSTRACT FROM AUTHOR]

Aims: Classification of acute heart failure (AHF) patients into four clinical profiles defined by evidence of congestion and perfusion is advocated by the 2016 European Society of Cardiology (ESC)guidelines. Based on the ESC-EORP-HFA Heart Failure Long-Term Registry, we compared differences in baseline characteristics, in-hospital management and outcomes among congestion/perfusion profiles using this classification.Methods and Results: We included 7865 AHF patients classified at admission as: 'dry-warm' (9.9%), 'wet-warm' (69.9%), 'wet-cold' (19.8%) and 'dry-cold' (0.4%). These groups differed significantly in terms of baseline characteristics, in-hospital management and outcomes. In-hospital mortality was 2.0% in 'dry-warm', 3.8% in 'wet-warm', 9.1% in 'dry-cold' and 12.1% in 'wet-cold' patients. Based on clinical classification at admission, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.78 (1.43-2.21) and 'wet-cold' vs. 'wet-warm' 1.33 (1.19-1.48). For profiles resulting from discharge classification, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.46 (1.31-1.63) and 'wet-cold' vs. 'wet-warm' 2.20 (1.89-2.56). Among patients discharged alive, 30.9% had residual congestion, and these patients had higher 1-year mortality compared to patients discharged without congestion (28.0 vs. 18.5%). Tricuspid regurgitation, diabetes, anaemia and high New York Heart Association class were independently associated with higher risk of congestion at discharge, while beta-blockers at admission, de novo heart failure, or any cardiovascular procedure during hospitalization were associated with lower risk of residual congestion.Conclusion: Classification based on congestion/perfusion status provides clinically relevant information at hospital admission and discharge. A better understanding of the clinical course of the two entities could play an important role towards the implementation of targeted strategies that may improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: Asthma exacerbations are common presentations to ED. Key guideline recommendations for management include administration of inhaled bronchodilators, systemic corticosteroids and titrated oxygen therapy. Our aim was to compare management and outcomes between patients treated for asthma in Europe (EUR) and South East Asia/Australasia (SEA) and compliance with international guidelines. Methods: In each region, prospective, interrupted time series studies were performed including adult (age >18 years) patients presenting to ED with the main complaint of dyspnoea during three 72 h periods. This was a planned sub‐study that included those with an ED primary diagnosis of asthma. Data was collected on demographics, clinical features, treatment in ED, diagnosis, disposition and in‐hospital outcome. The results of interest were differences in treatment and outcome between EUR and SEA cohorts. Results: Five hundred and eighty‐four patients were identified from 112 EDs (66 EUR and 46 SEA). The cohorts had similar demographics and co‐morbidity patterns, with 89% of the cohort having a previous diagnosis of asthma. There were no significant differences in treatment between EUR and SEA patients – inhaled beta‐agonists were administered in 86% of cases, systemic corticosteroids in 66%, oxygen therapy in 44% and antibiotics in 20%. Two thirds of patients were discharged home from the ED. Conclusion: The data suggests that compliance with guideline‐recommended therapy in both regions, particularly corticosteroid administration, is sub‐optimal. It also suggests over‐use of antibiotics. [ABSTRACT FROM AUTHOR]