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Acute right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale) is a life-threatening condition that may arise in different clinical settings. Patients at risk of developing or with manifest acute cor pulmonale usually present with an acute pulmonary disease (e.g. pulmonary embolism, pneumonia, and acute respiratory distress syndrome) and are managed initially in emergency departments and later in intensive care units. According to the clinical setting, other specialties are involved (cardiology, pneumology, internal medicine). As such, coordinated delivery of care is particularly challenging but, as shown during the COVID-19 pandemic, has a major impact on prognosis. A common framework for the management of acute cor pulmonale with inclusion of the perspectives of all involved disciplines is urgently needed., Competing Interests: Conflict of interest: H.A.I.S. has received honoraria from Abiomed, Boehringer Ingelheim, and AstraZeneca. A.V.-B. participates to a research advisory board from Air Liquide company. A.M. has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics and honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. No other relevant conflict of interest was reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., (© 2023 European Society of Cardiology.)

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., (© 2022. The Author(s).)

Aims: The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED., Methods and Results: In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings., Conclusion: Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

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., (© 2020 European Society of Cardiology.)

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., (© 2020 European Society of Cardiology.)

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Aims: Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment-elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy-terminal fragment of IGFBP-4 (CT-IGFBP-4) for all-cause mortality in emergency room patients with acute heart failure (AHF)., Methods and Results: CT-IGFBP-4, N-terminal pro brain natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) were measured at admission from the lithium-heparin plasma of 156 patients with AHF. All-cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan-Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT-IGFBP-4, NT-proBNP, CRP, and their combinations. During 1 year of follow-up, 52 (33.3%) patients died. CT-IGFBP-4 only weakly correlated with NT-proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT-IGFBP-4 for the prediction of all-cause mortality (0.727) was significantly higher than that of NT-proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT-IGFBP-4, NT-proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P < 0.01 for all). The addition of CT-IGFBP-4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT-IGFBP-4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT-proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT-IGFBP-4, NT-proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P < 0.0001) than patients with increased levels of one or none of the biomarkers., Conclusions: CT-IGFBP-4 was independently associated with all-cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT-IGFBP-4, NT-proBNP, and CRP improved the prediction of all-cause mortality in patients with AHF., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aim: To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions., Methods and Results: A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke., Conclusions: The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

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., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Objective: The primary objective of this study was to describe the epidemiology and management of dyspneic patients presenting to emergency departments (EDs) in an international patient population. Our secondary objective was to compare the EURODEM and AANZDEM patient populations., Patients and Methods: An observational prospective cohort study was carried out in Europe and the Asia-Pacific region. The study included consecutive patients presenting to EDs with dyspnea as the main complaint. Data were collected on demographics, comorbidities, chronic treatment, clinical signs and investigations, treatment in the ED, diagnosis, and disposition from ED., Results: A total of 5569 patients were included in the study. The most common ED diagnoses were lower respiratory tract infection (LRTI) (24.9%), heart failure (HF) (17.3%), chronic obstructive pulmonary disease (COPD) exacerbation (15.8%), and asthma (10.5%) in the overall population. There were more LRTI, HF, and COPD exacerbations in the EURODEM population, whereas asthma was more frequent in the AANZDEM population. ICU admission rates were 5.5%. ED mortality was 0.6%. The overall in-hospital mortality was 5.0%. In-hospital mortality rates were 8.7% for LRTI, 7.6% for HF, and 5.6% for COPD patients., Conclusion: Dyspnea as a symptom in the ED has high ward and ICU admission rates. A variety of causes of dyspnea were observed in this study, with chronic diseases accounting for a major proportion.

Objectives: The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED)., Patients and Results: We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B-lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography.CaTUS had a sensitivity of 100% (95% confidence interval: 91.4-100%), a specificity of 95.8% (95% confidence interval: 84.6-99.3%), and an area under the curve of 0.979 for diagnosing AHF (P<0.001). The diagnostic accuracy of CaTUS was higher than of either E/e' or LUS alone. Adding the inferior vena cava index to CaTUS did not improve diagnostic accuracy. CaTUS seemed helpful also for differential diagnostics of dyspnea, mainly regarding pneumonias and pulmonary embolisms., Conclusion: CaTUS, combining E/e' and LUS, provided excellent accuracy for diagnosing AHF.

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

To determine short-term outcomes after an episode of acute heart failure in patients with mid-range ejection fraction (40%-49%; HFmrEF) compared with patients with reduced (<40%) and preserved (>49%) ejection fractions (HFrEF and HFpEF, respectively) and according to their final destination after emergency department (ED) care. This is an exploratory, secondary analysis of the Epidemiology of Acute Heart Failure in the Emergency departments Registry, which includes consecutive acute heart failure patients diagnosed in 41 Spanish EDs. Patients with echocardiography data were included and divided into HFrEF, HFmrEF, and HFpEF. The primary outcome was 30-day all-cause mortality, and secondary outcomes were in-hospital all-cause mortality, hospital length of stay >10 days, and 30-day postdischarge ED revisit due to AHF and combined end point (ED revisit and/or death). We included 6,856 patients (age 79 [10]; 52.1% women): 21.6% had HFrEF, 14.3% HFmrEF, and 64.1% HFpEF. The main destinations for the 982 HFmrEF patients after ED management were internal medicine (293, 29.8%), cardiology (194, 19.9%) and not hospitalized (241, 24.5%), whereas the remaining 254 patients were admitted to other departments, including geriatric wards, short-stay units and intensive care units. Outcomes for HFmrEF did not differ compared with either HFrEF or HFpEF. Compared with HFmrEF admitted to cardiology, internal medicine admission or direct ED discharge increased the 30-day postdischarge ED revisit (hazard ratio [HR] 1.713, 95% confidence interval [CI] 1.042 to 2.816; and HR 1.683, 95% CI 1.046 to 2.708, respectively) and the 30-day postdischarge combined end point (HR 1.732, 95% CI 1.070 to 2.803; and HR 1.727, 95% CI 1.083 to 2.756, respectively). In conclusion, patients in the newly created HFmrEF category suffering from an acute decompensation have similar short-term outcomes as those in the classical HFrEF and HFpEF categories; nonetheless, HFmrEF patients handled in cardiology wards during decompensation obtain better outcomes, and reasons for these differences have to be unmasked and corrected., (Copyright © 2018. Published by Elsevier Inc.)

Aims: To compare short-term outcomes after an episode of acute heart failure (AHF) in patients with reduced and preserved ejection fractions (HFrEF, < 40%; and HFpEF, > 49%; respectively) according to their destinations after emergency department (ED) care., Methods and Results: This secondary analysis of the EAHFE Registry (consecutive AHF patients diagnosed in 41 Spanish EDs) investigated 30-day all-cause mortality, in-hospital all-cause mortality, prolonged hospitalisation (> 7 days), and 30-day post-discharge ED revisit due to AHF, all-cause death, and combined endpoint (ED revisit/death) in 5829 patients with echocardiographically documented HFrEF and HfpEF (HFrEF/HFpEF: 1,442/4,387). Adjusted ratios were calculated for patients admitted to internal medicine (IM), short stay unit (SSU), and discharged from the ED without hospitalisation (DEDWH) and compared with those admitted to cardiology. For HFrEF, the only significant differences were lower in-hospital mortality (OR = 0.26; 95% CI 0.08-0.81; p = 0.021) and prolonged hospitalisation (OR = 0.07; 95% CI 0.04-0.13; p < 0.001) related to SSU admission. For HFpEF, IM admission had a higher post-discharge 30-day mortality (HR = 1.85; 95% CI 1.05-3.25; p = 0.033) and combined endpoint (HR = 1.24; 95% CI 1.01-1.64; p = 0.044); SSU admission had a lower in-hospital mortality (OR = 0.43; 95% CI 0.23-0.80; p = 0.008) and prolonged hospitalisation (OR = 0.17; 95% CI 0.13-0.23; p < 0.001) but a higher post-discharge 30-day combined endpoint (HR = 1.29; 95% CI 1.01-1.64; p = 0.041); and DEDDWH had a lower 30-day mortality (HR = 0.46; 95% CI 0.28-0.75; p = 0.002) but higher post-discharge ED revisit (HR = 1.62; 95% CI 1.31-2.00; p < 0.001)., Conclusion: While HFrEF patients have similar short-term outcomes irrespective of the destination after ED care for an AHF episode, HFpEF patients present worse short-term outcomes when managed by non-cardiology departments, despite adjustment for different clinical patient profiles. Reasons for this heterogeneous specialty-related performance should be investigated.

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., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: It is unclear how to optimally monitor acute heart failure (AHF) patients. We evaluated the timely interplay of cardiac filling pressures, brain natriuretic peptides (BNPs), lung ultrasound (LUS) and symptoms during AHF treatment., Methods: We enrolled 60 patients who had been hospitalised for AHF. Patients were examined with a rapid cardiothoracic ultrasound (CaTUS) protocol, combining LUS and focused echocardiographic evaluation of cardiac filling pressures (i.e. medial E/e' and inferior vena cava index [IVCi]). CaTUS was done at 0, 12, 24 and 48 hours (±3 hours) and on the day of discharge, alongside clinical evaluation and laboratory samples. Patients free of congestion (B lines or pleural fluid) on LUS at discharge were categorised as responders, whereas the rest were categorised as non-responders. Improvement in congestion parameters was evaluated separately in these groups. The effect of congestion parameters on prognosis was also analysed., Results: Responders experienced a significantly larger decline in E/e' (2.58 vs. 0.38, p = 0.037) and dyspnoea visual analogue scale (1-10) score (7.68 vs. 3.57, p = 0.007) during the first 12 hours of treatment, while IVCi and BNPs declined later without no such rapid initial decline. Among patients experiencing a >3 U decline in E/e' during the first 12 hours of treatment, 18/21 were to become responders ( p < 0.001). LUS response was the only congestion parameter independently predicting both 6-month survival regarding all-cause mortality and the composite endpoint of all-cause mortality or rehospitalisation for AHF., Conclusion: E/e' seemed like the most useful congestion parameter for monitoring early treatment response, predicting prognostically beneficial resolution of pulmonary congestion.

Objective: Little is known about treatments provided by advanced life support (ALS) ambulance teams to patients with acute heart failure (AHF) during the prehospital phase, and their influence on short-term outcome. We evaluated the effect of prehospital care in consecutive patients diagnosed with AHF in Spanish emergency departments (EDs)., Methods: We selected patients from the EAHFE registry arriving at the ED by ALS ambulances with available follow-up data. We recorded specific prehospital ALS treatments (supplemental oxygen, diuretics, nitroglycerin, non-invasive ventilation) and patients were grouped according to whether they received low- (LIPHT; 0/1 treatments) or high-intensity prehospital therapy (HIPHT; > 1 treatment) for AHF. We also recorded 46 covariates. The primary endpoint was all-cause 7-day mortality, and secondary endpoints were prolonged hospitalisation (> 10 days) and in-hospital and 30-day mortality. Unadjusted and adjusted odds ratios were calculated to compare the groups., Results: We included 1493 patients [mean age 80.7 (10) years; women 54.8%]. Prehospital treatment included supplemental oxygen in 71.2%, diuretics in 27.9%, nitroglycerin in 13.5%, and non-invasive ventilation in 5.3%. The LIPHT group included 1041 patients (70.0%) with an unadjusted OR for 7-day mortality of 1.770 (95% CI 1.115-2.811; p = 0.016), and 1.939 (95% CI 1.114-3.287, p = 0.014) after adjustment for 16 discordant covariables. The adjusted ORs for all secondary endpoints were always > 1 in the LIPHT group, but none reached statistical significance., Conclusions: Patients finally diagnosed with AHF at then ED that have received LIPHT by the ALS ambulance teams have a poorer short-term outcome, especially during the first 7 days.

The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. However, negative or insufficient data have been collected regarding the effects of cardiac glycosides, catecholamines, and phosphodiesterase inhibitors on quality of life and survival. More recently, the calcium sensitizer and potassium channel-opener levosimendan has been proposed as a safer inodilator than traditional agents in some heart failure settings, such as advanced heart failure. At the 2017 annual congress of the Heart Failure Association of the European Society of Cardiology (Paris, April 30-May 2), a series of tutorials delivered by lecturers from 8 European countries examined how to use levosimendan safely and effectively in acute and advanced heart failure. The proceedings of those tutorials have been collated in this review to provide an expert perspective on the optimized use of levosimendan in those settings.

Background: The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown., Methods: Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes., Results: Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function., Conclusions: In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.

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., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Aims: There is little evidence-based therapy existing for acute heart failure (AHF), hospitalizations are lengthy and expensive, and optimal monitoring of AHF patients during in-hospital treatment is poorly defined. We evaluated a rapid cardiothoracic ultrasound (CaTUS) protocol, combining focused echocardiographic evaluation of cardiac filling pressures, that is, medial E/e' and inferior vena cava index, with lung ultrasound (LUS) for guiding treatment in hospitalized AHF patients., Methods and Results: We enrolled 20 consecutive patients hospitalized for AHF, whose in-hospital treatment was guided using the CaTUS protocol according to a pre-specified treatment protocol targeting resolution of pulmonary congestion on LUS and lowering cardiac filling pressures. Treatment results of these 20 patients were compared with those of a standard care sample of 100 patients, enrolled previously for follow-up purposes. The standard care sample had CaTUS performed daily for follow-up and received standard in-hospital treatment without ultrasound guidance. All CaTUS exams were performed by a single experienced sonographer. The CaTUS-guided therapy resulted in significantly larger decongestion as defined by reduction in symptoms, cardiac filling pressures, natriuretic peptides, cumulative fluid loss, and resolution of pulmonary congestion (P < 0.05 for all) despite a shorter mean length of hospitalization. Congestion parameters were significantly lower also at discharge (P < 0.05 for all), without any significant difference in these parameters on admission. The treatment arm displayed better survival regarding the combined endpoint of 6 month all-cause death or AHF re-hospitalization (log rank P = 0.017). No significant difference in adverse events occurred between the groups., Conclusions: The CaTUS-guided therapy for AHF resulted in greater decongestion during shorter hospitalization without increased adverse events in this small pilot study and might be associated with a better post-discharge prognosis., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Altered mental status is among the signs of hypoperfusion in cardiogenic shock, the most severe form of acute heart failure. The aim of this study was to investigate the prevalence of altered mental status, to identify factors associating with it, and to assess the prognostic significance of altered mental status in cardiogenic shock., Methods: Mental status was assessed at presentation of shock in 215 adult cardiogenic shock patients in a multinational, prospective, observational study. Clinical picture, biochemical variables, and short-term mortality were compared between patients presenting with altered and normal mental status., Results: Altered mental status was detected in 147 (68%) patients, whereas 68 (32%) patients had normal mental status. Patients with altered mental status were older (68 vs. 64 years, p=0.04) and more likely to have an acute coronary syndrome than those with normal mental status (85% vs. 74%, p=0.04). Altered mental status was associated with lower systolic blood pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, p<0.001) as well as higher levels of blood lactate (3.4 vs. 2.3 mmol/l, p<0.001) and blood glucose (11.4 vs. 9.0 mmol/l, p=0.01). Low arterial pH (adjusted odds ratio 1.6 (1.1-2.2), p=0.02) was the only factor independently associated with altered mental status. Ninety-day mortality was significantly higher (51% vs. 22%, p<0.001) among patients with altered mental status., Conclusions: Altered mental status is a common clinical sign of systemic hypoperfusion in cardiogenic shock and is associated with poor outcome. It is also associated with several biochemical findings that reflect inadequate tissue perfusion, of which low arterial pH is independently associated with altered mental status.

Aims: Heart failure oral therapies (HFOTs), including beta-blockers (BB), renin-angiotensin system inhibitors (RASi) and mineralocorticoid receptor antagonists, administered before hospital discharge after acute heart failure (AHF) might improve outcome. However, concerns have been raised because early administration of HFOTs may worsen patient's condition. We hypothesized that HFOTs at hospital discharge might be associated with better post-discharge survival., Methods and Results: The study population was composed of 19 980 AHF patients from the GREAT registry. The primary and secondary outcomes were 90-day and 1-year all-cause mortality, respectively. Survival was estimated with univariate and covariate-adjusted Cox proportional hazards regression models for the whole population and after propensity-score matching. HFOTs at discharge were consistently associated with no excess mortality in the unadjusted and adjusted analyses of the whole and matched cohorts. In the matched cohort, BB and RASi at discharge were associated with lower 90-day mortality risks compared to the respective untreated groups [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.69; and HR 0.53, 95% CI 0.42-0.66, respectively]. The favourable associations of BB and RASi at discharge with 90-day mortality were present in many subgroups including patients with reduced or preserved left ventricular ejection fraction and persisted up to 1 year after discharge. The combination of RASi and BB was associated with an even lower risk of death than RASi or BB alone., Conclusions: Administration of HFOTs at hospital discharge is associated with better survival of AHF patients., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality 'high-flow nasal cannula' seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

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., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Objective: The objective was to determine the relationship between short-term mortality and intravenous morphine use in ED patients who received a diagnosis of acute heart failure (AHF)., Methods: Consecutive patients with AHF presenting to 34 Spanish EDs from 2011 to 2014 were eligible for inclusion. The subjects were divided into those with (M) or without IV morphine treatment (WOM) groups during ED stay. The primary outcome was 30-day all-cause mortality, and secondary outcomes were mortality at different intermediate time points, in-hospital mortality, and length of hospital stay. We generated a propensity score to match the M and WOM groups that were 1:1 according to 46 different epidemiological, baseline, clinical, and therapeutic factors. We investigated independent risk factors for 30-day mortality in patients receiving morphine., Results: We included 6,516 patients (mean age, 81 [SD, 10] years; 56% women): 416 (6.4%) in the M and 6,100 (93.6%) in the WOM group. Overall, 635 (9.7%; M, 26.7%; WOM, 8.6%) died by day 30. After propensity score matching, 275 paired patients constituted each group. Patients receiving morphine had a higher 30-day mortality (55 [20.0%] vs 35 [12.7%] deaths; hazard ratio, 1.66; 95% CI, 1.09-2.54; P = .017). In patients receiving morphine, death was directly related to glycemia (P = .013) and inversely related to the baseline Barthel index and systolic BP (P = .021) at ED arrival (P = .021). Mortality was increased at every intermediate time point, although the greatest risk was at the shortest time (at 3 days: 22 [8.0%] vs 7 [2.5%] deaths; OR, 3.33; 95% CI, 1.40-7.93; P = .014). In-hospital mortality did not increase (39 [14.2%] vs 26 [9.1%] deaths; OR, 1.65; 95% CI, 0.97-2.82; P = .083) and LOS did not differ between groups (median [interquartile range] in M, 8 [7]; WOM, 8 [6]; P = .79)., Conclusions: This propensity score-matched analysis suggests that the use of IV morphine in AHF could be associated with increased 30-day mortality., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

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., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Objective: To define the short- and mid-term outcomes of patients discharged after an episode of acute-decompensated heart failure (ADHF) and evaluate the differences between patients discharged directly from the emergency department (ED) and those discharged after hospitalization., Methods: We performed a prospective, multicenter, cohort-designed study, including consecutive patients diagnosed with ADHF in 27 Spanish EDs. Thirty-four variables on epidemiology, comorbidity, baseline status, vital signs, signs of congestion, laboratory tests, and treatment were collected in every patient. The primary outcome was a combined endpoint of ED revisit (without hospitalization) or hospitalization due to ADHF, or all-cause death. Secondary outcomes were each of these three events individually. Outcomes were obtained by survival analysis at different timepoints in the entire cohort, and crude and adjusted comparisons were carried out between patients discharged directly from the ED and after hospitalization., Results: Of the 3233 patients diagnosed with ADHF during a 2-month period, we analyzed 2986 patients discharged alive: 787 (26.4%) discharged from the ED and 2199 (73.6%) after hospitalization. The cumulative percentages of events for the whole cohort (at 7/30/180 days) for the combined endpoint were 7.8/24.7/57.8; for ED revisit 2.5/9.4/25.5; for hospitalization 4.6/15.3/40.7; and for death 0.9/4.3/16.8. After adjustment for patient profile and center, significant increases were found in the hazard ratios for ED- compared to hospital-discharged patients in the combined endpoint, ED revisit and hospitalization, being higher at short-term [at 7 days, 2.373 (1.678-3.355), 2.069 (1.188-3.602), and 3.071 (1.915-4.922), respectively] than at mid-term [at 180 days, 1.368 (1.160-1.614), 1.642 (1.265-2.132), and 1.302 (1.044-1.623), respectively]. No significant differences were found in death., Conclusions: Patients with ADHF discharged from the ED have worse outcomes, especially at short term, than those discharged after hospitalization. The definition and implementation of effective strategies to improve patient selection for direct ED discharge are needed.

Background: Real-life data on the role of emergency medical services (EMS) in acute heart failure (AHF) are scarce. Our aim was to describe prehospital treatment of AHF and to compare patients using EMS with self-presented, non-EMS patients., Methods: Data were collected retrospectively from three university hospitals in Helsinki metropolitan area between July 1, 2012 and July 31, 2013. According to the use of EMS, patients were divided into EMS and non-EMS groups., Results: The study included 873 AHF patients. One hundred were (11.5%) EMS and 773 (88.5%) non-EMS. EMS patients more often had comorbidities. Initial heart rate (HR) and peripheral oxygen saturation (SpO 2 ) differed between EMS and non-EMS patients; mean HR 89.2 (SD 22.5) vs. 83.7 (21.5)/min (p=0.02) and SpO 2 90.3 (8.6) vs. 92.9 (6.6)% (p=0.01). However, on presentation to ED EMS patients' vital signs were similar to non-EMS patients'. On presentation to ED 46.0% were normotensive and 68.2% "warm and wet". Thirty-four percentage of EMS patients received prehospital medication. In-hospital mortality was 6.0% and 7.1% (p=0.84) and length of stay (LOS) 7.7 (7.0) and 8.5 (7.9) days (p=0.36) in EMS and non-EMS groups., Conclusion: The use of EMS and administration of prehospital medication was low. EMS patients had initially worse HR and SpO 2 than non-EMS patients. However, EMS patients' signs improved and were similar on presentation to ED. There were no differences in in-hospital mortality and LOS. This underscores the need for equal attention to any AHF patient independent of the arrival mode., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Many patients with acute heart failure are initially managed in emergency departments (EDs) worldwide. Although some require hospitalization for further management, it is likely that a sizeable proportion could be safely discharged either directly from the ED or after a more extended period of management in an observation-type unit. Identification of low-risk patients who are safe for such an approach to management continues to be a global unmet need. This is driven in part by a lack of clarity on postdischarge outcomes for lower risk patients and a nonexistent consensus on what may be acceptable event rates. The current paper reviews previous studies carried out on patients directly discharged from the ED, suggests a general disposition algorithm and focuses on discharge metrics, which are based on both evidence and expert opinion. In addition, we propose that the following variables be considered for future determination of acceptable event rates: (a) baseline characteristics and risk status of the patient; (b) access to follow-up;, ((c) ED capability to provide an extended period of observation before discharge; (d) the temporal relationship between the event and ED discharge decision; and (e) the type of event experienced.)

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: In the SURVIVE trial, including 1327 acute heart failure patients, no statistically significant difference between levosimendan and dobutamine in the 180-day all-cause mortality was seen. Country-specific differences in outcome were, however, present. In the Finnish sub-population in fact, mortality was significantly lower in levosimendan treated patients. We aim to understand the reasons for this disparity., Methods: The risk factors for all-cause mortality were identified in the whole study population using multivariate Cox proportional hazards regression analysis. Those factors were evaluated in the 95 patients of the Finnish sub-population., Results: The treatment by country interaction for mortality in Finland vs. other countries was significant, p=0.029. Levosimendan treated patients had a lower 180-day mortality compared to dobutamine treated (17% vs. 40%, p=0.023) in the Finnish sub-population. Baseline variables predicting survival in the whole SURVIVE trial population included age, systolic blood pressure, heart rate, myocardial infarction during admission, levels of NT-pro-BNP, glucose, creatinine, and alanine transferase, use of ACE inhibitors and β-blockers, oliguria, time from hospital admission to randomization, history of cardiac arrest, and left ventricular ejection fraction. Finnish patients were more frequently treated with β-blockers (88% vs. 52%, p<0.0001), their study treatment was started earlier (mean±SD 41±40h vs. 81±154; p<0.0001), and they had more often acute myocardial infarction at admission (39% vs. 16%, p<0.0001)., Conclusion: The lower mortality in the Finnish patients treated with levosimendan was associated with higher use of β-blockers, higher frequency of myocardial infarction at admission, and shorter delay between randomization and start of treatment., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

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., (© 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.)