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Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90–140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611–1956) versus 827 (448–1419) pg/mL, and 5890 (2959–12,162) versus 4068 (1986–8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24–71) versus 33 (19–59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31–2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

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]

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]

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]

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. [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]

Background: The most common aetiology of cardiogenic shock (CS) is acute coronary syndrome (ACS), but even up to 20%-50% of CS is caused by other disorders. ST-segment deviations in the electrocardiogram (ECG) have been investigated in patients with ACS-related CS, but not in those with other CS aetiologies. We set out to explore the prevalence of different ST-segment patterns and their associations with the CS aetiology, clinical findings and 90-day mortality.Methods: We analysed the baseline ECG of 196 patients who were included in a multinational prospective study of CS. The patients were divided into 3 groups: (a) ST-segment elevation (STE). (b) ST-segment depression (STDEP). (c) No ST-segment deviation or ST-segment impossible to analyse (NSTD). A subgroup analysis of the ACS patients was conducted.Results: ST-segment deviations were present in 80% of the patients: 52% had STE and 29% had STDEP. STE was associated with the ACS aetiology, but one-fourth of the STDEP patients had aetiology other than ACS. The overall 90-day mortality was 41%: in STE 47%, STDEP 36% and NSTD 33%. In the multivariate mortality analysis, only STE predicted mortality (HR 1.74, CI95 1.07-2.84). In the ACS subgroup, the patients were equally effectively revascularized, and no differences in the survival were noted between the study groups.Conclusion: ST-segment elevation is associated with the ACS aetiology and high mortality in the unselected CS population. If STE is not present, other aetiologies must be considered. When effectively revascularized, the prognosis is similar regardless of the ST-segment pattern in ACS-related CS. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists, intensivists, nurses and other health care providers have to cooperate to provide optimal benefit. However, many treatment decisions are opinion-based and few are evidenced-based. This consensus paper provides guidance to practicing physicians and nurses to manage acute heart failure in the pre-hospital and hospital setting. Criteria of hospitalization and of discharge are described. Gaps in knowledge and perspectives in the management of acute heart failure are also detailed. This consensus paper on acute heart failure might help enable contiguous practice. [ABSTRACT FROM AUTHOR]

Background Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Methods and Results Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF ( P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF ( P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07–3.79; P = .03). Conclusions Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. [ABSTRACT FROM AUTHOR]

Aims Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. However, definitions and prognostic impact of AKI in AHF have been variable. Cystatin C is a prospective new marker of AKI. The objective of this study was to investigate the use of cystatin C as a marker of early AKI in AHF. Methods and results Patients (n = 292) hospitalized for AHF had measurements of cystatin C on admission and at 48 h. We assessed the incidence of a rise in cystatin C between the two measurements and evaluated the effect of an increase in cystatin C on outcomes up to 12 months. The population was on average 75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L (interquartile range 0.99–1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48 h after hospitalization (AKIcysC) occurred in 16% of patients and resulted in 3 days (P = 0.01) longer hospital stay and was associated with significantly higher in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3–11.7, P = 0.01]. During follow-up, AKIcysC was an independent predictor of 90 days mortality, adjusted odds ratio 2.8 (95% CI 1.2–6.7, P = 0.02). Conclusion Cystatin C appears to be a useful marker of early AKI in patients hospitalized for AHF. A decline in renal function detected by cystatin C during the first 48 h after hospitalization occurs frequently in AHF and has a detrimental impact on prognosis. [ABSTRACT FROM PUBLISHER]

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: Background: Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF). Aims: To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF. Methods: FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed. Results: Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2–3.5, p =0.01) and cTnT (OR 2.6, 95% CI 1.5–4.4, p =0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2–13, p <0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0–1.8, p =0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8–0.9, p =0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality. Conclusions: cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers. [Copyright &y& Elsevier]

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]

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]

Aims Acute heart failure (AHF) is associated with poor prognosis and requires recurrent hospitalizations. However, studies on AHF characteristics, treatment, and prognostic factors are few. Our aim was to investigate the characteristics, treatment, and 1-year prognosis of AHF and identify prognostic factors in different clinical groups. [ABSTRACT FROM PUBLISHER]

Aims The objective of the EuroHeart Failure Survey II (EHFS II) was to assess patient characteristics, aetiology, treatment, and outcome of acute heart failure (AHF) in Europe in relation to the guidelines on the diagnosis and treatment of AHF published by the European Society of Cardiology. [ABSTRACT FROM PUBLISHER]

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]

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]

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient's hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents. [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]

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. [ABSTRACT FROM AUTHOR]

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 ± 40 h 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. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart failure. Methods: Patients with AHF (n=620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined. Results: The overall mortality was 60.3% (n=374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p<0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4–2.2; p<0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome. Conclusion: The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF. [Copyright &y& Elsevier]