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Heart transplantation (HTx) is the treatment of choice in patients with late-stage advanced heart failure (Advanced HF). Survival rates 1, 5, and 10 years after transplantation are 87%, 77%, and 57%, respectively, and the average life expectancy is 9.16 years. However, because of the donor organ shortage, waiting times often exceed life expectancy, resulting in a waiting list mortality of around 20%. This review aims to provide an overview of current standard, recent advances, and future developments in the treatment of Advanced HF with a focus on long-term mechanical circulatory support and HTx.

Background Improved understanding and assessment of the complex physiology of volume regulation in haemodialysis (HD) patients are required to improve patient care and reduce mortality associated with fluid overload (FO). Methods We searched for FO-related biomarkers among 184 peptides associated with cardiovascular disease in a cohort of 30 HD patients. First, we assessed the direct impact of HD on the peptides of interest by comparing plasma concentrations before and after treatment. Then, we compared cardiovascular peptide profiles between patients with and without FO as defined by bioimpedance analysis (BIA). The plasma concentration of selected candidate biomarkers for FO was determined by enzyme-linked immunosorbent assay (ELISA) and correlated with previously described FO-related clinical and laboratory parameters. For validation, results were confirmed in an independent cohort of 144 HD patients. Results We found seven peptides positively [NT-proBNP, B-type natriuretic peptide (BNP), vascular endothelial growth factor D (VEGFD), tumour necrosis factor-related apoptosis-inducing ligand receptor 2, growth differentiation factor 15, tumour necrosis factor ligand superfamily member 13B, chitinase-3-like protein 1] and five negatively (leptin, renin, epidermal growth factor receptor, interleukin-1 receptor antagonist, myeloblastin) correlated to FO. In addition to natriuretic peptides, VEGFD emerged as third peptide highly correlated with BIA (ρ = 0.619, P Conclusion VEGFD is a novel FO-related biomarker with unique diagnostic and prognostic properties.

The prognostic significance of the right ventricle (RV) has recently been recognised in several conditions, primarily those involving the left ventricle, the lungs and their vascular bed, or the right-sided chambers. Recent advances in imaging techniques have created new opportunities to study RV anatomy, physiology and pathophysiology, and contemporary research efforts have opened the doors to new treatment possibilities. Nevertheless, the treatment of RV failure remains challenging. Optimal management should consider the anatomical and physiological particularities of the RV and include appropriate imaging techniques to understand the underlying pathophysiological mechanisms. Treatment should include rapid optimisation of volume status, restoration of perfusion pressure and improvement of myocardial contractility and rhythm, and, in case of refractory RV failure, mechanical circulatory support.

Acute heart failure and acute pulmonary embolism share many features, including epidemiological aspects, clinical presentation, risk factors and pathobiological mechanisms. As such, it is not surprising that diagnosis and management of these common conditions might be challenging for the treating physician, in particular when both are concomitantly present. While helpful guidelines have been elaborated for both acute heart failure and pulmonary embolism, not many studies have been published on the coexistence of these diseases. With a special focus on diagnostic tools and therapeutic options, the authors review the available literature and, when evidence is lacking, present their own approach to the management of dyspnoeic patients with acute heart failure and pulmonary embolism.

Acute myocardial infarction complicated by cardiogenic shock (AMICS) is a critical syndrome with a high risk of morbidity and mortality. Current management consists of coronary revascularisation, vasoactive drugs, and circulatory and ventilatory support, which are tailored to patients mainly on the basis of clinicians' experience rather than evidence-based recommendations. For many therapeutic interventions in AMICS, randomised clinical trials have not shown a meaningful survival benefit, and a disproportionately high rate of neutral and negative results has been reported. In this context, an accurate definition of the AMICS syndrome for appropriate patient selection and optimisation of study design are warranted to achieve meaningful results and pave the way for new, evidence-based therapeutic options. In this Position Paper, we provide a statement of priorities and recommendations agreed by a multidisciplinary group of experts at the Critical Care Clinical Trialists Workshop in February, 2020, for the optimisation and harmonisation of clinical trials in AMICS. Implementation of proposed criteria to define the AMICS population-moving beyond a cardio-centric definition to that of a systemic disease-and steps to improve the design of clinical trials could lead to improved outcomes for patients with this life-threatening syndrome.

Accurate diagnosis and timely treatment initiation are crucial to optimize outcome of women affected by acute PPCM. Therapeutic interventions—in particular in pregnant women—may be limited, since they always need to consider both the health of the mother and the fetus. Particularly challenging are severe forms of acute PPCM leading to cardiopulmonary instability, as the mortality of these women is particularly high. Interdisciplinary approaches of cardiologists, intensivists, obstetricians, neonatologists, anesthetists, and cardiac surgeons are necessary in case of acute PPCM. As evidence from large randomized clinical trials is lacking, this chapter provides practical recommendations for the acute treatment of PPCM causing acute heart failure based on recent data and clinical experience.

Little is known about the evolution of diaphragmatic function in the early post-cardiac surgery period. The main purpose of this work is to describe its evolution using ultrasound measurements of muscular excursion and thickening fraction (TF). Single-center prospective study of 79 consecutive uncomplicated elective cardiac surgery patients, using motion-mode during quiet unassisted breathing. Excursion and TF were measured sequentially for each patient [pre-operative (D1), 1 day (D2) and 5 days (D3) after surgery]. Pre-operative median for right and left hemidiaphragmatic excursions were 1.8 (IQR 1.6 to 2.1) cm and 1.7 (1.4 to 2.0) cm, respectively. Pre-operative median right and left thickening fractions were 28 (19 to 36) % and 33 (22 to 51) %, respectively. At D2, there was a reduction in both excursion (right: 1.5 (1.1 to 1.8) cm, p

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-Non Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., Aims: Changes in echocardiographic parameters and biomarkers of cardiac and venous pressures or estimated plasma volume during hospitalization associated with decongestive treatments in acute heart failure (AHF) patients with either preserved left ventricular ejection fraction (LVEF) (HFPEF) or reduced LVEF (HFREF) are poorly assessed. Methods and results: From the metabolic road to diastolic heart failure: diastolic heart failure (MEDIA‐DHF) study, 111 patients were included in this substudy: 77 AHF (43 HFPEF and 34 HFREF) and 34 non‐cardiac dyspnea patients. Echocardiographic measurements and blood samples were obtained within 4 h of presentation at the emergency department and before hospital discharge. In AHF patients, echocardiographic indices of cardiac and venous pressures, including inferior vena cava diameter [from 22 (16–24) mm to 13 (11–18) mm, P = 0.009], its respiratory variability [from 32 (8–44) % to 43 (29–70) %, P = 0.04], medial E/e' [from 21.1 (15.8–29.6) to 16.6 (11.7–24.3), P = 0.004], and E wave deceleration time [from 129 (105–156) ms to 166 (128–203) ms, P = 0.003], improved during hospitalization, similarly in HFPEF and HFREF patients. By contrast, no changes were seen in non‐cardiac dyspnea patients. In AHF patients, all plasma biomarkers of cardiac and venous pressures, namely B‐type natriuretic peptide [from 935 (514–2037) pg/mL to 308 (183–609) pg/mL, P < 0.001], mid‐regional pro‐atrial natriuretic peptide [from 449 (274–653) pmol/L to 366 (242–549) pmol/L, P < 0.001], and soluble CD‐146 levels [from 528 (406–654) ng/mL to 450 (374–529) ng/mL, P = 0.003], significantly decreased during hospitalization, similarly in HFPEF and HFREF patients. Echocardiographic parameters of cardiac chamber dimensions [left ventricular end‐diastolic volume: from 120 (76–140) mL to 118 (95–176) mL, P = 0.23] and cardiac index [from 2.1 (1.6–2.6) mL/min/m2 to 1.9 (1.4–2.4) mL/min/m2, P = 0.55] were unchanged in AHF patients, except tricuspid annular plane systolic excursion (TAPSE) that improved during hospitalization [from 16 (15–19) mm to 19 (17–21) mm, P = 0.04]. Estimated plasma volume increased in both AHF [from 4.8 (4.2–5.6) to 5.1 (4.4–5.8), P = 0.03] and non‐cardiac dyspnea patients (P = 0.01). Serum creatinine [from 1.18 (0.90–1.53) to 1.19 (0.86–1.70) mg/dL, P = 0.89] and creatinine‐based estimated glomerular filtration rate [from 59 (40–75) mL/min/1.73m2 to 56 (38–73) mL/min/1.73m2, P = 0.09] were similar, while plasma cystatin C [from 1.50 (1.20–2.27) mg/L to 1.78 (1.33–2.59) mg/L, P < 0.001] and neutrophil gelatinase associated lipocalin (NGAL) [from 127 (95–260) ng/mL to 167 (104–263) ng/mL, P = 0.004] increased during hospitalization in AHF. Conclusions: Echocardiographic parameters and plasma biomarkers of cardiac and venous pressures improved during AHF hospitalization in both acute HFPEF and HFREF patients, while cardiac chamber dimensions, cardiac output, and estimated plasma volume showed minimal changes., This study was supported by a grant from the European Union funded by the Seventh Framework Programme for Health in 2010 (FP7-HEALTH-2010-MEDIA; Luxembourg) (F.Z., P.R., A. M) and research fellowship from Japan Heart Foundation (E. A.). P.R., N.G., T.C., and F.Z. are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” programmes Fighting Heart Failure (reference: ANR-15-RHU-0004), GEENAGE Impact Lorraine Université d’Excellence and by the Contrat de Plan Etat Lorraine IT2MP and FEDER Lorraine. LNLVA is supported by a training grant from the European Society of Cardiology (2015) and a travelling award from the International Society for Heart and Lung Transplantation (August 2015 and 2016). LNLVA gratefully acknowledges the financial support from the Fund for Cardiac Surgery through the Jacqueline Bernheim prize 2015.

Background We studied the course of plasma concentrations of 4 cardiovascular biomarkers: natriuretic peptides (BNP, NT-proBNP; mid-regional (MR) pro-atrial NP); and soluble endothelial CD146 (sCD146), in patients with severe mitral valve stenosis undergoing percutaneous mitral commissurotomy (PMC) to identify potential markers of procedural success. Methods Biomarkers were tested in 40 patients the day before and the day after PMC. Success was defined as mitral valve area ≥ 1.5 cm2; or an increase of ≥0.5 cm2 in mitral valve area associated with echocardiographic mitral regurgitation Results Average age was 63.5 ± 12.7 years; 32(80%) were female. Before PMC, mean valve area was 1.1 ± 0.2 cm2, mean gradient 9.1 ± 3.5 mmHg. PMC was successful in 30 (75%) and unsuccessful in 10 (25%). PMC yielded a significant reduction in MR-proANP and sCD146, driven by a significant reduction in these biomarkers in patients with successful procedure, whereas no reduction was observed in patients with unsuccessful procedure. A significant correlation was found between changes in plasma sCD146 and the relative change in mitral valve area. Elevated pre-procedural sPAP correlated with high sCD146, and accordingly, a significant correlation between the decrease in sPAP and sCD146 after PMC was shown. Conclusions MR-proANP and plasma sCD146 decreased significantly immediately after successful PMC. They appear to be markers of immediate success of PMC and of the hemodynamic improvement achieved by this procedure in patients with MS. Trial registration This study is part of the cohorts registered with ClinicalTrials.gov on June 16, 2011 under the number NCT01374880.

Acute heart failure (AHF) is a syndrome defined as the new onset (de novo heart failure (HF)) or worsening (acutely decompensated heart failure (ADHF)) of symptoms and signs of HF, mostly related to systemic congestion. In the presence of an underlying structural or functional cardiac dysfunction (whether chronic in ADHF or undiagnosed in de novo HF), one or more precipitating factors can induce AHF, although sometimes de novo HF can result directly from the onset of a new cardiac dysfunction, most frequently an acute coronary syndrome. Despite leading to similar clinical presentations, the underlying cardiac disease and precipitating factors may vary greatly and, therefore, the pathophysiology of AHF is highly heterogeneous. Left ventricular diastolic or systolic dysfunction results in increased preload and afterload, which in turn lead to pulmonary congestion. Fluid retention and redistribution result in systemic congestion, eventually causing organ dysfunction due to hypoperfusion. Current treatment of AHF is mostly symptomatic, centred on decongestive drugs, at best tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. As a consequence, AHF is still associated with high mortality and hospital readmission rates. There is an unmet need for increased individualization of in-hospital management, including treatments targeting the causative factors, and continuation of treatment after hospital discharge to improve long-term outcomes. Acute heart failure (AHF) is a syndrome characterized by signs and symptoms of heart failure (typically systemic congestion) that occurs in the presence of an underlying cardiac dysfunction (previously diagnosed, undiagnosed or new-onset) and precipitating factors. AHF is associated with high mortality and hospital readmission rates.

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. Chioncel, O (corresponding author), Univ Med & Pharm Carol Davila, Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest 950474, Romania. ochioncel@yahoo.co.uk

Objective: To investigate whether patients with an acute heart failure (AHF) episode triggered by infection present different outcomes compared to patients with no trigger and the effects of early antibiotic administration (EAA) and hospitalisation. Methods: Two groups were made according to the AHF trigger: infection (G1) or none identified (G2). The primary outcome was 13-week (91-days) all-cause mortality, and secondary outcomes were 13-week post-discharge mortality, readmission or combined endpoint. Comparisons are presented as unadjusted and adjusted (MEESSI risk score) hazard ratios (uHR/aHR) for G1 compared to G2 patients, also estimated by weeks. Stratified analysis by EAA (provided/not provided) and patient disposition (discharged/hospitalised) was performed. Results: We included 6727 patients (G1 = 3973; G2 = 2754). The 13-week mortality uHR was 1.11 (0.99-1.25; p = 0.06; with significant increases in the first 3 weeks), and the aHR was 0.91 (0.81-1.02; p = 0.11). There were no differences in unadjusted secondary post-discharge outcomes; however, G1 outcomes significantly improved after adjustment: aHR 0.83 (0.71-0.96; p = 0.01) for mortality, 0.92 (0.84-0.99; p = 0.04) for readmission, and 0.92 (0.85-0.99; p = 0.04) for the combined endpoint. We found a differentiated effect of hospitalisation (p < 0.05 for interaction; better post-discharge readmission and combined outcomes in G1), and a trend (p = 0.06) to lower mortality in G1 patients with EAA. Additionally, there were some differences between groups in baseline and acute episode characteristics. Conclusion: AHF triggered by infection is not associated with a higher mid-term mortality and has better post-discharge outcomes; however, the first 3 weeks are an extremely vulnerable period. Since hospitalisation could have a role in limiting adverse post-discharge events, and EAA in reducing mortality, these relationships should be prospectively explored in further studies.

Aim This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. Methods and results We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R2 = 0.94). Conclusion Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.

Background Accurate volume status evaluation and differentiation of cardiac and non-cardiac components of overhydration (OH) are fundaments of optimal haemodialysis (HD) management. Methods This study, by combining bioimpedance measurements, cardiovascular biomarkers and echocardiography, aimed at dissecting OH into its major functional components, and prospectively tested the association between cardiac and non-cardiac components of OH with mortality. In the first part, we validated soluble CD146 (sCD146) as a non-cardiac biomarker of systemic congestion in a cohort of 30 HD patients. In the second part, we performed a prospective 1-year follow-up study in an independent cohort of 144 HD patients. Results sCD146 incrementally increased after the short and long intervals after HD (+53 ng/mL, P = 0.006 and +91 ng/mL, P

Background: The assessment of acute heart failure (AHF) in patients with acute coronary syndrome (ACS) is challenging. This study tested whether measuring plasma adrenomedullin in patients admitted for ACS provides valuable information regarding the presence of AHF at admission or its occurrence during hospitalization. Methods and results: The study population consisted of 927 prospectively enrolled patients with ACS. Blood samples for the measurement of plasma bio-adrenomedullin (bio-ADM) were collected at admission. Patients with alveolar pulmonary edema and interstitial pulmonary edema on chest radiography at admission had stepwise higher plasma concentrations of bio-ADM compared to patients with no or mild pulmonary congestion: 54.3 ± 10.6 vs. 27.6 ± 2.1 vs. 22.5 ± 0.7 ng/L, overall P

Aims Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non-cardiac dyspnoea. Methods and results We compared echocardiographic and circulating biomarkers of congestion in 146 patients from the MEDIA-DHF study: 101 with acute HF (38 HFpEF, 41 HFrEF, 22 HF with mid-range ejection fraction) and 45 with non-cardiac dyspnoea. Compared with non-cardiac dyspnoea, patients with acute HF had larger left and right atria, higher E/e', pulmonary artery systolic pressure and inferior vena cava (IVC) diameter at rest, and lower IVC variability (all P 0.05) compared with HFrEF. Conclusion In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF.

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.

Background Acute dyspnoea is the leading cause of unscheduled admission of elderly patients. Several biomarkers are used to diagnose acute heart failure (AHF) and assess prognosis of dyspnoeic patients, but their value in elderly patients is unclear. Objective: To compare diagnostic and prognostic performances of conventional and novel cardiovascular biomarkers in 2 age groups: young ( vs . old (≥75 years old) dyspnoeic patients. Design Prospective observational registry. Setting Emergency department (ED). Subjects Acutely dyspnoeic adult patients. Methods Blood samples were collected at ED admission. The diagnostic value of 4 natriuretic peptides (BNP, proBNP, NT-proBNP, MR-proANP) for AHF was tested. We also assessed the prognostic value of same natriuretic peptides and of 3 novel cardiovascular biomarkers (galectin-3, sST2 and proenkephalin), using 1-year all-cause mortality as end-point. Diagnostic or prognostic performances are expressed as area under the receiveroperating characteristic curve (AUC) with 95% confidence interval. Results Two hundred one acutely dyspnoeic patients were studied. AHF was the cause of dyspnoea in 57% of old and 44% of young patients, respectively. All 4 natriuretic peptides performed well in diagnosing AHF in both age groups (all AUC > 0.7). BNP showed the best diagnostic performance in both old (AUC: 0.98 [0.97–1.00]) and young (AUC 0.98 [0.95–1.00]) patients. Galectin-3 showed the best prognostic performance in both old (AUC 0.74 [0.62–0.87]) and young patients (AUC 0.75 [0.56–0.94]). Conclusions BNP and galectin-3 show good clinical benefits in both oldand young acutely dyspnoeic patients.

BACKGROUND Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF. METHODS In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years. RESULTS The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years. CONCLUSIONS Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.

Background Electrical cardioversion (ECV) is the recommended treatment for atrial fibrillation (AFib) in critically ill patients, despite lacking data showing hemodynamic benefits of restoring sinus rhythm in this setting. The aim of this study was to assess the hemodynamic effect of successful ECV in a cohort of hemodynamically unstable critically ill patients. Methods and results This study included 66 successful ECV performed in hemodynamically unstable critically ill patients with new-onset AFib. The primary outcome was the requirement of norepinephrine and inotropes 6 h after successful ECV in relation to baseline. Baseline norepinephrine dose was 0.19 ± 0.02 μg/kg/min, and 67% of patients were treated with positive inotropic drugs. Six hours after ECV, 33 patients (50%) were considered hemodynamic non-responders. Overall, the mean norepinephrine dose at 6 h was 0.17 ± 0.02 μg/kg/min (P = 0.051 compared to baseline) and 61% of patients were on inotropes (P = 0.13 compared to baseline). During the 6-hour period after ECV the mean norepinephrine dose temporary increased to 0.20 ± 0.02 μg/kg/min (P = 0.033 compared to baseline). Conclusions ECV is associated with a large proportion of hemodynamic non-responders and a numerically modest, non-significant hemodynamic improvement in critically ill patients with new-onset AFib.

Background Hyperglycemia is common, regardless of diabetes mellitus (DM), and is associated with increased mortality in patients with acute heart failure (AHF). Current oral heart failure (HF) medications improve the outcome in patients with AHF. However, the relationships between HF medications, admission glucose levels, and prognosis in AHF patients remained unknown. Purpose This study sought to investigate the effect of oral HF medications on relationships between hyperglycemia at admission and 1-year all-cause mortality in patients with AHF. Methods From the GREAT (Global Research on Acute Conditions Team) registry, 13840 patients presenting with AHF whose admission glucose levels were available were included and followed up for 1-year all-cause mortality. Hyperglycemia was defined as a glucose levels of ≥7 mmol/L for patients without history of DM and ≥10 mmol/L for those with history of DM. Patients with hypoglycemia (defined as a glucose levels of ≤4 mmol/L, n=193, 1.4%) were excluded in this analysis. Results There were 6418 (%) patients with hyperglycemia and 7229 (%) patients with normoglycemia. One-year mortality was higher in patients with hyperglycemia than those with normoglycemia (1911 [30%] and 1821 [25%], respectively). Even after adjustment, the risk for 1-year mortality was significantly higher in hyperglycemia (HR 1.14, 95%-CI 1.04–1.26, P=0.008) compared with normoglycemia. Detrimental effects of hyperglycemia on 1-year mortality were more severe in de novo AHF patients than in patients with history of HF (p for interaction 0.004). Oral HF medications (beta blockers and/or angiotensin converting enzyme inhibitors/angiotensin receptor blockers) at discharge were effective in AHF patients with normoglycemia regardless of history of HF. Oral HF medications at discharge are very effective in de novo AHF patients with hyperglycemia and less effective in acute decompensated HF patients with hyperglycemia (Figure). HF medications and 1-year mortality Conclusions Hyperglycemia at admission is associated with increased risk for 1-year mortality. Current oral HF medications are effective in most of subgroups, though they were less effective in patients with acute decompensated HF and hyperglycemia. These patients might need more aggressive therapies to improve outcomes. Acknowledgement/Funding This work was supported by a research fellowship from Japan Heart Foundation (E.A.)

Significant improvement has been achieved in diagnostic accuracy, validation of probability scores, and standardized treatment algorithms for patients with suspected acute pulmonary embolism. These developments have provided the tools for a safe and cost-effective management for most of these patients. In our experience, however, the presence of medical myths and ongoing controversies seem to hinder the implementation of these tools in everyday clinical practice. This review provides a selection of such dilemmas and controversies and discusses the published evidence beyond them. By doing so, we try to overcome these dilemmas and suggest pragmatic approaches guided by the available evidence and current guidelines.

Purpose Few studies analyzed gender-related outcome differences of critically ill patients and found inconsistent results. This study aimed to test the independent association of gender and long-term survival of ICU patients. Materials and methods FROG-ICU was a prospective, observational, multi-center cohort designed to investigate the long-term mortality of critically ill adult patients. The primary endpoint of this study was 1-year mortality after ICU admission of women compared to men. Results The study included 2087 patients, 726 women and 1361 men. Women and men had similar baseline characteristics, clinical presentation, and disease severity. No significant difference in 1-year mortality was found between women and men (34.9% vs. 37.9%, P = 0.18). After multivariable adjustment, no difference in the hazard of death was observed [HR 0.99 (95% CI 0.77–1.28)]. Similar 1-year survival between women and men was found in a propensity score-matched patient cohort of 506 patients [HR 0.79 (95% CI 0.54–1.14)]. Conclusion Women constituted one-third of the population of critically ill patients and were unexpectedly similar to men regarding demographic characteristics, clinical presentation, and disease severity and had similar risk of death at 1 year after ICU admission. Trial registration ClinicalTrials.gov NCT01367093; registered on June 6, 2011.

Acute heart failure (AHF) is a relevant public health problem causing the majority of unplanned hospital admissions in patients aged of 65 years or more. AHF was historically described as a pump failure causing downstream hypoperfusion and upstream congestion. During the last decades a more complex network of interactions has been added to the simplistic haemodynamic model for explaining the pathophysiology of AHF. In addition, AHF is not a specific disease but the shared clinical presentation of different, heterogeneous cardiac abnormalities. Persistence of poor outcomes in AHF might be related to the paucity of improvements in the acute management of those patients. Indeed, acute treatment of AHF still mainly consists of intravenous diuretics and/or vasodilators, tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. Therefore, there is an unmet need for increased individualization of AHF treatment according to the predominant underlying pathophysiological mechanisms to, hopefully, improve patient's outcome. In this article we review current knowledge on pathophysiology and initial diagnosis of AHF.

Aims: Several clinical conditions may precipitate acute heart failure (AHF) and influence clinical outcome. In this study we hypothesized that precipitating factors are independently associated with 90-day risk of death in AHF. Methods and results: The study population consisted of 15 828 AHF patients from Europe and Asia. The primary outcome was 90-day all-cause mortality according to identified precipitating factors of AHF [acute coronary syndrome (ACS), infection, atrial fibrillation (AF), hypertension, and non-compliance]. Mortality at 90 days was 15.8%. AHF precipitated by ACS or by infection showed increased 90-day risk of death compared with AHF without identified precipitants [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.44-1.97, P < 0.001; and HR 1.51, 95% CI 1.18-1.92, P = 0.001), while AHF precipitated by AF showed lower 90-day risk of death (HR 0.56, 95% CI 0.42-0.75, P < 0.001), after multivariable adjustment. The risk of death in AHF precipitated by ACS was the highest during the first week after admission, while in AHF precipitated by infection the risk of death had a delayed peak at week 3. In AHF precipitated by AF, a trend toward reduced risk of death during the first weeks was shown. At weeks 5-6, AHF precipitated by ACS, infection, or AF showed similar risk of death to that of AHF without identified precipitants. Conclusions: Precipitating factors are independently associated with 90-day mortality in AHF. AHF precipitated by ACS or infection is independently associated with higher, while AHF precipitated by AF is associated with lower 90-day risk of death.

© Springer-Verlag Berlin Heidelberg 2016, Background Acute heart failure (AHF) with reduced leftventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown. Methods and results A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17–31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7–18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [-6.3 mmHg (95 % CI -7.4 to -5.2 mmHg) and -5.8 mmHg (95 % CI -7.6 to -4.0 mmHg), respectively] and RAP [-2.9 mmHg (95 % CI -3.8 to -2.1 mmHg) and -2.8 mmHg (95 % CI -3.8 to -1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs (r 2 = 0.90, p\0.001). Vasodilators and inotropes had no short-term effect of renal function. Conclusion The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.

Background: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. Methods: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. Results: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. Conclusions: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis.

WOS: 000374984300007, PubMed ID: 27812386, AimsAcute heart failure (AHF) is one of the leading causes of unscheduled hospitalization and is associated with frequent readmissions and substantial mortality. Precipitating factors of AHF influence short-term mortality, but their effect on outcome after hospital discharge is unknown. The present study assessed the effect of precipitating factors on readmission and long-term survival in the overall population and in patients aged 75years or younger. Methods and resultsPatients admitted with AHF (n=755) included in the multicentre cohort Biomarcoeurs' were included in the study. Precipitating factors of AHF were classified in four main groups: acute coronary syndrome, atrial fibrillation, acute pulmonary disease and other causes. Hospital readmission during 90days after discharge and survival at 1year were analysed. Precipitating factors influenced readmissions and survival. Acute pulmonary disease was associated with fewer readmissions (HR 0.61, 95% confidence interval (CI) 0.37-0.99, P=0.049), especially in patients aged 75years or younger (HR 0.20, 95% CI 0.06-0.63, P=0.006), whereas atrial fibrillation (HR 2.23, 95% CI 1.29-3.85, P=0.004) and acute coronary syndrome (HR 2.23, 95% CI 1.02-4.86, P=0.044) were associated with more readmissions. Patients with acute pulmonary disease at admission showed higher mortality (HR 1.59, 95% CI 1.04-2.43, P=0.034), especially in subjects aged 75years or younger (HR 2.52, 95% CI 1.17-5.41, P=0.018). ConclusionsPrecipitating factors of AHF substantially influenced outcome after hospitalization. In particular, patients with AHF precipitated by acute pulmonary disease showed fewer readmissions and higher 1year mortality, especially in patients aged 75years or younger.

Zusammenfassung. Akute Herzinsuffizienz (AHF) ist eine lebensbedrohliche Erkrankung, die eine sofortige Behandlung erfordert. Die initiale Therapie sollte die klinische Präsentation, die pathophysiologischen Mechanismen, die auslösenden Faktoren und die zugrundeliegende Herzpathologie berücksichtigen. Besondere Aufmerksamkeit sollte der Polymorbidität und der Vermeidung potentieller iatrogener Schäden gewidmet werden. Patientenpräferenzen, Langzeitoptionen und ethische Fragen sollten frühzeitig in den Behandlungsplan integriert werden. Die Prognose von AHF-Patienten ist ernst, und die kritischste Zeitspanne stellen die ersten drei Monate direkt nach der Spitalentlassung dar. Daher ist es für die Verbesserung der Prognose von AHF-Patienten unerlässlich, die persistierende subklinische systemische Stauung zu vermeiden, den Einsatz von krankheitsmodifizierenden Herzinsuffizienz-Therapien zu optimieren und optimale Versorgungsübergänge nach der Spitalentlassung sicherzustellen.

Acute heart failure (AHF) is a major health problem worldwide and trials to assess novel therapies are increasingly global, as a means to reduce costs, expedite timelines, provide broad applicability, and satisfy regulatory authorities.The significant geographic differences in patient characteristics, outcomes, and treatment effect may affect trial results and raise important questions about generalizability of the results to a broader population.

Background In sepsis, early outcome prediction would allow investigation of both adaptive mechanisms underlying survival and maladaptive mechanisms resulting in death. The aim of this study was to test whether early changes in heart rate monitored by telemetry could predict outcome in a long-term rat model of fecal peritonitis. Methods Male Wistar rats (n = 24) were instrumented with a central venous line for administration of fluids, antibiotics and analgesics. A telemetry transmitter continuously collected electrocardiogram signals. Sepsis was induced by intraperitoneal injection of fecal slurry, and the animals were observed for 48 h. Additional animals underwent arterial cannulation at baseline (n = 9), 4 h (n = 16), or 24 h (n = 6) for physiology and laboratory measurements. Results 48-h mortality was 33% (8/24), with all deaths occurring between 4 and 22 h. Septic animals were characterized by lethargy, fever, tachycardia, positive blood cultures, and elevated cytokine (IL-1, IL-6, TNF alpha) levels. An increase in heart rate ≥ 50 bpm during the first 4 h of sepsis predicted death with sensitivity and specificity of 88% (p = 0.001). Conclusions In this long-term rat sepsis model, prognostication could be made early by telemetry-monitored changes in heart rate. This model enables the study of underlying mechanisms and the assessment of any differential effects of novel therapies in predicted survivors or non-survivors.

Vorhofflimmern ist die haufigste Herzrhythmusstorung auf Notfall- und Intensivstationen und mit einer erhohten Morbiditat und Mortalitat assoziiert. Diese Rhythmusstorung kann bei kritisch kranken Patienten zu hamodynamischer Instabilitat und kardiogenem Schock fuhren. Die Mechanismen fur die Entstehung von Vorhofflimmern sowie dessen Behandlung unterscheiden sich bei kritisch kranken Patienten grundlegend von denen bei Patienten im ambulanten Umfeld. Bei neu aufgetretenem Vorhofflimmern sollen die hamodynamischen Auswirkungen beurteilt und die reversible Auslosefaktoren optimiert werden. Hamodynamisch instabile Patienten benotigen eine rasche Behandlung zur Wiederherstellung eines adaquaten Perfusionsdrucks. Die rasche Wiederherstellung des Sinusrhythmus spielt haufig eine zentrale Rolle in der hamodynamischen Stabilisierung. Die elektrische Kardioversion, wenn moglich nach Vorbehandlung mit einem Antiarrhythmikum zur Erhohung der Erfolgschance, ist eine wichtige therapeutische Masnahme. Bei stabilen Patienten soll initial eine Frequenzkontrolle mit einem kurzwirksamen intravenosen β-Blocker eingeleitet werden. Eine Konversion in den Sinusrhythmus kann haufig medikamentos versucht werden. Neu steht dafur Vernakalant, ein vorhofspezifischer Multikanalblocker, zur Verfugung. Nach 48 h mit Vorhofflimmern sollten alle Patienten zur Vermeidung kardioembolischen Ereignisse bezuglich Indikation zur Antikoagulation evaluiert werden. Erfreulicherweise persistiert Vorhofflimmern nach Abheilung der akuten Krankheit selten.

Objectives: Performing transcatheter aortic valve implantation (TAVI) with the use of minimal contrast in patients at high-risk for acute kidney injury Background: Contrast-induced nephropathy is a major cause of acute kidney injury following TAVI and is associated with increased morbidity and mortality. The amount of contrast media used increases the risk for contrast-induced nephropathy. Methods: Computed tomography was omitted during the screening process. For the procedure transfemoral access was default. The self-expanding CoreValve prosthesis was chosen in all patients to minimize the risk of annular rupture in case of oversizing. Valve sizing was based on echocardiography, aortography, calcification on fluoroscopy, as well as weight and height of the patient. A single contrast injection was performed to confirm correct position of the pigtail catheter at the level of the annulus. The pigtail then served as the marker for the device landing zone. Intraprocedural assessment of the implantation result relied on echocardiography and hemodynamics. Results: Five patients with severe aortic stenosis and at high risk for developing contrast-induced nephropathy were included. Device success was achieved in all patients and no major complications occurred. The median dose of injected contrast media was 8ml (4-9). All but one patients had improved renal function after the intervention compared to baseline. Conclusions: Our study shows feasibility of performing TAVI with a single minimal contrast media injection, using a self-expandable valve. This technique has the potential to reduce the incidence of contrast-induced nephropathy. This article is protected by copyright. All rights reserved.

Inotropes are indicated to restore cardiac output (CO) in the presence of signs of tissue hypoperfusion despite optimization of volume status, oxygenation and haematocrit level. Inotropes, especially catecholamines, cannot be widely used as they are associated with numerous and frequent shortand long-term adverse events. However, despite clear indications by the most prominent international societies of intensive care and cardiology to restrict their use, the current use of catecholamines is very frequent [1]. The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines and the 2014 European Society of Intensive Care Medicine (ESICM) Consensus on shock recommend that ‘‘inotropic agents should be added when the altered cardiac function is accompanied by a low or inadequate CO and signs of tissue hypoperfusion persist after preload optimization’’ (Level 2; QoE low) [2]. Furthermore, the 2014 ESICM Consensus on shock indicated that evaluation of CO and cardiac function, by any means, becomes crucial when deciding on whether inotropic agents have a place in the therapy of a given patient and in evaluating the haemodynamic impact of those therapeutic interventions [2]. We provide a brief overview on current and future inotropic agents with a special focus on the pharmacological and clinical characteristics of the different classes (Table 1). The ‘‘ideal’’ inotropic agent should improve stroke volume without increasing myocardial oxygen consumption or causing arrhythmias, should ameliorate diastolic function and upstream congestion, should have a short half-life so as to be easily titratable and should have positive effects on long-term outcome. The ‘‘ideal’’ agent has not yet been found.

Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

Background Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis. Methods Male Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography—high resolution mass spectrometry. Results In anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats. Conclusions In anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis.

Objectives: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock. Design: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality. Setting: Nine tertiary care university hospitals. Patients: Patients with cardiogenic shock caused by acute coronary syndrome (n=145). Interventions: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement. Measurements and Main Results: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, >= 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, >= 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients. Conclusions: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

Background The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5–10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score (P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS., published version, peerReviewed

Background: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM. Methods and Results: Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16–22] and 98 [IQR 78–126] ng/mL, respectively; P0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3–1.7] and 0.3 [IQR 0.3–1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101–4,050] ng/mL; P

Heart rate, blood pressure, and vascular tone, as well as ventilator drive, respiratory rate, and breathing pattern, are, at least in part, under the control of specific reflexes. These reflexes are mediated by a complex network of baroreceptors and chemoreceptors in the arterial system of the carotids, aorta, and left heart, including receptors in the left atrium, the ventricle, and the coronary arteries; irritants in the upper airways and stretch receptors in the lower airways; juxtacapillary-located nonmyelinated fibers in the alveoli and in the bronchial arterial system; and muscle spindles that evoke changes in the membrane potential upon alteration of sarcolemmal tension. Some of these reflexes, usually named after the first individual to describe them, have spread as eponyms into propaedeutic education and clinical work. Because these euphonic eponyms are enigmatic to most clinicians today, this article is intended to provide a short overview of these reflexes, including the historical context of their describers. As evidenced by their clinical implications, the eponyms discussed are revealed to be more than curiosities taught during undergraduate medical education.

Aims: Cardiac resynchronization therapy (CRT) induces reverse cardiac remodelling in heart failure (HF), but many patients receiving CRT remain non-responders. This study assessed the role of amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide (MR-proANP), and mid-regional-pro-adrenomedullin (MR-proADM) at the time of device implantation to predict favourable clinical course (CRT response and/or risk of MACE) in HF patients receiving CRT. Methods and results: A total of 137 HF patients were prospectively included. Blood was drawn from the coronary sinus (CS) at CRT implantation, and from a peripheral vein (PV) simultaneously and after 6 months. Clinical CRT response at 6 months and major adverse cardiovascular events (MACE) at 2 years were assessed. Baseline PV-levels of MR-proANP (202 vs. 318 pmol/L, P = 0.009) and MR-proADM (843 vs. 1112 pmol/L, P = 0.02) were lower in CRT responders compared with non-responders. At 6 months, CRT responders showed a decrease in MR-proANP levels, compared with an increase in non-responders (-32 vs. +7 pmol/L, P = 0.02). During the same period, NT-proBNP decreased by a similar way in responders and non-responders, while MR-proADM was unchanged in both groups. High baseline MR-proANP, either in PV (OR 0.41, 95% CI 0.24-0.71, P = 0.002) or CS (OR 0.32, 95% CI 0.15-0.70, P = 0.005) was associated with reduced likelihood of CRT response. Furthermore, PV and CS levels of NT-proBNP, MR-proANP, and MR-proADM were all associated with increased risk of 2-year MACE (all P < 0.01). Conclusion: Mid-regional-pro-atrial natriuretic peptide may assist prediction of clinical course in HF patients undergoing CRT implantation. Low circulating MR-proANP at the time of device implantation is associated with CRT response and more favourable outcome.