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Aims Soluble urokinase–type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS. Methods and results SuPAR levels were determined in serial plasma samples (0–96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2–6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0–15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category. Conclusion SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.

Altres ajuts: This study was supported by grants from the Finnish Foundation for Cardiovascular Research, and Aarne Koskelo Foundation, Helsinki, Finland. Roche Diagnostics provided kits for the analysis of NT-proBNP and TnT. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Tuija Sabell (néeJavanainen) received following personal research grants: Acute Coronary Syndromes and secondary prevention grant from the Finnish Cardiac Society, grant supported by Astra Zeneca and grants from Paavo Nurmi Foundation and Paavo Ilmari Ahvenaisen säätiö. Dr Lassus has served on an advisory board for Boehringer Ingelheim, Medix Biochemica, Novartis, Servier, and Vifor Pharma and received lecture fees from Bayer, Boehringer Ingelheim, Pfizer, Novartis, Orion Pharma, and Vifor Pharma. Dr Parissis has received honoraria from Novartis and Orion Pharma. Urgent revascularization is the mainstay of treatment in acute coronary syndrome (ACS) related cardiogenic shock (CS). The aim was to investigate the association of angiographic results with 90-day mortality. Procedural complications of percutaneous coronary intervention (PCI) were also examined. This CardShock (NCT01374867) substudy included 158 patients with ACS aetiology and data on coronary angiography and complications during PCI procedure. Survival analysis was conducted with Kaplan-Meier curves and Cox regression analysis. Median age was 67 ± 11 years, and 77% were men. During 90-day follow-up, 66 (42%) patients died. Patients with one-vessel disease (n = 49) had lower mortality than patients with two-vessel (n = 59) or three-vessel (n = 50) disease (25% vs. 48% vs. 52%, P = 0.011). Successful revascularization [Thrombolysis in Myocardial Infarction (TIMI) Flow 3 post-PCI) was achieved more often in survivors than non-survivors (81% vs. 60%, P = 0.019). The median symptom-to-balloon time was 340 (196-660) minutes, with no difference between survivors and non-survivors. In multivariable mortality analysis, multivessel disease (HR 2.59, CI 1.29-5.18) and TIMI flow

Aims Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. [GRAPHICS] .

Aims The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR‐423‐5p level to predict mortality and associations of miR‐423‐5p with prognostic markers in cardiogenic shock. Methods and results We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR‐423‐5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all‐cause mortality. Median miR‐423‐5p level was significantly higher in 90 day non‐survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003–0.017) vs. 0.004 AU (0.002–0.009), P = 0.003]. miR‐423‐5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P

Összefoglaló. Bevezetés: A cardiovascularis halálokok közül világszerte nagy jelentőségű a hirtelen szívhalál. Annak ellenére, hogy a cardiopulmonalis resuscitatio és a postresuscitatiós intenzív osztályos kezelés is komoly metodikai és technikai fejlődésen ment keresztül az elmúlt időszakban, kevés az olyan validált pontrendszer, amely jól becsülné a beteg intenzív osztályra kerülésekor a mortalitási rizikót. Célkitűzés: A sikeres újraélesztést követő intenzív osztályos kezelés kezdetekor felmért, a cardiogen shock rizikóstratifikációjára alkalmazott CardShock Risk Score (CSRS) és az általunk hozzáadott, specifikus súlyozófaktorokkal (iniciális ritmus, inotropigény) módosított CardShock Risk Score (mCSRS) összevetése a mortalitás előrejelzésében post-cardiac arrest szindrómás betegeknél. Módszerek: Retrospektív vizsgálatunk során 172, kórházon kívül sikeresen újraélesztett és klinikánkon ellátott consecutiv betegből a CSRS- és mCSRS-pontrendszerek segítségével végül 123 beteg adatait elemeztük. A CSRS- és mCSRS-változók és a korai/késői mortalitás közötti összefüggést Cox-regressziós analízissel vizsgáltuk. A pontszámok alapján 3 csoportba (1–3, 4–6, 7+) soroltuk a betegeket. Az összevont csoportok túlélését log-rank teszttel hasonlítottuk össze. Eredmények: A betegpopuláció átlagéletkora 63,6 év volt (69% férfi), és a hirtelen szívhalál hátterében 80%-ban akut coronaria szindróma állt. A korai/késői mortalitást leginkább a felvétel utáni neurológiai állapot, a szérumlaktátszint, a vesefunkció, az iniciális ritmus és a beteg katecholaminigénye határozta meg. A mCSRS alkalmazását követően mind az „1–3” és a „4–6” (p≤0,001), mind a „4–6” és a „7+” (p = 0,006) csoportok között szignifikáns különbséget találtunk a túlélésben. Következtetés: A felvételkori pontok alapján a mCSRS pontosabban definiálja és differenciálja egymástól az általunk beválasztott két extra súlyozófaktorral az enyhe, a közepes és a magas mortalitási rizikóval bíró betegpopulációkat, mint a CSRS. Orv Hetil. 2021; 162(2): 52–60. Summary. Introduction: Sudden cardiac death is one of the most significant cardiovascular causes of death worldwide. Although there have been immense methodological and technical advances in the field of cardiopulmonary resuscitation and following intensive care in the last decade, currently there are only a few validated risk-stratification scoring systems for the quick and reliable estimation of the mortality risk of these patients at the time of admission to the intensive care unit. Objective: Our aim was to correlate the mortality prediction risk points calculated by CardShock Risk Score (CSRS) and modified (m) CSRS based on the admission data of the post-cardiac arrest syndrome (PCAS) patients. Methods: The medical records of 172 out-of-hospital resuscitated cardiac arrest patients, who were admitted at the Heart and Vascular Centre of Semmelweis University, were screened retrospectively. Out of the 172 selected patients, 123 were eligible for inclusion to calculate CSRS and mCSRS. Based on CSRS score, we generated three different groups of patients, with scores 1 to 3, 4 to 6, and 7+, respectively. Mortality data of the groups were compared by log-rank test. Results: Mean age of the patients was 63.6 years (69% male), the cause of sudden cardiac death was acut coronary syndrome in 80% of the cases. The early and late mortality was predicted by neurological status, serum lactate level, renal function, initial rhythm, and the need of catecholamines. Using mCSRS, a significant survival difference was proven in between the groups “1–3” vs “4–6” (p≤0.001), “4–6” vs “7+” (p = 0.006). Conclusion: Compared to the CSRS, the mCSRS expanded with the 2 additional weighting points differentiates more specifically the low-moderate and high survival groups in the PCAS patient population treated in our institute. Orv Hetil. 2021; 162(2): 52–60.

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

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax >= and < 0.5 mu g/L, and IL-6 and CRPmax above/below median. Results: PCT peaked already at 24 h [median PCTmax 0.71 mu g/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax >= 0.5 mu g/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax >= 0.5 mu g/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. (C) 2020 Elsevier B.V. All rights reserved.

Background/aim: To describe seasonal variations in epidemiology, management, and short-term outcomes of patients in Europe presenting to an emergency department (ED) with a main complaint of dyspnea. Materials and methods: An observational prospective cohort study was performed in 66 European EDs which included consecutive patients presenting to EDs with dyspnea as the main complaint during 3 72-h study periods. Data were collected on demographics, comorbidities, chronic treatment, prehospital treatment, mode of arrival of patient to ED, clinical signs at admission, treatment in the ED, ED diagnosis, discharge from ED, and in-hospital outcome. Results: The study included 2524 patients with a median age of 69 (53–80) years old. Of the patients presented, 991 (39.3%) were in autumn, 849 (33.6%) were in spring, and 48 (27.1%) were in winter. The winter population was significantly older (P < 0.001) and had a lower rate of ambulance arrival to ED (P < 0.001). In the winter period, there was a higher rate for lower respiratory tract infection (35.1%), and patients were more hypertensive, more hypoxic, and more hyper/hypothermic compared to other seasons. The ED mortality was about 1% and, in hospital, mortality for admitted patients was 7.4%. Conclusion: The analytic method and the outcome of this study may help to guide the allocation of ED resources more efficiently and to recommend seasonal ED management protocols based on the seasonal trend of dyspneic patients. © TÜBİTAK., Lietuvos Mokslo Taryba: MIP-049/2015, We would like to thank Toine van den Ende and Ans Kluivers for their assistance in collecting data in Europe. The work of Justina Motiejunaite was supported by the Research Council of Lithuania (Grant No. MIP-049/2015), as well as by training grants from the French government, the Embassy of France in Lithuania, and the Erasmus Program. The EuroDEM study protocol and informed consent was received and reviewed by the institutional review board and ethical committee for each country (and/ or institution), and all participants provided informed consent. The EuroDEM study was done under the supervision of the EUSEM Research Committee. Data management in Europe was facilitated by the Jeroen Bosch Hospital., The work of Justina Motiejunaite was supported by the Research Council of Lithuania (Grant No. MIP-049/2015), as well as by training grants from the French government, the Embassy of France in Lithuania, and the Erasmus Program.

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc., Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate–dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

OBJECTIVES: Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non-invasive ventilation (NIV) for patients with respiratory acidosis. We aimed to determine compliance with guideline recommendations for patients with treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. METHODS: In each region, an observational prospective cohort study was performed that included patients presenting to EDs with the main complaint of dyspnoea during three 72-hour periods. This planned sub-study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in-hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. RESULTS: 801 patients were included from 122 EDs (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44% and 60.6% of patients with pH

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Funding: HoT-PE is an independent, investigator-initiated trial with an academic sponsor (Centre for Thrombosis and Haemostasis, University Medical Centre Mainz, Germany). The work of Stefano Barco, Philipp S. Wild, Stavros V. Konstantinides, and Mareike Lankeit was supported by the German Federal Ministry of Education and Research [BMBF 01EO1003 and 01EO1503]. In addition, the sponsor has obtained the study drug (rivaroxaban) and a grant from the market authorization holder of rivaroxaban, Bayer AG. AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (

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