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Purpose: The aim of this study was to assess the association between low body temperature and mortality in frail older adults in the emergency department (ED). Methods: Inclusion criteria were: ≥ 75 years of age, Clinical Frailty Scale (CFS) score of 4–8, and temperature documented at ED admission. Patients were allocated to three groups by body temperature: low ≤ 36.0 °C, normal 36.1–38.0 and high ≥ 38.1. Odds ratios (OR) for 30-day and 90-day mortality were analysed. Results: 1577 patients, 61.2% female, were included. Overall mortalities were 85/1577 (5.4%) and 144/1557 (9.2%) in the 30-day and 90-day follow-ups, respectively. The ORs for low body temperature were 3.03 (1.72–5.35; P < 0.001) and 2.71 (1.68–4.38; P < 0.001) for 30-day and 90-day mortality, respectively. This association remained when adjusted for age, CFS score and gender. Mortality of the high-temperature group did not differ significantly when compared to the normal-temperature group. Conclusions: Low body temperature in frail older ED patients was associated with significantly higher 30- and 90-day mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

Objective: Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients.Design: We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.Measurements and Results: Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]).Conclusions: In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death. [ABSTRACT FROM AUTHOR]

Up to 10% of acute coronary syndromes are complicated by cardiogenic shock (CS) with contemporary mortality rates of 40-50%. The extent of ischemic myocardium has a profound impact on the initial, in-hospital, and post-discharge management and prognosis in this patient population. Individualized patient risk assessment plays an important role in determining appropriate revascularization, drug treatment with inotropes and vasopressors, mechanical circulatory support, intensive care support of other organ systems, hospital level of care triage, and allocation of clinical resources. This review will outline the underlying causes and diagnostic criteria, pathophysiology, and treatment of CS complicating acute coronary syndromes with a focus on (a) potential therapeutic issues from the perspective an interventional cardiologist, an emergency physician, and an intensive care physician, (b) the type of revascularization, and (c) new therapeutic advancements in pharmacologic and mechanical percutaneous circulatory support. [ABSTRACT FROM AUTHOR]

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

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

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

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. Study identifier of CardShock study NCT01374867 at clinicaltrials.gov [ABSTRACT FROM AUTHOR]

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

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS). [ABSTRACT FROM AUTHOR]

The cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidneys. Evaluating renal function is an essential part of the assessment of every cardiac patient. It has become clear that serum creatinine is not an accurate enough marker of glomerular filtration rate (GFR) and should not be used to evaluate kidney dysfunction. Creatinine-based estimates of GFR are preferred, but require renal function to be stable and are not suitable when changes in kidney function occur. Cystatin C (CysC) has been the target of much interest in the search for an alternative measure of GFR. As an endogenous biomarker, CysC possesses many of the properties required of a good marker of renal function. Compared with that of creatinine, plasma concentrations of CysC are less influenced by factors other than GFR. Consequently, CysC correlates with true GFR more accurately than creatinine. Equations for estimating GFR from CysC values have also been developed, which makes values easier to interpret and facilitates the clinical use of this new marker. The use of CysC in acute kidney injury has also shown promising results. CysC has been studied as a risk marker for prognosis in cardiovascular disease. This effect is attributed to the strong impact of renal dysfunction on progressive cardiovascular disease and impaired survival. Higher levels of CysC have consistently been predictive of incident or recurrent cardiovascular events and adverse outcomes. CysC is a predictor of the development of heart failure and increased levels of CysC have an independent association with higher mortality in both chronic and acute heart failure. In conclusion, CysC appears to be an interesting marker of renal function and is useful for risk stratification in heart failure. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It increases myocardial contractility, reduces the filling pressure and dilates both the peripheral and coronary vessels. The circulating metabolites of levosimendan, OR-1855 and OR-1896, are formed and eliminated slowly after intravenous administration of levosimendan. The aim of this study was to investigate the effect of impaired renal function and haemodialysis on the pharmacokinetics of levosimendan, OR-1855 and OR-1896. STUDY DESIGN: This study was an open-label, nonrandomised, phase I pharmacokinetic study. Levosimendan was administered as a single-dose infusion of 0.1 μg/kg/minute for 24 hours. The follow-up period lasted 3 weeks. STUDY SETTING: Twenty-five patients were included: 12 patients with severe chronic renal failure (CRF) with creatinine clearance of <30 mL/minute/1.73m and 13 patients with end-stage renal disease (ESRD) undergoing haemodialysis. A group of 12 healthy subjects served as controls. RESULTS: Levosimendan, the parent drug, was eliminated rapidly from the plasma after discontinuation of its infusion, with an elimination half-life (t½) [mean ± standard error of mean] of 1.5 ± 0.09 hours in ESRD patients undergoing haemodialysis, 1.0 ± 0.2 hours in patients with severe CRF and 0.91 ± 0.03 hours in healthy subjects. The t½ of levosimendan was significantly longer (p < 0.001) in ESRD patients undergoing haemodialysis than in healthy subjects. The t½ of OR-1855 and OR-1896 were 94.0 ± 20.4 hours and 96.5 ± 19.5 hours, respectively, in ESRD patients undergoing haemodialysis compared with 60.8 ± 5.2 and 61.6 ± 5.2 hours, respectively, in healthy subjects (p = not significant). The t½ of OR-1855 was significantly longer (85.0 ± 13.6 hours) in patients with severe CRF than in healthy subjects (60.8 ± 5.2 hours, p < 0.05). The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (Cmax) of the metabolites were approximately 2-fold in patients with ESRD undergoing haemodialysis and patients with severe CRF compared with healthy subjects. The mean unbound fraction (fu) of levosimendan in plasma was approximately 2% in each study group, whereas the fu of the metabolites was considerably higher (63–70%). In contrast to levosimendan, the metabolites were dialysable, with dialysis clearance of approximately 100 mL/minute. The haemodynamic responses and adverse event profiles were similar in the study groups, with headache, palpitations and dizziness being the most frequently recorded adverse events. CONCLUSION: The t½ of the levosimendan metabolites was prolonged 1.5-fold and their AUC and Cmax were 2-fold in patients with severe CRF and ESRD patients undergoing haemodialysis as compared with healthy subjects. These results suggest that the dose should be reduced when levosimendan is used for the treatment of congestive heart failure in patients with severe renal insufficiency. [ABSTRACT FROM AUTHOR]

Because of a technical error, the code corresponding to the outcome for the Basir et al. cohort was mis-implemented in the original version of our article. Characteristics of the cohort are in fact the followings. [ABSTRACT FROM AUTHOR]