miR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients. METHODS: STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. RESULTS: Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003). CONCLUSIONS: Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.

Performance of Early Capillary Refill Time Measurement on Outcomes in Cardiogenic Shock: An Observational, Prospective Multicentric Study.

Rationale: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock. Objectives: To assess the correlation of capillary refill time values with 90-day mortality in cardiogenic shock patients or the need for venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Also to assess the correlation between capillary refill time and hemodynamic parameters. Methods: All consecutive patients with cardiogenic shock admitted to the intensive care unit of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction, and cardiac index) and peripheral tissue perfusion signs, such as capillary refill time on the index fingertip, mottling, and Pv-aCO2 (the difference between partial pressure of CO2 between venous and arterial blood) were recorded at inclusion (0 hour), 6 hours, 12 hours, 24 hours, and 48 hours. The composite primary endpoint was the association between 90-day mortality or the need for VA-ECMO support. Measurements and Main Results: A total of 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time points in nonsurvivors or patients needing VA-ECMO support. In univariate analysis, capillary refill time > 3 seconds at inclusion was associated with 90-day all-cause mortality or VA-ECMO support (hazard ratio, 12.38; 95% confidence interval, 2.91-52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93. Conclusions: In patients with cardiogenic shock admitted to the ICU, our preliminary data suggest that a prolonged capillary refill time >3 seconds was associated with an early prediction of 90-day mortality or the need for VA-ECMO support.

Red cell distribution width and mortality in older patients with frailty in the emergency department.

BACKGROUND: The red cell distribution width (RDW) reflects the degree of heterogeneity of red blood cells. Elevated RDW is associated both with frailty and with increased mortality in hospital-admitted patients. In this study we evaluate whether high RDW values are associated with mortality in older emergency department (ED) patients with frailty, and if the association is independent of the degree of frailty. METHODS: We included ED patients with the following criteria: ≥ 75 years of age, Clinical Frailty Scale (CFS) score of 4 to 8, and RDW % measured within 48 h of ED admission. Patients were allocated to six classes by their RDW value: ≤ 13%, 14%, 15%, 16%, 17%, and ≥ 18%. The outcome was death within 30 days of ED admission. Crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for a one-class increase in RDW for 30-day mortality were calculated via binary logistic regression analysis. Age, gender and CFS score were considered as potential confounders. RESULTS: A total of 1407 patients (61.2% female), were included. The median age was 85 with an inter-quartile range (IQR) of 80-89, median CFS score 6 (IQR: 5-7), and median RDW 14 (IQR: 13-16). Of the included patients, 71.9% were admitted to hospital wards. A total of 85 patients (6.0%) died during the 30-day follow-up. Mortality rate was associated with RDW increase (p for trend < .001). Crude OR for a one-class increase in RDW for 30-day mortality was 1.32 (95% CI: 1.17-1.50, p < .001). When adjusted for age, gender and CFS-score, OR of mortality for one-class RDW increase was still 1.32 (95% CI: 1.16-1.50, p < .001). CONCLUSION: Higher RDW values had a significant association with increased 30-day mortality risk in frail older adults in the ED, and this risk was independent of degree of frailty. RDW is a readily available biomarker for most ED patients. It might be beneficial to include it in risk stratification of older frail ED patients to identify those who could benefit from further diagnostic assessment, targeted interventions, and care planning.

Low body temperature and mortality in older patients with frailty in the emergency department.

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.

The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure: an ancillary analysis from the EURODEM study.

BACKGROUND: Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes. METHODS: This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression. RESULTS: Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p < 0.001), more often female (56.4% vs. 42.1%, p = 0.002) and had more dementia (18.7% vs. 7.2%, p < 0.001). On admission, EMS patients had more often confusion (14.2% vs. 2.1%, p < 0.001) and higher respiratory rate (24/min vs. 21/min, p = 0.014; respiratory rate > 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027). CONCLUSION: Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality.

Survival and quality of life after early discharge in low-risk pulmonary embolism.

INTRODUCTION: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes. METHODS: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism. RESULTS: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001). CONCLUSIONS: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.

Systematic geriatric assessment for older patients with frailty in the emergency department: a randomised controlled trial.

BACKGROUND: Comprehensive geriatric assessment provided in hospital wards in frail patients admitted to hospital has been shown to reduce mortality and increase the likelihood of living at home later. Systematic geriatric assessment provided in emergency departments (ED) may be effective for reducing days in hospital and unnecessary hospital admissions, but this has not yet been proven in randomised trials. METHODS: We conducted a single-centre, randomised controlled trial with a parallel-group, superiority design in an academic hospital ED. ED patients aged ≥ 75 years who were frail, or at risk of frailty, as defined by the Clinical Frailty Scale, were included in the trial. Patients were recruited during the period between December 11, 2018 and June 7, 2019, and followed up for 365 days. For the intervention group, systematic geriatric assessment was added to their standard care in the ED, whereas the control group received standard care only. The primary outcome was cumulative hospital stay during 365-day follow-up. The secondary outcomes included: admission rate from the index visit, total hospital admissions, ED-readmissions, proportion of patients living at home at 365 days, 365-day mortality, and fall-related ED-visits. RESULTS: A total of 432 patients, 63 % female, with median age of 85 years, formed the analytic sample of 213 patients in the intervention group and 219 patients in the control group. Cumulative hospital stay during one-year follow-up as rate per 100 person-years for the intervention and control groups were: 3470 and 3149 days, respectively, with rate ratio of 1.10 (95 % confidence interval, 0.55-2.19, P = .78). Admission rates to hospital wards from the index ED visit for the intervention and control groups were: 62 and 70 %, respectively (P = .10). No significant differences were observed between the groups for any outcomes. CONCLUSION: Systematic geriatric assessment for older adults with frailty in the ED did not reduce hospital stay during one-year follow-up. No statistically significant difference was observed for any secondary outcomes. More coordinated, continuous interventions should be tested for potential benefits in long-term outcomes. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov (registration number and date NCT03751319 23/11/2018).

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

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 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

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.

Current Use and Impact on 30-Day Mortality of Pulmonary Artery Catheter in Cardiogenic Shock Patients: Results From the CardShock Study.

BACKGROUND: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). METHODS: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. RESULTS: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices (P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. CONCLUSIONS: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.

Protein-based cardiogenic shock patient classifier.

AIMS: Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS. METHODS AND RESULTS: Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins-CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA). CONCLUSION: A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies.

Treatments targeting inotropy.

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

National Early Warning Score 2 (NEWS2) and 3-level triage scale as risk predictors in frail older adults in the emergency department.

BACKGROUND: The aim of the emergency department (ED) triage is to recognize critically ill patients and to allocate resources. No strong evidence for accuracy of the current triage instruments, especially for the older adults, exists. We evaluated the National Early Warning Score 2 (NEWS2) and a 3-level triage assessment as risk predictors for frail older adults visiting the ED. METHODS: This prospective, observational study was performed in a Finnish ED. The data were collected in a six-month period and included were ≥ 75-year-old residents with Clinical Frailty Scale score of at least four. We analyzed the predictive values of NEWS2 and the three-level triage scale for 30-day mortality, hospital admission, high dependency unit (HDU) and intensive care unit (ICU) admissions, a count of 72-h and 30-day revisits, and ED length-of-stay (LOS). RESULTS: A total of 1711 ED visits were included. Median for age, CFS, LOS and NEWS2 were 85 years, 6 points, 6.2 h and 1 point, respectively. 30-day mortality was 96/1711. At triage, 69, 356 and 1278 of patients were assessed as red, yellow and green, respectively. There were 1103 admissions, of them 31 to an HDU facility, none to ICU. With NEWS2 and triage score, AUCs for 30-day mortality prediction were 0.70 (0.64-0.76) and 0.62 (0.56-0.68); for hospital admission prediction 0.62 (0.60-0.65) and 0.55 (0.52-0.56), and for HDU admission 0.72 (0.61-0.83) and 0.80 (0.70-0.90), respectively. The NEWS2 divided into risk groups of low, medium and high did not predict the ED LOS (p = 0.095). There was a difference in ED LOS between the red/yellow and as red/green patient groups (p < 0.001) but not between the yellow/green groups (p = 0.59). There were 48 and 351 revisits within 72 h and 30 days, respectively. With NEWS2 AUCs for 72-h and 30-day revisit prediction were 0.48 (95% CI 0.40-0.56) and 0.47 (0.44-0.51), respectively; with triage score 0.48 (0.40-0.56) and 0.49 (0.46-0.52), respectively. CONCLUSIONS: The NEWS2 and a local 3-level triage scale are statistically significant, but poor in accuracy, in predicting 30-day mortality, and HDU admission but not ED LOS or revisit rates for frail older adults. NEWS2 also seems to predict hospital admission.

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock.

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5-10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1-3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.

Seasonal variations of patients presenting dyspnea to emergency departments in Europe: Results from the EURODEM Study

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: Anobservational 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 (53­80) 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.

Levels of Growth Differentiation Factor 15 and Early Mortality Risk Stratification in Cardiogenic Shock.

BACKGROUND: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS). METHODS AND RESULTS: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-150h level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-1512h cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-1512h >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality. CONCLUSIONS: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS.

Prognostic impact of baseline and residual SYNTAX scores in cardiogenic shock.

OBJECTIVES: The aim was to assess the extent of coronary artery disease and revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was evaluated and assessed for additive value over clinical risk scores. BACKGROUND: bSS and rSS have been proven to be useful in risk stratification in stable coronary artery disease as well as in acute coronary syndromes, but they have not been studied in STEMI related CS. METHODS: Patients from a multinational prospective study of CS were analyzed. The study population was divided into tertiles according to bSS. The Cox regression and receiver operating characteristic (ROC) curves were used to assess the predictive power of SS. RESULTS: Of the 61 studied patients, 85% were male and the mean age was 67 years. Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10). However, additive value over clinical risk scores was limited. rSS was not associated with mortality, whereas post-percutaneous coronary intervention (PCI) TIMI flow 3 of infarct-related artery (IRA) predicted better survival. CONCLUSIONS: In STEMI related CS, the added value of bSS and rSS over clinical assessment and risk scores is limited. Our results suggest that while immediate PCI in order to restore blood flow to the IRA is essential, deferring the treatment of residual lesions does not seem to be associated with worse prognosis.

Indications and practical approach to non-invasive ventilation in acute heart failure.

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

Levosimendan in Acute and Advanced Heart Failure: An Appraisal of the Clinical Database and Evaluation of Its Therapeutic Applications.

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

Predictive value of the baseline electrocardiogram ST-segment pattern in cardiogenic shock: Results from the CardShock Study.

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