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.

Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology.

Acute right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale) is a life-threatening condition that may arise in different clinical settings. Patients at risk of developing or with manifest acute cor pulmonale usually present with an acute pulmonary disease (e.g. pulmonary embolism, pneumonia, and acute respiratory distress syndrome) and are managed initially in emergency departments and later in intensive care units. According to the clinical setting, other specialties are involved (cardiology, pneumology, internal medicine). As such, coordinated delivery of care is particularly challenging but, as shown during the COVID-19 pandemic, has a major impact on prognosis. A common framework for the management of acute cor pulmonale with inclusion of the perspectives of all involved disciplines is urgently needed.

Speed and Nighttime Usage Restrictions and the Incidence of Shared Electric Scooter Injuries.

Importance: Electric scooter (e-scooter) crashes have become a serious health issue worldwide. The need for effective e-scooter regulations has been established in numerous instances. Objective: To investigate the association of restrictions on top speed and nighttime usage on the incidence of e-scooter-related injuries. Design, Setting, and Participants: A retrospective comparative cohort study of all patients with an injury related to shared e-scooter riding sustained in Helsinki, Finland. Data were collected from the electric patient database from 3 trauma hospitals representing all public hospitals treating patients with acute trauma in Helsinki. Shared e-scooter injuries from 2 periods were compared: an unrestricted period (January 1 to August 31, 2021) and a restricted period (January 1 to August 31, 2022). Data were analyzed from September 2022 to September 2023. Exposures: The restrictions established for shared e-scooters during the restricted period were: (1) the daytime top speed of 20 km/h, as opposed to the previous top speed of 25 km/h, (2) the use of shared e-scooters was prohibited on Friday and Saturday nights between 12 am and 5 am, and (3) the nighttime top speed was decreased to 15 km/h from Sunday to Thursday between 12 am and 5 am, as opposed to 25 km/h. Main outcome: The incidence of e-scooter injuries compared with the total trips made by e-scooters. Results: There were 528 e-scooter injuries requiring hospital care during the unrestricted period and 318 injuries during the restricted period of similar length. The median (IQR) age of the patients in the study periods was 25 (21-32) and 28 (22-37), respectively; 308 (58%) and 191 (60%) were male, respectively. The incidence of e-scooter injuries was 19 (95% CI, 17-20) for every 100 000 rides during the unrestricted period and 9 (95% CI, 8-10) per 100 000 rides during the restricted period. In the risk analysis, the odds ratio for shared e-scooter injuries was 0.5 (95% CI, 0.4-0.6) for the restricted period when adjusted for hourly temperature, rain amount, wind speed, and visibility. After introducing the restrictions, the number of e-scooter injuries decreased significantly between 11 pm and 5 am. Conclusion and Relevance: The number of injuries decreased after implementing restrictions on the top speed and nighttime usage of e-scooters. Similar restrictions in cities with shared e-scooter services should be explored.

Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology.

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.

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.

Cost-Effectiveness of Empagliflozin in Combination with Standard Care versus Standard Care Only in the Treatment of Heart Failure Patients in Finland.

Purpose: Sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin has recently been shown to improve the outcomes of heart failure (HF) patients regardless of patient's left ventricular ejection fraction by reducing the combined risk of cardiovascular death or hospitalization for worsening HF. The aim of this study was to assess the cost-effectiveness of adding empagliflozin to the standard care (SC) in comparison to SC only in the treatment of HF in Finland. Patients and Methods: The assessment was performed in the cost-utility framework using two Markov cohort state-transition models, one for HF with reduced ejection fraction (HFrEF) and one for HF with preserved ejection fraction (HFpEF). The models have been primarily developed based on the EMPEROR-Reduced and EMPEROR-Preserved trials which informed the modelled patient characteristics, efficacy of treatments in terms of associated risks for heart failure hospitalizations, cardiovascular (CV) and non-CV death, treatment related adverse events (AE), and state- and event-specific health-related quality of life weights (EQ-5D). Direct health care costs were estimated from Finnish published references. Cost-effectiveness was assessed from health care payer perspective based on incremental cost-effectiveness ratio (ICER; cost per quality adjusted life-year [QALY] gained) and probability of cost-effectiveness (at willingness-to-pay [WTP] of 35,000 euros/QALY). The ICER was reported as the weighted (HFrEF, 43.5%; HFpEF, 56.5%) average result of the two models. Results: Empagliflozin + SC treatment increased the average quality-adjusted life-expectancy, and treatment costs of HF patients by 0.15 QALYs and 1,594 euros, respectively, when compared to SC. An additional QALY with empagliflozin was thus gained at a cost of 10,621 euros. The probability of empagliflozin + SC being cost-effective compared to placebo + SC was 77.6% and 83.5% with WTP of 35,000 and 100,000 euros/QALY, respectively. Conclusion: Empagliflozin is a cost-effective treatment for patients with HF in the Finnish health care setting.

Characteristics and costs of electric scooter injuries in Helsinki: a retrospective cohort study.

BACKGROUND AND PURPOSE: The incidence of electric scooter (e-scooter) injuries has increased drastically in numerous countries after widespread availability of shared e-scooters. The economic impact on society from a broader perspective has not been studied. We aimed to estimate the incidence of e-scooter injuries, describe the injury patterns, and estimate the costs of e-scooter injuries. PATIENTS AND METHODS: We performed a retrospective cohort study including all e-scooter-related injuries presented in the three adult emergency departments in Helsinki in 2021. We collected the patient data from the university hospital information system. Injury severity was evaluated based on the Abbreviated Injury Score. The cost of the hospital treatment was analyzed based on our hospital district's service price listing. In addition, we recorded the total amount of sick leave days and estimated their economic impact. RESULTS: In total, 446 e-scooter injuries were identified and taken into the analysis (434 affecting riders and 12 non-riders). The median age of the patients was 26 (IQR 22-33), and 59% were male. 257 (58%) of the of the injuries were minor, whereas 155 (35%) were moderate, 30 (7%) serious, 3 (0.7%) severe, and one (0.2%) critical. Furthermore, 220 (49%) of the patients sustained head injuries. A major spike in accident incidence was seen during the weekend (Friday to Sunday) nights, accompanied by a proportional increase in patients with alcohol intoxication. Including both the costs of the hospital care and absence from work, the approximated total cost of e-scooter injuries was 1.7 million euros, with a median cost of a single accident being 1148 euros (IQR 399-4263 €). INTERPRETATION: Considerable number of the injuries are moderate, severe, or worse. Comprehensive preventive measures must be conducted to decrease the incidence of e-scooter injuries. The use of helmets should be strongly encouraged to prevent severe head injuries. The nighttime bans during weekends and speed limits on e-scooters appear to be justifiable.

Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock.

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.

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.

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.

Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock: results from the CardShock Study.

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.

Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest-A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial.

This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest. DESIGN: A randomized two-group single-blinded phase 2 clinical drug trial. SETTING: A multipurpose ICU in two university hospitals. PATIENTS: Of the 110 randomized comatose survivors after out-of-hospital cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24-76 yr old) with complete echocardiography were included in this study. INTERVENTIONS: Patients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia. MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (-9.0% ± 3.8% vs -8.1% ± 3.6%; p = 0.555) but better in xenon than control patients after hypothermia (-14.4.0% ± 4.0% vs -10.5% ± 4.0%; p = 0.006). In patients with coronary artery disease, longitudinal strain improved in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups. CONCLUSIONS: Among comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone.

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).

Outcome of patients with different clinical presentations of high-risk pulmonary embolism.

AIMS: The 2019 European Society of Cardiology (ESC) guidelines provide a revised definition of high-risk pulmonary embolism (PE) encompassing three clinical presentations: Cardiac arrest, obstructive shock, and persistent hypotension. This study investigated the prognostic implications of this new definition. METHODS AND RESULTS: Data from 784 consecutive PE patients prospectively enrolled in a single-centre registry were analysed. Study outcomes include an in-hospital adverse outcome (PE-related death or cardiopulmonary resuscitation) and in-hospital all-cause mortality. Overall, 86 patients (11.0%) presented with high-risk PE and more often had an adverse outcome (43.0%) compared to intermediate-high-risk patients (6.1%; P < 0.001). Patients with cardiac arrest had the highest rate of an in-hospital adverse outcome (78.4%) and mortality (59.5%; both P < 0.001 compared to intermediate-high-risk patients). Obstructive shock and persistent hypotension had similar rates of adverse outcomes (15.8% and 18.2%, respectively; P = 0.46), but the only obstructive shock was associated with an increased all-cause mortality risk. Use of an optimised venous lactate cut-off value (3.8 mmol/L) to diagnose obstructive shock allowed differentiation of adverse outcome risk between patients with shock (21.4%) and persistent hypotension (9.5%), resulting in a net reclassification improvement (0.24 ± 0.08; P = 0.002). CONCLUSION: The revised ESC 2019 guidelines definition of high-risk PE stratifies subgroups at different risk of in-hospital adverse outcomes and all-cause mortality. Risk prediction can be improved by using an optimised venous lactate cut-off value to diagnose obstructive shock, which might help to better assess the risk-to-benefit ratio of systemic thrombolysis in different subgroups of high-risk patients.

Venous lactate improves the prediction of in-hospital adverse outcomes in normotensive pulmonary embolism.

BACKGROUND: Arterial lactate is an established risk marker in patients with pulmonary embolism (PE). However, its clinical applicability is limited by the need of an arterial puncture. In contrast, venous lactate can easily be measured from blood samples obtained via routine peripheral venepuncture. METHODS: We investigated the prognostic value of venous lactate with regard to in-hospital adverse outcomes and mortality in 419 consecutive PE patients enrolled in a single-center registry between 09/2008 and 09/2017. RESULTS: An optimised venous lactate cut-off value of 3.3 mmol/l predicted both, in-hospital adverse outcome (OR 11.0 [95% CI 4.6-26.3]) and all-cause mortality (OR 3.8 [95%CI 1.3-11.3]). The established cut-off value for arterial lactate (2.0 mmol/l) and the upper limit of normal for venous lactate (2.3 mmol/l) had lower prognostic value for adverse outcomes (OR 3.6 [95% CI 1.5-8.7] and 5.7 [95% CI 2.4-13.6], respectively) and did not predict mortality. If added to the 2019 European Society of Cardiology (ESC) algorithm, venous lactate <2.3 mmol/l was associated with a high negative predictive value (0.99 [95% CI 0.97-1.00]) for adverse outcomes in intermediate-low-risk patients, whereas levels ≥3.3 mmol/l predicted adverse outcomes in the intermediate-high-risk group (OR 5.2 [95% CI 1.8-15.0]). CONCLUSION: Venous lactate above the upper limit of normal was associated with increased risk for adverse outcomes and an optimised cut-off value of 3.3 mmol/l predicted adverse outcome and mortality. Adding venous lactate to the 2019 ESC algorithm may improve risk stratification. Importantly, the established cut-off value for arterial lactate has limited specificity in venous samples and should not be used.

Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock.

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.

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study.

AIMS: This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock. METHODS AND RESULTS: Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP-SHOCK II score to predict in-hospital mortality and the additional value of GDF-15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co-morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in-hospital mortality (46% vs. 33%; P = 0.08), but 1 year post-discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP-SHOCK II score. Incorporating GDF-15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84. CONCLUSIONS: Elderly patients with cardiogenic shock have higher in-hospital mortality compared with the younger, but post-discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF-15 or sST2.

The FAST-FURO study: effect of very early administration of intravenous furosemide in the prehospital setting to patients with acute heart failure attending the emergency department.

AIMS: The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED. METHODS AND RESULTS: In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings. CONCLUSION: Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders.