Impact of the MEESSI-AHF tool to guide disposition decision-making in patients with acute heart failure in the emergency department: a before-and-after study.

OBJECTIVES: To determine the impact of risk stratification using the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with acute heart failure) scale to guide disposition decision-making on the outcomes of ED patients with acute heart failure (AHF), and assess the adherence of emergency physicians to risk stratification recommendations. METHODS: This was a prospective quasi-experimental study (before/after design) conducted in eight Spanish EDs which consecutively enrolled adult patients with AHF. In the pre-implementation stage, the admit/discharge decision was performed entirely based on emergency physician judgement. During the post-implementation phase, emergency physicians were advised to 'discharge' patients classified by the MEESSI-AHF scale as low risk and 'admit' patients classified as increased risk. Nonetheless, the final decision was left to treating emergency physicians. The primary outcome was 30-day all-cause mortality. Secondary outcomes were days alive and out of hospital, in-hospital mortality and 30-day post-discharge combined adverse event (ED revisit, hospitalisation or death). RESULTS: The pre-implementation and post-implementation cohorts included 1589 and 1575 patients, respectively (median age 85 years, 56% females) with similar characteristics, and 30-day all-cause mortality was 9.4% and 9.7%, respectively (post-implementation HR=1.03, 95% CI=0.82 to 1.29). There were no differences in secondary outcomes or in the percentage of patients entirely managed in the ED without hospitalisation (direct discharge from the ED, 23.5% vs 24.4%, OR=1.05, 95% CI=0.89 to 1.24). Adjusted models did not change these results. Emergency physicians followed the MEESSI-AHF-based recommendation on patient disposition in 70.9% of cases (recommendation over-ruling: 29.1%). Physicians were more likely to over-rule the recommendation when 'discharge' was recommended (56.4%; main reason: need for hospitalisation for a second diagnosis) than when 'admit' was recommended (12.8%; main reason: no appreciation of severity of AHF decompensation by emergency physician), with an OR for over-ruling the 'discharge' compared with the 'admit' recommendation of 8.78 (95% CI=6.84 to 11.3). CONCLUSIONS: Implementing the MEESSI-AHF risk stratification tool in the ED to guide disposition decision-making did not improve patient outcomes.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).

High-sensitivity cardiac troponin T 30 days all-come mortality in patients with acute heart failure. A Propensity Score-Matching Analysis Based on the EAHFE Registry. TROPICA4 Study.

BACKGROUND: Acute heart failure (AHF) patients with high troponin levels have a worse prognosis. High-sensitive troponin T (hs-TnT) has been used as a tool to stratify prognosis in many scales but always as a qualitative and not as a quantitative variable. OBJECTIVES: The main objective of this study was to determine the best hs-TnT cut-off for prediction of 30-day all-cause mortality. METHODS: The EAHFE registry, a prospective follow-up cohort of patients with AHF, was analysed. We performed a propensity score analysis of the optimal hs-TnT cut-off point previously determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 13 791 patients in the EAHFE cohort, we analysed 3190 patients in whom hs-TnT determination was available. The area under the ROC curve for 30-day all-cause mortality was 0.70 (CI95% 0.68 to 0.71; P < .001), establishing an optimal cut-off of hs-TnT of 35 ng/L. The sensitivity and specificity of this cut-off were 76.2 and 55.5%, respectively, with a negative predictive value (NPV) of 95.3%. A propensity score was made with 34 variables showing differences based on the cut-off of 35 ng/L for hs-TnT. In the analysis of the population obtained with the propensity score, patients with hs-TnT > 35 ng/L showed a greater 30-day all-cause mortality, with a HR of 2.95 (CI95% 1.83-4.75; P < .001). External validation reported similar results. CONCLUSIONS: An hs-TnT value of 35 ng/L is an adequate cut-off to evaluate the prediction of 30-day all-cause mortality with a NPV of 95.3%.

Iron deficiency and safety of ferric carboxymaltose in patients with acute heart failure. AHF-ID study.

INTRODUCTION: The presence of iron deficiency (ID) in patients with acute heart failure (AHF) is high. There are few studies on the characteristics of these patients and the safety of ferric carboxymaltose administration (FCM). OBJECTIVE: Study the differences among patients with AHF based on the presence and type of ID as well as the safety of FCM administration in these patients. METHOD: The AHF-ID study is a multicentre, analytical, prospective follow-up cohort including patients admitted to six Spanish hospitals for AHF. ID was defined as serum ferritin <100 µg/L (group A) or ferritin 100-299 µg/L with a TSAT <20% (group B). In cases receiving FCM the appearance of adverse events was analysed. Adjusted Cox regression was used to determine the association with 30-days reattendance for AHF after discharge. RESULTS: A total of 221 patients were recruited; 191 (86.4%) presented ID, 121 (63.4%) group A and 70 (36.6%) group B. There were scarce differences between the groups analysed. No differences were found in 30-days reattendance for AHF. FCM was administered to 158 (71.5%) patients, with 8 (5.1%) presenting adverse events, the most frequent being digestive alterations. Treatment was not discontinued in any case. CONCLUSIONS: There are scarce differences between the presence and the type of ID in patients with AHF. The administration of FCM in patients with ID and AHF is safe.

Effect of Barthel Index on the Risk of Thirty-Day Mortality in Patients With Acute Heart Failure Attending the Emergency Department: A Cohort Study of Nine Thousand Ninety-Eight Patients From the Epidemiology of Acute Heart Failure in Emergency Departments Registry.

STUDY OBJECTIVE: We assess the value of the Barthel Index (BI) in predicting 30-day mortality risk among patients with acute heart failure who are attending the emergency department (ED). METHODS: We selected 9,098 acute heart failure patients from the Acute Heart Failure in Emergency Departments registry who had BI score available both at baseline and the ED visit. Patients' data were collected from 41 Spanish hospitals during four 1- to 2-month periods between 2009 and 2016. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and BI score. c Statistics were used to estimate their prognostic value. RESULTS: The mean baseline BI score was 79.4 (SD 24.6) and the mean ED BI score was 65.3 (SD 29.1). Acute functional decline (≥5-point decrease between baseline BI and ED BI score) was observed in 5,771 patients (53.4%). Within 30 days of the ED visit, 905 patients (9.9%) died. There was a steep inverse gradient in 30-day mortality risk for baseline BI and ED BI score. For instance, compared with BI score=100, a BI score of 50 to 55 doubled the mortality risk both at baseline and the ED visit. At the ED visit, a BI score of 0 to 5 carried a 5-fold increase in risk after adjustment for other risk predictors. In comparison with baseline BI score, ED BI score consistently provided greater discrimination. Neither baseline BI score nor the change in BI score from baseline to the ED visit added further prognostic value to the ED BI score. CONCLUSION: Functional status assessed by the BI score at the ED visit is a strong predictor of 30-day mortality in acute heart failure patients, with higher predictive value than baseline BI score and acute functional decline. Routine recording of BI score at the ED visit may help in decisionmaking and health care planning.

Analysis of How Emergency Physicians' Decisions to Hospitalize or Discharge Patients With Acute Heart Failure Match the Clinical Risk Categories of the MEESSI-AHF Scale.

STUDY OBJECTIVE: The Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) is a validated clinical decision tool that characterizes risk of mortality in emergency department (ED) acute heart failure patients. The objective of this study is to compare the distribution of risk categories between hospitalized and discharged ED patients with acute heart failure. METHODS: We included consecutive acute heart failure patients from 34 Spanish EDs. Patients were retrospectively classified according to MEESSI-AHF risk categories. We calculated the odds of hospitalization (versus direct discharge from the ED) across MEESSI-AHF risk categories. Next, we assessed the following 30-day postdischarge outcomes: ED revisit, hospitalization, death, and their combination. We used Cox hazards models to determine the adjusted association between ED disposition decision and the outcomes among patients who were stratified into low- and increased-risk categories. RESULTS: We included 7,930 patients (80.5 years [SD 10.1 years]; women 54.7%; hospitalized 75.3%). Compared with that for low-risk MEESSI-AHF patients, odds ratios for hospitalization of patients in intermediate-, high-, and very-high-risk categories were 1.83 (95% confidence interval [CI] 1.64 to 2.05), 3.05 (95% CI 2.48 to 3.76), and 3.98 (95% CI 3.13 to 5.05), respectively. However, almost half (47.6%) of all discharged patients were categorized as being at increased risk by MEESSI-AHF, and 19.0% of all the increased-risk patients were discharged from the ED. Among the low-risk MEESSI-AHF patients, the 30-day postdischarge mortality did not differ by ED disposition (hazard ratio [HR] for discharged patients with respect to hospitalized ones 0.65; 95% CI 0.70 to 1.11), nor did it differ in the increased-risk group (HR 0.88; 95% CI 0.63 to 1.23). The discharged low-risk MEESSI-AHF patients had higher risks of 30-day ED revisit and hospitalization (HR 1.86, 95% CI 1.57 to 2.20; and HR 1.92, 95% CI 1.54 to 2.40, respectively) compared with the admitted patients, as did the discharged patients in the increased-risk group (HR 1.62, 95% CI 1.39 to 1.89; and HR 1.40, 95% CI 1.16 to 1.68, respectively), with similar results for the combined endpoint. CONCLUSION: The disposition decisions made in current clinical practice for ED acute heart failure patients calibrate with MEESSI-AHF risk categories, but nearly half of the patients currently discharged from the ED fall into increased-risk MEESSI-AHF categories.

The subset of patients with acute heart failure able to secrete relaxin-2 at pregnancy concentrations could have a longer survival: a pilot study.

OBJECTIVE: To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome. METHODS: In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 < 500 pg/mL). The primary outcome was all-cause death during follow-up. Secondary endpoints were prolonged hospitalisation (>10 days), combined endpoint (death, rehospitalisation, ED revisit) 30 days after discharge, and 30-day, one-year and three-year death rates. RESULTS: We included 814 patients [81 (SD = 9) years; 53.0% women] followed during 1.9 (SD 2.8) years; 517 (63.5%) died. Twenty patients (2.5%) formed the PLG (median relaxin-2 = 1459 pg/mL; IQR = 1722) and 794 the CG (median = 26; IQR = 44). There was no interaction with variables included on adjustment (age, sex, ischaemic cardiomyopathy, NT-proBNP, glycaemia, and sodium). PLG patients did not have better short-term secondary endpoints, but did show a significantly lower three-year mortality [ORadjusted = 0.17 (0.05-0.5), p = 0.003]. CONCLUSIONS: The small proportion of AHF patients achieving relaxin-2 concentrations similar to those observed in pregnancy may survive longer.

Predicting 30-Day Mortality for Patients With Acute Heart Failure in the Emergency Department: A Cohort Study.

Background: Physicians in the emergency department (ED) need additional tools to stratify patients with acute heart failure (AHF) according to risk. Objective: To predict mortality using data that are readily available at ED admission. Design: Prospective cohort study. Setting: 34 Spanish EDs. Participants: The derivation cohort included 4867 consecutive ED patients admitted during 2009 to 2011. The validation cohort comprised 3229 patients admitted in 2014. Measurements: 88 candidate risk factors and 30-day mortality. Results: Thirteen independent risk factors were identified in the derivation cohort and were combined into an overall score, the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score. This score predicted 30-day mortality with excellent discrimination (c-statistic, 0.836) and calibration (Hosmer-Lemeshow P = 0.99) and provided a steep gradient in 30-day mortality across risk groups (<2% for patients in the 2 lowest risk quintiles and 45% in the highest risk decile). These characteristics were confirmed in the validation cohort (c-statistic, 0.828). Multiple sensitivity analyses did not find important amounts of confounding or bias. Limitations: The study was confined to a single country. Participating EDs were not selected randomly. Many patients had missing data. Measurement of some risk factors was subjective. Conclusion: This tool has excellent discrimination and calibration and was validated in a different cohort from the one that was used to develop it. Physicians can consider using this tool to inform clinical decisions as further studies are done to determine whether the tool enhances physician decision making and improves patient outcomes. Primary Funding Source: Instituto de Salud Carlos III, Spanish Ministry of Health; Fundació La Marató de TV3; and Catalonia Govern.

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.

OBJECTIVE: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes. METHODS: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality. RESULTS: Seven patients (6.1%) died within 30 days and 43 (37.4%) within 1 year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953; p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients with galectin-3 concentrations >42 µg/L had an OR = 7.67(95%CI = 1.57-37.53; p = 0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT-proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint. CONCLUSION: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.

The utility of heart failure registries: a descriptive and comparative study of two heart failure registries.

BACKGROUND AND AIM: Registries are useful to address questions that are difficult to answer in clinical trials. The objective of this study was to describe and compare two heart failure (HF) cohorts from two Spanish HF registries. METHODS: We compared the RICA and EAHFE registries, both of which are prospective multicentre cohort studies including patients with decompensated HF consecutively admitted to internal medicine wards (RICA) or attending the emergency department (EAHFE). From the latter registry we only included patients who were admitted to internal medicine wards. RESULTS: A total of 5137 patients admitted to internal medicine wards were analysed (RICA: 3287 patients; EAHFE: 1850 patients). Both registries included elderly patients (RICA: mean (SD) age 79 (9) years; EAHFE: mean (SD) age 81 (9) years), with a slight predominance of female gender (52% and 58%, respectively, in the RICA and EAHFE registries) and with a high proportion of patients with preserved ejection fraction (58% and 62%, respectively). Some differences in comorbidities were noted, with diabetes mellitus, dyslipidaemia, chronic renal failure and atrial fibrillation being more frequent in the RICA registry while cognitive and functional impairment predominated in the EAHFE registry. The 30-day mortality after discharge was 3.4% in the RICA registry and 4.8% in the EAHFE registry (p<0.05) and the 30-day readmission rate was 7.5% in the RICA registry (readmission to hospital) and 24.0% in the EAHFE registry (readmission to emergency department) (p<0.001). CONCLUSIONS: We found differences in the clinical characteristics of patients admitted to Spanish internal medicine wards for decompensated HF depending on inclusion in either the RICA or EAHFE registry.

Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments. / Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios.

OBJECTIVES: To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1) to measure the predictive value of the usual decision points, 2) to identify patients at low risk for mortality who could be safely discharged from the ED, and 3) to measure the correlation between suPAR and other biomarkers. MATERIAL AND METHODS: Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. RESULTS: A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). CONCLUSION: A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes.

OBJETIVO: Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1) medir la capacidad de los `puntos de decisión habituales, 2) identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3) medir la correlación entre suPAR y otros biomarcadores. METODO: Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. RESULTADOS: Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR 4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR 6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR 6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. CONCLUSIONES: Un valor de suPAR 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR 6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial.

BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

QT interval and short-term outcome in acute heart failure.

OBJECTIVE: To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF). METHODS: We analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a QTc = 450 ms as reference. RESULTS: Of 1800 patients meeting entry criteria (median age 84 years (IQR = 77-89), 56% female), their median QTc was 453 ms (IQR = 422-483). The 30-day mortality was 9.7%, while need of hospitalization, in-hospital mortality and prolonged hospitalization were 77.8%, 9.0% and 50.0%, respectively. RCS curves found longer QTc was associated with 30-day mortality if > 561 ms, OR = 1.86 (1.00-3.45), and increased up to OR = 10.5 (2.25-49.1), for QTc = 674 ms. A similar pattern was observed for in-hospital mortality; OR = 2.64 (1.04-6.69), for QTc = 588 ms, and increasing up to OR = 8.02 (1.30-49.3), for QTc = 674 ms. Conversely, the need of hospitalization had a U-shaped relationship: being increased in patients with shorter QTc [OR = 1.45 (1.00-2.09) for QTc = 381 ms, OR = 5.88 (1.25-27.6) for the shortest QTc of 200 ms], and also increasing for prolonged QTc [OR = 1.06 (1.00-1.13), for QTc = 459 ms, and reaching OR = 2.15 (1.00-4.62) for QTc = 588 ms]. QTc was not associated with prolonged hospitalization. CONCLUSION: In ED AHF patients, initial QTc provides independent short-term prognostic information, with increasing QTc associated with increasing mortality, while both, shortened and prolonged QTc are associated with need of hospitalization.

Use of digoxin in the emergency department to treat patients with acute heart failure and its impact on short-term outcomes. / Uso de digoxina endovenosa en urgencias para tratar pacientes con insuficiencia cardiaca aguda y su impacto en la evolución a corto plazo.

OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.

OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.

[Impacto de la dependencia funcional de los pacientes mayores atendidos en los servicios de Urgencias españoles durante la primera ola pandémica de la COVID-19 sobre la mortalidad a 30, 180 y 365 días en función del diagnóstico (COVID versus no COVID).] / Impact of functional dependency of elderly patients seen in Spanish emergency departments during the first wave of the COVID-19 pandemic on mortality at 30, 180 and 365 days depending on the diagnosis (COVID versus non-COVID).

OBJECTIVE: Functional assessment is part of geriatric assessment. How it is performed in hospital Emergency Departments (ED) is poorly understood, let alone its prognostic value. The aim of this paper was to investigate whether baseline disability to perform basic activities of daily living (BADL) was an independent prognostic factor for death after the index visit to the ED during the first wave of the COVID-19 pandemic and whether it had a different impact on patients with and without diagnosis of COVID-19. METHODS: A retrospective observational study of the EDEN-Covid (Emergency Department and Elder Needs during COVID) cohort was carried out, consisting of all patients aged ≥65 years seen in 52 Spanish EDs selected by chance during 7 consecutive days (30/3/2020 to 5/4/2020). Demographic, clinical, functional, mental and social variables were analyzed. Dependence was categorized with the Barthel index (BI) as independent (BI=100), mild-moderate dependence (100>BI>60) and severe-total dependence (BI<60), and their crude and adjusted association was evaluated with mortality at 30, 180 and 365 days using COX proportional hazards models. RESULTS: Of 9,770 enrolled patients with a mean age of 79 years, 51% were men, 6,305 (64.53%) were independent, 2,340 (24%) had mild-moderate dependence, and 1,125 (11.5%) severe-total dependence. The number of deaths at 30 days in these three groups was 500 (7.9%), 521 (22.3%) and 378 (33.6%), respectively; at 180 days it was 757 (12%), 725 (30.9%) and 526 (46.8%); and at 365 days 954 (15.1%), 891 (38.1%) and 611 (54.3%). In relation to independent patients, the adjusted risks (hazard ratio) of dying within 30 days associated with mild-moderate and severe-total dependency were 1.91 (95% CI: 1.66-2.19) and 2.51. (2.11-2.98); at 180 days they were 1.88 (1.68-2.11) and 2.64 (2.28-3.05); and at 365 days they were 1.82 (1.64-2.02) and 2.47 (2.17-2.82). This negative impact of dependency on mortality was greater in patients diagnosed with COVID-19 than in non-COVID-19 (p interaction at 30, 180 and 365 days of 0.36, 0.05 and 0.04). CONCLUSIONS: The functional dependence of older patients who attend Spanish EDs during the first wave of the pandemic is associated with mortality at 30, 180 and 365 days, and this risk is significantly higher in patients treated for COVID-19.

OBJETIVO: La valoración funcional forma parte de la valoración geriátrica. No se conoce bien cómo se realiza en los servicios de Urgencias hospitalarios (SUH) y menos aún su valor pronóstico. El objetivo de este trabajo fue investigar si la dependencia funcional basal para realizar las actividades básicas de la vida diaria (ABVD) era un factor pronóstico independiente de muerte tras la visita índice al SUH durante la primera ola pandémica de la COVID-19 y si tuvo un impacto diferente en pacientes con y sin diagnóstico de COVID-19. METODOS: Se realizó un estudio observacional retrospectivo de la cohorte EDEN-Covid (Emergency Department and Elder Needs during COVID) formada por todos los pacientes de edad mayor o igual a 65 años atendidos en 52 SUH españoles, seleccionados por oportunidad durante siete días consecutivos (del 30 de marzo al 5 de abril de 2020). Se analizaron variables demográficas, clínicas, funcionales, mentales y sociales. La dependencia se categorizó con el índice de Barthel (IB) en independiente (IB=100), dependencia leve-moderada (100>IB>60) y dependencia grave-total (IB<60), y se evaluó su asociación cruda y ajustada con la mortalidad a 30, 180 y 365 días mediante modelos de riesgos proporcionales de COX. RESULTADOS: De 9.770 pacientes incluidos con una media de edad de 79 años, un 51% eran hombres, 6.305 (64,53%) eran independientes, 2.340 (24%) tenían dependencia leve-moderada y 1.125 (11,5%) dependencia grave-total. El número de fallecidos a 30 días en estos tres grupos fue 500 (7,9%), 521 (22,3%) y 378 (33,6%), respectivamente; a 180 días fue 757 (12%), 725 (30,9%) y 526 (46,8%); y a 365 días 954 (15,1%), 891 (38,1%) y 611 (54,3%). En relación a los pacientes independientes, los riesgos (hazard ratio) ajustados de fallecer a 30 días, asociados a dependencia leve-moderada y grave-total, fueron 1,91 (IC 95%: 1,66-2,19) y 2,51 (2,11-2,98); a 180 días fueron de 1,88 (1,68-2,11) y 2,64 (2,28-3,05); y a 365 días fueron 1,82 (1,64-2,02) y 2,47 (2,17-2,82). Este impacto negativo de la dependencia sobre la mortalidad fue mayor en pacientes diagnosticados de COVID-19 que en los no COVID-19 (p interacción a 30, 180 y 365 días de 0,36, 0,05 y 0,04). CONCLUSIONES: La dependencia funcional de los pacientes mayores que acuden a SUH españoles durante la primera ola pandémica se asocia a mortalidad a 30, 180 y 365 días, y este riesgo es significativamente mayor en los pacientes atendidos por COVID-19.

The Clinical outcomes, healthcare resource utilization, and related costs (COHERENT) model. Application in heart failure patients.

INTRODUCTION AND OBJECTIVES: Composite endpoints are widely used but have several limitations. The Clinical outcomes, healthcare resource utilization and related costs (COHERENT) model is a new approach for visually displaying and comparing composite endpoints including all their components (incidence, timing, duration) and related costs. We aimed to assess the validity of the COHERENT model in a patient cohort. METHODS: A color graphic system displaying the percentage of patients in each clinical situation (vital status and location: at home, emergency department [ED] or hospital) and related costs at each time point during follow-up was created based on a list of mutually exclusive clinical situations coded in a hierarchical fashion. The system was tested in a cohort of 1126 patients with acute heart failure from 25 hospitals. The system calculated and displayed the time spent in each clinical situation and health care resource utilization-related costs over 30 days. RESULTS: The model illustrated the times spent over 30 days (2.12% in ED, 23.6% in index hospitalization, 2.7% in readmissions, 65.5% alive at home, and 6.02% dead), showing significant differences between patient groups, hospitals, and health care systems. The tool calculated and displayed the daily and cumulative health care-related costs over time (total, €4 895 070; mean, €144.91 per patient/d). CONCLUSIONS: The COHERENT model is a new, easy-to-interpret, visual display of composite endpoints, enabling comparisons between patient groups and cohorts, including related costs. The model may constitute a useful new approach for clinical trials or observational studies, and a tool for benchmarking, and value-based health care implementation.

Evaluation of the HEFESTOS scale to predict outcomes in emergency department acute heart failure patients.

The HEFESTOS scale was developed in 14 Spanish primary care centres and validated in 9 primary care centres of other European countries. It showed good performance to predict death/hospitalisation during the first 30 days after an episode of acute heart failure (AHF), with c-statistics of 0.807/0.730 in the derivation/validation cohorts. We evaluated this scale in the emergency department (ED) setting, comparing it to the EHMRG and MEESSI scales in the ED and the EFFECT and GWTG scales in hospitalised patients, to predict 30-day outcomes, including death and hospitalisation. Consecutive AHF patients were enrolled in 34 Spanish EDs in January-February 2016, 2018, and 2019 with variables needed to calculate outcome scores. Thirty-day hospitalisation/death (together and separately) and post-discharge combined adverse event (ED revisit or hospitalisation for AHF or all-cause death) were determined for patients discharged home after ED care. Predictive capacity was assessed by c-statistic with 95% confidence intervals. Of 10,869 patients, 4,044 were included (median age: 83 years, 54% women). The performance of HEFESTOS was modest for 30-day hospitalisation/death, c-statistic=0.656 (0.637-0.675), hospitalisation, 0.650 (0.631-0.669), and death, 0.610 (0.576-0.644). Of 1,034 patients with scores for the 5 scales, HEFESTOS had the numerically highest c-statistic for hospitalisation/death at 30 days, 0.666 (0.627-0.704), vs. MEESSI= 0.650 (0.612-0.687, p=0.51), EFFECT=0.633 (0.595-0.672, p=0.21), GWTG=0.618 (0.578-0.657, p=0.06) and EHMRG=0.617 (0.577-0.704, p=0.07). Similar modest performances were observed for predicting hospitalisation [ranging from HEFESTOS=0.656 (0.618-0.695) to GWTG=0.603 (0.564-0.643)]. Conversely, prediction of 30-day death was good with the MEESSI=0.787 (0.728-845), EFFECT=0.754 (0.691-0.818) and GWTG=0.749 (0.689-0.809) scales, and modest with EHMRG=0.649 (0.581-0.717) and HEFESTOS=0.610 (0.538-0.683). Although the HEFESTOS scale was numerically better for predicting 30-day hospitalisation/death in ED AHF patients, its modest performance precludes routine use. Only 30-day mortality was adequately predicted by some scales, with the MEESSI achieving the best results.

Surviving Older Patients Show Preserved Cellular and Humoral Immunological Memory Several Months After SARS-CoV-2 Infection.

Understanding how older people respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical if we are to confront the coronavirus disease 2019 (COVID-19) pandemic and establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analyzed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by interferon-γ (IFN-γ) and granzyme B release by ELISpot; memory B-lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than 7 months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG.

MEESSI-AHF risk score performance to predict multiple post-index event and post-discharge short-term outcomes.

BACKGROUND: The multiple estimation of risk based on the emergency department Spanish score in patients with acute heart failure (MEESSI-AHF) is a risk score designed to predict 30-day mortality in acute heart failure patients admitted to the emergency department. Using a derivation cohort, we evaluated the performance of the MEESSI-AHF risk score to predict 11 different short-term outcomes. METHODS: Patients with acute heart failure from 41 Spanish emergency departments (n=7755) were recruited consecutively in two time periods (2014 and 2016). Logistic regression models based on the MEESSI-AHF risk score were used to obtain c-statistics for 11 outcomes: three with follow-up from emergency department admission (inhospital, 7-day and 30-day mortality) and eight with follow-up from discharge (7-day mortality, emergency department revisit and their combination; and 30-day mortality, hospital admission, emergency department revisit and their two combinations with mortality). RESULTS: The MEESSI-AHF risk score strongly predicted mortality outcomes with follow-up starting at emergency department admission (c-statistic 0.83 for 30-day mortality; 0.82 for inhospital death, P=0.121; and 0.85 for 7-day mortality, P=0.001). Overall, mortality outcomes with follow-up starting at hospital discharge predicted slightly less well (c-statistic 0.80 for 7-day mortality, P=0.011; and 0.75 for 30-day mortality, P<0.001). In contrast, the MEESSI-AHF score predicted poorly outcomes involving emergency department revisit or hospital admission alone or combined with mortality (c-statistics 0.54 to 0.62). CONCLUSIONS: The MEESSI-AHF risk score strongly predicts mortality outcomes in acute heart failure patients admitted to the emergency department, but the model performs poorly for outcomes involving hospital admission or emergency department revisit. There is a need to optimise this risk score to predict non-fatal events more effectively.

Early intravenous nitroglycerin use in prehospital setting and in the emergency department to treat patients with acute heart failure: Insights from the EAHFE Spanish registry.

BACKGROUND AND OBJECTIVE: Although recommended for the treatment of acute heart failure (AHF), the use of intravenous (IV) nitroglycerin (NTG) is supported by scarce and contradicting evidence. In the current analysis, we have assessed the impact of IV NTG administration by EMS or in emergency department (ED) on outcomes of AHF patients. METHODS: We analyze AHF patients included by 45 hospitals that were delivered to ED by EMS. Patients were grouped according to whether treatment with IV NTG was started by EMS before ED admission (preED-NTG), during the ED stay (ED-NTG) or were untreated with IV NTG (no-NTG, control group). In-hospital, 30-day and 365-day all-cause mortality, prolonged hospitalization (>7 days) and 90-day post-discharge combined adverse events (ED revisit, hospitalization or death) were compared in EMS-NTG and ED-NTG respect to control group. RESULTS: We included 8424 patients: preED-NTG = 292 (3.5%), ED-NTG = 1159 (13.8%) and no-NTG = 6973 (82.7%). preED-NTG group had the most severely decompensated cases of AHF (p < 0.001) but it had lower in-hospital (OR = 0.724, 95%CI = 0.459-1.114), 30-day (HR = 0.818, 0.576-1.163) and 365-day mortality (HR = 0.692, 0.551-0.869) and 90-day post-discharge events (HR = 0.795, 0.643-0.984) than control group. ED-NTG group had mortalities similar to control group (in-hospital: OR = 1.164, 0.936-1.448; 30-day: HR = 0.980, 0.819-1.174; 365-day: HR = 0.929, 0.830-1.039) but significantly decreased 90-day post-discharge events (HR = 0.870, 0.780-0.970). Prolonged hospitalization rate did not differ among groups. Five different analyses confirmed these findings. CONCLUSIONS: Early prehospital IV NTG administration was associated with lower mortality and post-discharge events, while IV NTG initiated in ED only improved post-discharge event rate. Further studies are needed to assess the role of early prehospital administration of IV NTG to patients with AHF.