Effect of seasonal influenza and COVID-19 vaccination on severity and long-term outcomes of patients with heart failure decompensations.

AIMS: To investigate whether seasonal influenza and COVID-19 vaccinations influence the severity of decompensations and long-term outcomes of patients with acute heart failure (AHF). METHODS AND RESULTS: We included consecutive AHF patients attended at 40 Spanish emergency departments during November and December 2022. They were grouped according to whether they had received seasonal influenza and COVID-19 vaccination. The severity of heart failure (HF) decompensation was assessed with the MEESSI scale, need for hospitalization, intensive care unit (ICU) admission, and in-hospital mortality. Long-term outcomes were 90-day and 1-year all-cause mortality. Associations between vaccination, HF decompensation severity, and long-term outcomes were investigated. Subgroup analyses were executed for 16 patient characteristics and their relationship with vaccination and 1-year mortality. We analysed 4243 patients (median age 85 years; interquartile range 77-90; 57% female): 1841 (43%) had received influenza vaccination, 3139 (74%) COVID-19 vaccination, 1773 (41.8%) received both vaccines (full vaccination) and 1036 (24.4%) none. Previous episodes of AHF, chronic obstructive pulmonary disease and chronic treatment with diuretics were associated with vaccination (either influenza, COVID-19 and full vaccination). High or very-high risk decompensation occurred in 18.6%; hospitalization in 72.3%, ICU admission in 1.1%, and in-hospital mortality in 8.4%. Influenza vaccination was associated with lower hospitalization rates (adjusted odds ratio [OR] 0.746, 95% confidence interval [CI] 0.636-0.876) and in-hospital mortality (OR 0.761, 95% CI 0.583-0.992), while COVID-19 vaccination was associated with increased hospitalizations (OR 1.215, 95% CI 1.016-1.454). Overall, 90-day and 1-year mortality were 20.3% and 34.4%. Both were decreased in influenza-vaccinated patients (adjusted hazard ratio [HR] 0.831, 95% CI 0.709-0.973; and HR 0.885, 95% CI 0.785-0.999, respectively) but only at 90 days in COVID-19 vaccinated patients (HR 0.829, 95% CI 0.702-0.980). Full vaccination achieved even greater reductions in in-hospital, 90-day, and 1-year mortality (HR 0.638, 95% CI 0.479-0.851; HR 0.702, 95% CI 0.592-0.833; and HR 0.815, 95% CI 0.713-0.931, respectively). Subgroup analysis based on patient-related characteristics demonstrated the consistence of vaccination with long-term survival. CONCLUSION: In HF patients, seasonal influenza vaccination appears to be associated with less severe decompensation and lower 1-year mortality, while no firm conclusions can be drawn from the results of the present study regarding the benefits of COVID-19 vaccination. Full vaccination is associated with the greatest reduction in short- and long-term mortality.

Association of intravenous digoxin use in acute heart failure with rapid atrial fibrillation and short-term mortality according to patient age, renal function, and serum potassium.

BACKGROUND: Intravenous digoxin is still used in emergency departments (EDs) to treat patients with acute heart failure (AHF), especially in those with rapid atrial fibrillation. Nonetheless, many emergency physicians are reluctant to use intravenous digoxin in patients with advanced age, impaired renal function, and potassium disturbances due to its potential capacity to increase adverse outcomes. OBJECTIVE: We investigated whether intravenous digoxin used to treat rapid atrial fibrillation in patients with AHF may influence mortality in patients with specific age, estimated glomerular filtration rate (eGFR), and serum potassium classes. DESIGN: A secondary analysis of patients included in in the Spanish EAHFE cohort, which includes patients diagnosed with AHF in the ED. SETTING: 45 Spanish EDs. PARTICIPANTS: Two thousand one hundred ninety-four patients with AHF and rapid atrial fibrillation (heart rate ≥100 bpm) not receiving digoxin at home, divided according to whether they were or were not treated with intravenous digoxin in the ED. OUTCOME: The relationships between age, eGFR, and potassium with 30-day mortality were investigated using restricted cubic spline (RCS) models adjusted for relevant patient and episode variables. The impact of digoxin use on such relationships was assessed by checking interaction. MAIN RESULTS: The median age of the patients was 82 years [interquartile range (IQR) = 76-87], 61.4% were women, 65.2% had previous episodes of atrial fibrillation, and the median heart rate at ED arrival was 120 bpm (IQR = 109-135). Digoxin and no digoxin groups were formed by 864 (39.4%) and 1330 (60.6%) patients, respectively. There were 191 deaths within the 30-day follow-up period (8.9%), with no differences between patients receiving or not receiving digoxin (8.5 vs. 9.1%, P  = 0.636). Although analysis of RCS curves showed that death was associated with advanced age, worse renal function, and hypo- and hyperkalemia, use of intravenous digoxin did not interact with any of these relationships ( P  = 0.156 for age, P  = 0.156 for eGFR; P  = 0.429 for potassium). CONCLUSION: The use of intravenous digoxin in the ED was not associated with significant changes in 30-day mortality, which was confirmed irrespective of patient age or the existence of renal dysfunction or serum potassium disturbances.

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.

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.

Cardiac resynchronization therapy in acute heart failure and left bundle-branch block in a real-life registry / Terapia de resincronización cardiaca en insuficiencia cardiaca aguda y bloqueo de rama izquierda en un registro real

Abstract Objectives: To determine the prevalence, characteristics, timing of implementation and prognosis of patients with left bundle branch block (LBBB) and acute heart failure (AHF) treated with cardiac resynchronization therapy (CRT) in a real-life registry. Methods: We analysed the characteristics of patients with AHF and LBBB at the time of inclusion in the EAHFE (Epidemiology Acute Heart Failure Emergency) cohort to determine the indication for CRT, the timing of implementation and its impact on 10-year all-cause mortality. Results: 729 patients with a median age of 82 years and there was a high burden of comorbidities and functional dependence. The median left-ventricle ejection fraction (LVEF) was 40%. Forty-six (6%) patients were treated with CRT at some point during follow-up, with a median time of delay for CRT implementation of 960 (IQR=1,147 days) and at least 108 more untreated patients fulfilled criteria for CRT. Patients receiving CRT were younger, had different comorbidities, less functional dependence (higher Barthel index) and lower LVEF values. The median follow-up was 5.7 years (95% CI: 5.6-5.8) and CRT was not associated with changes in 10-year mortality (adjusted HR 1.33, 95% CI: 0.72-2.48; p-value 0.4). When compared with untreated patients fulfilling criteria for CRT, very similar results were observed (adjusted HR 1.34, 95% CI: 0.67-2.68). Conclusions: CRT implementation was delayed and underused in patients with AHF and LBBB. Under these circumstances, CRT is not associated with a reduction in all-cause mortality in the long term.

Resumen Objetivos: Determinar la prevalencia, características, momento de implantación y pronóstico de los pacientes con bloqueo de rama izquierda del haz de His (BRIHH) e insuficiencia cardiaca aguda (ICA) tratados con terapia de resincronización cardiaca (TRC) en un registro real. Métodos: Se analizaron las características de los pacientes con ICA y BRIHH en el momento de su inclusión en la cohorte EAHFE (Epidemiology Acute Heart Failure Emergency) para determinar la indicación de TRC, el momento de implantación y su impacto en la mortalidad por cualquier causa a 10 años. Resultados: 729 pacientes con una mediana de edad de 82 años con una elevada carga de comorbilidades y dependencia funcional. La mediana de la fracción de eyección del ventrículo izquierdo (FEVI) fue del 40%. 46 pacientes (6%) fueron tratados con TRC en algún momento del seguimiento, con una mediana de tiempo de retraso para la implantación de la TRC de 960 dias (IQR=1,147 días) y al menos 108 pacientes no tratados cumplían criterios para TRC. Los pacientes que recibieron TRC eran más jóvenes, tenían comorbilidades diferentes, menor dependencia funcional (índice de Barthel más alto) y valores de FEVI más bajos. La mediana de seguimiento fue de 5.7 años (IC del 95%: 5.6-5.8) y la TRC no se asoció a cambios en la mortalidad a 10 años (HR ajustado: 1.33; IC del 95%: 0.72-2.48; p-valor 0.4). Cuando se comparó con pacientes no tratados que cumplían criterios para TRC, se observaron resultados muy similares (HR ajustado 1.34; IC del 95%: 0.67-2.68). Conclusiones: La implantación de la TRC se retrasó y se infrautilizó en pacientes con ICA y BRIHH. En estas circunstancias, la TRC no se asocia a una reducción de la mortalidad por cualquier causa a largo 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.

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.

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.

Cardiac resynchronization therapy in acute heart failure and left bundle-branch block in a real-life registry.

Objectives: To determine the prevalence, characteristics, timing of implementation and prognosis of patients with left bundle branch block (LBBB) and acute heart failure (AHF) treated with cardiac resynchronization therapy (CRT) in a real-life registry. Methods: We analysed the characteristics of patients with AHF and LBBB at the time of inclusion in the EAHFE (Epidemiology Acute Heart Failure Emergency) cohort to determine the indication for CRT, the timing of implementation and its impact on 10-year all-cause mortality. Results: 729 patients with a median age of 82 years and there was a high burden of comorbidities and functional dependence. The median left-ventricle ejection fraction (LVEF) was 40%. Forty-six (6%) patients were treated with CRT at some point during follow-up, with a median time of delay for CRT implementation of 960 (IQR=1,147 days) and at least 108 more untreated patients fulfilled criteria for CRT. Patients receiving CRT were younger, had different comorbidities, less functional dependence (higher Barthel index) and lower LVEF values. The median follow-up was 5.7 years (95% CI: 5.6-5.8) and CRT was not associated with changes in 10-year mortality (adjusted HR 1.33, 95% CI: 0.72-2.48; p-value 0.4). When compared with untreated patients fulfilling criteria for CRT, very similar results were observed (adjusted HR 1.34, 95% CI: 0.67-2.68). Conclusions: CRT implementation was delayed and underused in patients with AHF and LBBB. Under these circumstances, CRT is not associated with a reduction in all-cause mortality in the long term.

Objetivos: Determinar la prevalencia, características, momento de implantación y pronóstico de los pacientes con bloqueo de rama izquierda del haz de His (BRIHH) e insuficiencia cardiaca aguda (ICA) tratados con terapia de resincronización cardiaca (TRC) en un registro real. Métodos: Se analizaron las características de los pacientes con ICA y BRIHH en el momento de su inclusión en la cohorte EAHFE (Epidemiology Acute Heart Failure Emergency) para determinar la indicación de TRC, el momento de implantación y su impacto en la mortalidad por cualquier causa a 10 años. Resultados: 729 pacientes con una mediana de edad de 82 años con una elevada carga de comorbilidades y dependencia funcional. La mediana de la fracción de eyección del ventrículo izquierdo (FEVI) fue del 40%. 46 pacientes (6%) fueron tratados con TRC en algún momento del seguimiento, con una mediana de tiempo de retraso para la implantación de la TRC de 960 dias (IQR=1,147 días) y al menos 108 pacientes no tratados cumplían criterios para TRC. Los pacientes que recibieron TRC eran más jóvenes, tenían comorbilidades diferentes, menor dependencia funcional (índice de Barthel más alto) y valores de FEVI más bajos. La mediana de seguimiento fue de 5.7 años (IC del 95%: 5.6-5.8) y la TRC no se asoció a cambios en la mortalidad a 10 años (HR ajustado: 1.33; IC del 95%: 0.72-2.48; p-valor 0.4). Cuando se comparó con pacientes no tratados que cumplían criterios para TRC, se observaron resultados muy similares (HR ajustado 1.34; IC del 95%: 0.67-2.68). Conclusiones: La implantación de la TRC se retrasó y se infrautilizó en pacientes con ICA y BRIHH. En estas circunstancias, la TRC no se asocia a una reducción de la mortalidad por cualquier causa a largo plazo.

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.

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 ).

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.

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.

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.

Synergistic Impact of Systolic Blood Pressure and Perfusion Status on Mortality in Acute Heart Failure.

BACKGROUND: Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure (SBP) and hypoperfusion on short-term mortality. METHODS: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP (<90, 90-109, 110-129, and ≥130 mm Hg) and with manifestations of hypoperfusion (cold skin, cutaneous pallor, delayed capillary refill, livedo reticularis, and mental confusion) at admission. RESULTS: Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBP<90, SBP 90-109, SBP 110-129, and SBP≥130 mm Hg, respectively; P<0.001) and a positive association with hypoperfusion (8.0%, 14.8%, and 27.6% for those with none, 1, ≥2 signs/symptoms of hypoperfusion, respectively; P<0.001). After adjustment for 11 risk factors, the prognostic impact of hypoperfusion on 30-day mortality varied across SBP categories: SBP≥130 mm Hg (odds ratio [OR]=1.03 [95% CI, 0.77-1.36] and OR=1.18 [95% CI, 0.86-1.62] for 1 and ≥2 compared with 0 manifestations of hypoperfusion), SBP 110 to 129 mm Hg (OR=1.23 [95% CI, 0.86-1.77] and OR=2.18 [95% CI, 1.44-3.31], respectively), SBP 90 to 109 mm Hg (OR=1.29 [95% CI, 0.79-2.10] and OR=2.24 [95% CI, 1.36-3.66], respectively), and SBP<90 mm Hg (OR=1.34 [95% CI, 0.45-4.01] and OR=3.22 [95% CI, 1.30-7.97], respectively); P-for-interaction =0.043. CONCLUSIONS: Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.

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.

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.

The CRAS-EAHFE study: Characteristics and prognosis of acute heart failure episodes with cardiorenal-anaemia syndrome at the emergency department.

BACKGROUND: The coexistence of other comorbidities confers poor outcomes in patients with acute heart failure. Our aim was to determine the characteristics of patients with acute heart failure and cardiorenal anaemia syndrome and the relationship between renal dysfunction and anaemia, alone or combined as cardiorenal anaemia syndrome, on short-term outcomes. METHODS: We analysed the Epidemiology of Acute Heart Failure in Emergency Departments registry (cohort of patients with acute heart failure in Spanish emergency departments). Renal dysfunction was defined by an estimated glomerular filtration rate <60 ml/min/m2, anaemia by haemoglobin values <12/<13 g/dl in women/men, and cardiorenal anaemia syndrome as the presence of both. Comparisons were made according to cardiorenal-anaemia syndrome positive (CRAS+) with respect to the rest of patients (CRAS-) and according the presence of renal dysfunction (RD+) and anaemia (A+), (alone, RD+/A-, RD-/A+) or in combination (RD+/A+; i.e. CRAS+) with respect to patients without renal dysfunction and anaemia (RD-/A-). The primary outcome was 30-day mortality, and the secondary outcomes were need for admission, prolonged hospitalisation (>10 days), in-hospital mortality during the index event, and reconsultation and the combination of 30-day post-discharge reconsultation/death. These short-term outcomes were compared and adjusted for differences among groups. RESULTS: Of the 13,307 patients analysed, CRAS+ (36.4%) was associated with older age, multiple comorbidities, chronic use of loop diuretics, oedemas and hypotension. The 30-day mortality in CRAS+ was greater than in CRAS- (hazard ratio = 1.46, 95% confidence interval = 1.26-1.68) and RD-/A- (hazard ratio = 1.83, 95% confidence interval = 1.46-2.28) control groups. The mortality level was also higher in RD+/A- (hazard ratio = 1.40, 95% confidence interval = 1.10-1.78) and higher, but not statistically significant, in RD-/A+ (hazard ratio = 1.28, 95% confidence interval = 0.99-1.63) with respect to RD-/A-. All of the secondary outcomes, when related to CRAS- and RD-/A- control groups, were worse for CRAS+ and to a lesser extent, RD+/A-, being more rarely observed in RD-/A+. CONCLUSIONS: Cardiorenal anaemia syndrome in acute heart failure is related to greater mortality and worse short-term outcomes, and the impact of renal dysfunction and anaemia seems to be additive.