Predictive capacity of a multimarker strategy to determine short-term
mortality in patients attending a hospital emergency Department for
acute heart failure. BIO-EAHFE study
Pablo Herrero-Puente
a,
⁎, Belén Prieto-García
b
, María García-García
c
, Javier Jacob
d
, F. Javier Martín-Sánchez
e
,
Domingo Pascual-Figal
f
, Héctor Bueno
g
, Victor Gil
h
, Pere Llorens
i
, Joaquin Vázquez-Alvarez
a
,
Rodolfo Romero-Pareja
j
, Marta Sanchez-Gonzalez
a
, Òscar Miró
h
a
Unidad de Gestión Clínica de Urgencias, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain
b
Área de Gestión del Laboratorio de Medicina, Hospital Universitario Central de Asturias, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain
c
Area de Gestión del Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
d
Servicio de Urgencias, Hospital Universitario de Bellvitge, Spain
e
Servicio de Urgencias, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Madrid, Spain
f
Servicio de Cardiología, Hospital Universitario Arrixaca, Murcia, Spain
g
Multidisciplinary Translational Cardiovascular Research (MTCR) Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain
h
Área de Urgencias, Hospital Clinic, Barcelona, Grupo de Investigación “Urgencias: procesos y patologías”, IDIBAPS, Barcelona, Spain
i
Servicio de Urgencias-Unidad de Corta Estancia, Hospital Universitario General de Alicante, Spain
j
Servicio de Urgencias, Hospital de Getafe, Spain
abstract article info
Article history:
Received 6 November 2016
Received in revised form 5 January 2017
Accepted 5 January 2017
Available online 06 January 2017
Objective: A multimarker strategy may help determine the prognosis of patients with acute heart failure (AHF).
The aim of this study was to evaluate the capacity of mid-regional pro-adrenomedullin (MRproADM), copeptin
and interleukin-6 (IL-6) combined with conventional clinical and biochemical markers to predict the 30-day
mortality of patients with AHF.
Methods: We performed an observational, multicenter, prospective study of patients attended in the emergency
department (ED) for AHF. We collected clinical and biochemical data as well as comorbidities and biomarker
values. The endpoint variable was mortality at 7, 14, 30, 90 and 180 days. The clinical model included: gender,
age, blood pressure values, hemoglobin, sodium b 135 mmol/L and estimated glomerular filtration b 60 mL/
min/1.73 m2. We made receiver operating curves (ROC) curves, and areas under the curve (AUC) and survival
analysis for each model and calculated the hazard ratio (HR) and its 95% confidence interval.
Results: A total of 547 individuals were included: 55.6% were women with a mean age of 79.9 (9.5) years.
Copeptin alone showed greater discriminatory power for 30-mortality [AUC 0.70 (0.62–0.78)]. The AUC for 30-
day mortality of the clinical model plus copeptin and NTproBNP was 0.75 (0.67–0.83), being better than the clin-
ical model alone with 0.67 (0.58–0.76; p = 0.19). The discriminatory power of the different biomarkers alone, in
combination or together with the clinical model decreased over time.
Conclusions: The combination of a clinical model with copeptin and NTproBNP, which are available in the ED, is
able to prognose early mortality in patients with an episode of AHF.
© 2017 Elsevier B.V. All rights reserved.
Keywords:
Acute heart failure
Biomarkers
Copeptin
MRproadrenomedullin
Interleukin 6
Emergency department
Prognosis
1. Introduction
The health care costs of patients with heart failure are high largely
due to hospitalization for an exacerbation of this chronic disease [1].
The management of acute heart failure (AHF) is complex because of
the inherent characteristics of the syndrome and the high rates of
mortality and hospital readmission [2]. Consideration of clinical factors
and the presence of comorbidities allow early determination of the
prognosis of these patients [3,4,5,6,7,8]. Taking these factors into ac-
count and the results of routine biochemical parameters, mainly tropo-
nins and natriuretic peptides, the diagnosis and prognosis of patients
with AHF can be improved [9,10].
In addition to these factors, biomarkers are being increasingly used
to provide important information for stratification [11,12], and it has
been suggested that a multimarker strategy could be useful in the man-
agement of these patients [13]. Indeed, copeptin and mid-regional pro-
Clinica Chimica Acta 466 (2017) 22–30
⁎ Corresponding author at: Unidad de Gestión Clínica de Urgencias, Hospital
Universitario Central de Asturias, Avda. Roma s/n, 33011 Oviedo, Spain.
E-mail address: pabloherrero71@hotmail.com (P. Herrero-Puente).
http://dx.doi.org/10.1016/j.cca.2017.01.003
0009-8981/© 2017 Elsevier B.V. All rights reserved.
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