Time-pattern of adverse outcomes after an infection-triggered acute heart failure decompensation and the influence of early antibiotic administration and hospitalisation: results of the PAPRICA-3 study
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To investigate whether patients with an acute heart failure (AHF) episode triggered by infection present different outcomes compared to patients with no trigger and the effects of early antibiotic administration (EAA) and hospitalisation.
Two groups were made according to the AHF trigger: infection (G1) or none identified (G2). The primary outcome was 13-week (91-days) all-cause mortality, and secondary outcomes were 13-week post-discharge mortality, readmission or combined endpoint. Comparisons are presented as unadjusted and adjusted (MEESSI risk score) hazard ratios (uHR/aHR) for G1 compared to G2 patients, also estimated by weeks. Stratified analysis by EAA (provided/not provided) and patient disposition (discharged/hospitalised) was performed.
We included 6727 patients (G1 = 3973; G2 = 2754). The 13-week mortality uHR was 1.11 (0.99–1.25; p = 0.06; with significant increases in the first 3 weeks), and the aHR was 0.91 (0.81–1.02; p = 0.11). There were no differences in unadjusted secondary post-discharge outcomes; however, G1 outcomes significantly improved after adjustment: aHR 0.83 (0.71–0.96; p = 0.01) for mortality, 0.92 (0.84–0.99; p = 0.04) for readmission, and 0.92 (0.85–0.99; p = 0.04) for the combined endpoint. We found a differentiated effect of hospitalisation (p < 0.05 for interaction; better post-discharge readmission and combined outcomes in G1), and a trend (p = 0.06) to lower mortality in G1 patients with EAA. Additionally, there were some differences between groups in baseline and acute episode characteristics.
AHF triggered by infection is not associated with a higher mid-term mortality and has better post-discharge outcomes; however, the first 3 weeks are an extremely vulnerable period. Since hospitalisation could have a role in limiting adverse post-discharge events, and EAA in reducing mortality, these relationships should be prospectively explored in further studies.
KeywordsAcute heart failure Mortality Infeccion Trigger Outcomes
This study was partially supported by Grants from the Instituto de Salud Carlos III supported with funds from the Spanish Ministry of Health and FEDER (PI15/01019, PI15/00773, PI18/00393, PI19/00456) and Fundació La Marató de TV3 (2015/2510). The "Emergencies: Processes and Pathologies" research group of the IDIBAPS receives financial support from the Catalonian Government for Consolidated Groups of Investigation (GRC 2009/1385, 2014/0313, and 2017/1424). Xavier Rosselló has received support from the SEC-CNIC CARDIOJOVEN fellowship program. We thank Alícia Díaz for her professionalism in data management.
Other investigators of the ICA-SEMES (Research group on Acute Heart Failure of the Spanish Society of Emergency Medicine): Cristina Gil (Hospital Universitario de Salamanca). Eva Salvo (Hospital La Fe de Valencia). Rosa Escoda, Sira Aguiló, Carolina Xipell, Carolina Sánchez, Josep M. Gaytan (Hospital Clínic de Barcelona). Antonio Noval (Hospital Insular de Las Palmas de Gran Canaria). José M. Torres (Hospital Reina Sofía de Córdoba). Amparo Valero (Hospital Dr. Peset de Valencia). Alfons Aguirre, María Àngels Pedragosa (Hospital del Mar de Barcelona). Raquel Torres-Gárate (Hospital Severo Ochoa de Leganés, Madrid). María Isabel Alonso, Francisco Ruiz (Hospital de Valme de Sevilla). José Miguel Franco (Hospital Miguel Servet de Zaragoza). Susana Sánchez (Hospital Rio Ortega de Valladolid). Aitor Alquézar, Miguel Alberto Rizzi, Sergio Herrera (Hospital San Pau de Barcelona). Irene Cabello, Álex Roset (Hospital Universitari de Bellvitge, Barcelona). Héctor Alonso (Hospital Marqués de Valdecilla de Santander). Esther Rodríguez Adrada, Guillermo Llopis García (Hospital Clínico San Carlos, Madrid). José María Álvarez Pérez (Hospital Universitario de Burgos). Ana Belén Mecina (Hospital Universitario Fundación Alcorcón, Madrid). Joaquín Vázquez Álvarez, Marta Sánchez González, Belén Prieto, María García García (Hospital Universitario Central de Asturias). Víctor Marquina, Inmaculada Jiménez, Patricia Javaloyes, Néstor Hernández, BenjaminBrouzet, Ana López (Hospital General de Alicante). Juan Antonio Andueza (Hospital General Universitario Gregorio Marañón de Madrid), Rodolfo Romero (Hospital Getafe de Madrid). Roberto Calvache (Hospital de Henares de Madrid), María Teresa Lorca, Luis Calderón (Hospital del Tajo de Madrid) Beatriz Amores Arriaga, Beatriz Sierra (Hospital Clínico Lozano Blesa de Zaragoza), Pascual Piñera, José Andrés Sánchez Nicolás (Hospital General Universitario Reina Sofía de Murcia), Enrique Martín Mojarro (Hospital Sant Pau i Santa Tecla de Tarragona), LisetteTravería Bécquer (Hospital Universitario de Canarias de Tenerife), Lluís Llauger García, Gerard Corominas La Salle. (Hospital Universitari de Vic de Barcelona), Carmen Agüera Urbano (Hospital Costa del Sol de Marbella, Málaga), Ester Soy Ferrer (Hospital Josep Trueta de Girona).
Compliance with ethical standards
Conflict of interest
The authors state that they have no conflict of interests with the present work. The ICA-SEMES Research Group has received unrestricted support from Orion Pharma and Novartis. The present study has been designed, performed, analysed and written exclusively by the authors independently of these pharmaceutical companies.
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