@article{896c92a0bf8b441aa1f535a5704121be,
title = "Left atrial volume and cardiovascular outcomes in systolic heart failure: effect of antithrombotic treatment",
abstract = "Aims: Left atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments. Methods and results: Two-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range >60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034). Conclusions: In patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.",
keywords = "Anticoagulants, Aspirin, Echocardiography, Heart failure, Left atrium",
author = "{for the WARCEF Investigators} and {Di Tullio}, {Marco R.} and Min Qian and Thompson, {John L.P.} and Labovitz, {Arthur J.} and Mann, {Douglas L.} and Sacco, {Ralph L.} and Pullicino, {Patrick M.} and Freudenberger, {Ronald S.} and Teerlink, {John R.} and Susan Graham and Lip, {Gregory Y.H.} and Bruce Levin and Mohr, {Jay P.} and Richard Buchsbaum and Estol, {Conrado J.} and Lok, {Dirk J.} and Piotr Ponikowski and Anker, {Stefan D.} and Shunichi Homma",
note = "Funding Information: S.H. reports receiving payment from AGA Medical (now St. Jude Medical) for his work as a member of a data and safety monitoring board and consulting fees from Boehringer Ingelheim. B.L. reports receiving consulting fees from United Healthcare. Dr J.R.T. reports receiving research grants or consulting fees from Amgen, Bayer, Cardio3 Biosciences, Cytoki-netics, Mast Therapeutics, Medtronic, Novartis, St. Jude, and Trevena. A.J.L. reports receiving grant support from Boehringer Ingelheim and BMS Pfizer, lecture fees from Boehringer Ingelheim, and fees for the development of educational presentations from the American College of Cardiology. R.L.S. reports institutional research support from NIH, AHA/ASA, McKnight Foundation, and Boehringer Ingelheim. S.D.A. reports receiving consulting fees from Vifor Pharma, Bayer, Janssen, Novartis, Relypsa, ZS Pharma, and Thermo Fisher; grant support from Vifor Pharma and Abbott Vascular; and lecture fees from Vifor Pharma, Novartis, and Stealth Peptides. P.P. reports receiving consulting fees from Bayer, Boehringer Ingelheim, Coridea, Corthera, Johnson & Johnson, Pfizer, Respicardia, and Vifor Pharma; grant support from Vifor Pharma on behalf of himself and his institution; and lecture fees from Abbott, Boehringer Ingelheim, Merck Serono, Pfizer, Respicardia, Sanofi-Aventis, Servier, and Vifor Pharma. G.Y.H.L. reports consultancy for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi Sankyo; speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi Sankyo; no fees are received personally. The other authors report no conflicts. Funding Information: This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS; grant numbers U01-NS-043975 to S.H. and U01-NS-039143 to J.L.P.T.). Publisher Copyright: {\textcopyright} 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.",
year = "2018",
month = oct,
doi = "10.1002/ehf2.12331",
language = "English",
volume = "5",
pages = "800--808",
journal = "ESC Heart Failure",
issn = "2055-5822",
number = "5",
}