Author + information
- Received September 19, 2013
- Revision received January 2, 2014
- Accepted January 9, 2014
- Published online April 1, 2014.
- Ana Cristina Perez-Moreno, MD∗,
- Pardeep S. Jhund, MB ChB, PhD∗,
- Michael R. Macdonald, MD∗,
- Mark C. Petrie, MB, ChB, BSc∗,
- John G.F. Cleland, MD†,
- Michael Böhm, MD, PhD‡,
- Dirk J. van Veldhuisen, MD, PhD§,
- Lars Gullestad, MD, PhD‖,
- John Wikstrand, MD, PhD¶,
- John Kjekshus, MD, PhD‖,
- James D. Lewsey, PhD# and
- John J.V. McMurray, MD∗∗ ()
- ∗BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland
- †Imperial College, London, United Kingdom
- ‡Universitätsklinikum des Saarlandes, Homburg/Saar Germany
- §University Hospital Groningen, Groningen, the Netherlands
- ‖Department of Cardiology, Oslo University Hospital, Rikshospitalet, and K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway
- ¶Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
- #Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland
- ↵∗Reprint requests and correspondence:
Dr. John J. V. McMurray, Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, Scotland, United Kingdom.
Objectives The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF) ≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study.
Background Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis.
Methods At baseline in CORONA, fatigue “during the past few days” was measured using a 5-point exertion scale (0 = none, 1 = heavy exertion, 2 = moderate exertion, 3 = slight exertion, 4 = rest); a 4-point scale was used for dyspnea (1 to 4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n = 535), fatigue score 2 (n = 1,632), and fatigue score 3 to 4 (n = 1,663); and a dyspnea score of 1 (n = 292), dyspnea score of 2 (n = 1,695), and dyspnea score of 3 to 4 (n = 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality.
Results In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n = 810], vs. group 1, 30% [n = 160]; dyspnea: group 3, 50% [n = 918], vs. group 1, 28% [n = 82]) and all-cause mortality (fatigue: group 3, 38% [n = 623], vs. group 1, 24% [n = 130]; dyspnea: group 3, 38% [n = 697], vs. group 1, 23% [n = 66], log-rank p < 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes.
Conclusions In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment.
Dr. Perez-Moreno is funded by Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico, scholarship no. 31306, scholar no. 215001. Dr. Cleland has received honoraria for steering committee activity from AstraZeneca. Dr. McMurray is a member of advisory boards of Astra Zeneca, Bayer AG, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi-Aventis, and Servier; and the speaker bureaus of AstraZeneca, AWD Dresden, Bayer, Boehringer Ingelheim, Berlin-Chemie, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, and Medtronic. Dr. Wikstrand is a former advisor to AstraZeneca Research Laboratories. All other authors have reported they have no relationships relevant to the contents of this paper to disclose.
- Received September 19, 2013.
- Revision received January 2, 2014.
- Accepted January 9, 2014.
- American College of Cardiology Foundation