Fatigue as a predictor of outcome in patients with heart failure: analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).
OBJECTIVE
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.
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
Ana Cristina
AC
Perez-Moreno
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
Pardeep S
PS
Jhund
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
Michael R
MR
Macdonald
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
Mark C
MC
Petrie
Imperial College, London, United Kingdom.
John G F
JG
Cleland
Universitätsklinikum des Saarlandes, Homburg/Saar Germany.
Michael
M
Böhm
University Hospital Groningen, Groningen, the Netherlands.
Dirk J
DJ
van Veldhuisen
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.
Lars
L
Gullestad
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
John
J
Wikstrand
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.
John
J
Kjekshus
Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland.
James D
JD
Lewsey
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. Electronic address: john.mcmurray@glasgow.ac.uk.
John J V
JJ
McMurray
D000368:Aged; D004417:Dyspnea / Q000209:etiology / Q000503:physiopathology; D005221:Fatigue / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013318:Stroke Volume / Q000502:physiology; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium
dyspnea; fatigue; heart failure; outcomes; symptoms