The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction.
OBJECTIVE
Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF.


RESULTS
A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n=86) or HFnEF (n=142) and compared with healthy elderly controls (n=188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy.


CONCLUSIONS
Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.
Stahrenberg
Raoul
R
Department of Cardiology and Pneumology, University of Goettingen, 37075 Goettingen, Germany.
Edelmann
Frank
F
Mende
Meinhard
M
Kockskämper
Anke
A
Düngen
Hans-Dirk
HD
Lüers
Claus
C
Binder
Lutz
L
Herrmann-Lingen
Christoph
C
Gelbrich
Götz
G
Hasenfuss
Gerd
G
Pieske
Burkert
B
Wachter
Rolf
R
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D005919:Glomerular Filtration Rate; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006305:Health Status Indicators; D054143:Heart Failure, Systolic / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013318:Stroke Volume; D014463:Ultrasonography; D016138:Walking
D015415:Biomarkers; D055436:Growth Differentiation Factor 15