What is the clinical evidence from this study?

Study design: Observational. Population: Heart failure with normal ejection fraction (HFnEF) (n=416). Intervention: Growth differentiation factor 15 (GDF-15) measurement vs. Healthy elderly controls and HFrEF patients. Primary outcome: GDF-15 plasma levels and diagnostic accuracy for HFnEF.

September 14, 2010Open Access

The Novel Biomarker Growth Differentiation Factor 15 in Heart Failure with Normal Ejection Fraction

Key Result

In an observational study of 416 patients, GDF-15 levels were significantly elevated in HFnEF (n=142) compared to healthy controls (n=188), and combining GDF-15 with NT-proBNP improved diagnosis.

Study Design

Type

Observational (n=416)

Structured PICO

Does GDF-15 measurement improve the detection and clinical assessment of HFnEF in patients with suspected heart failure?

Population

416 participants from the DIAST-CHF observational trial, including patients with a history of chronic heart failure or positive Framingham criteria classified as HFrEF (n=86) or HFnEF (n=142), and healthy elderly controls (n=188).

Intervention

Measurement of Growth differentiation factor 15 (GDF-15) plasma levels

Comparator

Healthy elderly controls and HFrEF patients

Outcome

GDF-15 plasma levels and their association with HFnEF, echocardiographic markers of diastolic function, exercise capacity (6 min walk test), and quality of life (SF-36 physical score)surrogate

GDF-15 is a promising biomarker for HFnEF that is elevated to a similar degree as in HFrEF, correlates with physical impairment, and offers diagnostic accuracy comparable to NT-proBNP.

Abstract

AIMS: 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. METHODS AND 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. CONCLUSION: 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.