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The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction
Raoul Stahrenberg1, Frank Edelmann, Meinhard Mende
1Department of Cardiology and Pneumology, University of Goettingen, 37075 Goettingen, Germany.
Insights
Growth Differentiation Factor 15 (GDF-15) is elevated in heart failure with normal ejection fraction (HFnEF), similar to heart failure with reduced ejection fraction (HFrEF). GDF-15 indicates reduced exercise capacity and quality of life in HFnEF patients.
Area of Science:
- Cardiology
- Biomarker Discovery
- Heart Failure Research
Background:
- Heart failure with normal ejection fraction (HFnEF) is a significant clinical condition requiring better understanding.
- Growth Differentiation Factor 15 (GDF-15) is a novel biomarker known to be elevated in heart failure with reduced ejection fraction (HFrEF) and predicts poor outcomes.
Purpose of the Study:
- To investigate the clinical relevance and diagnostic utility of plasma GDF-15 levels in patients with HFnEF.
- To compare GDF-15 levels in HFnEF patients with those in HFrEF patients and healthy controls.
Main Methods:
- Analysis of a subgroup from the DIAST-CHF observational trial, classifying patients into HFnEF (n=142), HFrEF (n=86), and healthy elderly controls (n=188).
- Measurement of plasma GDF-15 levels and correlation with clinical characteristics, echocardiographic parameters, and functional tests (6 min walk test, SF-36).
- Comparison of GDF-15 diagnostic performance against N-terminal pro brain natriuretic peptide (NT-proBNP) for HFnEF detection.
Main Results:
- GDF-15 levels were significantly higher in HFnEF and HFrEF patients compared to controls, with similar levels between HFnEF and HFrEF groups.
- GDF-15 levels were independently associated with age, sex, estimated glomerular filtration rate (eGFR), and the presence of HFnEF or HFrEF.
- GDF-15 correlated with diastolic dysfunction markers and was associated with reduced exercise capacity and quality of life (SF-36 physical score).
- GDF-15 demonstrated diagnostic properties for HFnEF comparable or superior to NT-proBNP, with combined use improving accuracy.
Conclusions:
- GDF-15 is significantly elevated in HFnEF, mirroring levels seen in HFrEF.
- GDF-15 is an independent predictor of impaired exercise capacity and diminished quality of life in HFnEF.
- GDF-15 is a valuable biomarker for HFnEF diagnosis, potentially outperforming NT-proBNP and enhancing diagnostic accuracy when used in combination.
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.
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