Abstract
AimsThe prognostic value of biomarkers in patients with heart failure (HF) and mid‐range (HFmrEF) or preserved ejection fraction (HFpEF) has not been widely addressed. The aim of this study was to assess whether the prognostic value of growth differentiation factor 15 (GDF‐15) is superior to that of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in patients with HFmrEF or HFpEF.Methods and resultsHeart failure patients with either HFpEF or HFmrEF were included in the study. During their first visit to the HF unit, serum samples were obtained and stored for later assessment of GDF‐15 and NT‐proBNP concentrations. Patients were followed up by the HF unit. The main endpoint was all‐cause mortality. A total of 311 patients, 90 (29%) HFmrEF and 221 (71%) HFpEF, were included. Mean age was 72 ± 13 years, and 136 (44%) were women. No differences were found in GDF‐15 or NT‐proBNP concentrations between both HF groups. During a median follow‐up of 15 months (Q1–Q3: 9–30 months), 98 patients (32%) died, most (71%) of cardiovascular causes. Patients who died had higher median concentrations of GDF‐15 (4085 vs. 2270 ng/L, P < 0.0001) and NT‐proBNP (1984 vs. 1095 ng/L, P < 0.0001). A Cox multivariable model identified New York Heart Association Functional Class III (P = 0.04), systolic blood pressure (P = 0.01), left atrial diameter (P = 0.03), age >65 years (P < 0.0001), and GDF‐15 concentrations (P = 0.01) but not NT‐proBNP as independent predictors of all‐cause mortality. The area under the curve was 0.797 for the basic model including NT‐proBNP, and the area under the curve comparing the overall model was 0.819, P = 0.016 (DeLong's test). Integrated discrimination improvement index after the inclusion of GDF‐15 in the model with the mortality risk factors was 0.033; that is, the ability to predict death increased by 3.3% (P = 0.004). Net reclassification improvement was 0.548 (P < 0.001); that is, the capacity to improve the classification of the event (mortality) was 54.8%. GDF‐15 concentrations were divided in tertiles (<1625, 1625–4330, and >4330 ng/L), and survival curves were evaluated using the Kaplan–Meier technique. Patients in the highest tertile had the poorest 5 year survival, at 16%, whereas the lowest tertile had the best survival, of 78% (P < 0.001).ConclusionsGrowth differentiation factor 15 was superior to NT‐proBNP for assessing prognosis in patients with HFpEF and HFmrEF. GDF‐15 emerges as a strong, independent biomarker for identifying HFmrEF and HFpEF patients with worse prognosis.
Highlights
IntroductionHeart failure (HF) was classified according left ventricular ejection fraction (LVEF) in heart failure (HF) with reduced or preserved LVEF fraction, a ‘grey zone’ existed between both HF phenotypes.[1] The 2016 update of the European Society of Cardiology guidelines defined a new group, HF with mid-range EF (HFmrEF), as the HF with an LVEF between 40% and 49% and relevant structural heart disease or elevated concentrations of natriuretic peptides.[2] HFmrEF shares some characteristics with both HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF) and defines a group with an uncertain prognosis.[3,4,5,6] HF is a condition resulting from several cardiac processes, such as ischaemia, necrosis, stretch, neurohormonal activation, volume overload, inflammation, and oxidation, and all these processes have their respective biomarkers
MethodsUntil recently, heart failure (HF) was classified according left ventricular ejection fraction (LVEF) in HF with reduced or preserved LVEF fraction, a ‘grey zone’ existed between both HF phenotypes.[1]
Our results suggest that growth differentiation factor 15 (GDF-15) is a useful biomarker for identifying HF patients with non-reduced EF associated with worse prognosis
Summary
Heart failure (HF) was classified according left ventricular ejection fraction (LVEF) in HF with reduced or preserved LVEF fraction, a ‘grey zone’ existed between both HF phenotypes.[1] The 2016 update of the European Society of Cardiology guidelines defined a new group, HF with mid-range EF (HFmrEF), as the HF with an LVEF between 40% and 49% and relevant structural heart disease or elevated concentrations of natriuretic peptides.[2] HFmrEF shares some characteristics with both HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF) and defines a group with an uncertain prognosis.[3,4,5,6] HF is a condition resulting from several cardiac processes, such as ischaemia, necrosis, stretch, neurohormonal activation, volume overload, inflammation, and oxidation, and all these processes have their respective biomarkers. HFpEF and HFmrEF patients share some characteristics, including elevated natriuretic peptide concentrations. For this reason, some studies have analysed biomarkers other than natriuretic peptides for improving the prognosis of patients with both HF phenotypes,[7] but results were inconclusive. The lack of clear differences in the analysed biomarkers and the difficulty in using some of them in daily practice justifies the search for new prognostic biomarkers for both HF phenotypes
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