TY - JOUR
T1 - Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure
AU - Gürgöze, Muhammed T.
AU - van Vark, Laura C.
AU - Baart, Sara J.
AU - Kardys, Isabella
AU - Akkerhuis, K. Martijn
AU - Manintveld, Olivier C.
AU - Postmus, Douwe
AU - Hillege, Hans L.
AU - Lesman-Leegte, Ivonne
AU - Asselbergs, Folkert W.
AU - Brunner-la-Rocca, Hans-Peter
AU - van den Bos, Ewout J.
AU - Orsel, Joke G.
AU - de Ridder, Stijn P. J.
AU - Pinto, Yigal M.
AU - Boersma, Eric
N1 - Funding Information: Dr Asselbergs is supported by University College London Hospitals NIH and Care Research Biomedical Research Center. Dr Orsel is an employee of Philips Healthcare. Dr Pinto serves as a consultant and speaker for biotechnology and pharmaceutical companies that develop molecules that target myocardial disease, including Pfizer, Roche, Novartis, and Forbion. Dr Pinto is named inventor on patents related to cardiomyopathy therapy and holds minor shares (<5%) and spin-off aimed at developing therapies for heart disease. All other authors have nothing to disclose. Publisher Copyright: © 2022 The Authors. Circulation: Heart Failure is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates.
AB - Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates.
KW - biomarkers
KW - growth differentiation factor 15
KW - heart failure
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85144866888&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526
DO - https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526
M3 - Article
C2 - 36408685
SN - 1941-3289
VL - 16
SP - E009526
JO - Circulation. Heart failure
JF - Circulation. Heart failure
IS - 1
ER -