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November 21, 2022Circulation Heart Failure56 citationsOpen Access

Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure

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MGMuhammed T. GürgözeLVLaura C. van VarkSBSara J. Baart

Key Result

Serially measured GDF-15 independently predicted the risk of all-cause mortality and heart failure rehospitalization (HR 1.44; 95% CI 1.05-1.91 per 1 SD increase) over 1-year follow-up.

Study Design

Type

Cohort (n=496)

Multicenter

Yes

Structured PICO

Do serially measured biomarkers including GDF-15 predict adverse outcomes in patients with acute heart failure?

P
Population
496 patients with acute heart failure, median age 74 years, followed for 1 year with serial biomarker measurements.
E
Exposure
Serial measurement of multiple biomarkers (GDF-15, NT-proBNP, ST2, galectin-3, troponin I, and creatinine) at 7 time points over 1 year.
O
Outcome
Composite of all-cause mortality and HF rehospitalizationcomposite

Serial measurement of GDF-15, alongside NT-proBNP and troponin I, provides independent and dynamic prognostic value for predicting mortality and rehospitalization in acute heart failure.

Main Result

Hazard Ratio: 1.44 (95% CI 1.05–1.91)

Abstract

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. Multiple biomarkers should be considered for stratification in clinical practice. REGISTRATION: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).

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Cite This Study

Gürgöze et al. (2022) conducted a cohort in Acute heart failure (n=496). Serially measured GDF-15 was evaluated on Composite of all-cause mortality and heart failure rehospitalization (HR 1.44, 95% CI 1.05-1.91). Serially measured GDF-15 independently predicted the risk of all-cause mortality and heart failure rehospitalization (HR 1.44; 95% CI 1.05-1.91 per 1 SD increase) over 1-year follow-up.

synapsesocial.com/papers/6a1ff7bc1517a826fb04c11dhttps://doi.org/10.1161/circheartfailure.122.009526
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