Key result
Serial GDF-15 rises link to ~44% higher risk of death or HF rehospitalization per SD.
Why the study?
Studies evaluating serially measured GDF-15 in acute HF are limited, prompting exploration of its prognostic value within a multimarker approach.
Does serially measured GDF-15 improve risk prediction for all-cause mortality and HF rehospitalization in adults with acute heart failure?
Cohort (n=496)
Blinded adjudication committee and analysts
Yes
Does serially measured GDF-15 improve risk prediction for all-cause mortality and HF rehospitalization in adults with acute heart failure?
Repeated measurements of GDF-15, alongside NT-proBNP and troponin I, provide incremental prognostic value for adverse outcomes in acute heart failure, supporting a multimarker approach for risk stratification.
May support multimarker risk stratification in acute HF; hypothesis-generating and requires prospective validation before practice change.
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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Gürgöze et al. (2022) conducted a cohort in Acute Heart Failure (n=496). Serially measured GDF-15 vs. Lower GDF-15 levels was evaluated on Composite of all-cause mortality and HF rehospitalization (HR 1.44, 95% CI 1.05-1.91, p=0.022). Serially measured GDF-15 independently predicted the composite risk of all-cause mortality or heart failure rehospitalization with an adjusted HR of 1.44 per 1 SD increase when jointly modeled with other biomarkers.
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