Combining Two Blood Biomarkers Better Predicts Heart Failure Outcomes Than Either Alone

What the researchers found

The primary endpoint (death or heart failure rehospitalization at 1 year) occurred in 31 of 104 patients. Optimal GDF-15 cut-offs were 5115.5 pg/mL (admission), 4145 pg/mL (discharge), and 4218.5 pg/mL (30 days). NT-proBNP cut-offs were 6011 ng/L, 1250 ng/L, and 1456.5 ng/L at the same timepoints. Patients with both markers above cut-off had the highest risk at all three timepoints. The combined 30-day model achieved the best prediction (AUC 0.75) for the composite endpoint, outperforming single biomarker measurements.

Why it matters

NT-proBNP is already the standard heart failure biomarker, but it captures only one aspect of the disease — cardiac wall stress. By adding GDF-15 (reflecting inflammation, metabolic stress, and fibrosis), clinicians get a more complete picture. The serial measurement approach — tracking both biomarkers over time rather than relying on a single snapshot — better captures the dynamic nature of heart failure and identifies patients whose risk remains elevated after initial treatment.

How the study worked

Prospective observational study of 104 consecutive acute heart failure patients (mean age 65 years). Blood samples for NT-proBNP and GDF-15 were collected at admission, discharge, and 30-day follow-up. ROC analysis determined optimal cut-off values. The primary composite endpoint was all-cause mortality or heart failure rehospitalization at 1-year follow-up.

What this study cannot tell us

Small single-center study with only 104 patients, limiting statistical power and generalizability. The composite endpoint included both mortality and rehospitalization, which have different clinical implications. The AUC of 0.75, while reasonable, is moderate — suggesting room for improvement. GDF-15 is not yet routinely available in all clinical laboratories. The study did not validate findings in an independent cohort.

How to read the evidence

This is a single-center prospective observational study with a modest sample size (n=104). While the serial measurement design and pre-specified endpoints are strengths, the findings need external validation in larger, multicenter cohorts before clinical implementation.

When this study was published

Published in 2024, this study contributes to the active field of multi-biomarker heart failure risk stratification, building on decades of NT-proBNP research with the addition of the newer GDF-15 marker.

The bigger picture

Natriuretic peptides (BNP/NT-proBNP) have been the cornerstone of heart failure diagnosis and monitoring for two decades. The growing trend toward multi-biomarker strategies reflects the understanding that heart failure involves multiple pathological processes — not just wall stress. GDF-15 captures complementary pathways (inflammation, oxidative stress, fibrosis), and combining it with the established NT-proBNP peptide marker could improve risk stratification and help allocate limited healthcare resources to the highest-risk patients.

Questions still open

• Would a three-biomarker approach (adding a fibrosis or renal marker) further improve prediction beyond the dual NT-proBNP/GDF-15 model?
• Can the combined 30-day biomarker model guide treatment intensification decisions and improve outcomes?
• Is the combined model equally useful in heart failure with preserved versus reduced ejection fraction?

Common questions

Read the original research

Combined Use of GDF-15 and NT-Pro BNP for Outcome Prediction in Patients with Acute Heart Failure.

Journal of clinical medicine, 13(19)

Citation

Płonka, Joanna; Klus, Anna; Wężyk, Natalia; Dąbrowska, Klaudia; Rzepiela, Lidia; Gawrylak-Dryja, Ewa; Nalewajko, Krzysztof; Feusette, Piotr; Gierlotka, Marek. (2024). Combined Use of GDF-15 and NT-Pro BNP for Outcome Prediction in Patients with Acute Heart Failure.. Journal of clinical medicine, 13(19). https://doi.org/10.3390/jcm13195936