Ann Lab Med.  2023 May;43(3):253-262. 10.3343/alm.2023.43.3.253.

Prognostic Value of Combined Biomarkers in Patients With Heart Failure: The Heartmarker Score

• Stam JAvd
• Bouwmeester S
• Loon SLMv
• Riel NAWv
• Dekker LR
• Boer AK
• Houthuizen P
• Scharnhorst V

• KMID: 2551709
• DOI: http://doi.org/10.3343/alm.2023.43.3.253

Abstract

Background
Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF.
Methods
HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity.
Results
HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity.
Conclusions
The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

Keyword

Heart failure; Biomarkers; N-terminal pro-B-type natriuretic peptide; Soluble suppression of tumorigenesis-2; Growth differentiation factor-15

Figure

• 

  Fig. 1 Survival curves and percentage of patients of the HF biomarkers. (A) Kaplan–Meier survival curves for the biomarkers NT-proBNP, GDF-15, and ST-2. Lines indicate the survival curve, and shaded areas indicate the 95% confidence intervals. Numbers at the bottom of the graphs indicate the number of patients at risk and the corresponding percentage relative to the initial number of patients in the group. (B) Percentage of patients for which a specific biomarker exceeds predefined cut-off values. By definition, the totals of the bars are 0% for patients with no elevated biomarkers, 100% for the group with one elevated biomarker, 200% (2×100%) for the group with two elevated biomarkers, and 300% (3×100%) for the group with three elevated biomarkers. Abbreviations: GDF-15, growth differentiation factor-15; ST2, suppression of tumorigenesis-2; FGF-23, fibroblast growth factor-23; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

• 

  Fig. 2 Prognostic value and relation to 6MWT distance for both NYHA classification and Heartmarker Score. (A–D) Kaplan–Meier survival curves. Lines indicate the survival curves for heart failure (HF) patients grouped according to the (A, C) proposed Heartmarker biomarker score and (B, D) NYHA classification; shaded areas indicate the 95% confidence intervals. Numbers at the bottom of the graphs indicate the number of patients at risk and the corresponding percentage relative to the initial patients in the group. (C and D) The two highest classes of the classifications in (A) and (B), respectively. (E and F) Boxplots showing the distance covered in the 6MWT for the HF patients grouped according to (E) Heartmarker score and (F) the NYHA classification. Note that the 6MWT distance was unavailable for nine patients. Abbreviations: 6MWT, 6-min walking test; NYHA, New York Heart Association.

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