Diagnostic and prognostic value of dickkopf-3 in acute heart failure: impact of renal function

Background

Evidence from small cohorts has implicated Dickkopf-3 (DKK3) as a potential biomarker in heart failure, while renal function, as reflected by estimated glomerular filtration rate (eGFR), may modulate its performance in acute heart failure (AHF).

Aim

To assess the diagnostic and prognostic utility of DKK3 in AHF patients presenting with acute dyspnea to the emergency department (ED) with particular consideration of renal function.

Methods

DKK3 was available in 1.176 patients presenting with acute dyspnea to the ED. Diagnostic accuracy for AHF was evaluated using the area under the receiver operating characteristic curve (AUC). Prognostic outcomes were 720-day all-cause mortality and a composite of mortality or AHF rehospitalization. Analyses were stratified by eGFR.DKK3 levels were compared across eGFR strata (<30, 30–59, ≥60 mL/min/1.73 m²) using log-scaled boxplots and Kruskal–Wallis tests.

Results

A total of 604 patients (51%) had an adjudicated final diagnosis of AHF. Although DKK3 concentrations were higher in AHF patients, values did not differ significantly when compared to patients with different causes of dyspnea (438 vs. 337 pg/mg creatinine; p=0.17). DKK3 correlated weakly with NT-proBNP (ρ=0.15; p<0.0001) and lacked diagnostic discrimination across eGFR strata( ≥60=AUC 0.53; 30–59=AUC 0.5; <30=AUC 0.51 figure 1). Those with eGFR <30 exhibited significantly higher DKK3 levels on day 2, day 6, and at discharge(figure 2). Median DKK3 levels did not differ between patients with and without adverse outcomes at 720 days (all-cause mortality p=0.4; composite: p=0.8), and prognostic accuracy remained minimal (all-cause mortality: AUC 0.49 95% CI 0.45–0.52; composite endpoint: AUC 0.5 95% CI 0.46–0.53). DKK3 was neither an independent predictor for all-cause mortality nor the combined endpoint (p=0.2 and p=0.06, respectively) in Cox regression models.

Conclusions

In our cohort, DKK3 lacked diagnostic and prognostic utility in acute heart failure, irrespective of renal function.

Diagnostic accuracy of DKK3 Changes in DKK3 concentrations over time