Elevated plasma WIF‐1 levels are associated with worse prognosis in heart failure with pulmonary hypertension

AIMS: Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF‐PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF‐PH. METHODS: Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF‐PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization. RESULTS: Eleven proteins had elevated plasma levels in LHF‐PH compared with controls (P < 0.01), which decreased towards the controls' levels after HT (P < 0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF‐1) were associated with worse transplantation‐free survival in LHF‐PH (P < 0.05). When adjusted for age, sex and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels using multivariable cox regressions, only WIF‐1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001–1.024)]. WIF‐1 levels in LHF‐PH patients also correlated with the mean right atrial pressure (r(s) = 0.42; P < 0.01), stroke volume index (r(s) = 0.41; P < 0.01), cardiac index (r(s) = −0.42; P < 0.01), left ventricular stroke work index (r(s) = −0.41; P < 0.01), and NT‐proBNP (r(s) = 0.63; P < 0.01). CONCLUSIONS: The present study demonstrated that LHF‐PH patients have higher plasma WIF‐1 levels than healthy controls, suggesting that plasma WIF‐1 may be a potential future prognostic biomarker in LHF‐PH. Its prognostic capability could be further refined by including it in a multi‐marker panel. Further studies are needed to establish the potential role of WIF‐1 in LHF‐PH pathophysiology in larger cohorts to determine its clinical applicability.