Higher plasma IL-6 and PTX3 are associated with worse survival in left heart failure with pulmonary hypertension

Introduction: Left heart failure (LHF) is commonly complicated by pulmonary hypertension (PH), increasing morbidity and mortality. The present study aimed to evaluate the prognostic value of inflammatory proteins in LHF with PH (LHF-PH). Materials and methods: The levels of 65 plasma proteins, analysed with proximity extension assay, were compared between healthy controls (n = 20), patients with LHF-PH (n = 67) comprising both HFpEF-PH (n = 31) and HFrEF-PH (n = 36), and in a LHF subpopulation before and after heart transplantation (HT, n = 19). Haemodynamic parameters were measured using right heart catheterization. Results: Plasma levels of Interleukin 6 (IL-6) and Pentraxin related protein PTX3 (PTX3) were elevated in LHF-PH vs. controls (p < 0.001), and these decreased after HT compared to before HT (p < 0.001). Plasma IL-6 and PTX3 correlated to elevated NT-proBNP (r = 0.44, p = 0.0002 and r = 0.4, p = 0.0009, respectively). Additionally, IL-6 correlated with mean pulmonary arterial pressure (r = 0.4, p = 0.0009) and mean right atrial pressure (r = 0.51, p < 0.0001). Higher levels of IL-6 and PTX3 were associated with worse survival rates in patients with LHF-PH (Log rank p < 0.01). Discussion: In patients with LHF-PH, higher plasma levels of IL-6 and PTX3 were associated with worse survival rates. Future larger studies to validate and investigate the direct clinical applicability of IL-6 and PTX3 as potential prognostic biomarkers are encouraged.