Dynamics of the Novel Cardiac Biomarkers sST2, H-FABP, GDF-15 and suPAR in HFrEF Patients Undergoing Heart Failure Therapy, a Pilot Study

<b>Background:</b> Despite improvements in medical therapy, heart failure with reduced ejection fraction (HFrEF) is a major burden on the healthcare system and remains a leading cause of death with a 5-year mortality rate of more than 60%. Novel therapeutic agents such as angiotensin-receptor-neprilysin-inhibitors (ARNIs) lead to significant improvement in clinical outcomes. Optimal therapy monitoring under these novel drugs is crucial for improving the outcome. In this trial, the diagnostic potential of four novel cardiovascular biomarkers-GDF-15, sST2, H-FABP, and suPAR-was evaluated during follow-up in patients with HFrEF. <b>Methods:</b> In this prospective cohort pilot study, 70 patients with HFrEF with ischemic (n = 34) and non-ischemic (n = 36) origin were included. All included patients were on a stable treatment regimen and in a non-decompensated state. The clinical parameters NYHA class, LVEF, MPI/Tei index and ESC Score 2 and the laboratory parameters sST2 (remodeling, inflammation), GDF-15 (remodeling, inflammation), H-FABP (subclinical ischemia and ischemia), suPAR (remodeling, inflammation) and NT-proBNP were assessed before ARNI therapy initiation and at 3 to 6 months at follow-up. Before starting ARNI therapy with sacubitril/valsartan patients had stable and well-established heart failure therapy. <b>Results:</b> There was a sufficient response to therapy with significant improvement in ejection fraction from 29.9% to 38.5% (<i>p</i> < 0.001) and a significant decrease in NT-proBNP from 1402 pg/mL to 572.0 pg/mL (<i>p</i> = 0.003). Interestingly, along with that, a significant increase in sST2 levels from 9602 pg/mL to 12,001 pg/mL (<i>p</i> = 0.039) but no significant change in H-FABP (<i>p</i> = 0.397), GDF-15 (<i>p</i> = 0.382) or suPAR (<i>p</i> = 0.328) were observed. Furthermore, the baseline sST2 level correlated with the risk of cardiovascular events calculated with the ESC Score 2 and the GDF15 level at follow-up correlated with the right ventricular global function, assessed with the MPI/Tei index and this correlation persisted after correction for confounders (<i>r</i> = 0.323, <i>p</i> = 0.039; <i>r</i> = 0.504, <i>p</i> = 0.011). <b>Conclusions:</b> The novel biomarker sST2 but not H-FABP, GDF-15 and suPAR was significantly affected by medical therapy with ARNIs. Monitoring sST2 might offer new opportunities for therapy guidance and disease management. However, these results are hypothesis generating and should be interpreted with caution, given the pilot nature of this study.