Neurofilaments in heart failure-depicting the brain-heart axis

Abstract Introduction Experimental studies have fueled theoretical concerns about neurocognitive side effects of the angiotensin-receptor-neprilysin-inhibitor (ARNi) sacubitril/valsartan as neprilysin is not only involved in degradation vasoactive peptides, but also amyloid-β brain. To date, no study could demonstrate cognition- and dementia-related adverse following neprilysin-inhibition. Recent advances blood-based tests made it feasible to precisely measure concentration neurofilament light chain plasma (sNfL).sNfl has been found be altered neurodegenerative disease, making a potential biomarker for screening early detection cognitive impairment. This investigated association sNfL levels with severity disease prognosis heart failure reduced ejection fraction (HFrEF) explored response initiation ARNi. Methods HFrEF patients were prospectively enrolled clinically followed-up.sNfL measured by single-molecule array assay. The (HF) outcome was assessed. discriminatory power sNFL assessed using Harrell's C-statistic compared NT-proBNP. In subset 47 patients, determined before ARNi (baseline), 3±2 months (short-term) 12±3 (long-term) after. Results A total 177 included into study. Median age 61 years (IQR: 51–72) 75% male. 26.2 pg/ml 14.1–43.8).sNfL significantly associated HF reflected NT-proBNP (rs=0.361, p<0.001) NYHA class (p<0.001) (Figure 1A). Thirty-one (17.5%) died during median follow-up time 2.8 2.3–3.3). Increased indicative worse overall survival even after adjustment age, sex, kidney function [adj. HR ln[sNfL]: 1.78 (95% CI: 1.13–2.80, p=0.012] 1B). terms accuracy, sNfl comparable (C-index: 0.75 [CI: 0.67–0.83] vs. 0.71 0.63–0.80], p=0.299). Regarding effect ARNi-therapy significant change observed at short- long-term (26.0 [IQR: 15.1–51.4] 31.5 15.8–51.3]; 31.3 15.5–54.0], p>0.05 all) 2). Conclusions suggests that high performing marker predict independent NEP-inhibition does seem reasonably influence levels. nature release uncertain. As assumed specific axonal injury, increase may driven hypoperfusion due fixed peripheral vasoconstriction characteristic more severe states. Whether are able aid therapy decline elucidated further studies. Funding Acknowledgement Type funding sources: Foundation. Main source(s): Austrian Society Cardiology - Research Grant