Background: Heart failure (HF) is a major cause of mortality, hospitalizations, and impaired quality of life. Left ventricular assist devices (LVAD) are used in end-stage HF as bridging until transplantation, destination therapy or for myocardial recovery. Despite progress made in the field, patients often fail to respond to LVAD implantation, implying the existence of yet unidentified mechanisms, and highlighting the need for novel biomarkers to predict LVAD response. Amyloid-β 1-40 (Aβ1-40) is a 40 amino-acid long peptide, produced after clearance of amyloid precursor protein, and has been associated with myocardial ageing. Increased circulating Aβ1-40 is associated with worse outcomes in patients with HF, supporting the hypothesis of its utility as a biomarker in HF.

Aim: The aim of the present study was to evaluate the associations between circulating Aβ1-40 and: a) markers of HF severity in patients with end-stage HF, b) cardiac hemodynamics  after LVAD implantation.

Methods: We measured circulating Αβ1-40 levels by ELISA in 98 patients with end-stage HF, who were eligible for LVAD implantation before and 6 months after LVAD implantation.

Results: Most of the patients were male (N=84, 85.7%), relatively young (mean age=57.16 years, SD=16.30), with median duration of HF symptoms equal to 72 months [interquartile range (IQR)=13.49-120). Baseline Aβ1-40 positively correlated with right atrial pressure [(RAP), Spearman’s rho=0.240, p=0.029], pulmonary capillary wedge pressure [(PCWP), rho=0.226, p=0.025] and creatinine (rho=0.486, p<0.01). By linear regression analysis, Aβ1-40 was independently associated with RAP and PCWP (β coefficient=0.292, p=0.003 and β coefficient=0.237, p=0.019, respectively), after adjustment for age, creatinine, and cardiac output. Twenty patients had available Αβ1-40 after LVAD implantation, while 7 of them (35%) were classified as responders. Importantly, responders presented lower values of circulating Aβ1-40 compared to non-responders [69.66 (IQR=49.40-100.19) pg/mL vs 124.49 (IQR=78.29-139.05 ) pg/mL, p=0.011, Mann Whitney U-test]. By linear mixed model analysis, changes in Αβ1-40 were independently associated with changes in RAP (mean change=1.35 mmHg per 1 SD change in Aβ1-40, 95% CI 0.211-2.48, p=0.02) and PCWP (mean change=1.61mmHg per 1 SD change in Aβ1-40, 95% CI 0.191-3.02, p=0.026). LVAD-responders significantly decreased circulating levels of Aβ1-40 post implantation compared to non-responders (mean difference= -55pg/mL, 95% CI -98.3, -11.8, p for interaction=0.013).

Conclusion: Αβ1-40 may be critically involved in in end-stage biventricular HF and may serve as a predictive biomarker for therapy response post LVAD implantation. This conclusion is supported by the fact that changes in Aβ1-40 were associated with changes in RAP and PCWP after LVAD implantation, while LVAD responders had significantly lower levels of circulating Αβ1-40. Further research is warranted to clarify the role of this peptide as a biomarker in the spectrum of HF.