Circulating amyloid-beta 1-40 levels associate with cardiac remodelling and myocardial recovery in advanced heart failure

Abstract

Abstract Background A subgroup of left ventricular assist device (LVAD) patients may present reverse remodeling and myocardial recovery, but prognostic and therapeutic biomarkers are lacking. Amyloid-β 1-40 (Aβ1-40), a 40 amino-acid long peptide, has been associated with myocardial ageing, cardiac remodeling, increased risk for HF and worse outcomes in HF patients. Purpose To evaluate the associations between circulating Aβ1-40 and: a) markers of myocardial remodeling and hemodynamic status in advanced HF and b) post-LVAD myocardial unloading and recovery. Methods Plasma Αβ1-40, by ELISA was measured in 98 consecutive patients with advanced HF prior LVAD implantation and in 20 of them at 3-12 months after LVAD implantation. Response to LVAD was defined as LVEF >40% and LV end-diastolic diameter≤ 59 mm at 3 to 1 months after. 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 of 72 months [interquartile range = 13.49-120). After multivariable adjustment for biologically plausible confounders, Aβ1-40 was independently associated with RAP (18.7% increase per 1-SD increase of Αβ1-40), PCWP (12.6% increase per 1-SD increase of Αβ1-40), LVEF (8.5% decrease per 1-SD increase of Αβ1-40) and estimated arterial stiffness as calculated by estimated pulse wave velocity (ePWV, 2.9% increase per 1-SD increase of Αβ1-40) (log-level regression model). Aβ1-40 was independently associated with hemodynamic parameters, LVEF and ePWV (generalized linear model). Responders significantly decreased circulating levels of Aβ1-40 compared to non-responders (p for interaction = 0.013). 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, (0.211-2.48), p = 0.02) and PCWP (mean change = 1.61mmHg per 1-SD change in Aβ1-40, (0.191-3.02), p = 0.026), while a marginal association was observed with ePWV (p = 0.063). Discussion Circulating Αβ1-40 is associated with myocardial recovery after LVAD support, while changes in Aβ1-40 were independently associated with changes in right and left ventricular pre-load. From a mechanistic point of view, our findings are supported by current literature and warrant further research to clarify the role of this peptide as a biomarker of hemodynamic deterioration and myocardial recovery after LVAD implantation. Figure. A) Associations of Aβ1-40 with hemodynamic parameters in advanced heart failure patients prior to LVAD implantation. Standardized coefficient represents the number of standard deviations the dependent variable will change per one standard deviation increase in Aβ1-40. Generalized linear model adjusted for age, gender, eGFR, duration of heart failure symptoms cardiac index and Aβ1-40. B) Prospective changes of Aβ1-40 in responders vs non-responders. Mean difference= -55pg/mL, (-98.3, -11.8), p for interaction = 0.013.