Sympathetic Markers are Different Between Clinical Responders and Nonresponders After Left Ventricular Assist Device Implantation

Abstract

Background: Clinical response to left ventricular assist devices (LVAD), as measured by healthrelated quality of life (HRQOL), varies among patients following implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by HRQOL. Objective: The purpose of this study was to compare changes in sympathetic markers (βadrenergic receptor kinase-1 (βARK1), norepinephrine (NE), and 3,4-dihydroxyphenylglycol (DHPG)) between HRQOL clinical responders and non-responders from pre-to post-LVAD. Methods-We performed a secondary analysis on a subset of data from a cohort study of patients from pre-to 1, 3, and 6 months post-LVAD. Clinical response was defined as ≥ 5 points increase on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre-to 6-months post-LVAD. We measured plasma βARK1 with an ELISA and plasma NE and DHPG with high performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare trajectories of markers between groups. Results: Average age of the sample (n=39) was 52.9±13.2 years, and most were male (74.4%) and bridge to transplant (69.2%). Pre-implant plasma βARK1 was significantly higher in clinical responders (n=19) vs. non-responders (n=20) (p=0.001), but change was similar following LVAD (p=0.235). Pre-implant plasma DHPG was significantly lower in clinical responders vs. non

Biomarkers in Patients with Left Ventricular Assist Device: An Insight on Current Evidence

“…LVAD responders have low levels of β-adrenergic receptor kinase, which would promote internalization/desensitization of β receptors, and high levels of dihydroxyphenylglycol, a catabolite of norepinephrine. High levels of this molecule, with consequent ratio norepinephrine/dihydroxyphenylglycol approximately to 1, point out an active, capable process of catecholamines degradation, and thus, lower exposure [ 14 ]. Intriguingly, norepinephrine levels were comparable between responders and non-responders.…”

What gets on the nerves of cardiac patients? Pathophysiological changes in cardiac innervation

“…Increased neural excitability. Sympathetic hyperactivity elevates plasma levels of NA and its metabolite, dihydroxyphenylglycol, which are associated with poor patient outcomes in heart failure with either preserved or reduced ejection fraction (Denfeld et al 2019;Grassi et al 2019). Many studies have tried to elucidate the basis for enhanced sympathetic transmission and NA spillover in the failing heart (reviewed by Grassi et al 2019).…”

“…Sympathetic hyperactivity elevates plasma levels of NA and its metabolite, dihydroxyphenylglycol, which are associated with poor patient outcomes in heart failure with either preserved or reduced ejection fraction (Denfeld et al . 2019; Grassi et al . 2019).…”