Abstract 17312: Chemokine Receptor Down-regulation is Associated With Worse 1 Year Survival in Left Ventricular Assist Device (LVAD) Patients
Introduction: LVADs are approved for use both as Bridge To Transplant (BTT) and Destination Therapy in advanced heart failure. Current INTERMACS data reports 1 year survival with continuous flow devices at 80%. Pre-operative risk modeling is particularly important for patient selection and prognostication.
Hypothesis: Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. We have previously shown that pre-implant chemokine receptor down regulation predicts RV Failure (RVF) post-operatively. We hypothesized that baseline chemokine receptor under expression is associated with increased 1 year mortality after LVAD.
Methods: Chemokine receptor expression was examined in patient’s peripheral blood 24 hours prior to LVAD. RNA was isolated using PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold (CT) with more highly expressed genes having a lower CT and normalized to the average of GAPDH, B2M and HPRT1. Patients were dichotomized by median CT. Cox univariate and multivariate analyses were performed on retrospectively collected 1 year mortality data. Spearman correlation was performed on pre-operative data to determine which variables to include in the multivariate analysis.
Results: 113 LVAD patients (mean age 54 yrs, 82% male, 81% white, 48% ICM, 58% BTT) were included in the analysis. Down regulation of CCR3 (HR 2.057, p=0.046), CCR4 (HR 2.649, p=0.009), CCR6 (HR 2.663, p=0.01) and CCR7 (HR 2.769, p=0.007) was associated with increased 1 year mortality in LVAD patients. After adjusting for age, gender, pre implant Cr, total bilirubin, WBC, INR, RAP, PCWP, CI and HR- down regulation of CCR3 (HR 4.598, p=0.022), CCR4 (HR 3.783, p=0.03) and CCR7 (HR 2.914, p=0.058) predicted worse 1 year survival. When development of post-operative RVF was included in the model, CCR3 (HR 4.684, p=0.025), CCR4 (HR 3.114, p=0.069) and CCR7 (HR 3.248, p=0.039) continued to be associated with higher mortality.
Conclusion: Pre-LVAD chemokine receptor down regulation is associated with increased mortality after implant. Aberrant immune pathways may be determinants of long term outcome in this patient population.
Author Disclosures: A. Nayak: None. C. Neill: None. J.O. Larsen: None. I. Halder: None. T.N. Bachman: None. C. McTiernan: None. R. Kormos: None. O. Hunter: None. A. Inashvili: None. L. Lagazzi: None. J. Teuteberg: Speakers Bureau; Modest; HeartWare, CareDx. Consultant/Advisory Board; Modest; HeartWare, Abiomed, CareDx, Acorda Therapeutics. Other; Modest; Thoratec. K. Hanley-Yanez: None. D.M. McNamara: None. M.A. Simon: None.
- © 2016 by American Heart Association, Inc.