Background
Right Ventricular failure (RVF) complicates 9–44% of LVAD implants postoperatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. We aimed to study chemokine receptor regulation in LVAD recipients who develop RVF.
Methods
Expression of chemokine receptor genes 3–8 was examined in the peripheral blood of 111 LVAD patients, collected 24 hours prior to implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold and normalized to the average of 3 control genes- GAPDH, HPRT1 and B2M. Secondary outcomes studied were 1 year mortality and long-term RV failure (RVF-LT).
Results
Chemokine receptors CCR3, CCR4, CCR6, CCR7 and CCR8 were down regulated in LVAD recipients who had RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further down regulated in those that required mechanical support of their RV. Additionally, under-expression of CCR3–8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. Chemokine receptor expression did not predict RVF-LT in our patient cohort.
Conclusions
Pre-LVAD chemokine receptor down regulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play an important role in prognostication in this patient population.