The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Association of Pre-Implant Inflammatory Profile and Functional Recovery with Chronic LVAD Unloading


      Inflammatory pathways have been widely implicated as major players in the pathogenesis of heart failure. We hypothesized that the inflammatory profile of patients requiring left ventricular assist device (LVAD) support is associated with the improvement in structure and function with chronic mechanical unloading.


      From 2008–2014, tissue and serum samples were obtained in 105 patients receiving durable LVADs for stage D heart failure. Turn-down echocardiography was serially performed to assess criteria for recovery. Responders (R) were defined as having a relative increase in the left ventricular ejection fraction (LVEF) > 50%, a final resulting LVEF > 40 %, and a left ventricular end diastolic diameter (LVEDD) < 60mm. Protein levels of cytokines were measured in both myocardial tissue and in serum.


      Of the 105 patients analyzed, 20 were Responders (R) and 85 were Non-Responders (NR). Average duration of LVAD support was 474.8 days for Responders and 267.4 days for Non-Responders. Circulating cytokines GM-CSF, IL-1β, IL-5, and IL-2 were significantly higher in Responders (Table 1). In left ventricular tissue, GM-CSF, IL-10, and IL-7 were also significantly higher in Responders (Table 1). Ratios of pro- (TNFα and IL-1β) to anti-inflammatory (IL-10) cytokines were analyzed. Circulating TNFα/IL-10 and IL-1β/IL-10 were higher in Responders. Inversely, left ventricular tissue TNFα/IL-10 and IL-1β/IL-10 ratios were lower in Responders.


      Patients that exhibit functional recovery after mechanical unloading appear to present within an inflammatory milieu. Pro-inflammatory and counteracting, anti-inflammatory cytokines are more highly expressed. Moreover, these data suggest that both serum and tissue factors can be used to target patients that might benefit from focused clinical efforts aimed at bridging to recovery rather than defaulting straight to transplantation or destination therapy.
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