BackgroundThe interleukin‐33 (IL‐33)/suppressor of tumorigenicity 2 (ST2) pathway is suggested to play an important role in fibrosis, remodelling and the progression of heart failure (HF). Increased soluble (sST2) levels are associated with adverse outcome in the average HF population. Less is known about sST2 levels in end‐stage HF. Therefore, we studied sST2 levels in end‐stage HF and the effect of unloading by left ventricular assist device (LVAD) support on sST2 levels.Method and resultsSerial plasma measurements of sST2 were performed pre‐implantation and 1, 3 and 6 months after (LVAD) implantation in 38 patients. sST2 levels were elevated in end‐stage HF just prior to LVAD implantation (74.2 ng/mL [IQR 54.7‐116.9]; normal <35 ng/mL) and decreased substantially during LVAD support, to 29.5 ng/mL [IQR 24.7‐46.6](P < .001). Patients with INTERMACS profile I had significantly higher sST2 levels compared to patients in profile II and profile III. A moderate correlation was found between sST2 and C‐reactive protein (r = .580, P < .010).ConclusionLevels of sST2 are elevated in end‐stage HF patients with variability that suggests multiple inputs to a pro‐inflammatory and pro‐fibrotic pathway. Cardiogenic shock and increased C‐reactive protein levels are associated with higher sST2 levels. LVAD support results in a significant drop in sST2 levels with normalization within 3 months postimplantation. This suggests that LVAD support leads to lessening of fibrosis and inflammation, which might eventually be used to target medical policy: explantation of the LVAD versus permanent use or cardiac transplantation.

Poster Session 3 375 ventricular assist devices (cf-LVADs) are most often implanted. In The Netherlands, duration on MCS has increased because of an increasing waiting list for heart transplantation due to lack of donor hearts. Consequently, experience is built on longer term support. We present the long term results from our hospital. Purpose: To provide insight in long term mechanical circulatory support. Methods: Of all patients (pts) who received MCS between March 2006 and January 2016, data were prospectively collected in a central database, including baseline clinical characteristics as well as complications defined according to INTERMACS. Data were extracted for statistical analysis. Results: 203 cf-LVADs were implanted in our hospital. 67 pts were transplanted and 7 pts explanted. Actuarial survival at 5 years is 68% (figure 1).Death was most often caused by neurological complications and sepsis. Gastro-intestinal bleeding and intracerebral complications (hemorrhage and stroke) both occurred 0.15 times per patient year. Twenty-seven replacements were performed, most often due to pump thrombosis or technical defects. Conclusion: MCS in patients with end-stage HF has a 5-year survival of 68%. It is a promising therapy that might be a good alternative for heart transplantation in selected patients. However, further optimization of the therapy as well as management of long term complications is required.

End stage renal disease is an increasing problem worldwide driven by aging of the population and increased prevalence of metabolic disorders and cardiovascular disease. Currently, kidney transplantation is the only curative option, but donor organ shortages greatly limit its application. Regenerative medicine has the potential to solve the shortage by using stem cells to grow the desired tissues, like kidney tissue. Immune rejection poses a great threat towards the implementation of stem cell derived tissues and various strategies have been explored to limit the immune response towards these tissues. However, these studies are limited by targeting mainly T cell mediated immune rejection while the rejection process also involves innate and humoral immunity. In this study we investigate whether inhibition of the complement system in human induced pluripotent stem cells (iPSC) could provide protection from such immune injury. To this end we created knock-in iPSC lines of the membrane bound complement inhibitor CD55 to create a transplant-specific protection towards complement activation. CD55 inhibits the central driver of the complement cascade, C3 convertase, and we show that overexpression is able to decrease complement activation on both iPSCs as well as differentiated kidney organoids upon stimulation with anti-HLA antibodies to mimic the mechanism of humoral rejection.