Cardiac parameters of enrolled subject.

Background
Inflammation has been associated with progression and complications of chronic heart failure (HF) but no effective therapy has yet been identified to treat this dysregulated immunologic state. The selective cytopheretic device (SCD) provides extracorporeal autologous cell processing to lessen the burden of inflammatory activity of circulating leukocytes of the innate immunologic system.
Aim
The objective of this study was to evaluate the effects of the SCD as an extracorporeal immunomodulatory device on the immune dysregulated state of HF. HF.
Methods and results
SCD treatment in a canine model of systolic HF or HF with reduced ejection fraction (HFrEF) diminished leukocyte inflammatory activity and enhanced cardiac performance as measured by left ventricular (LV) ejection fraction and stroke volume (SV) up to 4 weeks after treatment initiation. Translation of these observations in first in human, proof of concept clinical study was evaluated in a patient with severe HFrEFHFrEF ineligible for cardiac transplantation or LV LV assist device (LVAD) due to renal insufficiency and right ventricular dysfunction. Six hour SCD treatments over 6 consecutive days resulted in selective removal of inflammatory neutrophils and monocytes and reduction in key plasma cytokines, including tumor necrosis factor-alpha (TNF-α),), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. These immunologic changes were associated with significant improvements in cardiac power output, right ventricular stroke work index, cardiac index and LVSV index…. Stabilization of renal function with progressive volume removal permitted successful LVAD implantation.
Conclusion
This translational research study demonstrates a promising immunomodulatory approach to improve cardiac performance in HFrEFHFrEF and supports the important role of inflammation in the progression of HFHF.

## 背景
炎症与慢性心力衰竭（HF）的进展及并发症密切相关，但目前尚未发现可有效干预这种失调免疫状态的治疗手段。选择性细胞吸附装置（SCD）可通过体外自体细胞处理，减轻先天免疫系统循环白细胞的炎症负荷。

## 研究目的
本研究旨在评估SCD作为体外免疫调节装置，对心力衰竭免疫失调状态的改善效果。

## 方法与结果
在收缩性心力衰竭或射血分数降低型心力衰竭（HFrEF）的犬类模型中开展的SCD治疗，可降低白细胞炎症活性，并在治疗启动后最长4周内，通过左心室（LV）射血分数与每搏输出量（SV）评估指标，改善心脏功能。本研究针对首个人体概念验证临床研究的转化结果展开评估，受试者为1名因肾功能不全与右心功能不全，无法接受心脏移植或左心室辅助装置（LVAD）的重度HFrEF患者。连续6天每日6小时的SCD治疗，可选择性清除炎性中性粒细胞与单核细胞，并降低血浆中关键细胞因子水平，包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-8以及单核细胞趋化蛋白-1（MCP-1）。上述免疫学变化与心脏功率输出、右心室每搏功指数、心脏指数及左心室每搏输出量指数的显著改善相关……通过渐进性容量清除实现肾功能稳定后，患者成功接受了LVAD植入术。

## 结论
本项转化研究证实，SCD是一种颇具前景的免疫调节策略，可改善HFrEF患者的心脏功能，同时印证了炎症在HF进展中的关键作用。