Jacob P Scioscia, Ivan Murrieta-Alvarez, Shiyi Li, Zicheng Xu, Guangyao Zheng, Jason Uwaeze, Carl P Walther, Zachary Gray, Katherine V Nordick, Vladimir Braverman, Alexis E Shafii, Gabriel Loor, Camila Hochman-Mendez, Ravi K Ghanta, Subhasis Chatterjee, O Howard Frazier, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal
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引用次数: 0
摘要
中风仍然是晚期充血性心力衰竭(CHF)患者植入持续流左心室辅助装置(CF-LVAD)后的主要不良事件。线粒体氧化磷酸化(OxPhos)异常与神经退行性疾病和脑缺血的发病机制有重要关系。我们推测,既往中风可能与全身线粒体 OxPhos 异常有关,CF-LVAD 后患者的线粒体 OxPhos 异常受损程度更高,且有发生新中风的风险。我们研究了 50 位 CF-LVAD 患者(25 位曾中风,25 位未中风);测量了血液白细胞中的 OxPhos 复合物蛋白(复合物 I [C.I] - 复合物 V [C.V])。在基线期(CF-LVAD 术前)和术后(CF-LVAD 术后),中风前组的 C.I、复合体 II (C.II)、复合体 IV (C.IV) 和 C.V 蛋白都明显低于未中风前组。与中风前相比,中风前组在中风后 LVAD 阶段的氧化磷酸化蛋白明显减少。机器学习最小绝对收缩和选择操作器(LASSO)和随机森林建模确定了预测术后中风的六个预后因素,其接收者操作特征曲线下面积(ROC)为 0.93。氧化磷酸化蛋白减少似乎与植入术后新发中风有关。我们的研究首次发现,即使在植入 CF-LVAD 之前就已发生缺血性中风的 CHF 患者,其外周水平也存在线粒体功能障碍。OxPhos 蛋白表达的变化可作为预测 CF-LVAD 植入后新发脑卒中的生物标记物。
Machine Learning Assisted Stroke Prediction in Mechanical Circulatory Support: Predictive Role of Systemic Mitochondrial Dysfunction.
Stroke continues to be a major adverse event in advanced congestive heart failure (CHF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. Abnormalities in mitochondrial oxidative phosphorylation (OxPhos) have been critically implicated in the pathogenesis of neurodegenerative diseases and cerebral ischemia. We hypothesize that prior stroke may be associated with systemic mitochondrial OxPhos abnormalities, and impaired more in post-CF-LVAD patients with risk of developing new stroke. We studied 50 CF-LVAD patients (25 with prior stroke, 25 without); OxPhos complex proteins (complex I [C.I]-complex V [C.V]) were measured in blood leukocytes. Both at baseline (pre-CF-LVAD) and postoperatively (post-CF-LVAD), the prior-stroke group had significantly lower C.I, complex II (C.II), complex IV (C.IV), and C.V proteins when compared to the no-prior-stroke group. Oxidative phosphorylation proteins were significantly decreased in prior-stroke group at post-CF-LVAD compared to pre-CF-LVAD. Machine learning Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest modeling identified six prognostic factors that predicted postoperative stroke with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93. Oxidative phosphorylation protein reduction appeared to be associated with the new stroke after implantation. Our study found for the first time the existence of mitochondrial dysfunction at the peripheral level in CHF patients with prior ischemic stroke even before CF-LVAD implantation. The changes in OxPhos protein expression could serve as biomarkers in predicting new post-CF-LVAD strokes.
期刊介绍:
ASAIO Journal is in the forefront of artificial organ research and development. On the cutting edge of innovative technology, it features peer-reviewed articles of the highest quality that describe research, development, the most recent advances in the design of artificial organ devices and findings from initial testing. Bimonthly, the ASAIO Journal features state-of-the-art investigations, laboratory and clinical trials, and discussions and opinions from experts around the world.
The official publication of the American Society for Artificial Internal Organs.