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.