CARD1: Impairment of Mitochondrial Oxidative Phosphorylation in Heart Failure Patients with History of Ischemic Stroke Undergoing CF-LVAD Implantation

Study: Abnormalities in systemic immune cell mitochondrial oxidative phosphorylation (OxPhos) found to be linked with ischemic stroke and post-stroke brain injury. It was unclear if prior ischemic stroke in patients undergoing continuous-flow left ventricular assist device(CF-LVAD) implantation were associated with OxPhos abnormalities which subsequently can be used to predict the increased risk of post-CF-LVAD stroke. In this study we investigated if prior ischemic stroke in patients receiving CF-LVAD had systemic OxPhos abnormalities compared to non-stroke patients and if OxPhos abnormalities was impaired more in stroke patients post-CF-LVAD implantation. Methods: During June 2020-January 2022, we performed 77 CF-LVAD implants and 32 patients signed informed consent to volunteer for this prospective study. Out of 32 patients, 20 had prior stroke(ST group) 30 days before CFLVAD implantation and 12 had no prior stroke(No-ST group). Blood samples were collected within 7 days pre-CFLVAD and on the day 7th post-CF-LVAD. OxPhos was measured via immunoblot of peripheral blood mononuclear cells(PBMCs) using a total OxPhos Complex kit, which quantifies 5 complex subunit proteins of mitochondria (C.I-C.V) after normalizing to porin. The data were displayed with violin plot distribution. Results and Conclusions: At baseline(Pre-CF-LVAD), the ST group had reduced (p<0.01) C.I, C.II and C.V expression in PBMCs when compared to the No-ST group (Fig.A,B,E). While the pre-CF-LVAD differences in C.III (p=0.07) and C.IV (p=0.21) were not significant between the two groups, there was more than 20% diminished expressions observed in the ST group (Fig.C,D). Our study found for the first time the existence of mitochondrial alterations at the peripheral level in the HF patients with prior ischemic stroke even before CF-LVAD implantation. The Post-CF-LVAD reduction in all 5 OxPhos markers were found to be significant in the ST group compared to the No-ST group. In ST group, severe reduction of OxPhos proteins were noticed at post-CF-LVAD compared to their corresponding pre-CFLVAD values, while in No-ST group these proteins were comparable between pre-and post-CF-LVAD values. During the post-CF-LVAD hospitalization period (median 29 days), there were no patients in the No-ST group developed post-CF-LVAD stroke while 3 patients in the ST group (3/20;15%) developed stroke at 7, 13 and 16 days after implantation. In the ST group, the percentage change in OxPhos proteins from pre-CF-LVAD to post-CF-LVAD ([(Pre–Post)/Post]x100) indicated 41% and 37% more decrease in C.II and C.III proteins respectively in those patients who developed new post-CF-LVAD stroke compared to non new stroke patients (p<0.05). This finding demonstrated that, the severe reduction of OxPhos appeared to be associated with the new onset of stroke after CF-LVAD implantation. The changes in OxPhos protein expression in the ST group may have a potential diagnostic role in predicting post-CF-LVAD strokes.