Accepted Manuscript. Expanding the Salvage Time Window of LVO Stroke Patients After Cardiovascular Surgery. SuK Jung Choo, MD, PhD

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1 Accepted Manuscript Expanding the Salvage Time Window of LVO Stroke Patients After Cardiovascular Surgery SuK Jung Choo, MD, PhD PII: S (19) DOI: Reference: YMTC To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 8 January 2019 Accepted Date: 9 January 2019 Please cite this article as: Choo SJ, Expanding the Salvage Time Window of LVO Stroke Patients After Cardiovascular Surgery, The Journal of Thoracic and Cardiovascular Surgery (2019), doi: doi.org/ /j.jtcvs This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 Expanding the Salvage Time Window of LVO Stroke Patients After Cardiovascular Surgery SuK Jung Choo, MD, PhD Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Running Title: Expanding the Salvage Time in Post Cardiovascular Surgery LVO Stroke Patients Word count: 1,043 Conflict of Interest: The author declares no conflicts of interests related to this editorial commentary Correspondence to: Suk Jung Choo, MD, PhD Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea Tel Fax

3 Expanding the Salvage Time Window of LVO Stroke Patients After Cardiovascular Surgery In this issue of the Journal, Sheriff F et al [1] investigated the incidence of large vessel occlusion (LVO) stroke after cardiovascular surgery and explored the feasibility of expanding the salvageable time window beyond the currently perceived time limit for reversing neurologic deficits. Timely restoration of circulatory perfusion prior to the establishment of irreversible damage is of the essence in any organ ischemia. With large major vessel occlusion stroke, partial or complete reversal of neurologic deficit through intracranial thrombectomy when possible has generally been believed to be achievable when performed within 6 hours of onset [2], and beyond this period additional benefits was believed to diminished [3]. To date, studies investigating the role of thrombectomy for large vessel stroke after cardiovascular surgery has been limited and there has also been difficulties relating to accurately determining the duration between last seen well (LSW) period and detection. The recently published DAWN [4] and DEFUSE 3 [5] trials showed that neurologic outcomes was better after thrombectomy vs standard medical treatment in large vessel occlusion (LVO) stroke patients in whom the duration from LSW was greater than 6 hours and complete infarction had not yet set in. The authors in the present issue reviewed their institutional cardiothoracic surgery database over a 5 year period in which large vessel occlusion (LVO) stroke was observed in 15 patients among 137 ischemic stroke patients from a total cohort of 5,947 cardiovascular surgery patients. Among the 15 LVO patients, 7 patients deemed candidates for emergent thrombectomy formed the basis of the present report. Although large vessel occlusion (LVO) stroke is a relatively rare subtype of ischemic stroke, its significance lies in causing the majority of stroke related death and severe disability [4,5]. In the present study, the overall incidence of postoperative stroke was relatively rare at 2.48% and most of the post cardiovascular surgery stroke in the affected patients was ischemic in origin comprising 92.5% of the patients with LVO comprising 10.9% of these patients. These are the types of stroke that may be amenable to treatment by interventional procedures aimed at removing thrombus, fat, or other solid materials with the ideal expectation of complete recovery if infarction had not yet set in. However, a strong dedicated stroke team with established protocols for rapid intervention is an essential element to reduce the latencies to treatment. According to the present authors, LVO stroke after cardiovascular surgery may fall into two categories; wake up stroke which is detected upon emergence from anesthesia and awake stroke in which neurologic deficit occurs after a period of having been awake. From a diagnostic standpoint the wake up stroke patients pose the greatest challenge as it is difficult to pinpoint the stroke onset once anesthesia induction has been completed. Considering that the majority of

4 cerebrovascular events associated with cardiothoracic surgery are macro-embolic in nature, the stroke onset may be blamed on any of the possible causative maneuvers and manipulations such as clamp placement/removal occurring after anesthesia. Therefore, the estimated ischemic duration may depend on when the specific culprit event is considered to have occurred. Although sudden changes in the intraoperative monitoring such as EEG activity may alert the surgeon to the possibility of an acute adverse event, it may not be possible to accurately pin point a neurologic event onset especially if there was a gradual decrease in EEG activity prior to a prolonged period of ACC time, after which further hints of any neurologic events may be even more difficult to decipher as the EEG wave activity may show significantly delayed recovery during rewarming, especially if it was combined with a period of hypothermic circulatory arrest. In addition, the normal wake up period from anesthesia after weaning from a complex cardiothoracic surgery may normally be prolonged, resulting in the detection of neurologic deficit being inadvertently delayed by the usual waiting period for postoperative neurologic recovery. These issues which may confound determination of the ischemic duration warrant implementation of measures to stimulate earlier arousal and acquisition of imaging studies in patients at risk. However the logistics of safely transferring these patients to the brain or MRI scanning facility let alone incurring additional travel and time away from the ICU to undergo thrombectomy may be prohibitive given the typically heavy dependence on invasive treatments such as LV assist devices amidst a complex web of medication lines connected to these patients. At the authors institution, a STAT CTA head and neck with delays are acquired in coordination with radiology in patients deemed at high risk of LVO as a proactive strategy during transport from the OR to the ICU while the patient is under the care of the anesthesia. These details highlight the necessity of a highly dedicated and coordinated multi-disciplinary team approach to overcome the daunting challenges of dealing with the multiple issues facing these patients. In the awake stroke patients, which was 5 total in the present study, the reaction time and ischemic times were relatively quicker with the LSW to detection time ranging between 10 to 150mins. As these patients were detected in the hospital setting, they were better positioned to benefit from rapid implementation of interventional measures and timely treatment. Nevertheless effective treatment of these patients in general would not be possible without a highly dedicated and efficient on hand stroke team. Limitations aside, for those patients in whom thrombectomy was possible, the overall outcomes, i.e., lower modified Rankin scores (mrs) tended to be better than non-thrombectomy patients. Although the present study was preliminary in nature due to the small case volume, the study nevertheless provides a glimpse into the possibility of treating LVO stroke patients that would otherwise have been regarded as being, too late for treatment or in the case of wake up patients more or less untreatable. However, the authors have shown that an aggressive strategy to treat these patients at the earliest time possible by a dedicated and tenacious stroke team may result

5 in significantly enhanced neurologic outcomes. Taking the lead from studies such as this, further studies over a larger cohort may be helpful in developing strategies that may better identify patients at risk as well as in determining the onset and duration of stroke so that these patients may be treated more effectively and proactively before the establishment of permanent neurologic deficit. Reference 1. Sheriff F, Hisch JA, Sheton K, D Allesandro D, Stapleton C, et al. Large vessel occlusion stroke after cardiothoracic surgery: Expanding time windows offer new salvage opportunities. J Thorac Cardiovasc Surg 2019 in presse 2. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a metaanalysis of individual patient data from five randomised trials. Lancet 2016; 387: Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016; 316: Nogueira RG, Jadhav AP, Ha 405 ussen DC, Bonafe A, Budzik RF, Bhuva P, et al.thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. New England Journal of Medicine. 2018; 378: Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al.thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. New England Journal of Medicine. 2018;378:

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