Imperial College London



Cerebral Embolization, Silent Cerebral Infarction and Neurocognitive Decline After Thoracic Endovascular Aortic RepairAnisha H Perera MRCS1, Nung Rudarakanchana PhD FRCS2, Leonardo Monzon FRCR3, Colin D Bicknell MD FRCS1, Bijan Modarai PhD FRCS4, O Kirmi FRCR5, Thanos Athanasiou MD PhD MBA FECTS FRCS6, Mohammad Hamady MD FRCR1, 7, Richard G Gibbs MD FRCS11 Imperial Vascular Unit, Department of Surgery and Cancer, Imperial College and Imperial Healthcare NHS Trust, London, UK2 Department of Vascular Surgery, Royal Free Hospital, London, UK3 Department of Interventional Radiology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK4 Academic Department of Vascular Surgery, King’s College London, BHF Centre of Research Excellence & NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, UK5 Department of Neuroradiology, Imperial Healthcare NHS Trust, London, UK6 Department of Surgery, Imperial College London, London, UK7 Department of Interventional Radiology, Imperial Healthcare NHS Trust, London, UKCorresponding author Colin BicknellDepartment of Surgery, Imperial College London, 10th floor QEQM, St Mary’s Hospital, South Wharf Road, London, W2 1NY, UK Telephone: +44 (0) 20 3312 6666, Email: colin.bicknell@imperial.ac.ukSources of funding This study was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London.Category Original article Previous communication Silent cerebral infarction and neurocognitive decline following thoracic endovascular aortic repair. Oral presentation Vascular Society AGM scientific prize session, Glasgow November 2014. Br J Surg. 2015; 102 (suppl. 2): 5.ABSTRACTBackgroundSilent cerebral infarction is brain injury detected incidentally on imaging, which can be associated with cognitive decline and future stroke. This study investigates cerebral embolization, silent cerebral infarction and neurocognitive decline following thoracic endovascular aortic repair (TEVAR). MethodPatients undergoing elective or emergency TEVAR at Imperial College Healthcare NHS Trust and Guys’ and St Thomas’ Hospital NHS Trust between January 2012 and April 2015 were recruited. Aortic atheroma graded 1 (normal) to 5 (mobile atheroma) was evaluated on pre-operative computed tomography. Patients underwent intra-operative transcranial Doppler (TCD), pre- and post-operative cerebral magnetic resonance imaging (MRI) and neurocognitive assessment. Results Fifty-two patients underwent TEVAR. Higher rates of TCD-detected embolization were detected with greater aortic atheroma (grade 4-5 median 207 versus grade 1-3 median 100, p=0.042), more proximal landing zones (zone 0-1=median 450 versus zones 3-4=median 72, p=0.001) and during stent-graft deployment and contrast injection (p=0.001). On univariable analysis, left subclavian bypass (? Coefficient=0.423, standard error=132.62, p=0.005), proximal landing zone 0-1 (?coef=0.504, SE=170.57, p=0.001) and arch hybrid procedure (?coef=0.514, SE=182.96, p=0.000) were predictors of cerebral emboli. Cerebral infarction was detected in 25/31(81%) undergoing MRI: 21 silent (68%) and four clinical strokes (13%). Neurocognitive decline was seen in 6/7 domains assessed in 15 patients with silent cerebral infarction, with age a significant predictor of decline.ConclusionThis study demonstrates a high rate of cerebral embolization and neurocognitive decline affecting patients following TEVAR. Brain injury following TEVAR is more common than previously recognised, with silent or overt stroke in over 80% of patients.MANUSCRIPT INTRODUCTION Thoracic endovascular aortic repair (TEVAR) has improved survival outcomes in patients with thoracic aortic disease (TAD) over open surgery, with reported elective 30-day mortality rates of 3-8%1-4. Neurological complications of stroke and paraplegia remain a significant risk however. Stroke occurs in up to 7% of patients following TEVAR and is associated with a significant increase in post-operative morbidity and mortality1, 4-6. Strokes are mainly embolic4, 5 as endovascular repair involves the advancement of stiff wires, catheters and delivery devices (up to 26Fr in size) through the aorta often diseased with significant atheroma. Risk factors for stroke include previous stroke, a more proximal extent of repair, high-grade aortic arch atheroma, intra-operative hypotension, chronic renal insufficiency and coverage of the left subclavian artery (LSCA) without revascularization (4-8). Only two studies to date have investigated cerebral embolization during TEVAR using transcranial Doppler (TCD)9, 10. Peri-operative embolization may also cause silent cerebral infarction. This is imaging evidence of cerebral infarction without acute neurologic dysfunction attributable to the lesion11, and is commonly investigated using magnetic resonance imaging (MRI). Studies have shown it is associated with an increased risk of future stroke, dementia, depression, cognitive impairment and early mortality independent of other vascular risk factors12, 13. It is well recognized following other catheter-based procedures (cerebral14,15 and coronary16 angiography, carotid stenting17 and transcatheter aortic valve implantation18), and a recent study of 19 patients reported a 63% incidence following TEVAR19. This study was performed to establish the incidence of TCD-detected cerebral embolization, silent cerebral infarction and neurocognitive decline following TEVAR, and evaluate patient and procedural risk factors for cerebral embolization and silent infarction.METHODSPatient populationEthical approval was obtained from the UK National Research Ethics Service Committee London- Fulham (08/H0711/59) and all patients gave written informed consent. Patients undergoing TEVAR as elective or emergency for any thoracic aortic pathology at two tertiary referral vascular surgery centres (St Mary’s Hospital, Imperial College Healthcare National Health Service Trust and St Thomas’ Hospital, Guys’ and St Thomas’ Hospital National Health Service Foundation Trust) between January 2012 and April 2015 were eligible for inclusion. Pre-operative evaluation of aortic atheroma All patients underwent computed tomography angiography (CTA) prior to surgery in accordance with standard clinical protocol with 1mm slice thickness and intravenous iodinated contrast. Multi-planar 3-dimensional image reconstruction was performed on dedicated CT workstations (Extended Brilliance Workspace, V3.5.0.2254, Philips Medical Systems). Two independent interventional radiologists conducted evaluation of the arch and descending thoracic aorta for the presence of aortic atheroma, calcification and mural thrombus. Atheroma was quantitatively graded based on thickness: grade 1= normal, grade 2= intimal thickening, grade 3= atheroma </=5 mm, grade 4= atheroma >5 mm, and grade 5= mobile lesion7, 20. Aortic arch type based on the relationship of the origins of the supra-aortic vessels to the parallel plane perpendicular to the outer curvature of the arch (I, II, III or bovine)8 and proximal landing zone (PLZ) according to Ishimaru’s classification (zone 0-4) was also assessed21. All elective patients underwent carotid and vertebral artery duplex by qualified Vascular Sonographers.The circle of willis was not assessed on CTA. Cerebral MRICerebral MRI was performed using the Discovery MR750w system (GE Healthcare, United Kingdom) with 3.0T magnet strength; axial Diffusion Weighted Imaging (DWI) and axial T2-weighted fluid-attenuated inversion recovery (FLAIR) with 5mm slice thickness. MRI was performed pre-operatively to identify any pre-existing infarcts, and repeated post-operatively within 72 hours or as soon as clinical condition of the patient allowed. Sensitivity and specificity of DWI in the detection of acute cerebral ischemia is 99% and 92% respectively22. A bright DWI signal indicates an early or sub-acute, but not chronic (>14 days old) ischaemic lesion. Two independent neuroradiologists blinded to clinical outcomes compared pre- and post-operative MRIs, reporting the number, laterality and vascular territory (anterior or posterior circulation or border-zone territory) of new lesions. Lesion surface area was measured on the slice on which the lesion had the largest diameter. Neurocognitive testingNeurocognitive testing was performed by a trained assessor pre-operatively (one day prior to TEVAR), post-operatively (when medically fit for discharge), and at first follow-up outpatient appointment (OPA), approximately six to eight weeks post-discharge. The test battery included the following tests which are the recommended core neuropsychological battery for assessment of neurobehavioral outcomes after cardiac surgery23: 1) REY auditory verbal learning test (verbal learning and memory), 2) Trail making test A (visual search and motor skills), 3) Trail making test B (higher level cognitive skills e.g. mental flexibility and switching), and 4) grooved pegboard (manual dexterity, fine motor skills and complex visual-motor co-ordination of both the dominant and non-dominant hand). The controlled oral word association test (COWA, FAS version), a measure of executive cognitive dysfunction, was also included. TEVAR (intervention group)All cases were performed under general anaesthesia (GA) at both centers, with intravenous heparin maintaining an activated clotting time of 250-350 seconds. In patients where satisfactory proximal sealing required coverage of the LSCA, the LSCA was maintained by left carotid-subclavian bypass or a proximal scalloped endograft custom-made in anatomically suitable cases. Extra-anatomical bypass with visceral debranching (visceral hybrid) or TEVAR with left carotid-subclavian bypass was performed as a single-stage procedure, whilst full arch debranching (left carotid-subclavian bypass and carotid-carotid bypass: arch hybrid) was staged. A spinal drainage catheter was inserted pre-operatively in all patients undergoing visceral hybrid or coverage of >25cm or >50% of aortic length. Access was via percutaneous common femoral artery (CFA) puncture or open surgical groin cut down, and a 22Fr sheath was inserted. Contralateral percutaneous CFA access was obtained with a 5Fr sheath for insertion of an imaging catheter. Pharmacological blood pressure manipulation using glyceryl trinitrate infusion was employed to achieve controlled systemic hypotension with a systolic blood pressure of 80mmHg for a short period of time only to aid precise deployment. All procedures were performed in a dedicated vascular hybrid suite by a team which included both an experienced vascular surgeon and interntional radiology consultant. Control groupPatients undergoing endovascular aortic repair (EVAR) or fenestrated endovascular aortic repair (FEVAR) of infra-renal or juxtra-renal abdominal aortic aneurysms (AAA) were recruited as a contemporaneous control group. All cases were performed under GA, with intravenous heparin maintaining an activated clotting time of 250-350 seconds. Access was via bilateral open surgical femoral access. In all control patients wires and catheters were placed in the proximal descending thoracic aorta and did not cross the aortic arch.Intra-operative TCD assessmentCerebral embolization detection was performed using bilateral TCD insonation of the middle cerebral artery (MCA). The TCD parameters included DWL? Doppler device with 2-channel emboli detection software and 2MHz transducer probes, sample volume 8mm, median softgain 25 (range 13-38), filter setting150Hz and intensity detection threshold >9dB. TCD signal was continuously recorded during procedures and manual offline analysis performed by a trained observer for identification of high intensity transient signals (HITS) characteristic of an embolus. Accepted criteria for emboli detection was used: QUOTE "" ADDIN REFMAN ?\11\05‘\19\01\00\00\00\00\01\00\00 c:\5Cmy documents\5Ccitations\5Cthesis\03\00\03558(558 /id Georgiadis, Grosset, et al. 1994\00(\00 alteration of Doppler signal to a high intensity (>3dB higher than background blood flow signal), short duration (<300 milliseconds) and unidirectional signals in the direction of flow accompanied by a characteristic clicking sound24, 25 (figure 1). Differentiation between gas and solid emboli was not conducted. A period of pre-operative monitoring was performed after induction of GA and before commencement of TEVAR to detect any spontaneous embolization. TCD was performed during carotid-subclavian bypass but not during full arch debranching for arch hybrids. Statistical analysisStatistical analysis was performed using SPSS software (version 22; SPSS, Chicago, IL). Continuous variables are presented as median (interquartile range, IQR) and categoric variables as frequency (percentage). Comparisons were made using Mann-Whitney U, Kruskal-Wallis, Wilcoxon Signed-Rank and Friedman’s test with p<0.05 considered statistically significant. Logarithmic transformation of non-normally distributed variables was used where required. Univariable and multivariable analysis was performed with entry criteria into multivariate analysis p<0.05. Univariable analysis for continuous variables was performed as a linear regression analysis and for binary variables as logistic regression.RESULTSSome fifty-two patients undergoing TEVAR and 24 control patients were recruited (table 1). Clinical outcomesAll stent-grafts were deployed satisfactorily, with no retrograde type A dissection or open surgical conversion. No endoleak was identified on completion angiography. Median hospital stay was 8.5 days (interquartile range 4-14), and median follow-up duration 16 months (IQR 6-27). Morbidity and mortality outcomes are detailed in table 2. Four patients (all male, two elderly) developed clinical stroke (7.7%), all detected immediately post-operatively (table 3). Procedures performed included one arch hybrid, two TEVAR with carotid-LSCA bypass, and one proximal stent extension for type Ia endoleak following previous visceral hybrid repair of type II thoracoabdominal aortic aneurysm. Two patients made a complete recovery following a period of rehabilitation. No patient with stroke suffered in-patient or 30-day mortality. Intra-operative TCD-detected cerebral embolizationTCD monitoring was performed in 42 patients; bilateral insonation in 30 patients, with left only in six patients and right only in six patients due to inadequate bilateral acoustical temporal bone window. The MCA was insonated in all patients (median depth 50mm, range 46-58mm) except for four where no MCA signal was identified on the right and therefore the posterior cerebral artery was insonated instead. Cerebral embolization was detected during TEVAR in all 42 patients. A 53-year old male undergoing emergency TEVAR and left carotid-subclavian bypass for acute type B dissection was the only patient in whom spontaneous embolization was detected during pre-operative monitoring, where two emboli were detected at the left MCA. The median procedural embolization rate for all patients was 179 (IQR 71-262), and excluding contrast injection related embolization was 104 (IQR 35-192). Embolization resulting from contrast injection was included in all analyses. Stent-graft manipulation and deployment (median 62, IQR 22-163) followed by contrast injection (median 61, IQR 18-117) resulted in the highest rates of embolization (p=0.001) (figure 2). Embolization varied depending on patient and procedural factors (figure 3), and was detected more frequently at the left MCA (p=0.018), with higher aortic atheroma grades 4 and 5 (p=0.042), at more proximal landing zones 0 and 1 (p=0.001), and during arch hybrid procedures (p=0.001). No significant difference in embolization rates were seen between the pathologies treated. In the control group ten patients had TCD assessment. In eight EVARs TCD HITS were detected in five patients; median 1, IQR 0-1.5, range 0-2, with 6 and 16 HITS detected during two FEVARs.Cerebral DW-MRIThirty-one patients underwent pre- and post-operative cerebral MRI (table 3). Not all patients completed the pre- and post-operative MRI protocol for reasons including emergency presentation with unstable patient (n=6), significant post-operative morbidity or death (n=5), patients declining MRI due to claustrophobia (n=7) and contra-indication due to pacemaker (n=3). Post-operative scans were performed at median four days (IQR 2-6) following TEVAR. Twenty-five patients (81%) had evidence of brain injury: 21 (68%) had procedure-related silent infarction (figure 4) and four patients had clinical stroke (13%). All strokes were confirmed as embolic on MRI or CT. There was a trend towards higher rates of embolization in patients with silent infarcts compared to those with no post-operative lesions, with the highest rates of embolization in those with clinical stroke (figure 3b). In 21 patients with silent infarction, there was a total of 120 new lesions detected (median 2 per patient, IQR 1-9) with a total silent infarct surface area of 5459mm2 (median 16mm2, IQR 9-81.5). The majority of lesions were left-sided and in the posterior or border-zone circulation. In the control group seven patients (six EVAR and one FEVAR) underwent pre- and post-operative MRI, and no patient had new silent infarction or stroke.Risk factors for cerebral embolization and brain injury Risk factors identified as predictors of TCD-detected cerebral embolization are detailed in table 4. The development of brain injury, both silent and stroke (p=0.510), and MRI lesion surface area (p=0.917) were not shown to be associated with embolization rate. No factors were independent predictors of embolization on multivariable analysis. Similar results were seen with TCD HITS excluding contrast embolization, with the same factors associated with higher embolization rates. On univariable analysis, smoking (odds ratio 8.00, 95% confidence interval 1.13-56.80, p=0.038) was the only factor significantly associated with the development of brain injury (both silent and stroke) as determined by new MRI lesions. Neurocognitive outcomesNeurocognitive testing was performed in 17 patients (figure 5). Post-operative assessment testing was conducted at a median time of eight days (IQR 5-13) post-TEVAR. Not all patients completed neurocognitive testing due to a change in the test battery mid-way during the study (n=24), emergency presentation with unstable patient (n=6) and significant post-operative morbidity or death (n=5). In 15 patients with silent cerebral infarction, significant post-operative neurocognitive decline was seen in 6/7 domains assessed (all except Trails B test). Univariable analysis revealed age to be a significant predictor of decline in all seven domains, male sex in five domains and TCD HITS (p=0.009) with memory and recall (table 5, supplementary data). To assess the effect of silent cerebral infarction on neurocognition, patients were divided into three groups; two patients who did not develop silent infarcts, eight patients with silent infarcts aged<69 years, and seven patients with silent infarcts aged=/>70 years. The median age of patients undergoing neurocognitive testing was 69 years, and this was chosen as the cut-off value between the two age groups. Patients in the older age group showed significant post-operative decline in all areas of neurocognition except Trails B test. This deficit persisted at follow-up OPA for the COWA test (p=0.050) and Trails A (p=0.028), with median follow-up results remaining below median pre-operative levels for both components of the auditory verbal learning test. Patients in the younger age group showed measurable and significant decline affecting both the dominant (p=0.018) and non-dominant hand (p=0.039) in the manual dexterity pegboard test, with persistent decline present at follow-up affecting the dominant hand (p=0.028). In the control group seven patients (5 EVAR and 2 FEVAR) underwent neurocognitive testing at the three time-points. Neurocognitive decline was seen in only 1/7 domains tested; COWA (p=0.002). The decline was seen between pre- and post-operative testing (p=0.018) and between pre-operative and OPA testing (p=0.027). DISCUSSIONThese results demonstrate TCD-detected cerebral embolization in all patients during TEVAR, with an overall brain injury (both silent and stoke) rate of 81% in patients undergoing MRI. The overall stroke rate was 7.7%, as this cohort includes high-risk patients requiring more proximal landing zones, with several undergoing arch hybrids and LSCA revascularization. The silent infarction rate of 68% is comparable to the 63% rate detected by Kahlert and colleagues19. Greater aortic atheroma burden, LSCA bypass, more proximal landing zones 0 and 1, and arch hybrid repairs were shown to be predictors of increased embolization. This is likely due to the more proximal landing zones which is a documented risk factor for stroke following TEVAR, increased instrumentation of arch vessels and higher atheroma load and mobile lesions contributing to increased embolization. There were minimal HITS and no silent infarcts in patients undergoing EVAR and FEVAR, likely due to the PLZ in the abdominal aorta and limited instrumentation in the aortic arch in the control patients. There was a trend towards a higher number of TCD HITS in patients who developed stroke, followed by patients with silent infarcts, with the lowest HITS in those with no post-operative lesions. There was no association however between number of TCD HITS and silent cerebral infarction. This is contrary to the findings of Bismuth and colleagues who showed a significant association between total HITS and post-operative stroke9. In that study of 20 patients undergoing TCD during TEVAR, the highest number of HITS was generated by catheter manipulation during the diagnostic phase and device deployment during the treatment phase. HITS during contrast injection were not examined. This differs from the present findings, where contrast injection contributed the highest HITS during the diagnostic phase and stent-graft deployment the highest HITS during the treatment phase. In a study investigating cerebral embolization during cerebral angiography, 150 patients were randomized into three groups: control group with conventional angiography, heparin group with systemic heparinization throughout the procedure, and an air filter group with an air filter between the catheter and contrast syringe26. There were equal numbers of MRI lesions in the heparin and air filter groups, which were significantly fewer than in the control group (p=0.002). TCD HITS were significantly lower in the air filter group (p<0.01) compared to the heparin and control groups, which did not differ from each other. This demonstrated the role of air embolization related to contrast injection and catheter flushing in the development of silent cerebral infarcts, and highlights the importance of reducing both gaseous and solid embolization. The results presented are in keeping with this, and show a high number of TCD HITS generated during both contrast injection and flushing. In addition, analysis of risk factors for embolization revealed comparable results both including and excluding contrast injection, and therefore results should include and be interpreted with embolization during contrast injection. Routine clinical examination assesses for focal neurological abnormalities including paresis, ataxia, visual defects and aphasia. Global brain dysfunction such as cognitive decline, memory and mood disturbances, reduction of psychomotor speed and personality changes may be missed because they require specific neurocognitive tests for diagnosis15, 27. In 2,229 Framingham Offspring Study participants silent cerebral infarcts predicted an increased risk of stroke and dementia independent of vascular risk factors, and also indicated an increased risk of mild cognitive impairment and death12. People with silent infarcts have more than double the risk of dementia, and in particular Alzheimer’s disease, compared to the general population28. Post-operative cognitive dysfunction (POCD) after GA and surgery is a recognised phenomenon with multifactorial aetiology29. In patients undergoing open cardiac surgery cognitive decline was seen in all patients with post-operative DW-MRI ischemic lesions, and 35% without imaging-identified lesions (p<0.001)30. There was also an association between the number of abnormal cognitive tests and ischemic burden (p<0.001)30. This demonstrates cognitive impairment is associated with peri-operative ischemia and degree of ischemic load, and not simply a consequence of POCD. One TAVI study showed that age was independently associated with longitudinal cognitive decline31. The neurocognitive control group consisted of an elderly cohort with a decline in only 1/7 areas, whereas the similarly elderly TEVAR group had a decline in 6/7 domains. This highlights that while elderly patients may be affected by GA-related POCD, the significant decline seen in multiple domains post-TEVAR is most likely a consequence of cerebral ischemic burden. Few studies have investigated neurocognitive decline following endovascular procedures to date. Two studies investigating silent cerebral infarction following coronary catheterization found a significant decline in learning and attention and verbal and non-verbal memory associated with silent infarcts32, 33. In this study follow-up assessment was performed six to eight weeks post-operatively, with no longer-term testing undertaken. A later cognitive assessment may be clinically relevant, but cognitive dysfunction in the post-operative period may predict further decline over the next five years30, 34. Significant post-operative decline affecting older patients was observed in 6/7 domains assessed, while persistent decline at follow-up was demonstrated in three domains. Of concern, even younger patients had significant post-operative decline in manual dexterity, with persistent decline in the use of their dominant hand at follow-up. Silent cerebral infarction and cognitive decline has implications for patients and should inform the clinical decision-making and consent process for TEVAR. Cerebral embolization needs to be evaluated further with differentiation between gaseous and solid emboli, and the efficacy of pharmacological and interventional strategies to reduce neurological injury in TEVAR and other endovascular procedures should be determined. Recent randomised control trials such as CLEAN-TAVI and MISTRAL-C which used the SentinelTM cerebral protection system in TAVI have shown a significant decrease in number and volume of new silent infarcts, with improved neurological outcome35,36. Robotic navigation has been shown to reduce contact with the aortic arch wall during TAVI, and cause significantly less cerebral embolization compared to manual techniques during TEVAR due to the active manuvrability and stability of the robotic system37,38. A dynamic bubble trap designed to reduce gaseous emboli has been shown to reduce TCD HITS, and congnitive function three-months post-operatively was significantly better compared to controls in patients undergoing coronary artery bypass grafting39. It has also been demonstrated that thoracic endo-grafts release significant amounts of air during deployment if flushed according to the instructions for use, and carbon dioxide flushing prior to standard saline flushing significantly reduces the amount of gas released40. This may have a potential role to reduce air embolism during TEVAR, particularly in more proximal landing zones41. Aortic atheroma severity can be addressed with pre-operative statin usage which leads to plaque stabilization and atheroma regression, and smoking cessation is beneficial for plaque stabilisation42.LimitationsDue to pragmatic issues with conducting clinical research of this nature it was not feasible for all patients to undergo all three investigations of TCD, MRI and neurocognitive testing. Follow-up neurocognitive assessment was only performed at the first OPA to coincide with routine follow-up and thereby limit the number of clinic visits. ACKNOWLEDGEMENTSWe would like to thank all members of the vascular surgery and anaesthetic team at St Mary’s Hospital, in particular Mr Michael Jenkins, Ms Celia Riga, Professor Alun Davies and Dr Nathalie Courtois for their assistance in conducting this study. Special thanks to Neuroradiologists Dr Siok Lim for setting up the MRI study and Dr Abhinav Singh for performing the MRI analysis. 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CLEAN-TAVI: A prospective, randomized trial of cerebral embolic protection in high-risk patients with aortic stenosis undergoing transcatheter aortic valve replacement. Transcatheter Cardiovascular Therapeutics Annual Meeting 2014.36.Van Mieghem NM, van Gils L, Ahmad H, et al. Filter-based cerebral embolic protection with transcatheter aortic valve implantation: the randomised MISTRAL-C trial. EuroIntervention. 2016;12:499-507.37.Rippel RA, Rolls AE, Riga CV, et al. The use of robotic endovascular catheters in the facilitation of transcatheter aortic valve implantation. Eur J Cardiothorac Surg. 2014;45:836-41.38.Perera AH, Riga CV, Monzon L, et al. Robotic Arch Catheter Placement Reduces Cerebral Embolization During Thoracic Endovascular Aortic Repair (TEVAR). Eur J Vasc Endovasc Surg. 2017;53:362-9.39.Gerriets T, Schwarz N, Sammer G, et al. Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: A randomized controlled trial. Eur Heart J. 2010;31:360-8.40.Rohlffs F, Tsilimparis N, Saleptsis V, et al. Air Embolism During TEVAR: Carbon Dioxide Flushing Decreases the Amount of Gas Released from Thoracic Stent-Grafts During Deployment. J Endovasc Ther. 2017;24:84-8.41.Kolbel T, Rohlffs F, Wipper S, et al. Carbon Dioxide Flushing Technique to Prevent Cerebral Arterial Air Embolism and Stroke During TEVAR. J Endovasc Ther. 2016;23:393-5.42.Yla-Herttuala S, Bentzon JF, Daemen M, et al. Stabilization of atherosclerotic plaques: an update. Eur Heart J. 2013;34:3251-8.LEGENDS FOR ILLUSTRATIONSFigure 1. Intra-operative transcranial Doppler at the left and right middle cerebral artery (MCA) in a 74-year-old male patient undergoing TEVAR and left carotid-subclavian bypass for repair of thoracic aortic aneurysm. Proximal landing zone at zone 1 using custom-made stent-graft with proximal scallop for the left common carotid origin.No spontaneous embolization detected during pre-operative monitoring3 HITS at left MCA and 8 HITS at right MCA (red arrows) during wire/catheter exchange47555155842000480060058420004641215584200042983155842000441261558420004457700584200038862005842000468630058420001714500584200091440058420008001005842000Multiple HITS bilaterally during stent-graft deployment Figure 2. Rate of embolization with each procedural phase of TEVARn=41 (1 patient excluded from graph as outlier for scaling purposes but not excluded from statistical analysis)Wire and catheter manipulation: median 20 (IQR 10-41)Stent related (manipulation and deployment): median 62 (IQR 22-163)Contrast injection total: median 61 (IQR 18-117)p=0.001Figure 3. Embolization rates with patient and procedural factorsAtheroma graden=41(1 patient excluded from graph as outlier for scaling purposes but not excluded from statistical analysis)Grade 1-3: median 100 (IQR 52-211)Grade 4 &5: median 207 (124-450)p=0.042MRI outcomen=42NAD- no lesions detected on MRI: median 97 (IQR 29-236)SCI- silent cerebral infarction on MRI: median 195 (IQR 138-280)Stroke- Stoke clinically, confirmed on MRI: median 299 (IQR 146-908)p=0.498Figure 4. Pre- and post-operative cerebral DW-MRI of 68-year old male patient undergoing arch hybrid for repair of thoracic aortic aneurysm. Multiple new silent cerebral infarcts are seen post-operatively (red arrows).Pre-operative DW-MRIPost-operative DW-MRI 9313342476500Figure 5. Neurocognitive outcomes Results of controlled oral word association test; executive cognitive dysfunctionSCI age </=69 years group: p=0.779SCI age >70 years group: p=0.009Pre-operative to post-operative p=0.027Pre-operative to OPA p=0.050Results of trails A; visual search and motor skillsThe higher the score, the longer the time taken to complete taskSCI age </=69 years group: p=0.050SCI age >70 years group: p=0.115Pre-operative to post-operative p=0.116Pre-operative to OPA p=0.028c. Results of pegboard test dominant (right) handThe higher the score, the longer the time taken to complete taskSCI age </=69 years group: p=0.018Pre-operative to post-operative p=0.046Pre-operative op to OPA p=0.028SCI age >70 years group: p=0.011Pre-operative op to post-operative p=0.028Pre-operative to OPA p=0.310Table 1. Patient demographics and procedural characteristicsVariables TEVAR group (n=52)Control group (n=24)Age, yearsMale sexAetiologyAtherosclerotic aneurysmDissection (Connective tissue disease) Anastomotic pseudoaneurysm following open aortic coarctation repair Penetrating aortic ulcer Mycotic aneurysm Pseudoaneruysm following aortic transection PathologyAneurysm Crawford type I Crawford type II Crawford type III Aortic arch aneurysm Descending thoracic aortic aneurysm Saccular aneurysm Abdominal aortic aneurysm Endoleak following previous TEVARChronic type B dissection + aneurysmal dilatationPenetrating aortic ulcer + aneurysmAcute aortic syndrome (type B dissection/IMH)Aneurysm size, cmAtheroscleroticSaccularPost-dissection Patient co-morbiditiesHypertension Hypercholesterolemia Diabetes mellitusSmoking history IHDRespiratory diseaseCancerPrevious cardiovascular surgery Chronic kidney diseaseMedicationSingle antiplatelet WarfarinStatinSignificant (>50%) carotid stenosis on duplexProceduresTEVAR with no adjunct procedures TEVAR with L carotid-subclavian bypass TEVAR with LSCA coverage Arch HybridVisceral HybridTEVAR with visceral vessel fenestrations Arch branched graftInfra-renal EVARFEVAR with visceral vessel fenestrationsUrgency ElectiveStent-graftsGore cTagValiant MedtronicCustom-made Bolton Relay proximal scallopCustom-made Bolton Relay arch branched graft Custom-made Cook with visceral fenestrations Medtronic Endurant IIGore ExcluderProximal landing zoneZone 0Zone 1Zone 2Zone 3Zone 4Abdominal aortaLength of stay, days66 (53.5-77)32 (62%)22112872246 (88%)1731111706466 (12%)6.7 (6.0-8.1) 4.8 (3.5-5.4) 7.3 (6.5-10.3)34 (65%)27 (52%)4 (8%)34 (65%)7 (14%)15 (29%)8 (15%)28 (54%)7 (13%)15 (29%)3 (6%)27 (52%)020 (38%) 14 (27%)4 (8%)5 (10%)5 (10%)3 (6%)1 (2%)0034 (65%)23 (44%)11 (21%) 11 (21%)1 (2%)6 (12%)003 (6%)4 (8%)25 (48%)14 (27%)6 (12%)08 (4-14)79 (73-81)22 (92%)2400000024 (100%)0000002400005.9 (5.7-6.1)N/AN/A17 (71%)13 (54%)2 (8%)15 (63%)10 (42%)3 (13%)05 (21%)3 (13%)10 (42%)2 (8%)13 (54%)N/A000000019 (79%)5 (21%)24 (100%)00005 (21%)15 (62%)4 (17%)0000024 (100%)4 (3-6)Continuous data are shown as median (interquartile range) and categorical data are shown as number (percentage)Table 2. Morbidity and mortality outcomes Re-interventionOpen repair of femoral pseudoaneurysm (following failure of percutaneous closure device)Late type Ib endoleakType III endoleakExtension of penetrating aortic ulcer requiring distal stent extensionIliac artery rupture 1 (2%)3 (6%)2 (4%)1 (2%)1 (2%)MorbidityDural leak with spinal drain (resolved spontaneously)Brachial plexus neuropraxia following carotid-subclavian bypass (resolved with physiotherapyParaplegia following visceral hybrid repairClinical stroke 1 (2%)1 (2%)2 (4%)4 (7.7%)30-day mortalityMyocardial infarction and cardiac arrest following arch hybrid sepsis secondary to bowel ischemia and cardiac arrest following visceral hybrid1 (2%)1 (2%)Table 3. MRI outcomesPatient numberMRI outcomeClinical outcomeNumber of lesionsLaterality of lesionsCerebral circulation1-6NilNil0N/AN/A7StrokeMRS 5MultipleBilateralPosterior8StrokeMRS 2 (Expressive dysphasia, resolved completely with rehab)Large single lesionLeftAnterior9StrokeMRS 5MultipleBilateralAnterior and posterior10StrokeMRS 2 (Right hand weakness. resolved completely with rehab)MultipleLeftAnterior and border-zone11DGSCINil1LeftAnterior12DMSCINil2BilateralAnterior and border-zone13ACSCINil2BilateralPosterior and border-zone14OMSCINil1LeftPosterior15SBSCINil2BilateralBorder-zone16QASCINil4BilateralAnterior and posterior17JPSCINil1LeftPosterior18AHSCINil1LeftPosterior19RLSCINil20BilateralAnterior, posterior and border-zone20DLSCINil14BilateralPosterior and border-zone21MBSCINil15BilateralPosterior and border-zone22RRSCINil25BilateralAnterior, posterior and border-zone23RBSCINil1LeftBorder-zone24SPSCINil3BilateralAnterior and posterior25BLSCINil1LeftBorder-zone26GDSCINil13BilateralPosterior27WESCINil5LeftAnterior28MCSCINil1LeftAnterior29MESCINil3BilateralPosterior30SCINil2LeftAnterior and border-zone31SCINil1LeftBorder-zoneN/A Non-applicableMRS Modified Rankin Scale 0-61 No significant disability (able to carry out all usual activities)2 Slight disability (unable to carry out all previous activity but able to look after own affairs without assistance)3 Moderate disability (requiring some help but able to walk without assistance)4 Moderately severe disability (unable to walk or attend to bodily needs without assistance)5 Severe disability (bedridden, incontinent, requiring constant care and attention)6 DeadTable 4. Predictors of TCD-detected cerebral emboliRisk factor? CoefficientStandard errorp value LSCA revascularisation (bypass and scallop graft)0.336130.280.030LSCA bypass0.423132.620.005Proximal landing zone0.45189.100.003PLZ 0 and 10.504170.570.001Procedure0.35661.380.021Arch hybrid0.514182.960.000 ADDIN EN.REFLIST ................
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