We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroe...
We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures. Brain circulation. 2019 Jan;5(1):36.
Our paper details our technique, the pros of anatomic orientation of the hand for both the patient and surgeon, as well as the theoretical safety of the distal radial approach with regards to ischemia. We detail how our access is performed with ultrasound, and depict 4 illustrative case examples with imaging including aneurysm stent coiling, head and neck embolization, posterior fossa parent vessel sacrifice, and carotid stenting via a sheathless approach. We had switched over our entire practice for surgeon (AL) to distal radial access in November of 2018. Since that time all diagnostic angiograms and most interventions were performed via distal radial access including ischemic strokes. We have a distal radial manuscript currently accepted to Brain Circulation detailing our use of a Balloon guide catheter for ischemic stroke, which we admit still has its limitations with the available current guides due to outside diameter (OD) and stiffness. However with newest Balloon guides recently approved by the FDA, such as those made by Q’Apel, Medical boasting an 087 ID with a flexible design may provide for sheathless radial use. A 7F 072 balloon guide is also advertised by the Q’Apel. Kuhn et al explains distal radial access can provide enough support for flow divertor deployment intracranially, we echo this finding, as we have also treated aneurysms and carotid cavernous fistulas via a distal radial approach with flow divertors in tandem or stacked fashion.
We again applaud the authors on their work, and are excited to see the field moving toward more distal radial access during the current radial revolution in the neuro endovascular world. We agree with the authors this technique is a safe and effective way to perform a variety of endovascular procedures and should be in every surgeons armamentarium.
Haussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an import...
Haussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an important one to keep in mind for any neurovascular center with a busy stroke practice. In addition to distal occlusions, it can also be used as a salvage technique for large proximal occlusions that would be otherwise inaccessible to large bore aspiration catheters.
We thank the respondents for providing their case experience and allowing further discussion of this important topic. We would first like to draw attention to specific points in the described case, before discussing some of the more general issues raised.
The respondents report one of many scenarios in which it may be undesirable to use dual antiplatelet therapy in the elective treatment of intracranial aneurysms with flow diverters. In this case, a 47-year-old woman with an 11 mm left ophthalmic aneurysm harbours a significant aspirin allergy. A single Pipeline Shield device under cover of ticagrelor was used to treat the aneurysm. The patient was well at discharge on postoperative day three but then developed symptomatic stent thrombosis on day 6. We draw attention to three points:
1) The respondents state that the stent achieved “perfect wall apposition improved with intra-stent balloon angioplasty.” Setting aside the impossibility of improving “perfect wall apposition” with angioplasty, this does allude to the increasingly understood importance of flow diverter wall apposition. [1] However, digital subtraction angiography assess stent apposition poorly. [1] The use of angioplasty suggests that there may have been some initial concern. Moreover, angioplasty itself may contribute to thrombosis if it promotes activation of the extrinsic clotting pathway by disrupting the endothelial layer. The phosphocholine “Shield” layer reduces thrombosis and platelet...
We thank the respondents for providing their case experience and allowing further discussion of this important topic. We would first like to draw attention to specific points in the described case, before discussing some of the more general issues raised.
The respondents report one of many scenarios in which it may be undesirable to use dual antiplatelet therapy in the elective treatment of intracranial aneurysms with flow diverters. In this case, a 47-year-old woman with an 11 mm left ophthalmic aneurysm harbours a significant aspirin allergy. A single Pipeline Shield device under cover of ticagrelor was used to treat the aneurysm. The patient was well at discharge on postoperative day three but then developed symptomatic stent thrombosis on day 6. We draw attention to three points:
1) The respondents state that the stent achieved “perfect wall apposition improved with intra-stent balloon angioplasty.” Setting aside the impossibility of improving “perfect wall apposition” with angioplasty, this does allude to the increasingly understood importance of flow diverter wall apposition. [1] However, digital subtraction angiography assess stent apposition poorly. [1] The use of angioplasty suggests that there may have been some initial concern. Moreover, angioplasty itself may contribute to thrombosis if it promotes activation of the extrinsic clotting pathway by disrupting the endothelial layer. The phosphocholine “Shield” layer reduces thrombosis and platelet aggregation via retarding activation of clotting factor XII at the stent surface(intrinsic pathway). It will exert no effect on the extrinsic pathway should it be activated.
2) The respondents do not mention if platelet response to ticagrelor was tested. This is not a criticism, as it is common to use new generation P2Y12 antagonists without testing their efficacy. However, it is also essential to understand ticagrelor resistance is reported in up to 3% of the population. [2] More recently we have experienced stent occlusions using the aspirin only technique in patients who were subsequently found to be aspirin non-responders. Given the loss of redundancy inherent in a single antiplatelet therapy (SAPT) technique, anti-platelet response testing should be reconsidered.
3) The timing of the symptomatic stent occlusion is noteworthy as it occurred three days post-discharge from hospital. This is somewhat unusual, as typically SAPT stent occlusions occur more acutely. Ticagerol’s shorter half-life means its effect will be subtherapeutic if discontinued for three days. Therefore, given the suspicious timing of the patient's stent occlusion, issues with patient compliance should be considered.
The use of the Pipeline Shield with aspirin only is a technique reserved for extreme circumstances. In aneurysmal SAH patients who cannot be treated successfully without the use of a stent and in whom antiplatelet therapy is undesirable or contraindicated, this technique may be appropriate. This has been stated in the original manuscript and is apparent in the description of the aneurysms treated. Our study reported an asymptomatic thromboembolic complication rate of 14.3% and a symptomatic rate of 7.1%. [3] Given the complex and extremely challenging nature of these cases, a symptomatic thromboembolic complication rate of 7.1% may be acceptable. The respondents point out that the combined rate is 21.4%. Any complications are too many, however, bear in mind that the thromboembolic complication rate in CLARITY was 12.5%. [4] Given the latter patient population underwent routine aneurysm coiling and the former represents patients without conventional treatment options this difference seems acceptable. Moreover, the symptomatic thromboembolic complication rate in the SAPT study is not very different from that reported in either ASPIRe or IntrePED. [5,6]
We believe that the addition of the phosphocholine "Shield" surface modification may allow greater flexibility in the use of antiplatelet therapy. It is increasingly clear that antiplatelet therapy is central to complications with flow diverting stents. Recent meta-analysis demonstrates that a hypo-response to DAPT increases the risk of thromboembolic complications and that a hyper-response increases the risk of haemorrhagic complications. [7] In the setting of acute aneurysm rupture, antiplatelet therapy is even more critical. The use of DAPT in such patients has been shown to increase the risks of haemorrhagic complications dramatically. [8] Therefore, any technology that may reduce our reliance on antiplatelet therapy should be fully explored.
The use of SAPT in complex ruptured aneurysms has nuanced advantages that may not be apparent to all readers. Many operators choose to delay treatment of ruptured aneurysms requiring a flow diverter to avoid dual antiplatelet therapy (DAPT) acutely. The mean time from subarachnoid haemorrhage (SAH) to aneurysm treatment in our study was one day. In comparison to 7 days in the meta-analysis reported by Cagnazzo et al. [9] This is particularly important to bear in mind when comparing retrospective studies as patients who re-ruptured before treatment will be excluded from analysis, however, undoubtedly represent treatment failure. This point is highlighted in a recent report by ten Brick and colleagues. [10] In this study, 44 patients with aneurysmal subarachnoid haemorrhage were treated with flow diverting stents on DAPT in five European centres. A range of flow diverters were used. However, none had the "Shield" surface modification. Aneurysm and patients characteristics were similar to the SAPT series we reported. Aneurysms were treated acutely (mean of three days post-SAH), although not as early as in the SAPT study. [3] Procedure-related complications occurred in 44%. Permanent neurological deficit due to procedure-related complications occurred in 27%. Perhaps of most interest to this discussion, post-procedure intracranial bleeding occurred in 22.7% including five aneurysm re-bleeds, two intraparenchymal haemorrhages not related to ventriculostomy, two ventricular shunt-related haemorrhages and one extra-axial haemorrhage. With extracranial haemorrhagic complications reported in another 9.1%. [10] In the SAPT series, two aneurysm re-bleeds occurred with one patient making a full recovery. The other patient, who was already a poor WFNS grade SAH never regained consciousness from the initial ictus. Both patients were being treated with postoperative heparin infusion at the time of aneurysm re-rupture, a practice which was subsequently abandoned as described in the original manuscript. In spite of similar patient and aneurysm characteristics, the DAPT case series reported good clinical outcomes in 45.5% compared to 64.3% in the SAPT series. Procedure-related mortality occurred in 11.4% and 7.1% of the DAPT and SAPT series, respectively.
Finally, it is essential to clarify the use of the term single antiplatelet therapy (SAPT). We are forced to take considerable responsibility for any misuse of this term. One should not consider the use of only one agent as the goal of this work. Instead, the goal is to offer patients with complex ruptured aneurysms, treatment using flow diverting (or other) stents with as little suppression of platelet function as is possible to avoid thromboembolic complications. The term "single antiplatelet therapy" has begun to appear in the literature, regarding the use of agents such as ticagrelor and prasugrel. Such terminology is literally correct; however, it misses the real goal of this work. As compared to P2Y12 antagonists, aspirin has a much less pronounced effect on platelet function and naturally, less haemorrhagic complication risk. [11] In most patients, agents such as ticagrelor and prasugrel likely suppress platelet function to such a degree that they make the addition of aspirin mostly redundant. [12,13]
We agree that further investigation of this technique is required, as stated in the original article. However, we think a randomised control trial would be inappropriate at this stage. It is somewhat facile to call for a randomised control trial to solve all medical dilemmas. It is safe to say that no treatment option is established for patients harbouring such complex ruptured aneurysms and therefore deciding on a control group would be somewhat arbitrary.
Furthermore, it is likely to be challenging to detect a significant difference in clinical outcomes given the uncertain prognosis of such patients independent of how their aneurysms are secured. Therefore, the number of patients that would need to be randomised likely exceeds 1000. We have elected to take a different approach and will study the Pipeline Shield SAPT technique in a multicentre, single-arm, prospective study. We hope that the first patients will be enrolled before this letter is published. The study will begin in Australia; however, it is planned to expand to other countries, and we encourage experienced and skilled centres such as yours to be a part of this investigation.
Thank you once again for an engaging discussion. Warm regards,
Nathan Manning
References:
1 Rouchaud A, Ramana C, Brinjikji W, et al. Wall Apposition Is a Key Factor for Aneurysm Occlusion after Flow Diversion: A Histologic Evaluation in 41 Rabbits. Am J Neuroradiol 2016;37:2087–91. doi:10.3174/ajnr.a4848
2 Warlo EM, Arnesen H, Seljeflot I. A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease. Thrombosis J 2019;17:11. doi:10.1186/s12959-019-0197-5
3 Manning NW, Cheung A, Phillips TJ, et al. Pipeline shield with single antiplatelet therapy in aneurysmal subarachnoid haemorrhage: multicentre experience. Journal of neurointerventional surgery 2019;11:694–8. doi:10.1136/neurintsurg-2018-014363
4 Pierot L, Cognard C, Anxionnat R, et al. Ruptured intracranial aneurysms: factors affecting the rate and outcome of endovascular treatment complications in a series of 782 patients (CLARITY study). Radiology 2010;256:916–23. doi:10.1148/radiol.10092209
5 Kallmes DF, Brinjikji W, Boccardi E, et al. Aneurysm Study of Pipeline in an Observational Registry (ASPIRe). Interventional Neurology 2016;5:89–99. doi:10.1159/000446503
6 Kallmes D, Hanel R, Lopes D, et al. International retrospective study of the pipeline embolization device: a multicenter aneurysm treatment study. American Journal of Neuroradiology 2015;36:108–15. doi:10.3174/ajnr.a4111
7 Ajadi E, Kabir S, Cook A, et al. Predictive value of platelet reactivity unit (PRU) value for thrombotic and hemorrhagic events during flow diversion procedures: a meta-analysis. J Neurointerv Surg 2019;11:1123. doi:10.1136/neurintsurg-2019-014765
8 Hudson JS, Prout BS, Nagahama Y, et al. External Ventricular Drain and Hemorrhage in Aneurysmal Subarachnoid Hemorrhage Patients on Dual Antiplatelet Therapy: A Retrospective Cohort Study. Neurosurgery Published Online First: 2018. doi:10.1093/neuros/nyy127
9 Cagnazzo F, di Carlo D, Cappucci M, et al. Acutely Ruptured Intracranial Aneurysms Treated with Flow-Diverter Stents: A Systematic Review and Meta-Analysis. American Journal of Neuroradiology 2018;39:1669–75. doi:10.3174/ajnr.a5730
10 ten Brinck MF, Jäger M, de Vries J, et al. Flow diversion treatment for acutely ruptured aneurysms. J Neurointerv Surg 2019;:neurintsurg-2019-015077. doi:10.1136/neurintsurg-2019-015077
11 Gresele P. Antiplatelet agents in clinical practice and their haemorrhagic risk. Blood Transfus Trasfusione Del Sangue 2013;11:349–56. doi:10.2450/2013.0248-12
12 KIRKBY N, LEADER P, CHAN M, et al. Antiplatelet effects of aspirin vary with level of P2Y12 receptor blockade supplied by either ticagrelor or prasugrel. J Thromb Haemost 2011;9:2103–5. doi:10.1111/j.1538-7836.2011.04453.x
13 Warner TD, Nylander S, Whatling C. Anti‐platelet therapy: cyclo‐oxygenase inhibition and the use of aspirin with particular regard to dual anti‐platelet therapy. Brit J Clin Pharmaco 2011;72:619–33. doi:10.1111/j.1365-2125.2011.03943.x
We read with interest the case series by Manning’s et al.[1] using a surface modified flow-diverter stent (Pipeline Flex with Shield Technology, Medtronic Neurovascular, Irvine, California, USA). In this retrospective series, 14 ruptured intracranial aneurysms have been treated in the acute phase after Sub-Arachnoid Hemorrhage (SAH) with the Pipeline shield device under a Single Anti-Platelet Therapy (SAPT). The article concluded the PED-Shield to be safe to use in the acute treatment of ruptured intracranial aneurysms with SAPT.
However, in this small series, the authors reported one case of total stent occlusion and two cases of platelet aggregation noted on the PED-Shield device requiring to switch from single to dual antiplatelet treatment. Considering those three patients, thrombotic complications have been observed in 21.4 % of cases (3/14) in the acute period. Furthermore, in two cases (14.3 %), the authors reported rebleeding of the culprit aneurysm leading to patient death, pointing out the fact that flow-diverter devices may not immediately prevent the risk of aneurysm rerupture.
Anti-thrombogenic coating might have an added value in case of very specific aneurysms cases requiring the placement of a stent in the acute phase after rupture. Those specific cases are mainly dissecting or blister aneurysms for which endovascular or even surgical approach are difficult and carry a high risk of morbi-mortality[2][3]. In case of endovascular treatment, rece...
We read with interest the case series by Manning’s et al.[1] using a surface modified flow-diverter stent (Pipeline Flex with Shield Technology, Medtronic Neurovascular, Irvine, California, USA). In this retrospective series, 14 ruptured intracranial aneurysms have been treated in the acute phase after Sub-Arachnoid Hemorrhage (SAH) with the Pipeline shield device under a Single Anti-Platelet Therapy (SAPT). The article concluded the PED-Shield to be safe to use in the acute treatment of ruptured intracranial aneurysms with SAPT.
However, in this small series, the authors reported one case of total stent occlusion and two cases of platelet aggregation noted on the PED-Shield device requiring to switch from single to dual antiplatelet treatment. Considering those three patients, thrombotic complications have been observed in 21.4 % of cases (3/14) in the acute period. Furthermore, in two cases (14.3 %), the authors reported rebleeding of the culprit aneurysm leading to patient death, pointing out the fact that flow-diverter devices may not immediately prevent the risk of aneurysm rerupture.
Anti-thrombogenic coating might have an added value in case of very specific aneurysms cases requiring the placement of a stent in the acute phase after rupture. Those specific cases are mainly dissecting or blister aneurysms for which endovascular or even surgical approach are difficult and carry a high risk of morbi-mortality[2][3]. In case of endovascular treatment, recent meta-analyses have demonstrated the superiority of reconstructive techniques with flow diverter against deconstructive techniques despite the need for dual antiplatelet treatment with standard flow-diverter[4]. However, those specific aneurysms represent a tiny minority of the endovascularly treated aneurysms. They account for only 0.3% to 1% of intracranial aneurysms and 0.9% to 6.5% of ruptured aneurysms[5–7]. Most of others ruptured aneurysms are suitable for surgical or endovascular treatments without any need for use of a stent in the acute phase. Also, in case of implantation of stent for unruptured aneurysms, the need for dual antiplatelet treatment does not carry a high ischemic risk[8] and new antiplatelet treatments such as ticagrelor or prasugrel [9–14] recently helped to reduce the occurrence of this complication.
Beyond the potential indication of using PED shield with SAPT for ruptured aneurysms, we assume that PED-shield might be used with a SAPT in the setting of unruptured aneurysms. We recently followed this strategy in the setting of a 47-year-old woman allergic to aspirin with a medical history of severe angioedema and harboring an unruptured 11 mm left ophthalmic aneurysm. This patient had been premedicated with ticagrelor (Brilique 90 mg twice a day) and a PED-shield had been implanted without any trouble with perfect wall apposition improved with intra-stent balloon angioplasty. As routinely performed in our center, an MRI has been performed 24 hours after the treatment showing a normal patency of the flow-diverter without any ischemic complication on the DWI sequence. The patient has been discharged home on day 3 but suffered on day 6 of transient right arm palsy and right eye ptosis. An MRI has been performed in emergency depicting minimal ischemic lesions in the right MCA territory with an acute thrombosis of the stent. This patient improved with no deficit thanks to efficient supply from the Willis polygon. However, this observation illustrates the risk of using SAPT in the setting of intracranial stent implantation for the treatment of aneurysms even with the PED-shield device which has been presumed to carry low thrombogenicity.
In light of this observation, we would recommend further randomized clinical trial in order to assess the security of using SAPT treatment with the PED-Shield flow-diverter device.
REFERENCES
1 Manning NW, Cheung A, Phillips TJ, et al. Pipeline shield with single antiplatelet therapy in aneurysmal subarachnoid haemorrhage: multicentre experience. Journal of NeuroInterventional Surgery 2019;11:694–8. doi:10.1136/neurintsurg-2018-014363
2 Gonzalez AM, Narata AP, Yilmaz H, et al. Blood blister-like aneurysms: Single center experience and systematic literature review. European Journal of Radiology 2014;83:197–205. doi:10.1016/j.ejrad.2013.09.017
3 Kaschner MG, Kraus B, Petridis A, et al. Endovascular treatment of intracranial ‘blister’ and dissecting aneurysms. The Neuroradiology Journal 2019;32:353–65. doi:10.1177/1971400919861406
4 Rouchaud A, Brinjikji W, Cloft HJ, et al. Endovascular Treatment of Ruptured Blister-Like Aneurysms: A Systematic Review and Meta-Analysis with Focus on Deconstructive versus Reconstructive and Flow-Diverter Treatments. American Journal of Neuroradiology 2015;36:2331–9. doi:10.3174/ajnr.A4438
5 Nakagawa F, Kobayashi S, Takemae T, et al. Aneurysms protruding from the dorsal wall of the internal carotid artery. Journal of Neurosurgery 1986;65:303–8. doi:10.3171/jns.1986.65.3.0303
6 McLaughlin N, Laroche M, Bojanowski MW. Blister-like aneurysms of the internal carotid artery – management considerations. Neurochirurgie 2012;58:170–7. doi:10.1016/j.neuchi.2012.02.025
7 Abe M, Tabuchi K, Yokoyama H, et al. Blood blisterlike aneurysms of the internal carotid artery. Journal of Neurosurgery 1998;89:419–24. doi:10.3171/jns.1998.89.3.0419
8 Pikis S, Mantziaris G, Mamalis V, et al. Diffusion weighted image documented cerebral ischemia in the postprocedural period following pipeline embolization device with shield technology treatment of unruptured intracranial aneurysms: a prospective, single center study. Journal of NeuroInterventional Surgery 2019;:neurintsurg-2019-015363. doi:10.1136/neurintsurg-2019-015363
9 Atallah E, Saad H, Bekelis K, et al. The use of alternatives to clopidogrel in flow-diversion treatment with the Pipeline embolization device. Journal of Neurosurgery 2018;129:1130–5. doi:10.3171/2017.5.JNS162663
10 Moore JM, Adeeb N, Shallwani H, et al. A Multicenter Cohort Comparison Study of the Safety, Efficacy, and Cost of Ticagrelor Compared to Clopidogrel in Aneurysm Flow Diverter Procedures. Neurosurgery Published Online First: 5 May 2017. doi:10.1093/neuros/nyx079
11 Choi HH, Lee JJ, Cho YD, et al. Antiplatelet Premedication for Stent-Assisted Coil Embolization of Intracranial Aneurysms: Low-Dose Prasugrel vs Clopidogrel. Neurosurgery 2018;83:981–8. doi:10.1093/neuros/nyx591
12 Soize S, Foussier C, Manceau P-F, et al. Comparison of two preventive dual antiplatelet regimens for unruptured intracranial aneurysm embolization with flow diverter/disrupter: A matched-cohort study comparing clopidogrel with ticagrelor. Journal of Neuroradiology Published Online First: February 2019. doi:10.1016/j.neurad.2019.01.094
13 Barra ME, Berger K, Tesoro EP, et al. Periprocedural Neuroendovascular Antiplatelet Strategies for Thrombosis Prevention in Clopidogrel‐Hyporesponsive Patients. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 2019;39:317–34. doi:10.1002/phar.2228
14 Dmytriw AA, Phan K, Salem MM, et al. The Pipeline Embolization Device: Changes in Practice and Reduction of Complications in the Treatment of Anterior Circulation Aneurysms in a Multicenter Cohort. Neurosurgery Published Online First: 12 March 2019. doi:10.1093/neuros/nyz059
Proprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific...
Proprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific Nature of Polymer Coating Emboli: An Optimal Approach For Future Investigations Related to Polymer Embolism. Journal of Neurointerventional Surgery.
2. U.S. Food and Drug Administration Lubricious Coating Separation From Intravascular Medical Devices FDA Safety Communication. Silver Spring MD: FDA; 2015. Available at: https://wayback.archive-it.org/7993/20161022044037/http://www.fda.gov/Me.... Accessed September 11, 2019.
3. Mehta RI, Rai AT, Vos JA, et al. Intrathrombus polymer coating deposition: a pilot study of 91 patients undergoing endovascular therapy for acute large vessel stroke. Part I: Histologic frequency. Journal of NeuroInterventional Surgery Published Online First: 18 May 2019. doi: 10.1136/neurintsurg-2018-014684
4. Mehta RI , Mehta RI. Hydrophilic polymer embolism: implications for manufacturing, regulation, and postmarketsurveillance of coated intravascular medical devices. J Patient Saf 2018 [Epub ahead of print 19 Mar 2019].doi:10.1097/PTS.0000000000000473
5. Mehta RI , Mehta RI , Solis OE , et al. Hydrophilic polymer emboli: an under-recognized iatrogenic cause of ischemia and infarct. Mod Pathol 2010;23:921–30.doi:10.1038/modpathol.2010.74
6. Mehta RI , Mehta RI. Hydrophilic polymer embolism: an update for physicians. Am J Med 2017;130:e287–90.doi:10.1016/j.amjmed.2017.01.032
Sincerely,
Rashi I. Mehta, MD
West Virginia University
Department of Neuroradiology
Ansaar T. Rai, MD
West Virginia University
Department of Neuroradiology
James W. Simpkins, PhD
West Virginia University
Department of Physiology and Pharmacology
Center for Basic and Translational Stroke Research
Rockefeller Neuroscience Institute
Rupal I. Mehta, MD
University of Rochester
Center for Translational Neuromedicine
Acknowledgments: RIM (Rashi I Mehta) is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health (5U54GM104942-03). RIM (Rupal I Mehta) is supported by a grant from the National Institute of Neurological Disorders and Stroke (K08NS089830).
Competing interests: ATR serves as a consultant for Stryker Corporation.
An increasing number of reports highlight polymer coating embolism as an iatrogenic complication of intravascular medical devices [1-3]. Autopsies, histologic evaluations of thrombectomy specimens, samples of captured debris, resected or biopsied tissues, are available methods used to study polymer emboli post investigative catherizations or interventional procedures. Reported data highlight the prevalence of this phenomenon and/or its clinicopathologic impacts, however, fall short of identifying higher-risk polymer emboli interventional devices. Consequently, an optimal approach for future investigations related to polymer coating embolism is required.
Mehta et. al investigate the histologic frequency of polymer emboli among patients who underwent endovascular thrombectomy for treatment of acute ischemic stroke due to large vessel occlusion by retrospectively evaluating thrombectomy specimens [2]. In this study, the reported frequency of polymer emboli includes the use of various devices and techniques among selected cases. However, literature highlights polymer coating embolism is device specific and dependent on coating integrity measured by particulates released [4]. Thus, the use of alternate devices with higher or lower particulate release for a given procedure may result in a large variation in incidence rates from reported results. Also, as mentioned by the authors, subsequent statistical correlations unless appropriately powered provide limited informatio...
An increasing number of reports highlight polymer coating embolism as an iatrogenic complication of intravascular medical devices [1-3]. Autopsies, histologic evaluations of thrombectomy specimens, samples of captured debris, resected or biopsied tissues, are available methods used to study polymer emboli post investigative catherizations or interventional procedures. Reported data highlight the prevalence of this phenomenon and/or its clinicopathologic impacts, however, fall short of identifying higher-risk polymer emboli interventional devices. Consequently, an optimal approach for future investigations related to polymer coating embolism is required.
Mehta et. al investigate the histologic frequency of polymer emboli among patients who underwent endovascular thrombectomy for treatment of acute ischemic stroke due to large vessel occlusion by retrospectively evaluating thrombectomy specimens [2]. In this study, the reported frequency of polymer emboli includes the use of various devices and techniques among selected cases. However, literature highlights polymer coating embolism is device specific and dependent on coating integrity measured by particulates released [4]. Thus, the use of alternate devices with higher or lower particulate release for a given procedure may result in a large variation in incidence rates from reported results. Also, as mentioned by the authors, subsequent statistical correlations unless appropriately powered provide limited information on higher-risk or culprit devices. Consequently, in addition to providing limited value, use of histologic evaluations of thrombi (or autopsies) to exclusively evaluate incidence rates may be time-consuming and have a high resource burden. Notably, this may not be the intent of the authors of this study who elude to an article series.
Few studies related to polymer coating embolism have included controls over procedures and specific devices used. For example, histologic evaluations of captured debris within cerebral protection devices during a mitral valve repair procedure highlighted polymer coating type material in 12 of 14 cases [5]. The source of polymer emboli was speculated to be from the mitral valve repair catheter and/or adjunct devices. In another study, intracranial polymer emboli incidence rates were determined for a branded hydrophilic coated guide sheath used for carotid and iliac stenting procedures respectively in Yucatan miniswine [6]. Since the experimental stents and stent delivery systems lacked any coating, impacts of polymer emboli were isolated to the coated guide sheaths, guide catheters and guidewires used during the procedures. These studies with controls over procedures and devices may be leveraged to understand an incidence rate from a specific set of interventional devices repetitively used during a given procedure. Notably however, even this approach is unable to provide device specific information or identify higher-risk interventional devices as the origin of emboli are difficult to determine.
Device type, coating composition-device substrate material combinations, coating application processes, coating thickness and degree of coating coverage are variables that impact polymer coating integrity on a device [4,7]. Particulate generation testing – the determination of a count, shape and size of particulates released from a device when used in an in-vitro vessel model – is the industry standard for evaluating polymer coating integrity from an intravascular device [8]. An intuitive correlation exists between particulates released in-vitro and the polymer emboli incidence rates [4]. Thus, particulate generation testing may be used to compare particulates released and understand relative incidence rates among intravascular devices. In-vitro particulate testing is an effective and efficient approach to determining higher-risk particulate release devices and may assist in identifying culprit interventional devices.
Based on the aforementioned study methodologies and outcomes, the following approach may be outlined for future investigations related to polymer coating embolism: a) Autopsy based studies that typically lack device information or controls over prior procedures should be limited to determining clinicopathologic impacts of polymer emboli. For these studies, estimating a particulate burden to correlate impacts with the quantity of polymer emboli for each area of assessment is relevant; b) Histologic evaluations of thrombi, captured debris, resected or biopsied tissues are also effective in determining localized disease processes. These methods may be used to determine incidence rates for a procedure if devices are consistently repeated for selected cases. For these studies (and postmortem investigations) combining incidence rates with particulate test data from devices will assist in categorizing embolic risk and determine higher risk devices; c) When clinical presentations preclude the consistent use of devices for a procedure, animal studies may be used to determine incidence rates. Extrapolating clinical impacts from healthy animals maybe acceptable, however, investigations that include relevant disease conditions are preferred; d) In-vitro particulate generation testing may be the optimal method to rank embolic risk and determine higher risk polymer emboli devices.
Inclusion and exclusion criteria for polymer emboli related investigations are essential for meaningful results. Patient history should be carefully evaluated as prior procedures may impact incidence rates. For this reason, patients with a history of multiple interventional procedures should be excluded from studies that attempt to determine polymer emboli frequencies. This patient subset may be included for studies determining potential impacts from polymer emboli for a worst-case scenario assessment. All investigations should include device specific information such as type, dimensions (e.g. length, diameter), brand, coating types (e.g. hydrophilic and/or hydrophobic) and coated dimensions. Other important parameters include patient baseline characteristics, procedural length, device in-dwell time (if available) and procedural outcomes.
Comparing particulate data among devices or reporting the magnitude of embolic burden may require assumptions to characterize total particulate volume. For the aforementioned studies, use of an efficient light obscuration methodology for particulate assessments that provides an equivalent circular diameter for particle areas may be used [9]. Combined with a uniform 1-micron height representing the typical lamellar nature of polymer particulates [3], a cylindrical volume calculation for each particle may be optimal. Summation of particle volumes may provide a total particulate burden per device or affected area of inspection.
The FDA continues to work with stakeholders to create tools which permit the standardization of particulate test methods and enable comparisons among devices [10]. Till these standards become available, investigations should include assumptions used to generate particulate data. In the future, an accumulation of procedural and device particulate data with associated incidence rates and clinicopathologic impacts may provide actionable input for regulators for setting device particulate limits. Given the sparse literature on this subject, more studies with controls over procedural parameters and devices used are required. Procedures with devices exposed to larger frictional forces (e.g. chronic total occlusions, aortic repair, or atherectomy), or aqueous environments for longer durations (e.g. percutaneous mechanical circulatory support) should be prioritized for future studies.
Acknowledgements, Funding Sources, Disclosures & Author Contributions
Acknowledgements: None. No persons other than the listed authors have made contributions to this manuscript.
Funding Sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosures: None. Authors declare no current relationship with industry and no conflicts of interest.
Author Contributions: All authors have contributed to this manuscript.
References:
1. Chopra AM, Mehta M, Bismuth J, et al. Polymer coating embolism from intravascular medical devices - a clinical literature review. Cardiovasc Pathol 2017;30:45-54.
2. Mehta RI, Rai AT, Vos JA, Solis OE, Mehta RI. Intrathrombus polymer coating deposition: a pilot study of 91 patients undergoing endovascular therapy for acute large vessel stroke. Part I: Histologic frequency. J Neurointerv Surg. Epub ahead of print 18 May 2019. doi: 10.1136/neurintsurg-2018-014684.
3. Hickey TB, Honig A, Ostry AJ, et al. Iatrogenic embolization following cardiac intervention: postmortem analysis of 110 cases. Cardiovasc Pathol 2019;40:12-18.
4. Babcock DE, Hergenrother RW, Craig DA, Kolodgie FD, Virmani R. In Vivo Distribution of Particulate Matter from Coated Angioplasty Balloon Catheters. Biomaterials 2013;34(13):3196-205.
5. Frerker C, Schlüter M, Sanchez OD, et al. Cerebral Protection During MitraClip Implantation: Initial Experience at 2 Centers. JACC Cardiovasc Interv. 2016;9(2):171-9.
6. Stanley JR, Tzafriri AR, Regan K, et al. Particulates from Hydrophilic-Coated Guiding Sheaths Embolize to the Brain. EuroIntervention 2016;11(12):1435-41.
7. Work JW. Technical white paper: considerations for hydrophilic surface coatings on medical devices [internet]. Biocoat, Inc. Horsham, PA, USA. 2016. Available from www.biocoat.com. Accessed 22 Apr 2016.
8. Center for Devices and Radiological Health Recognized Consensus Standards. Recognition number 3-99: AAMI TIR42:2010 Evaluation of Particulates Associated with Vascular Medical Devices (cardiovascular) [Internet]. 2010. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/detail.cf.... Accessed Jan. 13, 2019.
9. AAMI TIR42:2010. Evaluation of Particulates Associated with Vascular Medical Devices. Arlington, VA: Association for the Advancement of Medical Instrumentation, 2010.
10. ASTM WK60510. New Test Method for Simulated Use Testing of Neurointerventional Device in Tortuous Vasculature. West Conshohocken, PA: American Society for Testing and Materials International, 2018.
Dear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our gr...
Dear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our group is collaborating with multiple centers across the United States and Canada in the Stroke Thromboembolism Registry of Imaging and Pathology and are in the process of performing histological and imaging analysis of over 1200 collected clots from stroke patients. Combining our findings with those of other ongoing multicenter studies may ultimately help us reach meaningful conclusions regarding the association between clot composition and imaging, outcomes and etiology.
References:
[1] Fitzgerald S, Dai D, Wang S, et al. Platelet-rich emboli in cerebral large vessel occlusion are associated with a large artery atherosclerosis source. Stroke 2019;50(7):1907-1910.
Recently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
It is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questiona...
Recently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
It is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questionable, if histological composition can be compared between different circulations as it is known that there are different pathophysiological mechanisms (e.g. more underlying stenosis in the posterior circulation) as well as different flow conditions that would influence thrombus evolution and consequently composition [4].
Second, and more important, using an in-homogenous collective for perviousness assessment would stringently lead to technical difficulties in data acquisition: to make measurements comparable, direct contact from fresh flooding contrast agent in CTA is required, preventing the problem of a stationary blood column, which can be observed in occlusions of the ICA, for example. From own experience, identifying exact thrombus location is challenging for cases of ICA occlusions, that complicates the perviousness assessment. To circumvent these risks for falsified measurements, we used in our study a homogenous collective of 32 MCA occlusions. It would be interesting if Benson et al. would reproduce their results in the subgroup of 38 MCA occlusions.
Third, technical issues about perviousness assessment should be discussed as they differ between the groups. We used a co-registration process for native CT and CTA images to exactly identify the thrombus, although the thrombus is not visible in the native CT scan. Benson et al. did not apply a co-registration process between native CT and CTA images, and they excluded patients, “if the inciting clot was too small to be visualized”. Especially fibrin-rich clots are not obviously visible on native CT, and they can be included in the analysis by using a co-registration process to avoid a systematical selection bias.
Fourth, we excluded patients because of non-occluding thrombi when contrast agent passed the thrombus. We think, that perviousness cannot be assessed adequately for these cases, because perviousness would be measured artificially high. Consequently, these cases also present with tendentially better clinical outcome. It would be interesting, if such cases are included in the study of Benson et al. and how they present.
From the majority of histological studies, an association between fibrin-rich clots and cardioembolic origin is known [5, 6]. This fact makes the perviousness assessment interesting as it can predict stroke cause early on (for detailed discussion see [2]). Benson et al. report a cardioembolic origin as most common (59.6% of thrombi). They also report that 66.7% appeared pervious, however with higher RBC density. It would be interesting if their data would show a possible correlation between histological thrombus composition and etiology, and, secondly, a correlation between perviousness and etiology.
Benson et al. based their hypotheses on a positive correlation between pervious clots and good clinical outcome, that seems plausible as the dependent tissue behind an occlusion is better supplied with blood and nutrients when the clot is pervious [7]. RBC-rich clots show better clinical outcome, that is, among others, based on an easier removal in mechanical thrombectomy [8]. Due to the predominant subgroup of cardioembolic, presumably fibrin-rich clots in the anterior circulation, these clots dominate the analyses. Possibly, the assumed tendency between perviousness and good clinical outcome is based on this predominant subgroup. Consequently, it would not contradict the possible association between higher perviousness and fibrin-rich clots.
In summary, association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet and warrants further research, especially in a larger patient group in a multi-centric setting.
Literature
1. Benson JC, Fitzgerald ST, Kadirvel R, Johnson C, Dai D, Karen D et al. Clot permeability and histopathology: is a clot's perviousness on CT imaging correlated with its histologic composition? J Neurointerv Surg. 2019. doi:10.1136/neurintsurg-2019-014979.
2. Berndt M, Friedrich B, Maegerlein C, Moench S, Hedderich D, Lehm M et al. Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology. Stroke. 2018;49(11):2674-82. doi:10.1161/STROKEAHA.118.021873.
3. Borggrefe J, Kottlors J, Mirza M, Neuhaus VF, Abdullayev N, Maus V et al. Differentiation of Clot Composition Using Conventional and Dual-Energy Computed Tomography. Clin Neuroradiol. 2017. doi:10.1007/s00062-017-0599-3.
4. Boeckh-Behrens T, Pree D, Lummel N, Friedrich B, Maegerlein C, Kreiser K et al. Vertebral Artery Patency and Thrombectomy in Basilar Artery Occlusions. Stroke. 2019;50(2):389-95. doi:10.1161/STROKEAHA.118.022466.
5. Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T et al. Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? Stroke. 2017;48(8):2206-10. doi:10.1161/STROKEAHA.117.016590.
6. Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J et al. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47(7):1864-71. doi:10.1161/STROKEAHA.116.013105.
7. Santos EM, Marquering HA, den Blanken MD, Berkhemer OA, Boers AM, Yoo AJ et al. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke. Stroke. 2016;47(3):732-41. doi:10.1161/STROKEAHA.115.011187.
8. Hashimoto T, Hayakawa M, Funatsu N, Yamagami H, Satow T, Takahashi JC et al. Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy. Stroke. 2016;47(12):3035-7. doi:10.1161/STROKEAHA.116.015228.
The authors describe two endovascular techniques for delivering IA chemotherapy to retinoblastoma patients. Technique A where a 1.2 Fr or 1.5 Fr micro catheter with continuous verapamil flush is advanced without a guide and technique B where a1.5 Fr or 1.7 Fr micro catheter is advanced within a 4 Fr catheter, through a 4 Fr sheath. We usually use a no sheath technique, using a 4Fr diagnostic catheter as a guide catheter for neonatal and pediatric cases. Most importantly, we do not use Echelon or Marathon micro catheters in neonatal and pediatric patients because their use is contraindicated per "instructions for use".
We read with interest the article by Soize et al. “Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?”[1] Based on their results, the authors concluded that early neurological improvement (ENI) 24 hours after thrombectomy is a straightforward surrogate of long-term outcome. However, all patients in this study were treated with conscious sedation (CS), and not general anesthesia (GA). The residual effects of GA may mask ENI and limit its utility as a surrogate for long-term outcome.[2]
We performed a similar analysis of patients enrolled in a prospective single-center registry. The ability of ENI to predict 3-month functional independence was assessed by the area under the receiver operating characteristic curve (AUC) and compared using the independent-samples Hanley test. Multivariable linear regression assessing the relationship between anesthetic technique and ENI was also performed. The analysis received ethics approval.
291 patients were treated with thrombectomy, with 261 (89.7%) procedures performed with GA, and 30 (10.3%) with CS. All patients were de-sedated and extubated more than 12 hours before 24-hour National Institutes of Health Stroke Scale assessment. 174 (59.8%) patients achieved 3-month functional independence. Baseline and procedural characteristics did not differ between GA and CS patients (all P>0.05). ENI demonstrated better prognostic ability in CS (AUC 0.91, 95% confiden...
We read with interest the article by Soize et al. “Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?”[1] Based on their results, the authors concluded that early neurological improvement (ENI) 24 hours after thrombectomy is a straightforward surrogate of long-term outcome. However, all patients in this study were treated with conscious sedation (CS), and not general anesthesia (GA). The residual effects of GA may mask ENI and limit its utility as a surrogate for long-term outcome.[2]
We performed a similar analysis of patients enrolled in a prospective single-center registry. The ability of ENI to predict 3-month functional independence was assessed by the area under the receiver operating characteristic curve (AUC) and compared using the independent-samples Hanley test. Multivariable linear regression assessing the relationship between anesthetic technique and ENI was also performed. The analysis received ethics approval.
291 patients were treated with thrombectomy, with 261 (89.7%) procedures performed with GA, and 30 (10.3%) with CS. All patients were de-sedated and extubated more than 12 hours before 24-hour National Institutes of Health Stroke Scale assessment. 174 (59.8%) patients achieved 3-month functional independence. Baseline and procedural characteristics did not differ between GA and CS patients (all P>0.05). ENI demonstrated better prognostic ability in CS (AUC 0.91, 95% confidence interval [CI], 0.80-1.00) than it did with GA treated patients (AUC 0.73, 95% CI, 0.67-0.80; P=0.008). Multivariable regression showed that GA was independently associated with attenuated ENI (P=0.03).
Our findings are in agreement with Soize et al, in that ENI does seem to predict long-term outcome in thrombectomy patients treated with CS, with comparable AUCs (0.91 and 0.93 respectively).[1] However, our results also suggest that ENI is worse at predicting long-term outcome following thrombectomy performed with GA. Furthermore, GA was independently associated with attenuated ENI, suggesting that GA might mask early neurologic recovery. These trends would appear to be in agreement with the SIESTA trial, which reported a greater likelihood of achieving 3-month functional independence in GA than CS patients, in the absence of significant differences in ENI.[3] Post-hoc analysis of SIESTA showed that propofol dose during thrombectomy was independently associated with reduced ENI.[2] The possible mechanisms for GA attenuating ENI may include the residual pharmacological effects of benzodiazepines, opioids, neuromuscular blockers, and intravenous or volatile anesthetic agents, or transient complications of endotracheal intubation such as ventilator-associated complications.[4]
[1] Soize S, Fabre G, Gawlitza M, et al. Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome? J. Neurointerv. Surg. 2019;11(5):450-454.
[2] Schönenberger S, Uhlmann L, Ungerer M, et al. Association of Blood Pressure With Short- and Long-Term Functional Outcome After Stroke Thrombectomy: Post Hoc Analysis of the SIESTA Trial. Stroke. 2018;49:1451–1456.
[3] Schönenberger S, Uhlmann L, Hacke W, et al. Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA. 2016;316:1986–1996.
[4] Sinclair RCF, Faleiro RJ. Delayed recovery of consciousness after anaesthesia. Continuing Education in Anaesthesia, Critical Care & Pain. 2006;6:114–118.
Dear Editor:
We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroe...
Show MoreHaussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an import...
Show MoreWe thank the respondents for providing their case experience and allowing further discussion of this important topic. We would first like to draw attention to specific points in the described case, before discussing some of the more general issues raised.
The respondents report one of many scenarios in which it may be undesirable to use dual antiplatelet therapy in the elective treatment of intracranial aneurysms with flow diverters. In this case, a 47-year-old woman with an 11 mm left ophthalmic aneurysm harbours a significant aspirin allergy. A single Pipeline Shield device under cover of ticagrelor was used to treat the aneurysm. The patient was well at discharge on postoperative day three but then developed symptomatic stent thrombosis on day 6. We draw attention to three points:
1) The respondents state that the stent achieved “perfect wall apposition improved with intra-stent balloon angioplasty.” Setting aside the impossibility of improving “perfect wall apposition” with angioplasty, this does allude to the increasingly understood importance of flow diverter wall apposition. [1] However, digital subtraction angiography assess stent apposition poorly. [1] The use of angioplasty suggests that there may have been some initial concern. Moreover, angioplasty itself may contribute to thrombosis if it promotes activation of the extrinsic clotting pathway by disrupting the endothelial layer. The phosphocholine “Shield” layer reduces thrombosis and platelet...
Show MoreWe read with interest the case series by Manning’s et al.[1] using a surface modified flow-diverter stent (Pipeline Flex with Shield Technology, Medtronic Neurovascular, Irvine, California, USA). In this retrospective series, 14 ruptured intracranial aneurysms have been treated in the acute phase after Sub-Arachnoid Hemorrhage (SAH) with the Pipeline shield device under a Single Anti-Platelet Therapy (SAPT). The article concluded the PED-Shield to be safe to use in the acute treatment of ruptured intracranial aneurysms with SAPT.
However, in this small series, the authors reported one case of total stent occlusion and two cases of platelet aggregation noted on the PED-Shield device requiring to switch from single to dual antiplatelet treatment. Considering those three patients, thrombotic complications have been observed in 21.4 % of cases (3/14) in the acute period. Furthermore, in two cases (14.3 %), the authors reported rebleeding of the culprit aneurysm leading to patient death, pointing out the fact that flow-diverter devices may not immediately prevent the risk of aneurysm rerupture.
Anti-thrombogenic coating might have an added value in case of very specific aneurysms cases requiring the placement of a stent in the acute phase after rupture. Those specific cases are mainly dissecting or blister aneurysms for which endovascular or even surgical approach are difficult and carry a high risk of morbi-mortality[2][3]. In case of endovascular treatment, rece...
Show MoreProprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific...
Show MoreAn increasing number of reports highlight polymer coating embolism as an iatrogenic complication of intravascular medical devices [1-3]. Autopsies, histologic evaluations of thrombectomy specimens, samples of captured debris, resected or biopsied tissues, are available methods used to study polymer emboli post investigative catherizations or interventional procedures. Reported data highlight the prevalence of this phenomenon and/or its clinicopathologic impacts, however, fall short of identifying higher-risk polymer emboli interventional devices. Consequently, an optimal approach for future investigations related to polymer coating embolism is required.
Mehta et. al investigate the histologic frequency of polymer emboli among patients who underwent endovascular thrombectomy for treatment of acute ischemic stroke due to large vessel occlusion by retrospectively evaluating thrombectomy specimens [2]. In this study, the reported frequency of polymer emboli includes the use of various devices and techniques among selected cases. However, literature highlights polymer coating embolism is device specific and dependent on coating integrity measured by particulates released [4]. Thus, the use of alternate devices with higher or lower particulate release for a given procedure may result in a large variation in incidence rates from reported results. Also, as mentioned by the authors, subsequent statistical correlations unless appropriately powered provide limited informatio...
Show MoreDear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our gr...
Show MoreRecently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
Show MoreIt is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questiona...
The authors describe two endovascular techniques for delivering IA chemotherapy to retinoblastoma patients. Technique A where a 1.2 Fr or 1.5 Fr micro catheter with continuous verapamil flush is advanced without a guide and technique B where a1.5 Fr or 1.7 Fr micro catheter is advanced within a 4 Fr catheter, through a 4 Fr sheath. We usually use a no sheath technique, using a 4Fr diagnostic catheter as a guide catheter for neonatal and pediatric cases. Most importantly, we do not use Echelon or Marathon micro catheters in neonatal and pediatric patients because their use is contraindicated per "instructions for use".
We read with interest the article by Soize et al. “Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?”[1] Based on their results, the authors concluded that early neurological improvement (ENI) 24 hours after thrombectomy is a straightforward surrogate of long-term outcome. However, all patients in this study were treated with conscious sedation (CS), and not general anesthesia (GA). The residual effects of GA may mask ENI and limit its utility as a surrogate for long-term outcome.[2]
We performed a similar analysis of patients enrolled in a prospective single-center registry. The ability of ENI to predict 3-month functional independence was assessed by the area under the receiver operating characteristic curve (AUC) and compared using the independent-samples Hanley test. Multivariable linear regression assessing the relationship between anesthetic technique and ENI was also performed. The analysis received ethics approval.
291 patients were treated with thrombectomy, with 261 (89.7%) procedures performed with GA, and 30 (10.3%) with CS. All patients were de-sedated and extubated more than 12 hours before 24-hour National Institutes of Health Stroke Scale assessment. 174 (59.8%) patients achieved 3-month functional independence. Baseline and procedural characteristics did not differ between GA and CS patients (all P>0.05). ENI demonstrated better prognostic ability in CS (AUC 0.91, 95% confiden...
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