Radiol med DOI 10.1007/s11547-015-0501-9
EMERGENCY RADIOLOGY
Sequential endovascular thrombectomy approach (SETA) to acute ischemic stroke: preliminary single‑centre results and cost analysis Alessio Comai · Thomas Haglmüller · Federica Ferro · Elisa Dall’Ora · Roberto Currò Dossi · Giampietro Bonatti
Received: 27 August 2014 / Accepted: 19 January 2015 © Italian Society of Medical Radiology 2015
Abstract Introduction We report the preliminary results of a singlecentre experience in the endovascular treatment (ET) of acute ischemic stroke (AIS) with a sequential endovascular thrombectomy approach (SETA), which comprehends a direct aspiration first-pass technique (ADAPT) eventually followed by stent retriever thrombectomy. Materials and methods We prospectively analyzed data from 16 patients with severe to moderate AIS and CT angiography demonstration of large intracranial vessel occlusion treated with SETA between July 2013 and March 2014. We evaluated recanalization rate, clinical outcome after 90 days as well as differential costs of aspiration and stent-assisted thrombectomy. Results A group of 16 patients met the eligibility criteria to undergo ET with a baseline NIHSS score of 22 (range 12–39). In 15/16 cases, we obtained target vessel recanalization, 11 cases with ADAPT technique alone. Modified rankin score (mRS) at 90 days follow-up was ≤2 in 9/16 patients (56 %). ADAPT technique had a lower devicerelated cost than stent-assisted thrombectomy leading to an overall saving of −2,747.28 €. Conclusions Our preliminary data suggest that a SETA beginning with direct aspiration could be useful to optimize ET of stroke in terms of invasiveness, safety and cost-effectiveness allowing recanalization with low complication rate. A. Comai (*) · T. Haglmüller · F. Ferro · G. Bonatti Department of Radiology, Bolzano Central Hospital, Bolzano, Italy e-mail: [email protected] E. Dall’Ora · R. Currò Dossi Stroke Unit, Department of Internal Medicine, Bolzano Central Hospital, via Lorenz Boehler 5, 39100 Bolzano, Italy
Keywords Stroke · Endovascular treatment · Mechanical thrombectomy · Aspiration thrombectomy
Introduction Stroke is the third cause of death and the first cause of disability in Europe. It is commonly associated with significant neurological deficit, high level of dependency and high mortality. Intravenous tissue plasminogen activator [tPA; alteplase (Actilyse, Boehringer Ingelheim)] is the only proven reperfusion therapy for acute ischemic stroke (AIS) according a high-level evidence [1]. Early vessel recanalization in AIS has been shown to strongly correlate with improved clinical outcome and reduced mortality [2]. Nevertheless, only few patients with AIS meet current eligibility criteria for the administration of intravenous thrombolytic agents. Particularly critical is the time window from symptom onset to treatment, which has to be inferior to 4.5 h [3]. Endovascular treatment (ET) with various thrombectomy devices has been recently shown to be effective up to 8 h after the onset of stroke symptoms with a low complications rate [4–6]. Moreover, mechanical thrombectomy techniques proved better recanalization rates than intravenous tPA or intra-arterial thrombolysis alone, especially in large intracranial vessel occlusion [7, 8]. Although recent randomized controlled trials (RCT) showed that ET is not superior to systemic tPA for AIS in terms of clinical outcome, selected patients may still take advantage of an endovascular approach [9–11]. A limit of these RCTs is heterogeneity of technical approaches to thrombectomy including intra-arterial t-PA, merci retrievers, stent retrievers as Solitaire, first generation aspiration catheter of penumbra system. The aim of our study was to report preliminary results of a standardized sequential approach to
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ET of AIS in patients not responsive to intravenous t-PA or with contraindications to pharmacological treatment.
Radiol med
Before treatment, informed consent was obtained from either the patient, if conscious, or a legal representative. The study protocol has been approved by our Ethic Committee.
Patient selection From July 2013, we prospectively acquired a database of consecutive patients, who underwent sequential endovascular thrombectomy approach (SETA) and followed them up for a period of at least 90 days. All patients were included in the international registry of SITS (safe implementation of treatments in stroke), an academic-driven, non-profit, international collaboration based at Karolinska Institutet and Karolinska University Hospital in Sweden. Criteria for selection of patients were: moderate to severe ischemic stroke with an NIHSS score ≥12 and a time window of less than 6 h for anterior circulation and 12 h for posterior circulation; no or poor neurologic response to iv rt-PA (decrease of NIHSS score of at least four points) or contraindications to iv rt-PA. All patients with moderate to severe ischemic stroke underwent native CT to exclude hemorrhage and assess ASPECT (alberta stroke program early CT) score and immediate CT angiography to demonstrate a large-vessel occlusion, i.e., internal carotid artery (ICA), M1 tract of middle cerebral artery (MCA) and basilar artery (BA). In patients with undetermined onset time, as for example wake-up stroke, MRI was obtained to evaluate DWI/FLAIR mismatch, defined as visible acute ischemic lesion on DWI with no traceable parenchymal hyperintensity in the corresponding region on FLAIR imaging [12]. All patients were evaluated by a stroke-dedicated neurologist and treatment was performed by a general interventional radiologist available on-call 24 h a day. Decision to ET was collegially taken by a neurologist and a general interventional radiologist. Technical success was defined as recanalization of the target vessel as assessed by two experienced interventional radiologists according to TICI score including score 2a, 2b and 3 (thrombolysis in cerebral ischemia) [13]. All patients underwent dual-energy CT immediately after the procedure and 24 h later to evaluate extent of ischemic area and detect eventual hemorrhage. Symptomatic intracranial hemorrhage (sICH) was defined as parenchymal hematoma type II or subarachnoid hemorrhage with neurologic deterioration leading to an increase of National Institutes of Health Stroke Scale (NIHSS) score >4 or leading to death within 36 h of treatment [14]. Neurologic evaluation was quantified according to NIHSS at admission, 24 h and 7 days after intervention. Modified rankin scale (mRS) score was assessed at 90 days follow-up. Good neurological outcome was defined as mRS ≤2.
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Technique Sequential endovascular thrombectomy approach followed systemic thrombolytic treatment, when indicated, and consisted of first-line manual aspiration by means of 5MAX or 4MAX reperfusion catheter (Penumbra, Alameda/CA, USA) brought at the proximal site of occlusion with a 0.025 coaxial velocity microcatherer (Penumbra, Alameda/CA, USA) and a 0.014 microwire. Thromboaspiration maneuvers were repeated until recanalization of target vessel. If no thrombotic material was withdrawn and angiographic controls appeared unmodified, we switched to a second-line mechanical thrombectomy maneuver delivering a Solitaire flow restoration (FR) stent retriever (ev3/Covidien Vascular Therapies, Irvine/CA, USA) through the reperfusion catheter itself (Fig. 1). The latter acts as a distal access catheter facilitating delivery of the stent retriever through the occlusion site and consenting distal aspiration during retrieval.
Cost analysis Current cost of all angiographic devices involved in standardized procedures was calculated and compared, including femoral sheath, diagnostic catheter, guide catheter and microcatheter, guidewires, reperfusion catheter and stent retriever. Exceptional devices as, for example, stents for ICA dissection or optional catheters were not considered. Pricing data were obtained by the Bursar office of the hospital at the time of study. We excluded costs of consumable goods, negligible in the order of magnitude and common to different techniques, such as sterile table kit, syringes, needles, heparinized saline solution and drip infusion set. Personnel and administrative costs were also excluded because they are common to different techniques and do not contribute to the differential cost.
Results In the period between July 2013 and March 2014, 58 patients presented at our hospital with AIS and underwent systemic thrombolysis and/or mechanical thrombectomy. 16/58 patients affected by a large-vessel AIS met the selection criteria and were treated with SETA, nine cases with occlusion of M1 tract of a MCA, three cases with carotid
Radiol med Fig. 1 Treatment flow chart of patients with a documented large intracranial vessel occlusion according to the sequential endovascular approach (SETA) adopted in our center
Table 1 Clinical and technical data Patient no.
Age (years)
Target vessel
Base NIHSS
Iv t-PA
TICI
DTP (min)
PTR (min)
Aspiration device
Additional device
mRS 90 days
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
83 53 46 75 47 44 55 65 73 80 52 74 74 53 80
Basilar artery Right MCA Right MCA Left MCA Basilar artery Left ICA Right ICA Right MCA + ICA* Left MCA Left MCA Right MCA Right MCA Right MCA Left MCA Left ICA
33 12 20 19 22 20 18 16 19 27 17 23 19 21 26
3 3 3 3 2b 3 2b 3 2b 1 2b 2b 3 2a 3
76 104 37 114 227 111 161 66 164 155 66 82 175 149 111
36 38 108 43 101 106 117 122 35 121 74 38 53 43 31
5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX
None None Solitaire FR None None Solitaire FR Solitaire FR Solitaire FR None Solitaire FR None None None None None
0 0 1 6 5 3 3 0 1 6 2 0 6 2 6
16
69
Basilar artery
39
+ + + − + + + + + − + − − + +
2b
61
24
4MAX
None
0
+
Comments
Stent ACI
TICI thrombolysis in cerebral infarction, DTP door to puncture, PTR puncture to revascularization time *Tandem occlusion: acute dissection of ICA with embolic occlusion of omolateral MCA
apex occlusion, three cases with BA occlusion and one tandem occlusion of ICA and omolateral MCA. Table 1 reports complete data for the treated patients. Mean NIHSS score at baseline was 22, ranging from 12 to 39.
Recanalization of target vessel was obtained in 15/16 (94 %) cases (TICI 2/3) with an optimal revascularization of distal capillary bed (TICI score 2b/3) in 14/16 cases. All patients had a baseline TICI score of 0 at presentation. In
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Radiol med
Fig. 2 CT angiography shows an occlusion of left MCA (a; white arrow). Left internal carotid angiography (b) confirms the MCA occlusion just downstream to the lenticulostriate arteries (white arrow)
11/15 (73 %) cases, recanalization was obtained with firstline aspiration approach alone, i.e., with direct aspiration technique (ADAPT). In the remaining 4/15 cases, an adjunctive stent retriever was needed to complete recanalization. In the ADAPT group, mean procedural time from groin puncture to recanalization was 47 min [Puncture Time to Recanalization (PTR)] (24–101 min). In the combined aspiration and stent retriever group, it was 115 min (106–122 min). Nine patients (56 %) had a good clinical outcome (mRS ≤ 2) at day 90 after procedure, two of whom had requested the adjunctive use of stent retriever to obtain recanalization. Overall mortality was 4/16, in one case owing to massive reperfusion hemorrhage and in one case, where thrombectomy was inefficient, to cerebral infarction with massive edema. The other two deceases were related to non-cerebral events. Regardless of the thrombectomy technique, our common approach consisted of a femoral sheath, a diagnostic 5F catheter and a 0.035 in hydrophilic guidewire for diagnostic phase, followed by a 8F or 7F guide catheter on an exchange wire. For aspiration thrombectomy, the largest caliber aspiration catheter that the vessel would accomodate was advanced through the guide catheter and coaxially over a 0.025 in. microcatheter. Total cost of materials for aspiration thrombectomy in our center was 2,585.93 €, and that of a two-step thrombectomy including reperfusion catheter and stent retriever was 6,329.93 €. Total cost of a stent retriever thrombectomy without aspiration catheter, not adopted as a first-line technique in this study, is 5,333.75 €. The latter includes a guide catheter, a microcatheter and a Solitaire FR stent retriever besides the previously mentioned devices. Differential cost between ADAPT technique and stent-assisted thrombectomy is −2,747.82 €. Given the fact that in 11/16 cases aspiration alone was efficient to obtain recanalization, we can estimate a saving of 32,226 € in our case series by choosing the more costeffective aspiration approach.
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Discussion The first PS aspiration system (Penumbra, Alameda/CA, USA) for ET of intracranial large-vessel occlusion became available in 2008 and included a reperfusion catheter (0.041, 0.032 and 0.028 in.) and a separator guidewire [15, 16]. Previously endovascular techniques for stroke treatment included intra-arterial administration of pro-urokinase and the first world-wide available device for mechanical thrombectomy called merci retriever (Concentric Medical, Mountain View/CA, USA) [17, 18]. Nowadays, the most widely adopted device for vessel recanalization is stent retriever due to the large amount of studies reporting good technical and clinical results. In particular, higher recanalization rates with stent retrievers than with the merci retriever have been described [7, 19]. Aspiration thrombectomy approach made a comeback thanks to advances in catheter technology allowing largebore catheter to reach intracranial vessels at the site of occlusion and directly aspirate the clot, a technique defined with the acronym ADAPT (a direct pass first-pass aspiration technique) [20, 21]. We adopted the largest catheter fitting the occluded vessel and that was penumbra 5MAX reperfusion catheter (Penumbra, Alameda/CA, USA) in all cases but one. Aspiration technique is less invasive than stent-assisted thrombectomy and easier to perform even by a general interventional radiologist: the reperfusion catheter has to be advanced proximally to the occlusion without navigating in distal intracranial vessels and without perforating and disrupting the thrombus (Figs. 2, 3). When this technique is successful, it consents to reduce the use of other devices, such as stent retriever or separator, leading to a much lower device-related cost [23]. In cases where aspiration technique proves ineffective, a second level technique can be adopted as, for example, by introducing a stent retriever through the same reperfusion catheter. In this case, the reperfusion catheter facilitates delivery of
Radiol med Fig. 3 Left internal carotid artery angiogram demonstrates reperfusion of MCA (a). Whitish Y-shaped embolus is shown near the reperfusion catheter (b). The peculiar shape represents the middle cerebral artery bifurcation
the retriever at the occlusion site acting as a distal access catheter. Moreover, distal aspiration can be performed during stent retrieval, a combinative technique that has been already described as “Solumbra”, a crasis of Solitaire and penumbra [24]. Such a two-step approach to thrombectomy has been already described with positive technical and clinical results [22–25]. ADAPT technique has proved to be faster and more effective than any series reported in the literature [20–22]. In our series, 11 of 16 cases were successfully recanalized with aspiration alone limiting the use of stent retriever to five cases. Combining the two techniques, good recanalization rate (TICI > 2a) was obtained in almost all cases (15/16). Moreover, there is a temporal trend toward a higher recanalization rate with ADAPT approach as technical confidence grows and devices improve [22]. Direct aspiration of thrombus was previously described as an alternative technique to more conventional strategies or with previous generation smaller catheter [26–28]. The increased internal diameter of the 5MAX reperfusion catheter provides an increased contact area at the catheter tip-thrombus interface. In addition, it is more capacious along its proximal segment, increasing its luminal volume and thereby resulting in an increased aspiration capacity and force over previous versions of aspiration catheters [21, 28]. Four patients died during hospitalization (25 %), two for other reasons than stroke itself (sepsis in acute cholecystitis and myocardial infarct). 2 of 4 patients deceased because of stroke, both 80 years old, one with poor recanalization of the left MCA (TICI 1) despite combined technique, and the other one after developing a post-reperfusion parenchymal hematoma with massive edema requiring craniotomy. The latter had been successfully treated with aspiration alone 142 min after onset of a left ICA occlusion. This complication was probably due to a large infarction core, a condition which can sometimes appear within the usual timing
range for treatment. In this case, a poor collateralization was shown at CT angiography favouring rapid evolution of the ischemic process. Perfusion CT and MRI can play an important role in the selection of patients allowing the distinction of ischemic penumbra and infarct core [29]. This was the only symptomatic hemorrhagic complication in our series (6 %). Despite the low number of cases, incidence of sICH is much lower than the cutoff value of 12 % stipulated as standards of practice by the international multisociety guidelines of 2013 [30]. Complications have been reported to be higher with stent retriever thrombectomy than with penumbra system thrombectomy, albeit with similar positive clinical outcome rates [20–22]. We had two cases of emboli to new territories (ENT) occurring one after aspiration thrombectomy and the other after combined aspiration–stent retrieve technique. Aspiration alone is considered to be associated with a lower ENT rate than with other mechanical techniques because of complete engaging and removal of thrombus without its fragmentation, as possible using separator or stent retrievers. In fact, ENT has been reported to occur in up to 14 % of cases with stent retrievers [7, 19]. SETA-combined technique includes, in case of stent retriever delivery, the possibility to apply aspiration during stent withdrawal to preclude the spread of emboli. Moreover, fragmentation of thrombus with the separator has been shown to originate small emboli that migrate in peripheral vessels, not suitable for distal thrombectomy and unfavorable for collateralization [31]. Future development thrombectomy should aim to better patient selection, as for example, on the basis of stroke etiology. The cause of occlusion could be related to the composition and the physical characteristics of thrombus such as hardness and elasticity and influence responsivity to different thrombectomy approaches as well as lysability [32–34].
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Major limitation of our study is the low patient’s number. Although preliminary, our results are encouraging not only in terms of technical success, similarly to other reports on the aspiration technique, but above all in terms of clinical outcome also which is reported to be approximately 40 % [30]. At 90 days follow-up after treatment, 9 patients of 16 had a positive clinical outcome with mRS = 0 in 5 patients, mRS = 1 in 2 patients, mRS = 2 in 2 patients. We adhered to the quality benchmarks suggested by the international multispeciality document recently issued by a consensus of many principal international societies, in particular by strictly applying selection criteria [30]. Time to treatment is another fundamental parameter, which affects clinical efficacy of stroke therapy and adherence to the time intervals suggested by the same paper could have positively affected clinical outcomes of our patients [30, 35]. Our differential cost analysis considered only current price of devices we use in standardized ETs. The most expensive devices are reperfusion catheter for ADAPT technique and stent retriever for stent-assisted thrombectomy. The cost ratio of these two devices is about 1:3 and mainly accounts for the high differential cost of the techniques. The use of aspiration as an initial approach is on average the less expensive method to achieve acceptable recanalization rates with low complication rates. Stent retrievers consent to obtain higher recanalization rate in difficult cases. As suggested by Turk et al. [22], the most cost-effective approach to a large-vessel occlusion might be what we define SETA, i.e., to attempt a brief direct aspiration with a large bore first and if this fails then proceed with other devices, such as a stent retriever. Interventional treatment strategies with adjunctive mechanical thrombectomy or intra-arterial thrombolysis appear to have an acceptable cost-effectiveness profile compared to IV tPA alone for large-vessel stroke based on currently available data [36]. Heterogeneous technique and devices have been included in recent RCTs possibly limiting the demonstration of clinical efficacy of endovascular approach and resulting in non-superiority of mechanical thrombectomy to systemic treatment [10–12]. We consider endovascular approach as a rescue treatment in patients affected by occlusion of large intracranial vessel who receive full dose iv t-PA treatment without showing any neurological response or who have contraindication to pharmacological treatment. Standardization of endovascular approach should be needed to evaluate effective contribution of interventional radiology in the treatment of these patients. We adopted a sequential approach, which could consent to shorten procedural time, to grade invasiveness and likely to limit complications and to reduce procedural costs. Nevertheless, a wider number of cases are required to confirm efficacy and safety of our approach.
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Radiol med
Conclusions Our preliminary data suggest that sequential endovascular approach (SETA) with first-line direct aspiration could be useful to optimize ET of stroke in terms of efficacy, safety and cost-effectiveness. Conflict of interest The authors declare no conflict of interest
References 1. The National Institute of Neurological Disorders and Stroke rt-PA Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587 2. Lees KR, Bluhmki E, von Kummer R et al (2010) Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375:1695–1703 3. La Rosa FDLR, Khoury J, Kissela BM et al (2012) Eligibility for intravenous recombinant tissue-type plasminogen activator within a population: the effect of the European Cooperative Acute Stroke Study (ECASS) III trial. Stroke 43:1591–1595 4. Furlan A, Hogashida R, Wechsler L et al (1999) Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. JAMA 282:2003–2011 5. Tenser MS, Amar AP, Mack WJ (2011) Mechanical thrombectomy for acue ischemic stroke using the merci retriever and penumbra aspiration systems. World Neurosurg 76(6 Suppl):S16–S23 6. Saver JL, Jahan R, Levy EI et al (2012) Solitaire flow restoration device versus the merci retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 380:1241–1249 7. Wechsler LR, Roberts R, Furlan AJ et al (2003) Factors influencing outcome and treatment effect in PROACT II. Stroke 34:1224–1229 8. Nogueira RG, Schwamm LH, Hirsch JA et al (2009) Endovascular approaches to acute ischemic stroke, part 1: drugs, devices, and data. Am J Neurorad 30:649–661 9. Broderick JP, Palesch YY, Demchuk AM et al (2013) Endovascular therapy after intravenous rt-PA versus rt-PA alone for stroke. N Engl J Med 368:893–903 10. Ciccone A, Valvassori L, Nichelatti M et al (2013) Endovascular treatment for acute ischemic stroke. N Engl J Med 368:904–913 11. Kidwell CS, Jahan R, Gornbein J et al (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 368:914–923 12. Thomalla G, Cheng B, Ebinger M et al (2011) DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicenter observational study. Lancet Neurol 10(11):978–986 13. Higashida RT, Furlan AJ, Roberts H et al (2003) Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 34:e109–e137 14. Wahlgren N, Ahmed N, Davalos A et al (2007) Thrombolysis with alteplase for acute ischaemic stroke in the safe implementation of thrombolysis in stroke-monitoring study (SITS-MOST): an observational study. Lancet 369:275–282 15. Bose A, Henkes H, Alfke K et al (2008) The penumbra system: a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR 29:1409–1413 16. Kulcsar Z, Bonvin C, Pereira VM et al (2010) Penumbra system: a novel mechanical thrombectomy device for large-vessel occlusions in acute stroke. AJNR 31:628–633
Radiol med 17. Furlan A, Higashida R, Wechsler L et al (1999) Intra-arterial prourokinase for acute ischemic stroke. JAMA 282:2003–2011 18. Gobin YP, Starksman S, Duckwiller GR et al (2004) Merci 1: a phase 1 study of mechanical embolus removal in cerebral ischemia. Stroke 35:2848–2854 19. Nogueira RG, Lutsep HL, Gupta R et al (2012) Trevo versus merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomized trial. Lancet 380:1231–1240 20. Turk AS, Spiotta A, Frei D et al (2014) Initial clinical experience with the ADAPT technique: a direct aspiration first pass technique for stroke thrombectomy. J Neurointerv Surg 6:231–237 21. Turk AS, Frei D, Fiorella D et al (2014) ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. JNIS 6:260–264 22. Turk AS, Campbell JM, Spiotta A et al (2014) An investigation of the cost and benefit of mechanical thrombectomy for endovascular treatment of acute ischemic stroke. J Neurointerv Surg 6:77–80 23. Spiotta AM, Chaudry MI, Hui FK et al (2014) Evolu tion of thrombectomy approaches and devices for acute stroke: a technical review. J Neurointerv Surg. doi:10.1136/ neurintsurg-2013-011022 24. Kang DH, Kim YW, Hwang YH et al (2013) Switching strategy for mechanical thrombectomy of acute large vessel occlusion in the anterior circulation. Stroke 44:3577–3579 25. Spiotta AM, Hussain MS, Sivapatham T et al (2011) The versatile distal access catheter: the Cleveland Clinic experience. Neurosurgery 8:1677–1686 26. Jankowitz B, Aghaebrahim A, Zirra A et al (2012) Manual aspiration thrombectomy: adjunctive endovascular recanalization technique in acute stroke interventions. Stroke 43:1408–1411 27. Kang DH, Hwang YH, Kim YS et al (2011) Direct thrombus retrieval using the reperfusion catheter of the penumbra system: forced-suction thrombectomy in acute ischemic stroke. AJNR 32:283–287
28. Simon SD, Grey CS (2014) Hydrodynamic comparison of the penumbra system and commonly available syringes in forcedsuction thrombectomy. J Neurointerv Surg 6:205–211 29. Wintermark M, Flanders AE, Velthuis B et al (2006) PerfusionCT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke 37:979–985 30. Sacks D, Black CM, Cognard C et al (2013) Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society of Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. J Vasc Interv Radiol 24:151–163 31. Chueh JY, Wakhloo AK, Gounis MY (2012) Effectiveness of mechanical endovascular thrombectomy in a model system of cerebrovascular occlusion. AJNR 33:1998–2003 32. Ciccone A, dal Zoppo GJ (2014) Evolving role of endovascular treament of acute ischemic stroke. Curr Neurol Neurosci Rep 14:416 33. Matias-Guiu JA, Serna-Candel C, Matias-Guiu J et al (2014) Stroke etiology determines effectiveness of retrievable stents. J Neurointerv Surg 6:e11 34. Moftakhar P, English JD, Cooke DL et al (2013) Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke. Stroke 4:243–245 35. Khatri P, Abruzzo T, Yeatts SD et al (2009) Good clinical outcome after ischemic stroke with successful revascularization is time-dependent. Neurology 73:1066–1072 36. Kim AS, Nguyen-Huynh M, Johnston SC (2011) A cost-utility analysis of mechanical thrombectomy as an adjunct to intravenous tissue-type plasminogen activator for acute large-vessel ischemic stroke. Stroke 42(7):2013–2018
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EMERGENCY RADIOLOGY
Sequential endovascular thrombectomy approach (SETA) to acute ischemic stroke: preliminary single‑centre results and cost analysis Alessio Comai · Thomas Haglmüller · Federica Ferro · Elisa Dall’Ora · Roberto Currò Dossi · Giampietro Bonatti
Received: 27 August 2014 / Accepted: 19 January 2015 © Italian Society of Medical Radiology 2015
Abstract Introduction We report the preliminary results of a singlecentre experience in the endovascular treatment (ET) of acute ischemic stroke (AIS) with a sequential endovascular thrombectomy approach (SETA), which comprehends a direct aspiration first-pass technique (ADAPT) eventually followed by stent retriever thrombectomy. Materials and methods We prospectively analyzed data from 16 patients with severe to moderate AIS and CT angiography demonstration of large intracranial vessel occlusion treated with SETA between July 2013 and March 2014. We evaluated recanalization rate, clinical outcome after 90 days as well as differential costs of aspiration and stent-assisted thrombectomy. Results A group of 16 patients met the eligibility criteria to undergo ET with a baseline NIHSS score of 22 (range 12–39). In 15/16 cases, we obtained target vessel recanalization, 11 cases with ADAPT technique alone. Modified rankin score (mRS) at 90 days follow-up was ≤2 in 9/16 patients (56 %). ADAPT technique had a lower devicerelated cost than stent-assisted thrombectomy leading to an overall saving of −2,747.28 €. Conclusions Our preliminary data suggest that a SETA beginning with direct aspiration could be useful to optimize ET of stroke in terms of invasiveness, safety and cost-effectiveness allowing recanalization with low complication rate. A. Comai (*) · T. Haglmüller · F. Ferro · G. Bonatti Department of Radiology, Bolzano Central Hospital, Bolzano, Italy e-mail: [email protected] E. Dall’Ora · R. Currò Dossi Stroke Unit, Department of Internal Medicine, Bolzano Central Hospital, via Lorenz Boehler 5, 39100 Bolzano, Italy
Keywords Stroke · Endovascular treatment · Mechanical thrombectomy · Aspiration thrombectomy
Introduction Stroke is the third cause of death and the first cause of disability in Europe. It is commonly associated with significant neurological deficit, high level of dependency and high mortality. Intravenous tissue plasminogen activator [tPA; alteplase (Actilyse, Boehringer Ingelheim)] is the only proven reperfusion therapy for acute ischemic stroke (AIS) according a high-level evidence [1]. Early vessel recanalization in AIS has been shown to strongly correlate with improved clinical outcome and reduced mortality [2]. Nevertheless, only few patients with AIS meet current eligibility criteria for the administration of intravenous thrombolytic agents. Particularly critical is the time window from symptom onset to treatment, which has to be inferior to 4.5 h [3]. Endovascular treatment (ET) with various thrombectomy devices has been recently shown to be effective up to 8 h after the onset of stroke symptoms with a low complications rate [4–6]. Moreover, mechanical thrombectomy techniques proved better recanalization rates than intravenous tPA or intra-arterial thrombolysis alone, especially in large intracranial vessel occlusion [7, 8]. Although recent randomized controlled trials (RCT) showed that ET is not superior to systemic tPA for AIS in terms of clinical outcome, selected patients may still take advantage of an endovascular approach [9–11]. A limit of these RCTs is heterogeneity of technical approaches to thrombectomy including intra-arterial t-PA, merci retrievers, stent retrievers as Solitaire, first generation aspiration catheter of penumbra system. The aim of our study was to report preliminary results of a standardized sequential approach to
13
ET of AIS in patients not responsive to intravenous t-PA or with contraindications to pharmacological treatment.
Radiol med
Before treatment, informed consent was obtained from either the patient, if conscious, or a legal representative. The study protocol has been approved by our Ethic Committee.
Patient selection From July 2013, we prospectively acquired a database of consecutive patients, who underwent sequential endovascular thrombectomy approach (SETA) and followed them up for a period of at least 90 days. All patients were included in the international registry of SITS (safe implementation of treatments in stroke), an academic-driven, non-profit, international collaboration based at Karolinska Institutet and Karolinska University Hospital in Sweden. Criteria for selection of patients were: moderate to severe ischemic stroke with an NIHSS score ≥12 and a time window of less than 6 h for anterior circulation and 12 h for posterior circulation; no or poor neurologic response to iv rt-PA (decrease of NIHSS score of at least four points) or contraindications to iv rt-PA. All patients with moderate to severe ischemic stroke underwent native CT to exclude hemorrhage and assess ASPECT (alberta stroke program early CT) score and immediate CT angiography to demonstrate a large-vessel occlusion, i.e., internal carotid artery (ICA), M1 tract of middle cerebral artery (MCA) and basilar artery (BA). In patients with undetermined onset time, as for example wake-up stroke, MRI was obtained to evaluate DWI/FLAIR mismatch, defined as visible acute ischemic lesion on DWI with no traceable parenchymal hyperintensity in the corresponding region on FLAIR imaging [12]. All patients were evaluated by a stroke-dedicated neurologist and treatment was performed by a general interventional radiologist available on-call 24 h a day. Decision to ET was collegially taken by a neurologist and a general interventional radiologist. Technical success was defined as recanalization of the target vessel as assessed by two experienced interventional radiologists according to TICI score including score 2a, 2b and 3 (thrombolysis in cerebral ischemia) [13]. All patients underwent dual-energy CT immediately after the procedure and 24 h later to evaluate extent of ischemic area and detect eventual hemorrhage. Symptomatic intracranial hemorrhage (sICH) was defined as parenchymal hematoma type II or subarachnoid hemorrhage with neurologic deterioration leading to an increase of National Institutes of Health Stroke Scale (NIHSS) score >4 or leading to death within 36 h of treatment [14]. Neurologic evaluation was quantified according to NIHSS at admission, 24 h and 7 days after intervention. Modified rankin scale (mRS) score was assessed at 90 days follow-up. Good neurological outcome was defined as mRS ≤2.
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Technique Sequential endovascular thrombectomy approach followed systemic thrombolytic treatment, when indicated, and consisted of first-line manual aspiration by means of 5MAX or 4MAX reperfusion catheter (Penumbra, Alameda/CA, USA) brought at the proximal site of occlusion with a 0.025 coaxial velocity microcatherer (Penumbra, Alameda/CA, USA) and a 0.014 microwire. Thromboaspiration maneuvers were repeated until recanalization of target vessel. If no thrombotic material was withdrawn and angiographic controls appeared unmodified, we switched to a second-line mechanical thrombectomy maneuver delivering a Solitaire flow restoration (FR) stent retriever (ev3/Covidien Vascular Therapies, Irvine/CA, USA) through the reperfusion catheter itself (Fig. 1). The latter acts as a distal access catheter facilitating delivery of the stent retriever through the occlusion site and consenting distal aspiration during retrieval.
Cost analysis Current cost of all angiographic devices involved in standardized procedures was calculated and compared, including femoral sheath, diagnostic catheter, guide catheter and microcatheter, guidewires, reperfusion catheter and stent retriever. Exceptional devices as, for example, stents for ICA dissection or optional catheters were not considered. Pricing data were obtained by the Bursar office of the hospital at the time of study. We excluded costs of consumable goods, negligible in the order of magnitude and common to different techniques, such as sterile table kit, syringes, needles, heparinized saline solution and drip infusion set. Personnel and administrative costs were also excluded because they are common to different techniques and do not contribute to the differential cost.
Results In the period between July 2013 and March 2014, 58 patients presented at our hospital with AIS and underwent systemic thrombolysis and/or mechanical thrombectomy. 16/58 patients affected by a large-vessel AIS met the selection criteria and were treated with SETA, nine cases with occlusion of M1 tract of a MCA, three cases with carotid
Radiol med Fig. 1 Treatment flow chart of patients with a documented large intracranial vessel occlusion according to the sequential endovascular approach (SETA) adopted in our center
Table 1 Clinical and technical data Patient no.
Age (years)
Target vessel
Base NIHSS
Iv t-PA
TICI
DTP (min)
PTR (min)
Aspiration device
Additional device
mRS 90 days
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
83 53 46 75 47 44 55 65 73 80 52 74 74 53 80
Basilar artery Right MCA Right MCA Left MCA Basilar artery Left ICA Right ICA Right MCA + ICA* Left MCA Left MCA Right MCA Right MCA Right MCA Left MCA Left ICA
33 12 20 19 22 20 18 16 19 27 17 23 19 21 26
3 3 3 3 2b 3 2b 3 2b 1 2b 2b 3 2a 3
76 104 37 114 227 111 161 66 164 155 66 82 175 149 111
36 38 108 43 101 106 117 122 35 121 74 38 53 43 31
5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX 5MAX
None None Solitaire FR None None Solitaire FR Solitaire FR Solitaire FR None Solitaire FR None None None None None
0 0 1 6 5 3 3 0 1 6 2 0 6 2 6
16
69
Basilar artery
39
+ + + − + + + + + − + − − + +
2b
61
24
4MAX
None
0
+
Comments
Stent ACI
TICI thrombolysis in cerebral infarction, DTP door to puncture, PTR puncture to revascularization time *Tandem occlusion: acute dissection of ICA with embolic occlusion of omolateral MCA
apex occlusion, three cases with BA occlusion and one tandem occlusion of ICA and omolateral MCA. Table 1 reports complete data for the treated patients. Mean NIHSS score at baseline was 22, ranging from 12 to 39.
Recanalization of target vessel was obtained in 15/16 (94 %) cases (TICI 2/3) with an optimal revascularization of distal capillary bed (TICI score 2b/3) in 14/16 cases. All patients had a baseline TICI score of 0 at presentation. In
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Radiol med
Fig. 2 CT angiography shows an occlusion of left MCA (a; white arrow). Left internal carotid angiography (b) confirms the MCA occlusion just downstream to the lenticulostriate arteries (white arrow)
11/15 (73 %) cases, recanalization was obtained with firstline aspiration approach alone, i.e., with direct aspiration technique (ADAPT). In the remaining 4/15 cases, an adjunctive stent retriever was needed to complete recanalization. In the ADAPT group, mean procedural time from groin puncture to recanalization was 47 min [Puncture Time to Recanalization (PTR)] (24–101 min). In the combined aspiration and stent retriever group, it was 115 min (106–122 min). Nine patients (56 %) had a good clinical outcome (mRS ≤ 2) at day 90 after procedure, two of whom had requested the adjunctive use of stent retriever to obtain recanalization. Overall mortality was 4/16, in one case owing to massive reperfusion hemorrhage and in one case, where thrombectomy was inefficient, to cerebral infarction with massive edema. The other two deceases were related to non-cerebral events. Regardless of the thrombectomy technique, our common approach consisted of a femoral sheath, a diagnostic 5F catheter and a 0.035 in hydrophilic guidewire for diagnostic phase, followed by a 8F or 7F guide catheter on an exchange wire. For aspiration thrombectomy, the largest caliber aspiration catheter that the vessel would accomodate was advanced through the guide catheter and coaxially over a 0.025 in. microcatheter. Total cost of materials for aspiration thrombectomy in our center was 2,585.93 €, and that of a two-step thrombectomy including reperfusion catheter and stent retriever was 6,329.93 €. Total cost of a stent retriever thrombectomy without aspiration catheter, not adopted as a first-line technique in this study, is 5,333.75 €. The latter includes a guide catheter, a microcatheter and a Solitaire FR stent retriever besides the previously mentioned devices. Differential cost between ADAPT technique and stent-assisted thrombectomy is −2,747.82 €. Given the fact that in 11/16 cases aspiration alone was efficient to obtain recanalization, we can estimate a saving of 32,226 € in our case series by choosing the more costeffective aspiration approach.
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Discussion The first PS aspiration system (Penumbra, Alameda/CA, USA) for ET of intracranial large-vessel occlusion became available in 2008 and included a reperfusion catheter (0.041, 0.032 and 0.028 in.) and a separator guidewire [15, 16]. Previously endovascular techniques for stroke treatment included intra-arterial administration of pro-urokinase and the first world-wide available device for mechanical thrombectomy called merci retriever (Concentric Medical, Mountain View/CA, USA) [17, 18]. Nowadays, the most widely adopted device for vessel recanalization is stent retriever due to the large amount of studies reporting good technical and clinical results. In particular, higher recanalization rates with stent retrievers than with the merci retriever have been described [7, 19]. Aspiration thrombectomy approach made a comeback thanks to advances in catheter technology allowing largebore catheter to reach intracranial vessels at the site of occlusion and directly aspirate the clot, a technique defined with the acronym ADAPT (a direct pass first-pass aspiration technique) [20, 21]. We adopted the largest catheter fitting the occluded vessel and that was penumbra 5MAX reperfusion catheter (Penumbra, Alameda/CA, USA) in all cases but one. Aspiration technique is less invasive than stent-assisted thrombectomy and easier to perform even by a general interventional radiologist: the reperfusion catheter has to be advanced proximally to the occlusion without navigating in distal intracranial vessels and without perforating and disrupting the thrombus (Figs. 2, 3). When this technique is successful, it consents to reduce the use of other devices, such as stent retriever or separator, leading to a much lower device-related cost [23]. In cases where aspiration technique proves ineffective, a second level technique can be adopted as, for example, by introducing a stent retriever through the same reperfusion catheter. In this case, the reperfusion catheter facilitates delivery of
Radiol med Fig. 3 Left internal carotid artery angiogram demonstrates reperfusion of MCA (a). Whitish Y-shaped embolus is shown near the reperfusion catheter (b). The peculiar shape represents the middle cerebral artery bifurcation
the retriever at the occlusion site acting as a distal access catheter. Moreover, distal aspiration can be performed during stent retrieval, a combinative technique that has been already described as “Solumbra”, a crasis of Solitaire and penumbra [24]. Such a two-step approach to thrombectomy has been already described with positive technical and clinical results [22–25]. ADAPT technique has proved to be faster and more effective than any series reported in the literature [20–22]. In our series, 11 of 16 cases were successfully recanalized with aspiration alone limiting the use of stent retriever to five cases. Combining the two techniques, good recanalization rate (TICI > 2a) was obtained in almost all cases (15/16). Moreover, there is a temporal trend toward a higher recanalization rate with ADAPT approach as technical confidence grows and devices improve [22]. Direct aspiration of thrombus was previously described as an alternative technique to more conventional strategies or with previous generation smaller catheter [26–28]. The increased internal diameter of the 5MAX reperfusion catheter provides an increased contact area at the catheter tip-thrombus interface. In addition, it is more capacious along its proximal segment, increasing its luminal volume and thereby resulting in an increased aspiration capacity and force over previous versions of aspiration catheters [21, 28]. Four patients died during hospitalization (25 %), two for other reasons than stroke itself (sepsis in acute cholecystitis and myocardial infarct). 2 of 4 patients deceased because of stroke, both 80 years old, one with poor recanalization of the left MCA (TICI 1) despite combined technique, and the other one after developing a post-reperfusion parenchymal hematoma with massive edema requiring craniotomy. The latter had been successfully treated with aspiration alone 142 min after onset of a left ICA occlusion. This complication was probably due to a large infarction core, a condition which can sometimes appear within the usual timing
range for treatment. In this case, a poor collateralization was shown at CT angiography favouring rapid evolution of the ischemic process. Perfusion CT and MRI can play an important role in the selection of patients allowing the distinction of ischemic penumbra and infarct core [29]. This was the only symptomatic hemorrhagic complication in our series (6 %). Despite the low number of cases, incidence of sICH is much lower than the cutoff value of 12 % stipulated as standards of practice by the international multisociety guidelines of 2013 [30]. Complications have been reported to be higher with stent retriever thrombectomy than with penumbra system thrombectomy, albeit with similar positive clinical outcome rates [20–22]. We had two cases of emboli to new territories (ENT) occurring one after aspiration thrombectomy and the other after combined aspiration–stent retrieve technique. Aspiration alone is considered to be associated with a lower ENT rate than with other mechanical techniques because of complete engaging and removal of thrombus without its fragmentation, as possible using separator or stent retrievers. In fact, ENT has been reported to occur in up to 14 % of cases with stent retrievers [7, 19]. SETA-combined technique includes, in case of stent retriever delivery, the possibility to apply aspiration during stent withdrawal to preclude the spread of emboli. Moreover, fragmentation of thrombus with the separator has been shown to originate small emboli that migrate in peripheral vessels, not suitable for distal thrombectomy and unfavorable for collateralization [31]. Future development thrombectomy should aim to better patient selection, as for example, on the basis of stroke etiology. The cause of occlusion could be related to the composition and the physical characteristics of thrombus such as hardness and elasticity and influence responsivity to different thrombectomy approaches as well as lysability [32–34].
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Major limitation of our study is the low patient’s number. Although preliminary, our results are encouraging not only in terms of technical success, similarly to other reports on the aspiration technique, but above all in terms of clinical outcome also which is reported to be approximately 40 % [30]. At 90 days follow-up after treatment, 9 patients of 16 had a positive clinical outcome with mRS = 0 in 5 patients, mRS = 1 in 2 patients, mRS = 2 in 2 patients. We adhered to the quality benchmarks suggested by the international multispeciality document recently issued by a consensus of many principal international societies, in particular by strictly applying selection criteria [30]. Time to treatment is another fundamental parameter, which affects clinical efficacy of stroke therapy and adherence to the time intervals suggested by the same paper could have positively affected clinical outcomes of our patients [30, 35]. Our differential cost analysis considered only current price of devices we use in standardized ETs. The most expensive devices are reperfusion catheter for ADAPT technique and stent retriever for stent-assisted thrombectomy. The cost ratio of these two devices is about 1:3 and mainly accounts for the high differential cost of the techniques. The use of aspiration as an initial approach is on average the less expensive method to achieve acceptable recanalization rates with low complication rates. Stent retrievers consent to obtain higher recanalization rate in difficult cases. As suggested by Turk et al. [22], the most cost-effective approach to a large-vessel occlusion might be what we define SETA, i.e., to attempt a brief direct aspiration with a large bore first and if this fails then proceed with other devices, such as a stent retriever. Interventional treatment strategies with adjunctive mechanical thrombectomy or intra-arterial thrombolysis appear to have an acceptable cost-effectiveness profile compared to IV tPA alone for large-vessel stroke based on currently available data [36]. Heterogeneous technique and devices have been included in recent RCTs possibly limiting the demonstration of clinical efficacy of endovascular approach and resulting in non-superiority of mechanical thrombectomy to systemic treatment [10–12]. We consider endovascular approach as a rescue treatment in patients affected by occlusion of large intracranial vessel who receive full dose iv t-PA treatment without showing any neurological response or who have contraindication to pharmacological treatment. Standardization of endovascular approach should be needed to evaluate effective contribution of interventional radiology in the treatment of these patients. We adopted a sequential approach, which could consent to shorten procedural time, to grade invasiveness and likely to limit complications and to reduce procedural costs. Nevertheless, a wider number of cases are required to confirm efficacy and safety of our approach.
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Radiol med
Conclusions Our preliminary data suggest that sequential endovascular approach (SETA) with first-line direct aspiration could be useful to optimize ET of stroke in terms of efficacy, safety and cost-effectiveness. Conflict of interest The authors declare no conflict of interest
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