Introduction

  • mechanical recanalization (thrombectomy/endovascular treatment) is an essential therapeutic method for large vessel occlusions (LVO)
  • the goal is to achieve rapid and complete recanalizationTICI 2b/3 (AHA/ASA 2019 I/A)
  • mechanical treatment is performed after preceding IVT (bridging therapy) or as direct thrombectomy (dMT) if IVT is contraindicated (ESO-ESMINT 2019)
  • start treatment ASAP!
  • intravenous thrombolysis (IVT) should not be omitted before thrombectomy in eligible patients   IVT+MT vs. IVT alone (ESMINT, 2019)
    • IVT+MT is favored over IVT alone
    • ESO guidelines 2021 prefer TNK 0.25mg/kg over t-PA 0.9 mg/kg in patients scheduled for thrombectomy

Time ≤ 6 hours from onset of symptoms

  • the effectiveness of MT performed ≤6h from the onset of stroke was demonstrated by trials using retrievers (published in 2015)
  • trials showed high efficacy (recanalization rate up to 90%) and low risk of sICH (MR CLEAN 6%, ESCAPE 3.6%, EXTEND IA 0%, REVASCAT 1.9%)
  • the absolute effect of treatment in achieving patient independence is 14-31%!
  • stent retrievers and/or PENUMBRA are currently used (according to the ASTER and COMPASS trials, the efficacy is comparable)  Outcome comparison of ADAPT vs. retriever (ESO 2019)

Time > 6 hours from onset of symptoms

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  • thrombolysis facilitates the effect of mechanical thrombectomy
    • the MR-CLEAN NoIV, SWIFT-DIRECT, and DIRECT-SAFE  trials failed to show the superiority of dMT
    • meta-analyses show better outcomes with combination therapy compared to dMT [Vidale, 2020] [Katsanos, 2019] [Wang, 2020]
    • IVT led to peripheral thrombus migration in 54% of patients in the INTERRSeCT trial, with 27% experiencing significant thrombus shift, which was associated with a better outcome. Another 27% had a moderate shift with no effect on the outcome  [Ohara, 2020]
    • sometimes, thrombus displacement to a more peripheral location may not lead to clinical improvement and can make subsequent endovascular procedures difficult or impossible [Flint, 2020]
  • thrombolysis should not significantly delay the initiation of MT → do not wait for its effect and immediately transfer the patient to the center performing MT (ESO-ESMINT 2019, AHA/ASA 2019)
  • the RACECAT trial should answer whether it is better to thrombolyse the patients in the Stroke Center and then transport them to the Comprehensive Stroke Center (“drip and ship”) or transport the patient directly to the CSC (“mothership”)

Overview of mechanical recanalization methods

  • stent retrievers
    • SOLITAIRE, TREVO, BONNNET, ERIC
    • 4th.generation – EMBOTRAP, SOLITAIRE PLATINUM
  • distal aspiration catheters (DAC)
    • PENUMBRA
    • PENUMBRA JET7, SOFIA PLUS
Methods rarely used or obsolete :

  • proximal thrombectomy – disruption of the proximal part of the thrombus with/without aspiration (EKOS, EPAR)
  • distal thrombectomy – pulling the distal portion of the thrombus (MERCI)
  • stenting – compression of the thrombus to the vessel wall
  • mechanical disruption of the thrombus with a microcatheter (e.g., during IAT)
Solitaire
  • at first, the stent is deployed over the entire length of the thrombus (for 3-10 minutes)
  • this is followed by extraction of the stent with thrombus
    • during extraction, proximal balloon occlusion of the artery with simultaneous aspiration to achieve retrograde flow is recommended
  • permanent unbundling of the stent is not currently approved
  • method may be combined with local administration of tPA (IAT) to enhance clot dissolution
  • approved by FDA in 3/2012 for the treatment of acute stroke based on the results of the SWIFT trial
    • the Solitaire device achieved better angiographic, safety, and clinical outcomes than the Merci Retrieval System
  • a meta-analysis of 6 European trials included 141 patients (mean NIHSS 18) with intracranial vessel occlusion and confirmed good results [Dávalos, 2012]
    • recanalization (TICI ≥ 2b) was achieved in 86% of cases; 55% had a favorable clinical outcome
  • other positive trials (EXTEND-IA, ESCAPE a SWIFT PRIME ) were published in 2015
  • Solitaire X is a next-generation revascularization device with a unique parametric design to improve the performance and safety    Solitaire X
Solitaire
SOLITAIRE - successful recanalization of M1 occlusion
Trevo
  • approved by FDA in 8/2012 based on the findings of the TREVO-2 trial
    • 60 patients; TICI ≥ 2a was achieved in 91.7%, TICI 2b and 3 in 78.3%
    • mRS 0-2 in 55%, sICH 5%
TREVO
TREVO retriever used to recanalize M2 occlusion
TREVO retriever - full recanalization of an occluded terminal ICA (TICI 3)
Penumbra
  • proximal thrombectomy device
  • it combines mechanical disruption of the thrombus with aspiration of the fragments
  • aspiration is expected to reduce the risk of distal embolization compared to mechanical disruption with conventional catheters
  • in the Penumbra Pivotal Stroke Trial with 125 patients, recanalization (TIMI 2-3) was achieved in 81.6%, but in the group with complete or partial recanalization, only 37% had mRS 0-1. [Stroke 2009]
  • the Penumbra system was also evaluated in the IMS-III
Penumbra
Recanalization of M2 segment with PENUMBRA
Tigertriever
  • approved by FDA in 3/2021 → see here
  • comparable efficacy and safety to other retrievers [Gupta, 2021]
    • n=160
    • the primary endpoint (TICI 2b-3): 84.6%; the first pass successful reperfusion rate was 57.8%
    • after all procedures, successful reperfusion (modified Thrombolysis in Cerebral Ischemia score ≥2b) was achieved in 95.7%, and excellent reperfusion (modified Thrombolysis in Cerebral Ischemia score 2c-3) in 71.8%
    • the primary safety composite endpoint rate of mortality and symptomatic intracranial hemorrhage was 18.1%, compared to the 30.4% performance target and the 20.4% historical rate 
    • good clinical outcome was achieved in 58% at 90 days
  • TIGERTRIEVER13 can be used in vessels as small as 1 mm in width and up to a maximum of 2.5 mm, where larger retrievers would be appropriate

→ see more about TIGERTRIEVER

Tigertriever
Eric
  • The Embolus Retriever with Interlinked Cages (ERIC) is one of the latest devices
  • it has several architectural features designed to enhance its ability to retrieve clots and prevent distal embolization
  • in a large multicenter registry, the ERIC device provided equivalent angiographic and clinical results to conventional retrievers  (Ducroux, 2020)
Bonnet
  • design similar to the Solitaire device
Bonnet
Recanalization of M1 segment with the Bonnet retriever
EKOS

EKOS Endovascular System – Ultrasound-Assisted Catheter-Directed Thrombolysis

  • EKOS was the first interventional device indicated for the treatment of pulmonary embolism
  • EKOS fragments the thrombus using low-energy intravascular ultrasound (1.7Mh US probe) delivered directly to the thrombus + facilitates thrombolytic drug penetration
  • tested in the IMS II and IMS III trials
EKOS system
Epar

Endovascular Photo Acoustic Recanalization (EPAR)

  • laser-tipped endovascular catheter
  • approx. 1000 pulses/s;  laser energy is converted to acoustic energy
  • recanalization in ~40% of patients, according to small studies [Berlis, 2004]
Endovascular Photo Acoustic Recanalization - EPAR
Merci
  • a guidewire is first inserted into the artery and advanced to the site of the clot
  • the Merci retriever catheter is then advanced over the guidewire and positioned distal to the clot
  • the corkscrew-shaped platinum wire within the catheter is deployed to capture and ensnare the clot
  • once the clot is captured, the physician inflates a balloon within the guide catheter to temporarily stop the flow of blood; then, the clot is pulled back into the catheter and extracted from the body
  • efficacy in achieving recanalization was demonstrated in the MERCI and MultiMERCI trials
  • currently, stent retrievers are preferred because they have a higher rate of successful recanalization and a lower risk of complications
Merci cathether
Stenting
  • data on stenting in acute stroke are limited
  • several small studies have shown a high recanalization potential with stenting (79%-95%), but there are no randomized trials demonstrating clinical benefit
  • according to AHA/ASA, the procedure is considered experimental, and retrievers are preferred
  • the advantage over other methods is the speed and rate of recanalization
  • disadvantages:
    • thrombus compression against the vessel wall increases the risk of perforator occlusion
    • high restenosis rate (up to 32%)
    • need for subsequent DAPT to prevent thrombosis → increased risk of bleeding (especially after thrombolysis)
  • stenting appears to be beneficial in acute extracranial ICA occlusion with distal embolization (⇒ consider distal embolectomy followed CAS)
  • intracranial stenting may be performed as a rescue procedure after a failed embolectomy Acute stenting of occluded MCA after failed thrombectomy

Advantages and disadvantages of MT

  • wider therapeutic window
  • high recanalization potential
  • can be used in patients with a major IVT contraindication (e.g., after recent surgery, during anticoagulation therapy) or where IVT has failed
  • effective in thrombolysis-resistant occlusions
  • can be used in combination with other revascularization procedures (IVT + IAT + mechanical recanalization)
  • results highly depend on the experience of the neurointerventionalist 
  • high costs and requirements for instrumentation and personnel
  • delayed initiation of therapy compared to IVT
  • complications associated with endovascular procedures (dissection, perforation, etc.)
  • risk of thrombus fragmentation leading to multiple distal embolizations

Indications

The CTP selection discussed below refers to anterior circulation strokes. BAO can be treated within 24 hours without CTP selection
Acute ischemic stroke with a significant deficit and intracranial artery occlusion
(occlusion detected by CTA, MRA, or TCCD)

  • ICA, M1, BA occlusion  (I/A)
    • BAOCHE trial showed the benefit of MT within 24h without CTP selection
  • M2/3, ACA, VA, PCA occlusion  (IIb/B-R)
  • there is no limit for NIHSS or age to indicate thrombectomy  (ESO-ESMINT 2019)
    • patients with low NIHSS should be treated in case of disabling or progressive deficits (ESO-ESMINT 2019)
  • start ASAP; the goal is to achieve TICI 3 or 2b (ESO-ESMINT 2019)
Time window 0-6 hours
  • pre-stroke mRS 0-1, age ≥ 18 years, NIHSS ≥ 6, ASPECTS ≥ 6, extent of ischemia < 70ml, start treatment within 6 hours of stroke onset
    • M1 occlusion  (AHA/ASA 2019 I/A)
    • M2/M3 occlusion (AHA/ASA 2019 IIb/B-R)
    • ACA, VA, BA, PCA occlusion (AHA/ASA 2019 IIb/C-LD)
  • thrombectomy may be beneficial and may be considered for patients with mRS>1, ASPECTS<6, NIHSS<6 with ICA and/or M1 occlusion (AHA/ASA 2019 IIb/B-R)
    • RESCUE-Japan trial showed benefit in patients with ASPECTS 3-5
  • in young patients (<18 y), treatment can be initiated within 6 hours, but the benefit is undetermined
  • perfusion studies or collateral assessment are not necessary in this time window
Time window 6-7 hours 18 minutes
  • MT may be indicated without perfusion imaging (ESO-ESMINT 2019)
Time window 6-16 hours
  • inclusion criteria used in DEFUSE or DAWN trial (AHA/ASA 2019 I/A)
  • 6-16 hours to procedure initiation
  • NIHSS ≥ 6, pre-stroke mRS 0-2, age 18-90 years
  • ICA and/or M1 occlusion
  • ASPECTS ≥ 6
  • CTP – core <70 mL + mismatch >1.8 + penumbra > 15mL (RAPID software)
Time window 16-24 hours
  • inclusion criteria from the DAWN trial  (AHA/ASA 2019 IIa/B-R)
  • prestroke mRS 0-1, age > 18 years, NIHSS ≥10
  • infarct in < 1/3 of the MCA territory on baseline imaging
  • patients either did not meet the usual criteria for treatment with tPA or had persistent occlusion despite the treatment
  • clinical-radiologic mismatch (DWI, CTP-RAPID)
    • group A: age > 80y, NIHSS ≥ 10, infarct volume < 21 mL
    • group B: age < 80y, NIHSS ≥ 10, infarct volume < 31 mL
    • group C: age < 80y, NIHSS ≥ 20, infarct volume  31-50 mL
Time window 6-24 hours
  • patients with low ASPECT score  –  TENSION, IN EXTREMIS (LASTE part)
  • patients with minor deficitIN EXTREMIS (MOSTE part), ENDOLOW
  • concomitant neuroprotection
    • overall negative results of the ESCAPE-NA1 trial with nerinetide (NA1); some benefit was reported in patients  without prior IVT (interaction of NA1 with alteplase?) → see here
  •  IVT in patients with basilar artery occlusion during the extended time window – POST-ETERNAL

Contraindications

Contraindications are derived from individual trials with thrombectomy, which may differ slightly from each other.

Imaging findings

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Personal history, laboratory and clinical findings

  • pregnancy is a relative CI
    • relevant data on thrombectomy in pregnant women are not yet available; the risk of serious complications and risk-benefit ratio must be considered
  • age
    • age < 18 years is not a contraindication; MT may be beneficial
    • advanced age is not a contraindication to MT; even patients ≥ 85 years may benefit from it (Mc Donough, 2022)
  • expected survival < 3 months (not because of cerebral infarction)
  • intra-axial and metastatic tumors (assess individual prognosis)
  • allergies
    • history of severe allergic reaction to contrast agent (relative CI)
    • allergy to nickel or titanium!
  • mRS > 3 points (relative CI)
  • NIHSS > 25 points (relative CI)
  • thrombocytopenia is not a CI

Anticoagulant therapy

  • using anticoagulants is not a contraindication to mechanical recanalization; the benefit is clear for large vessel occlusions  → see here

Thrombectomy procedure

Periprocedural monitoring

  • the procedure is performed by a neurointerventionalist and supervised by an anesthesiologist and/or neurologist
  • MT is performed in general anesthesia (GA) or conscious sedation (CS)/analgosedation
    • this decision is made individually, with a preference for CS
    • the GOLIATH, ANSTROKE, and SIESTA  trials did not indicate a worse outcome with GA compared with CS  Comparison of general anesthesia and conscious sedation
    • data from an Italian registry show worse outcomes for patients treated under GA [Cappellari, 2020]
    • disadvantages of GA:
      • difficulty in monitoring neurostatus
      • delay in the initiation of therapy 
      • a higher risk of periprocedural hypotension
  • monitor BP every 5 minutes and continuously monitor pulse and oxygen saturation
    • maintain BP < 180/105 mmHg during and after the procedure (for 24h) (AHA/ASA 2019 IIa/B-NR)
    • according to the analysis of MR CLEAN data, optimal SBP appears to be ~ 135 mmHg, and the mean BP during MT should be ~ 150 mmHg → see here
    • RIGHT-2 and MR ASAP trials are currently ongoing
  • a repeated bolus of midazolam (2.5mg) + sufentanil (25ug) is recommended for sedation
  • regularly check neurological status (level of consciousness, speech, visual field, motor skills)

Periprocedural anticoagulation

  • dilute heparin with NS – Heparin 4ml (1mL=5000IU) + NS 16mL (⇒ 20mL of solution = 20000 IU of heparin)
  • initial bolus injection
    • 2000 IU of undiluted heparin (0.4 mL) or 30 IU/kg
    • skip the bolus if thrombolysis preceded the procedure
  • continue with a diluted heparin (20mL=20 000jj)
    • at a dose of 500 IU/h (0.5mL/h) (PROACT trial protocol)
    • at a dose of 450 IU/h (SWIFT PRIME trial protocol)

Thrombus extraction

  • initial assessment of the location and extent of occlusion and collateral circulation
  • after passing the catheter through the thrombus, assess the patency of the distal segments; then, thrombectomy is initiated
  • perform follow-up angiographic controls after stent passage and at the end of the procedure
  • if tight stenosis or occlusion of the ICA is present, acute angioplasty with/without carotid stenting can be performed [Cohen,2015]   (AHA/ASA 2019 IIb/B-R)
    • fresh occlusion can usually be easily passed through with the guiding wire
    • thrombus extraction followed by carotid angioplasty seems to give better results → see here
    • subsequent antiplatelet therapy (contraindicated after IVT) is problematic if the stent is inserted
    • in addition, moving wires through the stented segment may lead to local complications
  • the goal of the procedure is to achieve a TICI of 2b-3
  • the procedure can be combined with the administration of intra-arterial thrombolysis (IAT) (AHA/ASA 2019 IIb/C-LD)
    • to treat inaccessible segment thrombosis or distal embolizations [Kaesmacher, 2019]
    • good clinical effect of MT with TICI 2a-3 followed by IAT was reported in the CHOICE trial; the effect can be explained by the dissolution of microthrombi in the peripheral circulation
  • in selected cases, angioplasty with/without stenting may be performed if extraction is not successful   Acute stenting of occluded MCA after failed thrombectomy
  • if recanalization is achieved, wait ~ 15 minutes and perform a control examination to rule out early reocclusion
  • with residual occlusions in distal segments, consider the benefit and risk of complications of the continued procedure
  • if recanalization is not achieved, the procedure is terminated:
    • after repeated unsuccessful extraction attempts (approximately 6 attempts)
    • when sICH is suspected
  • after successful extraction, seek Early Venous Filling (EVF) at follow-up injection Early venous filling (EVF)
    • EVF is defined as the filling of any vein earlier than the late arterial phase (Elands, 2021)
    • EVF is a marker of hyperperfusion and increased risk of hemorrhagic transformation
    • EVF is assessed simply as present or absent
ICA recanalization with the ERICretriever

M1 occlusion treated with Solitaire retriever

Quality indicators of the neurointervention program
  • number of recanalizations TICI 2b-3
  • door to groin time
  • CT to groin time
  • groin to recanalization time
  • complications rate

Postprocedural care

  • the sheath is extracted in the angio suite, and the entry is secured with an occluder (Perclose, Mynxgrip, AngioSeal ) Angioseal
    • an alternative to the occluder is groin compression (manual, using Femostop, etc.)  Femostop
  • the patient is transported to the ICU;  if SAH or ICH is suspected, a repeat CT scan should be performed
  • in the ICU, continue close monitoring of vital signs (BP every 15min for the first hour, then every 30 minutes for at least 24 hours)
  • maintain BP < 180/105 mmHg (AHA/ASA 2018 IIb/B-NR)
    • the optimal threshold for SBP remains to be determined (140-180 mmHg) and may vary from case to case
    • conflicting results have been published:
      • aggressive BP treatment (< 130/80 mmHg) may be beneficial   Blood pressure after mechanical thrombectomy and mRS  Blood pressure after mechanical thrombectomy  [Choi, 2019]
      • other data show that using an antihypertensive drug to target SBP < 160 mm Hg or 140 mm Hg may not be beneficial (MEDSCAPE)
  • monitor neurological status (NIHSS, GCS) and search for complications
  • if bridging therapy with tPA was used:
    • monitor for bleeding (puncture, gingival, GIT, urogenital bleeding, etc.) and angioedema  → see protocol of IV thrombolysis
    • NG tube and central venous catheter placement and arterial puncture should be avoided in the first 24 hours
    • IM injections should not be administered for ~ 1h after the thrombolysis initiation
    • check CBC + coagulation tests (aPTT, TT, INR) at 6 and 12 hours, CBC+coagulation tests+metabolic panel the next day
  • perform a follow-up CT scan within 22-36 hours

Postprocedural antithrombotic medication

  • the antithrombotic regimen after direct mechanical recanalization is not clearly defined in guidelines; there is no clear contraindication to ASA within 24 hours after dMT
    • in the ESCAPE trial, ASA 160 mg was administered immediately after the initial CT scan
  • with  bridging therapy (IVT+MT), antiplatelet therapy, and mini-heparinization (as DVT prophylaxis) may be started after 24 h (after the exclusion of hemorrhagic complications on CT) → see Intravenous thrombolysis
    • ASA can be given within 24 hours if a significant benefit is expected (e.g., after stenting) (AHA/ASA 2019 I/A)
  • there is no standardized antithrombotic protocol for emergent stenting in thrombolyzed patients
    • consider the risk of bleeding vs. the risk of stent thrombosis – it may be better to perform acute angioplasty with delayed stenting (on appropriate antithrombotic therapy)
    • if a stent is implanted, it is necessary to start antithrombotic treatment immediately; various protocols can be found in the literature (not yet specified in guidelines)
      • aspirin 500mg IV bolus given immediately after the procedure + clopidogrel added after 24h [Panpangiotou, 2011]
      • abciximab (INTEGRILIN) IV bolus  + continuous IV infusion for 12 hours, followed by ASA+CLP [Wang, 2007]
EPTIFIBATID

(Integrilin) usually 1mL/2mg or 1mL/0.75 mg

  • IV bolus:  0.2 mg/kg within 5 minutes, followed by infusion  (Sedat, 2014)
  • IV infusion:  5mL(10mg) + 45mL of NS (1mL=0.2 mg)  …… 3mL/h (0.6 mg/h) 0.125ug/kg/min (max 10ug/min!)
  • IA bolus:  5mL /10mg) + 45 mL of NS (1mL=0.2 mg) …… bolus 10 mL (2mg) every 5 minutes till max dose 10 mg

ABCIXIMAB

(Reopro) 1mL/2mg

  • a monoclonal anti-glycoprotein IIb/IIIa receptor antibody
  • IV bolus: 0.25 mg/kg within 5 minutes, followed by infusion
  • IV infusion: 5mL (10mg) + 45mL NS (1mL of solution = 0.2 mg) ……   3mL/h (0.6 mg/h)   0.125ug/kg/min (max rate 10ug/min!)
  • IA bolus: 5mL (10mg) + 45 mL NS (1mL of solution = 0.2 mg) …… bolus 10 mL (2mg) every 5 minutes, max dose 10mg

Grading of cerebral revascularization

Complications

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Mechanical recanalization in acute stroke
link: https://www.stroke-manual.com/mechanical-recanalization-in-acute-stroke/