Abstract
When used alone, intravenous and intra-arterial thrombolysis have yielded low recanalization rates of proximal large-vessel occlusions (LVO). The endovascular trials utilizing first-generation devices such as the Merci retriever and the Penumbra aspiration system were essentially neutral and failed to demonstrate superiority of mechanical thrombectomy over IV tPA (MR RESCUE, SYNTHESIS, IMS-III). In 2015, however, six trials – MR CLEAN, EXTEND-IA, SWIFT PRIME, ESCAPE, REVASCAT, and THRACE – led to a fundamental shift in how we acutely manage LVOs today. All six trials compared endovascular thrombectomy (EVT) to IV tPA alone and demonstrated clear superiority of thrombectomy in patients presenting within 6 hours from the time they were last known well (LKW) if they met specific imaging criteria.
When used alone, intravenous and intra-arterial thrombolysis have yielded low recanalization rates of proximal large-vessel occlusions (LVO). The endovascular trials utilizing first-generation devices such as the Merci retriever and the Penumbra aspiration system were essentially neutral and failed to demonstrate superiority of mechanical thrombectomy over IV tPA (MR RESCUE, SYNTHESIS, IMS-III).1–3 In 2015, however, six trials – MR CLEAN, EXTEND-IA, SWIFT PRIME, ESCAPE, REVASCAT, and THRACE – led to a fundamental shift in how we acutely manage LVOs today.4–9 All six trials compared endovascular thrombectomy (EVT) to IV tPA alone and demonstrated clear superiority of thrombectomy in patients presenting within 6 hours from the time they were last known well (LKW) if they met specific imaging criteria. In addition to faster recanalization times and selection of patients with favorable imaging profiles, the long-awaited success of mechanical thrombectomy was in part made possible by the safer profile and higher recanalization rates offered by the newer clot retrieval devices known as stent retrievers or “stentrievers.”
More recently, two large multicenter trials – DAWN and DEFUSE 3 – extended the time window for the use of mechanical thrombectomy in patients with LVOs to up to 24 hours from LKW, if they again met specific imaging criteria.10, 11 Wake-up strokes and strokes with “delayed” presentation will be discussed later in this chapter.
It is the responsibility of the practitioner in charge of the initial evaluation of the case to identify those patients eligible for EVT and activate the chain of actions that will lead to expedited clot retrieval. Planning a thrombectomy requires coordination between various teams including EMS, emergency medicine, vascular neurology, neurointerventionist, anesthesia, and neurointensive care teams.
Time is Still Important
While the “time window” for EVT is longer than for tPA, getting the artery open as fast as possible is equally important to achieve the best possible outcome. It has been estimated that every hour’s delay in achieving recanalization by EVT results in 8% decreased probability of good outcome.12 Each minute saved in onset-to-treatment time grants on average 4.2 days of extra healthy life, and every 20 minutes decrease in treatment delay leads to an average gain equivalent of 3 months of disability-free life.13 Furthermore, in the delayed time window, as time elapses since symptom onset, the ability of collateral flow to sustain tissue viability gradually diminishes, and consequently fewer patients will have a favorable imaging profile and the amount of salvageable tissue is reduced.
Planning an Endovascular Case
Your patient is suspected or confirmed to have an LVO. Whether the patient is in your ED or being transferred from another facility, deciding to send a patient to the angiography suite for mechanical thrombectomy requires moving down the following sequence of steps in an expedited fashion:
1. Ensure patient receives intravenous thrombolysis if they qualify.
2. Review patient’s eligibility for EVT.
3. Promptly discuss the case with the attending neurologist (or vascular neurologist if available), neurointerventionist, and neurointensivist.
4. Initiate transfer of the patient to the EVT center or, if already on site, facilitate transport to the interventional suite.
5. Obtain consent for the procedure.
6. Activate the interventional and anesthesia teams (this task can be carried by the interventional team as well).
7. Reassess patient eligibility for EVT if time has elapsed since the initial evaluation.
Each step is discussed in more detail below.
1. Is My Patient Eligible to Receive IV tPA?
All patients presenting to the ED or requiring transfer to an EVT center should promptly receive tPA within the 3–4.5-hour window if they qualify. Waiting to see whether tPA has an effect before considering the patient for EVT is not recommended. Sometimes, because of an absolute contraindication to thrombolysis, such as presence of coagulopathy, active bleeding, a history of ICH, or being outside the time window, tPA will be omitted and the patient taken directly to EVT. The question whether tPA can be omitted in all patients going for EVT is being addressed in ongoing randomized studies. Existing data are inconclusive. For now, omitting tPA should only be considered in tPA-ineligible patients and perhaps in selected patients in whom the EVT procedure can be done very quickly after arrival at the ED.
2. Is My Patient Eligible to Receive EVT?
a. Age ≥ 18 – None of the available RCTs enrolled patients under 18 years of age. Some case reports and case series have however demonstrated high recanalization rates in patients < 18 years old.
b. Favorable premorbid condition (mRS 0–1) – In general, the recent trials required patients to have a good premorbid function (mRS 0 or 1) to be eligible for EVT. In our practice, however, we still do consider patients with baseline mRS 2–4 for EVT after discussion with family and assessment of possible gains from the patient’s baseline condition. The amount of benefit to be expected in disabled patients is deserving of further study.
c. Demonstrable LVO in ICA or MCA M1
Whenever possible, patients should undergo a non-invasive angiographic study, such as a CTA, to confirm an LVO. In the case of CTA, this entails availability of the imaging modality, appropriate vascular access, and absence of contraindications to iodinated contrast (advanced renal failure or severe contrast allergy such as anaphylaxis). MRA is an alternative to CTA if the latter is not feasible. In some cases, the clinical picture is highly suggestive of an LVO and the angiographic study can reasonably be bypassed to get the patient to the interventional suite as fast as possible.
Most of the occlusions treated with EVT in the trials were in the distal ICA or proximal MCA M1. Occlusions of other vessels (MCA M2, MCA M3, ACA, PCA, basilar or vertebral arteries) were either excluded or underrepresented, so no strong evidence exists yet to claim benefit of EVT in those cases. Treatment of patients with relatively distal occlusions should be individualized, taking into consideration the severity of the deficit and difficulty accessing the clot. Patients with proximal carotid occlusive disease or dissection were also underrepresented in the randomized trials. While at relatively higher risk of procedural complications, these proximal lesions can be carefully negotiated to achieve successful distal thrombectomy. Whether the proximal lesions should be stented or have angioplasty at the time of thrombectomy will depend on anatomy, ability to access the distal clot, and adequacy of collaterals.
d. Significant acute neurological deficits (NIHSS ≥ 6) – Although some of the trials enrolled patients with lower NIHSS on presentation, there are insufficient data to document the benefit of EVT in that patient population. Further RCTs are required to study EVT in patients with minor, yet disabling, strokes and LVO.
e. Favorable neuroradiographic findings – Safe and efficacious clot retrieval depends on the absence of extensive ischemic changes (i.e., small infarct volumes) and the presence of a relatively large penumbra to salvage. A robust collateral circulation gives patients the ability to be considered for delayed reperfusion attempts. This becomes very important for patients presenting with wake-up strokes or strokes of delayed presentation (> 6 hours from LKW). The role of perfusion studies in the “early” window (up to 6 hours) is not very well established. In the “late” window (6–24 hours), however, these studies are important for the appropriate selection of patients for EVT.
Strokes presenting within 6 hours from LKW – This section is based on the results of the following trials: MR CLEAN, EXTEND-IA, SWIFT PRIME, ESCAPE, REVASCAT, and THRACE (Table 6.1).
i. ASPECTS ≥ 6 – The ASPECTS scoring system is a tool to quickly and reliably obtain an estimate of the extent of ischemic changes. The majority of the 2015 trials used ASPECTS to select patients for EVT. ASPECTS ≥ 6 was associated with better outcome from EVT, whereas a score < 6 was associated with no benefit and potentially greater harm from reperfusion injury. The 2018 AHA/ASA guidelines for the early management of acute ischemic stroke give the estimation of ASPECTS a strong recommendation.14
ii. Small infarct core volumes and large penumbra–core mismatch – SWIFT PRIME and EXTEND-IA showed benefit for patients with a small infarct core size (< 50 mL and < 70 mL, respectively), and a large mismatch ratio (> 1.8 and > 1.2, respectively). These studies used CT or MR perfusion coupled with an automated software that calculates volumes and ratios based on designated CBF and Tmax thresholds. However, the latest guidelines do not routinely recommend obtaining perfusion studies to determine patient eligibility for EVT in the early reperfusion window.
iii. Collateral status – ESCAPE further selected patients on the basis of collateral circulation. This study enrolled patients with moderate-to-good collaterals, defined as 50% or greater filling of MCA pial arterial circulation as seen on multiphase CTA.
Trial | Selection characteristics and outcomes |
---|---|
MR CLEAN | Less strict mRS and NIHSS inclusion criteria |
Did not select based on any specific radiographic criteria | |
Lowest recanalization rate of all the studies (used IA tPA and first-generation devices in minority) | |
Lowest effect size (NNT = 7) | |
ESCAPE | Used multiphase CTA |
Selected moderate-to-good collateral circulation filling (i.e., > 50% of MCA pial arterial circulation) | |
SWIFT PRIME | Used perfusion studies (MRI/CT) – core infarct and penumbra criteria |
EXTEND-IA | Largest effect size (NNT = 3–4) |
Highest recanalization rate of all the studies | |
REVASCAT | Used CT or MRI ASPECTS |
Strokes presenting within 6–24 hours from LKW – The DAWN and DEFUSE 3 trials addressed the topic of strokes with delayed presentation (Tables 6.2 and 6.3). DAWN enrolled patients 6–24 hours from LKW, while DEFUSE 3 limited the time window to 6–16 hours. The common feature between these two trials was the selection of patients on the basis of their infarct core–penumbra mismatch as obtained by CT or MR perfusion studies and measured by automated software. In both trials, the infarct core was determined as the tissue with a CBF falling below 30% of the unaffected contralateral hemispheric CBF.
i. DAWN – DAWN’s particularity is that it looked at a clinical–radiographic mismatch. It categorized patients into three groups as depicted in Table 6.2. Patients in groups A and B had a statistically larger benefit from EVT compared to IV tPA alone.
ii. DEFUSE 3 – To be enrolled, patients had to have an initial infarct volume smaller than 70 mL and a penumbra–core mismatch ratio greater than 1.8. The penumbra was determined as the tissue with Tmax longer than 6 seconds.
Clinical deficit–infarct volume mismatch (DAWN trial) | Infarct core–penumbra mismatch (DEFUSE 3 trial) |
---|---|
Group A: ≥ 80 y.o., NIHSS ≥ 10, infarct volume < 21 mL | Initial infarct volume < 70 mL |
Group B: < 80 y.o., NIHSS ≥ 10, infarct volume < 31 mL | Mismatch ratio > 1.8 |
Group C: < 80 y.o., NIHSS ≥ 20, infarct volume 31–51 mL |
Characteristics | DAWN | DEFUSE 3 |
---|---|---|
Selection criteria | ||
Last known well (hours) | 6–24 | 6–16 |
Age (years) | ≥ 18 | 18–90 |
National Institute of Health Stroke scale | ≥ 10 | ≥ 6 |
Baseline modified Rankin scale | 0–1 | 0–2 |
Maximum infarct volume (mL) | 51 | 70 |
Results | ||
Functional independence (modified Rankin scale 0–2, EVT vs. MM) at 90 days | 49% vs. 13% (p > 0.999) | 44.6% vs. 16.7% (p < 0.001) |
Symptomatic ICH, EVT vs. MM | 6% vs. 3% (non-significant) | 7% vs. 4% (non-significant) |
All-cause mortality, EVT vs. MM | 19% vs. 18% (non-significant) | 14% vs. 26% (p = 0.05) |
3. Three-way Discussion Between Stroke, Neurointerventionist, and Neurocritical Care Teams
a. Decision to go for mechanical thrombectomy requires the involvement of the vascular neurology, neurointerventionist, and neurocritical care teams.
b. Once you have identified that (or are unsure whether) a patient is suitable for EVT, you should contact the attending neurologist or vascular neurologist on call and discuss the case with them. Ensuring that you have a maximum of pertinent information such as time of LKW, premorbid condition, labs, imaging, and neurological exam (NIHSS) will expedite the process and avoid delays.
c. Familiarity with how to contact the neurointerventionist team is also very helpful (pager numbers, on-call schedule, etc.).
d. After the procedure is completed, the patient will be admitted to the neurointensive care unit for close monitoring, creating the need to contact the ICU staff and keep them updated with the progress of the case. The ICU should be made aware of the patient upfront so that arrangements for bed assignment and personnel mobilization can be made.
4. Facilitate Timely Transfer of the Patient to the Interventional Suite
The patient could be in the emergency room, at an outside hospital, or in a different unit/floor within the hospital. Regardless of the location, it is the responsibility of the practitioner initially evaluating the patient to facilitate transfer to the angio suite.
This may mean physically helping with patient transport, or contacting the admitting office, bed management office, and/or air medical service your hospital is contracted with (if the patient is to be flown in).
5. Obtain Consent for the Procedure
Consent can be obtained from patient or family, or, if that is not possible, an emergency two-physician consent can be signed.