transforming stroke care through advancements in ......acute ischaemic stroke. as originally...
TRANSCRIPT
©ORUEN LTDCNS 2019: 5:(2). DECEMBER 2019 46
IntroductionWhen an individual presents with a large artery occlusion,
rapid identification of the artery is crucial if patients are to
survive and avoid major disability. If clinicians choose not to
treat, or are unable to recognise the problem, 84% of patients
will either die or become disabled, and in the developing
world an inability to recognise and treat this condition leads
to more deaths than disability. The prognosis for malignant
middle cerebral artery (MCA) syndrome is 80% mortality,1 and
internal carotid artery (ICA) “T” occlusion has a 73% mortality
in non-recanalised patients.2 However, in the last few years
advances have been made in the development of powerful
and extremely effective treatments for stroke patients.3-7
Unfortunately, time is not on our side especially when the
subject is stroke, and the problem lies with the events that
©ORUEN LTD
Transforming Stroke Care Through Advancements in Technology and an Overview of the
PROSPR-SEA Post-Market Surveillance Study ITALO LINFANTE MD, FAHA1 and PROF. DR. PHAM MINH THONG2
1Medical Director of Interventional Neuroradiology and Endovascular Neurosurgery, Miami Clinic and Vascular Institute, 8900 North Kendall Drive, Miami, Florida, FL 33176.2Deputy Director in charge of Expertise, Bach Mai Hospital, 78 Gial Phong, Phuong Mai, Dong Da, Hanoi, Vietman.
Received – 6th December 2019; Accepted – 9th December 2019
Abstract Stroke is the second leading cause of disability and death worldwide, and many new techniques and tools are now available which improve clinical outcomes of stroke patients. New technologies currently being developed and used in surgical procedures are discussed in this meeting summary, along with an overview of a post-market registry study of stroke patients treated with Medtronic neuro-thrombectomy devices. The results of the important study known as PROSPR-SEA will provide essential real world data of stroke patient treatment outcomes in South East Asia.
KEYWORDS: ATRIAL FIBRILLATION; CARDIOVASCULAR DISEASE, CHRONIC KIDNEY DISEASE, DIABETES, ISCHAEMIC HEART DISEASE; STROKE.
Corresponding author: Allison Kirsop – [email protected]
Disclosures: Dr. Linfante is a consultant, speaker and proctor for Medtronic.
Acknowledgements: We thank Dr Allison Kirsop and Oruen Ltd. for medical writing and editorial assistance in the preparation of this manuscript.
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the team members who take care of the patients. Using AI,
images can be sent immediately which allow you to see
exactly how big the penumbra is, or how much tissue there
is subject to the core, leading to faster identification of the
arterial occlusion (Figure 1a and 1b). In 2018, the workflow
intervention for Miami Clinic and Vascular Institute was:
Door-to-CT 30 min, Door-to-Groin 60 min, and Door-to-
Recanalisation 90 mins, and stroke teams throughout the
world are becoming continually faster.
In the US, one interesting developing technology is found
in the angiography room where CT scans can be obtained.13
unfold once an artery occludes. The formation of a core leads
to expansion of the core to the penumbra area and core
progression must be halted to achieve a strong outcome.
It is a very important concept and time plays a major role.
A large meta-analysis of several well-known trials shows a
very strong inverse correlation between symptom onset
to reperfusion time and good clinical outcome; mortality
is very high – every 20 minutes of delayed recanalisation.8
Supporting data of Modified Rankin Scale (mRS) scores from
these trials clearly shows a reduced percentage of patients
with good clinical outcome from the time from symptom
onset to reperfusion.9
Reiterating the importance of time in acute stroke, an intere-
sting analysis shows that every minute in time you save, you
can save over one week of extra healthy life, and every 20
minute decrease in treatment delays equals a three-month
gain of disability-free life.10 These data emphasise the
importance of being fast and all medical professionals
in stroke care are continuing to learn more about the
importance of time.
Core expansion, workflow and intervention
The phrase “time is brain” highlights the rapid loss of
nervous tissue with stroke. The brain dies fast in acute stroke
and although previously estimated at a rate of 1.9 million
neurons per minute,11 there are now data that show a large
variability among patients. In a group of patients known
as slow progressors (typically younger patients with good
collateral circulation), the estimated neuronal death rate
was <35,000 neurons per minute. In the group known as
fast progressors (older patients, very hypertensive with poor
collateral circulation), these patients progress much faster
with an estimated loss of 27 million neurons per minute.12
Stroke has a very multidisciplinary type of approach, and
the assistance of many people is needed to provide a fast
response and quick action. Improvements to the workflow
of this complex chain is where change happens first; from
emergency room to physicians for scans, to the neurologist,
neuroradiologist, and finally the surgeon to recanalise the
artery. Some extremely interesting technologies will be
available in the near future that use artificial intelligence
(AI) to analyse data going from a sequential workflow to
a parallel workflow. In this system, all data are analysed in
an extremely fast manner and automatically distributed to
MEDTRONIC SYMPOSIUM, WFITN 2019 NAPLES.
Figure 1. a) AI used to automate workflow from a serial to parallel process, b) AI powered detection and triage.
Abbreviations: AI, artificial intelligence
b)
a)
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Innovation: Techniques and Devices to Achieve First Pass
Effect
We have several techniques today that do not work especially
well, or fast, with a tremendous amount of data on balloon
guide and stent-triever methods which do improve outcomes.
However, since the large bore aspiration catheter came into
use, things have changed somewhat. Advancements in
device technology include the Solitaire™ X Revascularisation
Device that can be delivered through a smaller microcatheter
(Figure 3). We will soon see an increase in the number of
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Patients are taken straight to the angiography suite equipped
with flat detector computed tomography [FDCT] technology,
bypassing CT. The images produced are of a higher quality
than standard CT images; Figure 2 clearly demonstrates the
presence of haemorrhage, a main exclusion criteria.
Thrombolysis in Cerebral Infarction (TICI 3): First Pass
Effect
The Thrombolysis in Cerebral Infarction scale, TICI, helps
standardise how angiographic outcomes are graded, and
is especially relevant for trials of endovascular treatment of
acute ischaemic stroke. As originally described by Higashida
et al (2003),14 categories of TICI range from grade 0 to grade
3, (no perfusion to complete perfusion, respectively).15 The
TICI 3 first pass effect is an alternative method used to
reduce time to recanalisation, and is described in a study of
a large cohort of patients from the North American Solitaire
Acute Stroke (NASA) Registry.16 The metric known as first
pass effect (FPE) is defined as a single pass/use of a device
and complete revascularisation with no rescue therapy used;
data reveal the best outcomes, not only in terms of disability
and mortality, and are achieved with the TICI 3 first pass.
First pass is extremely rapid and also less traumatic which
translates to excellent outcomes, and a possible benchmark
when selecting new devices that would be effective in saving
a patient’s life or reducing disability.
Figure 2. Images from the angiography suite, reproduced from Psychogios et al.,13 a) clearly demonstrate the presence of a haemorrhage; and b) white arrows show early ischaemic signs delineated on right caudate, lentiform nucleus and insula (A) while (D) highlights maximum inten sity projections of first arterial phase of biphasic flat detector CT angiography depicting distal M1 occlusion of right middle cerebral artery. Abbreviations: CT, computed tomography.
b)a)
Figure 3. New advancements in device technology showing the Solitaire™X revascularisation device, micro-catheter, and large- bore catheter.
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When patients are very elderly, it is useful to perform recana-
lisation of the artery using tools such as:
• 8 French Short Sheath, 0.088”
• Long Sheath, 0.071”
• React™ 71 Catheter
• 0.027” Marksman™ 160 cm Micro Catheter
• 0.014” Guide Wire
• 4x40 Solitaire™ Platinum device (aspiration and
thrombectomy).
In this patient, the 360 degree loop of the carotid was
navigated easily with the device (Figure 7). The patient had
to be intubated due to a decreased level of consciousness.
different aspiration systems; particularly interesting
is the alternating aspiration system. In addition,
there are very powerful aspirators and large-bore
catheters. Medtronic products React™68 and
React™71 catheters are very large-bore and built
with technology that allows navigation of the device
in extremely tortuous vessels as well as in elderly
patients (Figure 4). Several combinations of the
device can be used and tailored to suit an individual’s
requirements. The approach to which one is optimally
suited will depend upon that patient’s anatomy and
no single method is considered superior (Figure 5).
Today, it is very exciting to bring new devices and
new technology to the patient’s bedside and the
following section will focus on some case studies.
Case StudiesPatient 1: 95-year-old with atrial fibrillation:
• Left hemiplegia, neglect, H&E deviation and decreased
level of consciousness.
Unfortunately, symptoms were not recognised as stroke
by the emergency medical services (EMS) which resulted
in no activation from the field. There are several datasets
that demonstrate how these strokes are deadly in patients
over 90 years of age; if symptoms are not recognised fast
enough the outcome is not going to be successful, and
these patients will not survive. The patient’s NIHSS was 18
and M1-M2 occlusion was a very tortuous aorta (Figure 6).
Figure 5. Medtronic Solitaire™X with Phenom™21.Figure 4. Medtronic React™ 68 and 71 catheters with coil braid (COBRA) technology.
Figure 6. Case study of Patient 1: images of tortuous aorta.
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Patient 3:84-year-old with atrial fibrillation, last seen as normal the
previous evening.
• Right hemiplegia, aphasia, H&E deviation and decreased
level of consciousness.
The patient had a high NIHSS = 17 and left M1 occlusion.
RAPID imaging revealed a small core and large penumbra,
and again, the same tools were used as described previously.
Figure 10 shows how the REACT catheter can travel to
the distal M1 without any particular problem and gave an
excellent result for this 84-year-old.
Follow-up revealed:
• CT-to-Groin time 84 min
• Groin-to-First Pass 19 min
• CT-to-First Pass 103 min
• Groin-to-Recanalisation 28 min
• NIHSS = 6 after three days.
Patient 2: 72-year-old with atrial fibrillation:
• Right hemiplegia, aphasia, H&E deviation, decreased
level of consciousness.
The patient had NIHSS = 17, left ICA T occlusion, and was
intubated in the angiography room due to the decreased
level of consciousness. Figure 8 shows the pseudo-oc-
clusion at the cervical section due to a more distal occlusion.
Inserting a balloon guide catheter is not recommended
where there may be a large 360 degree loop of the carotid,
and the same tools were used as for Patient 1. The images in
Figure 9 show the recanalisation TICI 3 First Pass and recana-
lised carotid.
Follow up revealed:
• Door-to-CT 15 min (IV tissue-type Plasminogen Activator
(t-PA))
• Door-to-Groin 45 min
• Groin-to-Recanalisation 35 min with TICI 2b (2 passes due
to carotid)
• NIHSS = 8 after three days.
Figure 8. Pseudo-occlusion at the cervical section.
Figure 9. The recanalisation TICI 3 First Pass and recanalised carotid artery on the right hand side.
Figure 7. Navigation of the 360-degree loop with the device for recanalisation of the artery.
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out a thrombectomy in the M2 occlusion, with the hope of
removing the clot without destroying the AVM.
The best option is for aspiration alone, to remove the clot
while keeping the AVM intact. In this case, the same tools
were used as for the previous case study patients with the
exception of no stent-triever. A large-bore catheter was
inserted into the M2 occlusion with local aspiration to
remove the clot, a surprisingly remarkable procedure with
this gigantic catheter. The artery was recanalised successfully
and the AVM remained intact. A CT scan was performed in
the angiography room immediately following the procedure,
and again after 24 hours (Figure 12). The patient responded
extremely well with only mild aphasia after three days.
Follow up revealed:
• Door-to-CT 20 min (IV t-PA)
• Door-to-Groin 45 min
• Groin-to-Recanalisation 25 min with TICI 3 One Pass
• NIHSS = 4 after three days.
Patient 4:91-year-old – a very interesting and challenging case as the
patient is on t-PA therapy.
• Aphasia and right hemiparesis.
The patient was taken to the hospital very quickly, around
one hour after symptom onset. Nevertheless, NIHSS =
18 and she received IV t-PA. Imaging by CT Angiography
revealed a suspected left M2 occlusion, but the patient also
had an arteriovenous malformation (AVM) (Figure 11).
The challenge is in deciding on options for mechanical
thrombectomy on a 91-year-old who is on t-PA and has
an AVM. One recommendation might be to do nothing
due to the patient’s age and the risk of causing a massive
brain haemorrhage. Other options include balloon guide
and stent-triever, aspiration and stent-triever, or aspiration
alone. In this case, a stent-triever would not be the correct
approach due to the added complication of the AVM
while on t-PA treatment. Aspiration with the stent-triever
might be considered as it is a distal vessel; the large-bore
catheter could be parked in the M1 segment while carrying
Figure 10. a) RAPID images showing the core and penumbra; b) image of REACT catheter in a distal M1 occlusion.
b)a)
Figure 11. Imaging shows the presence of arteriovenous malfor-mation (AVM).
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criterion all patients had AIS due to large intracranial vessel
occlusion within 8 hours of symptom onset.
At the enrolling hospital, individuals were enrolled on arrival,
if they were an existing in-patient, or a transfer from a referral
hospital, and all were treated with a Medtronic market-re-
lease neurothrombectomy device (Figure 13). Follow-up was
90-days (± 15) post-procedure. For the visit and assessment
schedule at baseline and according to standard of care,
pre-stroke mRS and pre-treatment NIHSS were completed
and ASPECTS evaluated from baseline imaging at the
enrolling hospital. Post-procedure NIHSS reflected the most
recent score within the 24 ± 8 hour post-procedure window.
The primary endpoint was mRS at 90 days and safety end-
points included symptomatic intracranial haemorrhage
(sICH) at 24 ± 8 hours post-procedure, all-cause mortality at
90 days, and emboli in new territory (ENT) at 24 ± 8 hours
post-procedure. Secondary endpoints included re vas cu -
larisation using the mTICI score, workflow metrics, NIHSS
score at hospital discharge, post-acute discharge disposi-
tion, and subject disposition at study exit. Adverse events
were sICH and death (neurological or non-neurological).
The intent of the study was to assess clinical outcomes
associated with the use of the Solitaire™ devices and the
workflow for management of stroke patients within the
region. Data from the PROSPR-SEA study were comparable
with studies such as the HERMES trials previously mentioned
and the STRATIS Registry,23 and an initial review showed
there were sufficient data to demonstrate intent had been
achieved. Enrollment was therefore stopped early at 183
patients; it was unnecessary to continue enrolling up to 500
subjects as the sample size was not hypothesis driven.
SummaryTechnology use in acute stroke is advancing rapidly with
device development for TICI 3 First Pass which will likely
be the benchmark for new technology in the future. Large
bore aspiration catheters are impressive technology and
are changing the landscape of acute stroke treatment. As
thrombectomy tools, REACT™ catheters and Solitaire™ X
add to the existing options, and the REACT™ 71 catheter
is especially easy to navigate with high aspiration power.
Analysis of the data from the PROSPR-SEA study will soon
be finalised with the results presented at major conferences.
Follow up revealed:
No haemorrhage
24 hour post-NIHSS = 4.
Post-Market Registry of Stroke Patients Treated With
Medtronic Neuro Thrombectomy Devices to Collect Real
World Data in South East Asia (PROSPR-SEA): Study
Overview
With more than 60% of the world’s population, the stroke
burden in Asia is a serious problem. Variations in stroke
epidemiology and a lack of data is apparent for many South
East Asian developing countries.17 Trends of stroke incidence
studied over four decades between 1970–2008 revealed a
42% decrease in high-income countries, whereas low-to-
middle income countries experienced greater than 100%
increase; examples include Singapore with an incidence rate
of 180 per 100,000 person-years, and Vietnam with 250 per
100,000 person-years which is extremely high. Existing studies
known collectively as the HERMES trials,6,18-21 (REVASCAT,
MR CLEAN, ESCAPE, SWIFT PRIME, and EXTEND IA) do
not appear representative of all Asian countries, and more
data are needed to establish robust clinical evidence of
mechanical thrombectomy in South East Asia.
PROSPR-SEA is a prospective, multi-centre, non-randomised,
observational registry study designed to assess post-market
clinical outcomes of Medtronic Solitaire™ neuro-thrombe-
ctomy devices.22 Approximately 500 patients were enrolled
from three South East Asian countries (Vietnam, 4 sites;
Thailand, 3 sites; and Singapore, 3 sites) and as an inclusion
Figure 12. CT image 24 hours after aspiration-only procedure to remove clot while successfully keeping AVM intact.
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5. Saver J, Goyal M, Bonafe A, et al. SolitaireTM with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke. Int J Stroke. 2015;10(3):439-448.
6. Jovin T, Chamorro A, Cobo E, et al. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke. N Engl J Med. 2015;372:2296-2306.
7. Jovin T, Saver J, Ribo M, et al. Diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention with Trevo (DAWN) trial methods. Int J Stroke. 2017;12(6):641-652.
8. Linfante I, Walker G, Castonguay A, et al. Predictors of Mortality in Acute Ischemic Stroke Intervention: Analysis of the North American Solitaire Acute Stroke Registry. Stroke. 2105;46(8):2305-2308.
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surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6(3):215-222.
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SOLITAIRE™ DEVICE MODELS
ModelRecommended Vessel
Diameter (mm) Minimum Microcatheter ID Push Wire Length Radiopaque Markers
Min Max (mm) (in) (cm) Distal Prox.
SRD-4-15 SFR-4-15SFR2-4-15
2.0 4.0 0.5 0.021 180 3 1
SRD-4-20 SFR-4-20SFR2-4-20SFR3-4-20-10
2.0 4.0 0.5 0.021 180 3 1
SFR2-4-40 SFR3-4-40-10
2.0 4.0 0.5 0.021 180 3 1
SRD-6-20 SFR-6-20SFR2-6-20SFR3-6-20-10
3.0 5.5 0.7 0.027 180 4 1
SRD-6-30 SFR-6-30SFR2-6-30
3.0 5.5 0.7 0.027 180 4 1
Figure 13. All Medtronic market-released Solitaire™ device models assessed during post-market surveillance of patients in South East Asia enrolled in the PROSPR-SEA study.
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