Transforming Stroke Care Through Advancements in ......acute ischaemic stroke. As originally...

©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

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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.

46-54_Medtronic Symposium.indd 4646-54_Medtronic Symposium.indd 46 13/12/2019 12:0513/12/2019 12:05

CNS 2019: 5:(2). DECEMBER 2019 47 ©ORUEN LTD

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

CNS 2019: 5:(2). DECEMBER 2019 48 ©ORUEN LTD

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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CNS 2019: 5:(2). DECEMBER 2019 49

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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CNS 2019: 5:(2). DECEMBER 2019 50

Patient 3:84-year-old with atrial fibrillation, last seen as normal the

previous evening.

• Right hemiplegia, aphasia, H&E deviation and decreased


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


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)


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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CNS 2019: 5:(2). DECEMBER 2019 51

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


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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CNS 2019: 5:(2). DECEMBER 2019 52

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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CNS 2019: 5:(2). DECEMBER 2019 53

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.

References1. Vahedi K, Hofmeiher J, Juettler E, et al. Early decompressive

surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6(3):215-222.

2. Flint A, Duckwiler G, Budzik R, Liebeskind D, Smith W. Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. Stroke. 2007;38(4):1274-1280.

3. Campbell B, Mitchell P, Yan B, et al. A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA). Int J Stroke. 2014;9(1):126-132.

4. ClinicalTrials.gov. Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE). https://clinicaltrials.gov/ct2/show/study/NCT01778335. Published 2015. Accessed 23 November, 2019.

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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CNS 2019: 5:(2). DECEMBER 2019 54

18. Berkhemer O, Fransen P, Beumer D, et al. A randomized trial of intra-arterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11-20.

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13. Psychogios M, Behme D, Schregel K, et al. One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times. Stroke. 2017;48(11):3152-3155.

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