Aneurysm Coiling and

Flow Diverters

Italo Linfante MD, FAHA Director

Endovascular Neurosurgery

Baptist Neuroscience Center

Baptist Cardiac and Vascular Institute

Cerebral Aneurysms

TREATMENT

Traditional Surgery

Microsurgical

Clipping

Endovascular Embolization

Multicentric prospective RCT

comparing Endovascular

coiling and Neurosurgical

clipping for ruptured intra-

cerebral aneurysms.

Lancet. 2002;360:1267–1274

Funding agencies: UK Medical Research Council

Canadian Institute of Health Research

French Health Ministry

Stroke Association of the UK for

Neuropsychological assessments

ISAT ISAT was a randomized controlled trial of

patients with aSAH

2143 patients with ruptured intracranial

aneurysms randomly assigned to MC and

ET

95% of the aneurysms were < 10 mm in

size and 54% were < 5 mm in size.

Primary outcome at 1 year n=1528

Endovascular Neurosurgical

0

20

40

60

80

100

0-no symptoms

1-minor symptoms

2-some restriction

3-significant

restriction

4-partly dependent

5-fully dependent

6-dead

Pro

portio

n (%

)

Treatment allocation

p value for 0-2 vs 3-6=0.00082 2 for trend = 11.4

p=0.00075

Long-term ISAT

• Early survival advantage of endovascular maintained to 7 years and remained significant

• In SAH coiling results in absolute reduction in the risk of death or dependency of 7.4% compared to clipping

• Non significant increased risk of hemorrhage in endovascular group (0.2;0.1)

Lancet 2005 3-9;366:809-17

AJNR Procedural Complications of Coiling of

Ruptured Intracranial Aneurysms:

Incidence and Risk Factors in a

Consecutive Series of 681 Patients

W.J. van Rooija, M. Sluzewskia, G.N. Beuteb and P.C.

Nijssenc

Complications for Coiling of

Ruptured Aneurysms

Complications 40 of 681 patients 5.87%

Death in 18 patients 2.6%;

Disability in 22 patients 3.2%; 95% CI, 2.0% to

4.9%).

There were 8 procedural ruptures

The use of a temporary supporting balloon was

the only significant risk factor (OR, 5.1; 95% CI,

2.3 to 15.3%) for the occurrence of procedural

complications.

58 yo woman with SAH

Balloon assisted coil embolization

12 months f/u months angiography

73 year old with ICH and SAH (AP view 66 yo with right HP

)

3D

R MCA (M1)

R MCA (M2)

R MCA (M2)

Final (AP view)

Final ( unsubtracted AP view)

Unruptured Aneurysms

Hospital Mortality and Complications of

Electively Clipped or Coiled Unruptured

Intracranial Aneurysms

Amer Alshekhlee, Sonal Mehta, Randall C. Edgell, Nirav Vora, Eli Feen, Afshin

Stroke 2010, 41:1471-1476:

Clip vs Coil

National Inpatient Sample database for the years

2000 through 2006

3738 (34.3%) clipping 3498 (32.1%) coiling

Hospital mortality higher with clipping 60

(1.6%) vs 20 (0.57%) (p=0.001)

Hospital Stay: longer with clipping (4 vs 1 day;

p=0.0001), incurring a higher hospital charges

($42,070 vs $38,166; P=0.0001)

Clip vs Coil

Perioperative intracerebral hemorrhage and acute

ischemic stroke were higher in the clipped

population.

The rate of hospital use of coil embolization has

increased over the years (P = 0.0001)

61 yo man with headaches

Bioactive coils

3D 6 m follow-up angiograms

12 month f/u

Wide Neck Aneurysms

Neurostents Design

68 yo w fusiform left MCA aneurysm

3D

Stent assisted coil embolization

Before

1 year follow-up

First stent

Second stent

Reconstruction of the ICA with 2 stents

Final Post Coil Embolization

One Year F/U Angiography

Closed-Cell Stent for Coil Embolization of

Intracranial Aneurysms: Clinical and

Angiographic Results

Wakhloo AK, Linfante, Silva C, Dabus G,Segal E, Samaniego E,

Gounis M

Stent Assisted Coil

Embolization • 147 consecutive patients in 2 centers with 161 wide-neck

ruptured and unruptured

• Procedure-related mortality 2 patients (both

ruptured)(1.4%)

• Permanent neurological deficits 5 patients (3.4%),

respectively

• Follow-up angiography showed recanalization occurred in

12 aneurysms (10%), requiring retreatment in 7 (5.8%)

• Moderate in-stent stenosis 1 (0.8%), which remained

asymptomatic

Complications No (%)

Intraop. Thrombus* 7.4%

Intraop. Perforation

1.4%

TIA 2.2%

Minor Stroke 3.0%

Major Stroke 2.2%

Access Site 3.5%

Deaths^ 3.0%

0 2 4 6

Results: Montreal Shift

Although post-procedure shows many Class II

and III results (pts on ASA, Plavix, and Heparin)

– follow-up shows mostly Class I

16% 82%

Scale defined in: D Roy, G Milot, & J Raymond. Stroke 2001; 32:1998

Class III:

23% Class I: 48% Class II: 29%

2%

Flow Diversion

Flow Diversion

Disruption of the fluid momentum

transfer from the parent vessel into

into the aneurysmal sac

Endothelial growth

Particle Image Velocimetry

Side wall aneurysm – Shear-driven Flow (I)

Lieber, Nikolaidis, Wakhloo Ann Biomed Eng 1998

0

1( ) where: ( )

T

m

A

t dt V ndAT

Average hydrodynamic circulation

Convection Diffusion

+ 0

1

2

t

e e t-h (h-m) 2

t1 2s 2

t1

dh sp

- -

* f(t)=r1

1

0

1- 1 t t

e (h-m) 2

t2 2s 2

r2 s 2p

- -

-

dh e

÷ ÷

MATHEMATICAL MODEL

Use of Functional Angiography

s,m = Contrast injection related parameters.

r1 = Relative magnitude of contrast convected out of aneurysm.

t1 = Convection time constant.

r2 = Relative magnitude of contrast diffused out of aneurysm.

t2 = Diffusion time constant.

Lieber, Gounis, Chander, Wakhloo Crit. Rev Biomed Eng 2004

21days

90 days

180 days

Wakhloo et al Stroke 2007

Surpass ltd

Clinical Data

Pipeline

2009 2010 2011 2012 2013 2014 2015

Buenos Aires

Experience

n= 53 patients

12 month follow up

PITA

n=31 patients

6 month follow up

Budapest

Experience

n= 18 patients

6 month follow up

Australian Registry

n=54 patients

Up to 1 year follow up

Ankara

Experience

n=191 patients

Up to 24 months

follow up

Hong Kong

Experience

n=143 patients

Up to 18 months

follow up

PUFs n=108 patients

6 months follow up

IntrePED n=793 patients

12 to 24 month follow up

ASPIRe n=191 patients

7 Years of Publications on

Pipeline™

PUFs (Pipeline™ Embolization

Device for Uncoilable or Failed

Aneurysms) : Results from a Multicenter

Clinical Trial

Tibor Becske et al Radiology 2013;267:858-68

PUFs Aneurysm Characteristics: Size • Prospective, multi-center trial 108 patients

• Large or Giant & Wide-Necked

o ≥10 mm diameter

o ≥ 4 mm neck

|

Mean Size

(mm)

Range (mm)

Aneurysm 18.2 6.2* – 36.1

Neck 8.8 4.1 – 36.1

*One 6.2 mm aneurysm was treated but excluded from

efficacy analysis because <10 mm diameter. PUFs FDA Summary of Safety & Effectiveness Data (SSED)

Endpoints Independently Adjudicated

Core Radiology Lab

3 physicians

Adjudicated all

angiograms

Clinical Events

Committee

3 physicians

Adjudicated all SAEs

EFFECTIVENESS SAFETY

PUFs FDA Summary of Safety & Effectiveness Data (SSED)

PUFs Primary Safety

Endpoint Event Descriptions

Primary Safety Endpoint Event Descriptions* # %

Hemorrhage (parenchymal bleeds not SAH) 2 1.9%

>50% stenosis with major stroke 1 0.9%

Thrombosis with major stroke 2 1.9%

Probable neurologic death** 1 0.9%

Total 6 5.6%

* Safety events that did not result in a major stroke or neurologic death were not classified as primary safety endpoint events.

** Event was classified as probably neurologic death of unknown cause. No head CT or autopsy completed.

PUFs FDA Summary of Safety & Effectiveness Data (SSED)

PUFs Summary • Prospective, multi-center trial 108 patients

• Challenging aneurysm characteristics – 20% giant,

18.2 mm average size

• High rates of occlusion – 82% at 180 days, 86% at

1 year

• Complications – 5.6% rate of major

stroke/neurological death at 180 days

• Approval by the FDA in April 2011

PUFs FDA Summary of Safety & Effectiveness Data (SSED)

International Retrospective Study of the Pipeline

Embolization Device: A Multicenter Aneurysm

Treatment Study (IntrePED)

D Kelmes et al AJNR 2015

Neurological death

0

5

10

15

20

25

30

35

40

24 hr 30 hr 180 days Complete f/up

1.0%

2.9%

3.2% 3.8%

All Patients

Median follow-up 19 months

days

Posterior – 5 Ruptured – 6

Safety Outcome:

Ischemic Stroke

Total

incidence

52/793

(6.6%) Minor

15

(1.9%)

Major

37

(4.7%)

• Anterior location – 33/737 (4.5%) ; Posterior location – 4/56 (7%)

• Outcome of event Resolved – 26 (3.2) ; death – 11 (1.5%)

95% CI [3.3% - 6.4%]

Total M&M

• The overall M&M rate, consisting of major

ischemic stroke, hemorrhage, neurological

death, delayed rupture, stenosis and

permanent cranial neuropathy was 8.3%

(66/793).

Treatment Study % F/u &

Duration

Pts M&M Intracranial

Hemorrhages

Pipeline PUFs 96% /

1 year 107

5.6% 1.9%

Pipeline IntrePED 19.3 mo

median 793

8.3% 2.4%

Stent-Coiling Fiorella et al,

2009

62%

13 mo 284

8.1% 1.4%

Meta- analysis

Stent-Coiling

Shapiro et al,

2012

13 mo

avg

1517 pts (763 pts reported

M&M)

5.3% 2.2%

Safety profile compared to

stent assisted coiling

Clinical History

16 yr old woman developed generalized

tonic clonic seizure

She had associated transient diplopla

without headaches

No significant past medical history

Head CT demonstrated possible brain mass

MRI/MRA brain showed a 30mm LICA

fusiform aneurysm with bony erosion

First PED deployment

Initial Deployment in Distal Left ICA

Pipeline 5.0 x 35mm

Distal end dislodged while trying to free

proximal end to undo twist

Second PED (4.5mm x 35mm)

Third PED 4.5 x 20 mm

Final Angiogram

Immediate Clinical Followup

Occasional headaches after procedure treated

with steroids and tylenol

Partial left 6th nerve palsy with left eye

minimally crossing midline to the left

Small area of visual defect affecting the left

inferior aspect of field of view with

progressive improvement

No other neurological deficits

Clinical History

64 yr old woman with progressive

deterioration of her cognitive functions

On exam is deeply drowsy requiring

intubation

Head CT demonstrated possible brain mass

53 y/o man with a SAH

SCENT Trial

The Surpass intraCranial aneurysm

EmbolizatioN system pivotal Trial to

treat large or giant wide neck aneurysms

Surpass Deployment

Surpass Deployment

Surpass Deployed

Cone beam CT

Final Angiogram

Deployment

5.3mmx50mm

6 month follow-up Pre-Implant

Conclusions

The treatment of intracranial aneurysms is

Endovascular

Overall M&M is inferior to clipping

Undoubtedly, FD is a mayor advancement in

the treatment of large and giant aneurysms,

previously considered “untreatable”

Trials ongoing for small aneurysms