Intravascular stents A biased and limited account.

Intravascular stents

A biased and limited account

Outline

• Background– Occlusive vascular disease and its treatment by PCI

and stenting

• Assessment of a novel compliance matching stent and comparison with a commercially available device– In vivo radiographic measurement in pig carotid and

iliac arteries– Development of a micro CT method for stented vessel

morphometry on excised arteries

Cardiovascular Disease statistics

• Heart and circulatory disease are the UK's biggest killers.

• In 2006, cardiovascular disease caused 40% of deaths in the UK, and killed over 245,000 people.

• Coronary arterial disease causes over 120,000 deaths a year in the UK: approximately one in four deaths in men and one in six deaths in women.

Revascularisation techniques

• Coronary Artery Bypass Graft (CABG)

• Percutaneous Coronary Intervention (PCI)– Angioplasty– Plus stenting (94%)

Balloon angioplasty

What is an intravascular stent?

• A small tubular mesh usually made of either stainless steel or Nitinol. (Shape memory alloy)

• Inserted into stenotic (blocked) arteries to keep the lumen patent. Normally during angioplasty.

• Used at various sites including the coronary, renal, carotid and femoral arteries.

• Non-arterial uses e.g. in bronchus, trachea, ureter, bile duct.

History

• The concept of vascular stents is accredited to Charles Dotter in 1969, who implanted stainless steel coils in canine peripheral arteries.– Not followed up in humans because of

haemodynamically significant narrowing.

• Not in clinical practice until 1980s.• Market leader is the Palmaz stent designed by

Julio Palmaz in 1985.– Initially, 18 grafts placed in canine vessels, with

patency rates approaching 80% at 35 weeks.

Varied stent geometries

11651216

70,142

73,612

0

200

400

600

800

1000

1200

1400

1600

1800

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

PC

I pe

r m

illio

n

0

10000

20000

30000

40000

50000

60000

70000

80000

PC

I P

roce

dure

Num

bers

PCI per million

PCI Procedures

PCI activity to 2006 (UK) 2006 data: Ludman

From: British Cardiovascular intervention Society, Audit 2006. http://www.bcis.org.uk/resources/audit/audit_2006

High Tech 2007, MarseilleHigh Tech 2007, Marseille

Nombres de PCI dans certains pays Européens

0

500

1000

1500

2000

2500

3000

3500

4000

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Par 106

habitantsGEGE

BEBE

UKUK

Bernard De Bruyne, Aalst, Belgium

Demographics2006 data: Ludman Age (mean) 64.2 yrs

Diabetic 17.5%

Previous CABG 8.9%

Ethnic Origin

Caucasian 91.2%

Asian 7.5%

Black 1.1%

Oriental 0.2%http://www.bcis.org.uk/resources/audit/audit_2006

Demographics - Age2006 data: Ludman

02000400060008000

100001200014000

No. PCIs<

=30

31-4

0

41-5

0

51-6

0

61-7

0

71-8

0

81-9

0

>90

Age (yrs)

Male

Female

Male: mean = 62.3Female: mean = 67.4

http://www.bcis.org.uk/resources/audit/audit_2006

Procedures using Stents

94.4

0102030405060708090

100

% of Procedures

'92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06

Year

2006 data: Ludman


The problem with stents.

Restenosis. (7 – 20%)

Rate depends on

lesion type, length and severity

Mechanical cause of restenosis

• ↓ shear stress• Intimal Hyperplasia• ↓ lumen• ↑ shear stress• If baseline shear stress not restored – continuing

intimal hyperplasia and RESTENOSIS

Factors Which Contribute toIn-stent Restenosis (1)

• Thrombus/platelet/fibrin adherence to stent struts.– Anticoagulants

• Heparin – systemically or coated on stent.• Inhibition of the GP IIb-IIIa receptor:

– Prevents platelet aggregation.

– Associated with raised incidence of MI.– PTFE coated stents.


• Metabolic disorder/smoking/atherogenic diet.– Life style changes– Restenosis rate double in insulin dependent

diabetics.


• Intimal hyperplasia due to wall injury from the stent– Brachytherapy:

• Delivery: Radioactive stents, catheter radiation.• May cause necrosis.

– Drug eluting stents• Anti-proliferative agents e.g. rapamycin (Sirolimus)• Improved short term survival and maintenance of vessel patency• More work needed to clarify longer term outcome (Circulation

2008, 118, 1817

• No improvement in outcome in insulin dependent diabetics when compared to bare metal stents

• Impaired ‘healing’ late thrombosis, some doubt about how serious this is. More studies needed. (Circulation 2008, 118, 1783)

Drug Eluting Stent cases2006 data from 86 of 91 centres

?

17

5362 63.5

01020304050607080

% D

ES

ca

se

s

2002 2003 2004 2005 2006

2006 data: Ludman Mean of % use by Centres


BMS and DES use V PCI for Restenosis

0

10

20

30

40

50

60

70

80

90

100

'92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06

0

2

4

6

8

10

12

14

% Stent

%DES

% Restenosis

2006 data: Ludman



• Mechanical factors– Stress concentration/bending at end of stent.

• Raised hoop and bending stress sensed by vascular smooth muscle cells → fibrosis/ remodelling

– Flow disturbance within stented region.• Time varying shear stress sensed by vascular endothelium →

release of vasoactive mediators in the short term and remodelling/intimal hyperplasia in the longer term

– Compliant-ended stent

Compliant Ended Stent

• Rigid in the centre to provide recoil resistance

• Parabolic and cantilevered struts– gradual change in compliance and

matching to native vessel– reduces stress concentration and

bending– Less disturbed flow

Experimental assessment of compliant ended stent

Aims• To compare the performance of the CES

and SMART stents over 28 days on vessel and stent dimensions. – To compare the effect of 2 levels of stent

stiffness– To compare the effect of stent oversize

Stents used in the Study

SMART stent

(Commercially available)

Compliant Ended Stent

Method

• 65 stents implanted in the iliac and carotid arteries of 17 Large White pigs

• Lumen diameter determined before and after implantation by angiography– Follow-up angiography on days 3,7 and 28 – At day 28 the arteries were pressure perfused

and removed for histology and micro CT scanning

CESSM

CES

CES

P9 Iliac (day 3)

P12 Carotid (day 7)

CES & Smart stents in common iliac arteries

Vessel dimensions

4

5

6

7

0 5 10 15 20 25 30 35

Position along stent [mm]

Lum

en d

iam

eter

[m

m]

MeasurementsSD Stent diameterLD Lumen diameter

SOS Stent OversizeLOS Lumen OversizeMH Migration/Hyperplasia

100.

pre

prepost

LD

LDSDSOS

LOS LDpost LDpre

LDpre.100

MH SDpost LDpost

LDpost.100

Changes in % lumen oversize with time

SMART (n = 16)

CES (n = 28)

*

LOS LDpost LDpre

LDpre.100

Lumen tends to pre implant dimensions within 1 month

LOS

[%]

5

10

15

20

25

0 10 20 30

Time since implant [day]

Changes in % stent oversize with time

SMART

CES

SOS SDpost LDpre

LDpre

.100

Stent diameter changes little up to 1 month after implantation

SO

S [%

]

15

20

25

30

35

40

0 10 20 30


Changes in stent migration orintimal hyperplasia with time

SMART

CES

MH SDpost LDpost

LDpost.100

CES induces less migration or intimal hyperplasia than Smart stent control

MH

[%]

0

10

20

30

40

50

0 10 20 30


*

*

Palmaz CES

6 week post implantation

Limitations

• Limited resolution of in-vivo X-ray images• Limited study duration

– Part of a larger study with later endpoint

• Can not distinguish between stent migration and intimal hyperplasia– Histology in progress

• Difference in stiffness not yet quantified• Response of carotids & iliacs different to that of

coronaries– NIH develops more slowly

Conclusions

• Lumen diameter relative to immediate post implant diameter decreases with time

• Stent diameter changes little with time• Degree of stent migration or intimal hyperplasia

increases with time.– Effect is small in the compliant ended stent

Micro CT of excised vessels

• Vessels pressure fixed in situ (10% formol saline)

• Excised and immersed in oil based contrast medium

• Custom built Micro CT scanner (Dental Biophysics QMUL)

• Voxel size (30 x 30 x 30µm)

• Images processed on custom software developed under

KS400 (Zeiss) image analysis system

Image processing

Original slice Thresholded Media/Adventita only

Stent struts Ellipse fitted

Slice measurements

x-position [μm]

Intimal hyperplasia in vicinity of struts.Less wall movement?

3D rendering

3D rendering

xy yzxz

Future work1.44-01

1.35-01

1.25-01

1.16-01

1.06-01

9.70-02

8.76-02

7.82-02

6.89-02

5.93-02

4.99-02

4.05-02

3.11-02

2.17-02

1.23-02

2.91-03

0

0.2

0.4

0.6

0.8

1.0

1.2

0 5 10 15 20 25 30 35 40

Axial Position (mm)

Nor

mal

ized

Com

plia

nce

CMS Palmaz

• More extensive experimental study– Effect of stent oversize and stiffness on

intimal hyperplasia– Comparison of different stent types

• Modelling & measurement of interactions between blood/arterial wall/stent

– Haemodynamics and solid mechanics

Who did the work.Joel Berry Engineer Stent designDepartment of Biomedical EngineeringWake Forest UniversityWinston-Salem NC, USA

James Moore Jr. Engineer Stent designDepartment of Biomedical EngineeringTexas A & M UniversityCollege Station, TX, USA

Gemma Ryder PhD student In vivo studyInstitute of Cell and Molecular ScienceBarts and the LondonSchool of Medicine and DentistryLondon, UK

Graham Davis Physicist Micro CTDepartment of Dental BiophysicsQueen Mary, University of LondonLondon, UK

Luke Timmins PhD student Image processingDepartment of Biomedical EngineeringTexas A & M UniversityCollege Station, TX, USA

Intravascular stents A biased and limited account.

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