very late scaffold thrombosis: intracoronary imaging ... · bvs stemi first plague 19 rai polar-acs...

Very Late Scaffold Thrombosis: Intracoronary Imaging, Histopathological

and Spectroscopy Findings

Lorenz Räber, Salvatore Brugaletta, Kyohei Yamaji, Crochan J. O’Sullivan, Shuji Otsuki, Tobias Koppara,

Masanori Taniwaki, Yoshinobu Onuma, Xavier Freixa,Franz R. Eberli, Patrick W. Serruys, Michael Joner,

Manel Sabate, Stephan Windecker

Moses et al. NEJM 2003;349:1315-23.

Drug eluting stents reduced restenosis

SIRIUS

91.1%

Eve

nt-

free S

urv

ival (%

)Days after Initial Procedure

100

90

80

0 30 60 90 270120 150 180 210 240

Sirolimus-stent

Standard-stent

78.6%30

100

3900

94.1%

70.9%

90

80

70

60

50

40

360330300270240210180150120906030

Days after Implantation

Eve

nt-

free S

urv

ival (%

of

patients

)

Sirolimus stent

Standard stent

RAVEL

Morice et al. NEJM 2002;346:1773-80.

McFadden et al. Lancet 2004

Late drug eluting stent thrombosis emerged as Achilles’ heel of DES

Underlying mechanisms ofvery late metallic DES thrombosis by means of OCT

Taniwaki et al. Circulation 2016;133:650-60.

2009-201488 patients with VLST

64 patients with DES

58 patients analyzed

24 patients with BMS

6 patients withPoor image quality

Newer generation DES with biocompatible polymer and thin struts reduced the risk of late stent thrombosis

BERN ROTTERDAM STUDY

Fully bioresorbable vascular scaffolds were introduced to further attenuate late device related adverse events

MLA 5.96 mm2

MLD 2.75 mmMLA 3.38 mm2

MLD 2.07 mmMLA 3.41 mm2

MLD 2.08 mm

Post 1-year 5-year

Complete absorption at ≈ 3 years in the swine model Nakatani et al. JACC Interv 2016

Bern caseABSORB BVS

-20

0

20

40

60

80

100

120

0 1 2 3 4 5 6

No data on very late scaffold thrombosis available from registries

Ghost-EU

ABSORB B

BVS STEMI First

PLAGUE 19RAI

POLAR-ACS

ABSORB EXTEND

ASSURE

AMC

Follow-up duration (years)

AC

S p

rese

nta

tio

n (%

)

BVS-Save

BVS EXAMINATION

Costopoulos et al.

ESHC-BVS

ISAR-ABSORB

Jaguszewski et al.

Moscarella et al.

0

GABI-R

REPARA

Gori et al.

Imaging substudy Clinical endpoint

All but ABSORB B are limited within 2 years.

Aims

1) To examine whether very late scaffold thrombosis occurs whenresorption is assumed to be complete or nearby complete.

2) To describe mechanisms involved in thrombosis formation bymeans of intracoronary optical coherence tomography.

BernBern University Hospital

BarcelonaUniversity Hospital Clinic Barcelona

ZurichTriemlispital

Very late scaffold thrombosis

4 patients (2.3%)

From February 2011 to August 2013

ABSORB BVS implanted

171 patients

Methods: Study population

OCTVery latescaffold thrombosis

BVS 3.0 x 18

Thrombus aspiration

Methods: OCT assessments

Quantitative 2D OCT analysis

Distal reference Minimum lumen area Minimum scaffold area Proximal reference

1mm

ScaffoldThrombus

8.51 mm2 1.98 mm2 4.18 mm2 7.22 mm2

Analysis interval 0.2mm

Very latescaffold thrombosis

BVS 3.0 x 18

OCT

after thrombus aspiration or

dilatation with small size balloon3D OCT analysis

3D color-coded OCT(Fly-through)

3D color-coded OCT(Spread out)

Methods: OCT assessments

Pydicom package version 0.9.8 on Python version 2.7.9.

Apposed uncoveredApposed covered Apposed coveredby thrombus

Malappositionwith discontinuity

Methods: Stent strut characteristics

Malappositionwithout discontinuity

Analysis interval0.2mm

Results: Case 1

BVS 3.0 x 18

68 years old, maleStable AP

Post dilatation3.25x15mm, 16 atm

Discharge ASA/Clopidogrel

Pre PostVLScT

@44 months

ASA monotherapy

■ Vessel■ Apposed struts■Malapposed struts■ Thrombus

Total struts N=381

Malapposed

with thrombus 27 (7.1%)

uncovered 1 (0.3%)

Apposed

covered 304 (79.8%)

uncovered, no thrombus 5 (1.3%)

uncovered, thrombus 5 (1.3%)

possibly uncovered 39 (10.2%)

Lesion level

Lesion length 19.8 mm2

Reference lumen area 5.53 mm2

Minimal lumen area 1.61 mm2

Area stenosis 70.9 %

Mimimal scaffold area 2.44 mm2

Scaffold expansion 44.1 %

Eccentricity index 0.78

Movat pentachrome staining

CVPath, Gaithersburg, USA

Spectroscopy

McCroneAssociates, Inc., Westmont, USA

BVS 3.0 x 18


without postdilatation

Pre Post

1mm1mm1mm

Results: Case 2

BVS 3.0 x 18


without postdilatationDischarge ASA/Clopidogrel

Pre Post

*) Revascularization 3 days after symptom onset.

VLScT @19mo*

ASA monotherapy

Results: Case 2

Total struts N=697

Malapposed


uncovered 9 (1.3%)

Apposed

covered 537 (77.0%)




Lesion level








Scaf

fold

Side branch

Calcification

IVUS after BVS implantation 19 months VLScT

Side branch

Disintegrity

Calcification

1mm

1mm

1mm

1mm

1mm

1mm

A

B

C

OCT at VLScT and IVUS at baseline

Scaffold strut discontinuity

BVS 3.5 x 1214 atm

BVS 3.0 x 18

BVS 2.5 x 28


Pre Post VLScT @19mo

without postdilatationDischarge ASA/Prasugrel

ASA/Prasugrel

Results: Case 4

Total struts N=574

Malapposed


uncovered 3 (0.5%)

Apposed

covered 428 (74.6%)




Lesion level





Mimimal scaffold area 4.57mm2



55 years old, maleNSTE-ACS

Pre Post VLScT @21 mo

without postdilatationDischarge ASA/Prasugrel

ASA/Prasugrel

BVS 2.5 x 2816 atm

Results: Case 3

Distal

Proximal

Total struts N=950

Malapposed


uncovered 0 (0.0%)

Apposed

covered 784 (82.5%)




Lesion level








Underlying mechanism Case 1 Case 2 Case 3 Case 4

Malapposition withdiscontinuity ✓ ✓

Malapposition withoutdiscontinuity ✓

Uncovered ✓ ✓ ✓

Lumen loss ✓ ✓ ✓

Conclusions

• Very late scaffold thrombosis may occur at advanced stages of scaffold resorption.

• Potential mechanisms specific for VLScT

– scaffold discontinuity

– Restenosis

• Resorption process may be delayed in humans suggesting an extended period of vulnerability for thrombotic events.

Outstanding Questions

• Incidence of VLScT compared to NG DES

• Impact of implantation technique

• Consequence of further iterations (reducedabsorption time, thinner struts etc.)

very late scaffold thrombosis: intracoronary imaging ... · bvs stemi first plague 19 rai polar-acs...

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