BVS Thrombosis, Focus on Bifurcation · 2014. 11. 13. · BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 5 Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele

BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 1

Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy

Davide Capodanno, MD, PhD Ferrarotto Hospital, University of Catania, Italy

10th European Bifurcation Club Meeting. BRS (2) - Time for clinical data

BVS Thrombosis, Focus on Bifurcation



Scaffold Thrombosis: Lecture Roadmap

Magnitude of the problem Is there a worrying signal beyond the trials reality?

Putative mechanisms Patient-, lesion-, and/or procedure-related?

Focus on Bifurcation Lesions Is bifurcation an independent predictor? 3

1

2






Focus on Bifurcation Lesions Is bifurcation an independent predictor?

1



ABSORB II – Scaffold thrombosis

BVS (N=355)

EES (N=166) Difference (95% CI) P value

1-year definite ST 2 (0.6%) 0 0.61% (-1.72 to 2.19) 1.00

Acute (0-1 day) 1 (0.3%) 0 0.30% (-1.98 to 1.67) 1.00

Subacute (2-30 days) 1 (0.3%) 0 0.30% (-1.98 to 1.68) 1.00

Late (31-365 days) 0 0 0.00% (NA) 1.00

Definite or probable ST 3 (0.9%) 0 0.91% (-1.45 to 2.65) 0.55

Serruys PW et al. Lancet. 2014 [Ahead of print]

501 patients with coronary artery disease 2:1 randomized to BVS or EES

“Two myocardial infarctions in the BVS group (one Q-wave and one non-Q-wave) were attributed to definite scaffold thrombosis, in one case involving overlapping

scaffolds and in the other case involving bifurcation scaffolding (a protocol deviation)”



Absorb BVS in Daily Practice

Capodanno D, et al. Eurointervention 2014 [Ahead of print]

1,189 patients, 1,440 lesions, 1,731 BVS from 10 centers. Median FU 189 (IQR 120-284) days

0

1

2

3

4

5

6

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180

Eve

nts

Days

Cum

ulative events (%)

0

1.0

2.5

2.0

0.5

1.5

Acute/subacute scaffold thrombosis Late scaffold thrombosis Cumulative events

1.5%

2.1%

87% of ST occurred while patients still on DAPT 91.3% of patients with ST had a clinical sequelae (Death, MI or TLR)



Early And Total Scaffold Thrombosis

Adapted from Ishibashi Y, et al. Eurointervention 2014 [Ahead of print]

Weighted averages from 4,309 patients undergoing BVS-PCI in 18 studies

EHJ: European Heart Journal; EIJ: EuroIntervention; JACC CI: JACC Cardiovascular Interventions.

2,2% 0,3%

1,2% 0,4%

0,0% 0,0% 0,0%

0,6% 0,0% 0,0%

1,4% 0,0% 0,0% 0,0%

2,4% 0,0%

1,4% 1,3%

0,8%

Kraak et al, AMC single-centre (EIJ 2014) ABSORB FIRST (EuroPCR 2014)

Azzalini et al (EuroPCR 2014) Abizaid et al, ABSORB EXTEND (EIJ 2014)

Serruys et al, ABSORB B (EIJ 2014) Onuma et al, ABSORB A (JACC CI 2013)

CORONARY CTO (EuroPCR 2014) Serruys et al, ABSORB II (Lancet 2014)

ASSURE registry (EuroPCR 2014) BVS EXPAND (EuroPCR 2014)

Gori et al (EIJ 2014) POLAR ACS (EuroPCR 2014)

Kajiya et al (EIJ 2013) Diletti et al, BVS STEMI (EHJ 2014)

Kocka et al, PRAGUE-19 (EHJ 2014) Wiebe et al (CRC 2014)

Ielasi et al, RAI registry (EIJ in press) Capodanno et al, GHOST-EU (EIJ 2014)

Weighted average

30-Day ST: 0.8% u  Acute: 0.2% u  Subacute: 0.6% Total ST: 1.2% u  Stable CAD: 0.9% u  ACS: 2.2% u  STEMI: 1.2%






Focus on Bifurcation Lesions Is bifurcation an independent predictor?

2



Determinants of Stent (Scaffold) Thrombosis

Kirtane AJ, Stone GW. Circulation 2011;124:1283-1287

Patient- and lesion-related factors P

atie

nt-r

elat

ed

Smoking Diabetes mellitus Chronic kidney disease ACS presentation Thrombocytosis HPPR DAPT discontinuation Surgical procudures

Lesi

on-r

elat

ed

Diffuse coronary artery disease with long treated segment Small vessel disease Bifurcation disease Thrombus containing lesion Significant lesions proximal or distal to the treated segment



Procedure-Related Factors of Thrombosis

1 2 3 4

5 6 7 8

Device and strut geometry

Poor expansion, acute ISA

Strut fractures

Flow-limiting edge dissections

Delayed or absent endothelialization

Neo-atherosclerosis with plaque rupture

Late ISA, aneurysm formation

Hypersensitivity, inflammatory, thrombotic reactions




1 2 3 4

5 6 7 8



Strut fractures








Impact of Strut Geometry on Thrombogenicity

Kolandaivelu K, et al. Circulation. 2011;123:1400-1409

3-day adherent thrombus (mm2) in animal models treated with thin- (81x81 µm) or thick-strut (162x81 µm) BMS

0,13 0,21

Thin-strut BMS (81 um) Thick-strut BMS (162 um)

P=0.004

High endothelial shear stress

Low endothelial shear stress



Strut Thickness of BRS Resembles 1st Gen DES

cvPipeline and company presentations

ART Reva

ReZolve Amaranth Fortitude

Biotronik DREAMS-2

Template Thickness ~122 µm X 2 ~160 µm ~150 µm ~125 µm

Support Time

Resorption Time

Degradation Products

≤ 3 months

> 48 months ~ 36 months ~18 months 9 – 12 months

Soft Hydroxyapatite H2O & CO2 H2O & CO2

3 – 6 months ≤ 3 months

I2DAT, I2DT, PCL, Tyrosine

~6 months

Template Thickness

Tyrosine-derived Polycarbonate PDLA PLLA Magnesium

(very fast) (very fast) (slow) (very slow)

Elixir DESolve

~150 µm

3 – < 6 months

18 – 24 months

H2O & CO2

PLA-based

(fast)

Abbott Vascular Absorb

~150 µm

6 months

< 36 months

PLLA

(slow)

H2O & CO2

Commercially Available



Strut Layering In Bailout 2-Stenting (And Overlaps)

T stenting Internal crush Culotte TAP

Triple layer ++

With BVS 468 µm

Double layer +++ +

With BVS 312 µm 312 µm



Promises of Next Device Iteration

Rapoza R. BRS 2014, Boston

Next generation Absorb BVS Current generation Absorb BVS




1 2 3 4

5 6 7 8



Strut fractures








The Four ‘Ps’ For Optimal Implantation 1.  Prepare the Lesion

•  Possibly with a NC balloon. Useful for sizing. Aim at <40% residual stenosis before scaffold implantation. Lesion preparation is key. Constant forward pressure, avoid dottering.

2.  Properly Size the Vessel •  Use IC nitro, imaging if necessary, balloon sizing, plan to upsize the scaffold

for any RVD by visual estimation.

3.  Pay Attention to Expansion Limits •  Stay within the nominal size (+0.5mm), 2 atm increments every 5 seconds.

Mantain target pressure for 30 seconds.

4.  Post-Dilate with a Non-Compliant Balloon •  Aim at <10% residual stenosis after scaffold implantation.



Malapposition after BVS Implantation

Brown AJ, et al. Catheter Cardiovasc Interv. 2014;84:37-45

OCT pre- and post-analysis of 25 patients with BVS

•  6.18% of all scaffold struts were malapposed

•  Malapposition was observed more with fibrotic calcific plaque than with all other plaques

p=0.10

p=0.14

Mal

appo

sed

Stru

t Dis

tanc

e (m

m)

1:1 pre-dilatation did not impact malapposition distance but improved BVS expansion




1 2 3 4

5 6 7 8



Strut fractures








Inflammatory Reaction to BVS and Xience V

Otsuka F, et al. Circ Cardiovasc Interv. 2014;7:330-42

Pathology analysis of of 263 BVS and 72 Xience implanted in 136 nonatherosclerotic swine

BVS demonstrated comparable long-term safety to Xience V in porcine coronary arteries with mild to moderate inflammation




1 2 3 4

5 6 7 8



Strut fractures








Early Delay in Strut Coverage in Overlapping BVS

Farooq V, et al. JACC Cardiovasc Interv. 2013;6:523-32

Serial OCT assessments in 41 swine at 28 and 90 days (1,407 cross-sections)

80,1%

99,5% 98,2% 99,8%

28 days 90 days

Overlap Nonoverlap

99,4% 100,0% 99,8% 100,0%

28 days 90 days

Overlap Nonoverlap

P<0.0001

P=0.26 P=0.33 P=0.26

Absorb BVS Xience V EES



Delayed Endothelization and ISA

Gomez-Lara J, et al. JACC Cardiovasc Interv. 2011;4:992-1001

Serial OCT assessments in 25 patients at baseline and 6 months (3,686 struts)

Lack of strut apposition at baseline was related to the presence of uncovered struts and intraluminal masses at 6 month

P<0.01 P=0.94

P<0.01




1 2 3 4

5 6 7 8


Poor expansion, ISA

Strut fractures








Still A Source of Late Vascular Complications?

Ferrarotto Hospital

Neoatherosclerosis Late-Acquired ISA JACC Interv 2014, In press






Focus on Bifurcation Lesions Is bifurcation an independent predictor? 3



Scaffold Thrombosis in Bifurcations

•  PubMed/MedLine search for “scaffold(s)” AND bifurcation(s)” AND thrombosis

•  (scaffold [Title/abstract] OR scaffolds [Title/abstract] OR ABSORB [Title/abstract]) AND (bifurcation [Title/abstract] OR bifurcation [Title/abstract]) AND thrombosis

•  Search to October 18, 2014 •  6 manuscript indexed, 5 excluded at the title level •  Result: 1 study reporting scaffold thrombosis in

bifurcation lesion(s)



Only 1 published case of bifurcation thrombosis with BVS!

Schiattarella G, et al. Int J Cardiol 2014;174:93-95

68 years, NSTEMI, LCX-MO1 2 BVS (2.5*18mm, 2.5*28mm) Technique not described Discharged on DAPT (no HPR) Pre-procedure Post-procedure



Only 1 published case of bifurcation thrombosis with BVS!

Schiattarella G, et al. Int J Cardiol 2014;174:93-95

Authors’ comments: 1.  “it is probable that the wrong utilization of BVS with the inadequate apposition of devices into

the side branch, finally led to thrombotic occlusion” 2.  “The view of the occluded “ghost” stent is not easy. Thus, these procedures are really difficult

and, potentially, hazardous” 3.  “The choice of strategies to perform these procedures is not codified” 4.  “We did not perform thrombectomy due to lack of data in BVS”

2 days later: STEMI Subacute ST Difficult wiring, 1.25*15mm and 2.0*15 balloons ZES 2.75*17mm



Early Scaffold Thrombosis And Bifurcation Rate

Capodanno D. Tamburino C. Unpublished

Meta-regression of 3,386 patients undergoing BVS-PCI from 8 Registries

*Fixed-effects regression. Registries are plotted according to the logit of early scaffold thrombosis and the prevalence of bifurcation lesions. Slope p value = 0.43 by removing GHOST-EU

% bifurcation lesions

Logi

t Sca

ffold

Thr

ombo

sis

GHOST-EU Bif. 27%

ABSORB EXTEND Bif. 0%

B-SEARCH Bif. 0%

L’Allier et al Bif. 5%

AMC Bif. 15%

Elabassi et al. Bif. 9% ABSORB First

Bif. 12%

ASSURE Bif. 14%

Slope P Value 0.051



8/23 ST were in bifurcations

Naganuma T, Latib A, et al. GHOST-EU Investigators

Kaplan-Meier 30-day and 6-mo ST in bifurcations: 1.5% and 3.1%, respectively

1,1,1 38%

1,0,0 12%

0,1,0 12%

1,1,0 38%

ACS = acute coronary syndromes; PD = main branch post-dilatation; IG = intravascular guidance; DAPT = on dual antiplatelet therapy

Case Days ACS Strategy PD KBI IG DAPT

#1 149 No Single Yes No Yes No

#2 69 No Single No No No Yes

#3 2 Yes Single No No Yes Yes

#4 0 Yes Single No No No Yes


#6 34 Yes Double Yes No No No



Medina classes in 8 bifurcations ST



Closing Remarks 1.  The rates of 30-day BVS thrombosis apparently

resemble those of first generation DES, with higher rates in ACS.

2.  While the benefits of BVS are expected to accrue at late and very late term, clustering of thrombosis within the first 30 days suggests that procedure-related factors are at play.

3.  Bifurcation PCI is associated per se with a higher risk of thrombosis. Whether this also independently applies to BVS requires further confirmation, large numbers, and dedicated studies.

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BVS Thrombosis, Focus on Bifurcation · 2014. 11. 13. · BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 5 Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele