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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 2
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 3
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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?
1
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 4
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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)”
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 5
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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)
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 6
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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%
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 7
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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?
2
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 8
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 9
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 10
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 11
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 12
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 13
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 14
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
Promises of Next Device Iteration
Rapoza R. BRS 2014, Boston
Next generation Absorb BVS Current generation Absorb BVS
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 15
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 16
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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.
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 17
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 18
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 19
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 20
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 21
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 22
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 23
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
Procedure-Related Factors of Thrombosis
1 2 3 4
5 6 7 8
Device and strut geometry
Poor expansion, ISA
Strut fractures
Flow-limiting edge dissections
Delayed or absent endothelialization
Neo-atherosclerosis with plaque rupture
Late ISA, aneurysm formation
Hypersensitivity, inflammatory, thrombotic reactions
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 24
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
Still A Source of Late Vascular Complications?
Ferrarotto Hospital
Neoatherosclerosis Late-Acquired ISA JACC Interv 2014, In press
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 25
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 26
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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)
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 27
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 28
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 29
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 30
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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
#5 34 Yes Single No No No Yes
#6 34 Yes Double Yes No No No
#7 0 Yes Single No No No Yes
#8 12 Yes Single No No No Yes
Medina classes in 8 bifurcations ST
BVS Thrombosis - Capodanno EBC 2014, October, 18, 2014 – Slide 31
Ferrarotto Hospital AOU Policlinico-Vittorio Emanuele Catania, Italy
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.