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Magmaris: the impact of scaffold design and materials on reducing
thrombogenicity
Michael Joner, MD
Deutsches Herzzentrum München und Deutsches Zentrum für Herz-Kreislaufforschung e.V.
Speaker's name: Michael Joner
I have the following potential conflicts of interest to report:
Receipt of honoraria or consultation fees: Boston Scientific, Biotronik, OrbusNeich, Coramaze, Astra Zeneca, Bristol-Myers Squibb
Potential conflicts of interest
2.8%
0.0%0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
4.0%
Absorb Xience
Def
init
e/P
rob
able
Sca
ffo
ld T
hro
mb
osi
s (i
n %
)Scaffold thrombosis in ABSORB BVS
Recent studies show increased thrombosis tendency in BVS vs DES.
Thrombosis in general however has multifactorial causes, thick strut design being one of them
1) Adapted from Serruys P. et al., The Lancet 2016; 388(10059):2479-2491 2) Adapted from Ellis S.G.oral abstract presentation at ACC 2017 3) Adapted from Wykrzykowska J.J. et al., New England Journal of Medicine 2017, published online ahead of print
ABSORB II – 3-year data1 ABSORB III – 2-year data2
P=0.03
1.9%
0.8%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
4.0%
Absorb Xience
Def
init
e/P
rob
able
Sca
ffo
ld T
hro
mb
osi
s (i
n %
)
P=NS
AIDA – 2-year data3
3.5%
0.9%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
4.0%
Absorb XienceD
efin
ite/
Pro
bab
le S
caff
old
Th
rom
bo
sis
(in
%)
P<0.001
Scaffold thrombosis in Magmaris
BIOSOLVE-I36-month follow-up
Definite/Probable Scaffold Thrombosis
0.0%
BIOSOLVE-II24-month follow-up
Definite/Probable Scaffold Thrombosis
0.0%
BIOSOLVE-III6-month follow-up
Definite/Probable Scaffold Thrombosis
0.0%
1) BIOSOLVE-I data from Haude M. et al., EuroIntervention 2016;12:e160-e1662) BIOSOLVE-II data from Haude M., oral abstract presentation, EuroPCR 20173) BIOSOLVE-III data from Haude M., oral abstract presentation, EuroPCR 2017
DREAMS-1G Magmaris
Scaffold Thrombosis Factors
Stent geometry
Late-aquired incomplete device apposition
Delayed or incomplete endothelialisation of device struts
Hypersensitivity or inflammatory reactions to device components
Modified from : Capodanno D, et al., EuroIntervention, 2015;11 Suppl V:V181-4
Stent geometry
Scaffold Thrombosis Factors
Stent geometry
Late-aquired incomplete device apposition
Delayed or incomplete endothelialisation of device struts
Hypersensitivity or inflammatory reactions to device components
Modified from : Capodanno D, et al., EuroIntervention, 2015;11 Suppl V:V181-4
Stent geometry
Computed flow dynamics aims to explain how strut thickness may influence device
thrombogenicityGreater strut thickness is associated with increased platelet activation due to higher shear stress. In addition,
platelet aggregation is increased due to larger areas of regional flow reverse and stasis.
1) Foin, N., et al. IJCA . 2014;143 (09), 2) Tolentino, A. Cardiov.Nurse/Tech. Symp. 2016, 3) Koskinas K., J Am Coll Cardiol. 2012 Apr 10;59(15):1337-49
1) 2)
3)
Computed flow dynamics suggest accelerated endothelialization in Magmaris relative to Absorb
IIB(R)03_2017_Entwurf BIOTRONIK data on file
Magmaris
Absorb
The Magmaris backbone design was found to optimize the wall shear stress compared to the Absorb design.
High WSS in between strut crowns (green areas) is physiologic and is associated with accelerated endothelialization.
highlow
Evaluation of acute thrombogenicity in a well established porcine arteriovenous shunt model
Stent geometry, coating and backbone composition impact on acute thrombogenicity
Thicker stent struts show greater thrombus deposition as compared with thinner stent struts
Evaluation of acute thrombogenicity in Magmaris vs. Absorb vs. Orsiro
Shunt model
AV-shunt with a sylgard tube (inner diameter 2.70mm)
1h blood flow or until >50% reduction of blood flow
Target blood activated clotting times (ACT) were kept between 150-190s by i.v. Administration of heparin (low heparin model)
No antiplatelet agents (e.g. Aspirin, clopidogrel) were used
Shunt study 1: Comparison of acute thrombogenicity of Absorb vs Magmaris vs. Orsiro
Detection of platelets and inflammatory cells by immunofluorescence
Estimation of thrombus deposition by SEM
Otsuka et al., JACC Cardiovasc Interv. 2015 Aug 17;8(9):1248-60.Waksman R. et al., In press Circulation Intervention
Results Shunt Study 1:Magmaris vs. Absorb vs. Orsiro
Shunt study 1: Comparison of acute thrombogenicity of Absorb vs Orsiro and Magmaris
Detection of platelets and inflammatory cells by immunofluorescence
Estimation of thrombus deposition by SEM
Photo
IF
SEM
Absorb Orsiro Magmaris
Waksman R. et al., In press Circulation Cardiovascular Intervention
Results Shunt Study 1: Magmaris vs. Absorb vs. OrsiroScanning Electron Microscopy
Significantly less thrombus deposition in Magmaris compared to Absorb
Less inflammatory cells in Magmaris compared to Absorb
Arrows: thrombus deposition, arrowhed: inflammatory cells
Waksman R. et al., In press Circulation Cardiovascular Intervention
Results Shunt Study 1: Magmaris vs. Absorb vs. Orsiro
Immunoflurescence Significantly less platelet coverage in Magmaris and Orsiro compared to Absorb
Waksman R. et al., In press Circulation Cardiovascular Intervention
Evaluation of acute thrombogenicity in Magmaris vs. 316L-Equivalent
Shunt model
AV-shunt with a sylgard tube (inner diameter 2.70mm)
1h blood flow or until >50% reduction of blood flow
Target blood activated clotting times (ACT) were kept between 150-190s by i.v. Administration of heparin (low heparin model)
No antiplatelet agents (e.g. Aspirin, clopidogrel) were used
Shunt study 2: Effect of magnesium backbone on acute thrombogenicity of Magmaris vs Magmaris scaffold design in stainless steel (316L-equivalent):
Detection of platelets and inflammatory cells by immunofluorescence
Estimation of thrombus deposition by SEM
Otsuka et al., JACC Cardiovasc Interv. 2015 Aug 17;8(9):1248-60.Waksman R. et al., In press Circulation Intervention
Results Shunt Study 2: Magmaris vs 316L-Equivalent
Shunt study 2: Effect of magnesium backbone on acute thrombogenicity of Magmaris vs 316L-Equivalent:
Detection of platelets and inflammatory cells by immunofluorescence
Estimation of thrombus deposition by SEM
Photo
IF
SEM
Magmaris 316L-Equivalent
Results Shunt Study 2: Magmaris vs 316L-EquivalentScanning Electron Microscopy
Significantly less thrombus deposition in Magmaris compared to 316L-Equivalent
Less inflammatory cells in SEM
Magmaris 316L-Equivalent
Arrows: thrombus deposition, arrowhed: inflammatory cells
Results Shunt Study 2: Magmaris vs 316L-Equivalent
Immunofluorescence Significantly less platelet coverage in Magmaris compared to stainless steel Magmaris
P<0.0001
316L-Equivalent
Magmaris
stainless steel Magmaris
Scaffold Thrombosis Factors
Stent geometry
Late-aquired incomplete device apposition
Delayed or incomplete endothelialisation of device struts
Hypersensitivity or inflammatory reactions to device components
Modified from : Capodanno D, et al., EuroIntervention, 2015;11 Suppl V:V181-4
Stent geometry
Computed flow dynamics aims to explain how late recoil may cause malapposition which in turn may influence device thrombogenicity
Magmaris showed no recoil increase, whereas Absorb diameter decreased >20% within 1st hour in a bench test.1
Therefore, the polymeric scaffold struts are less apposed to the vessel wall which causes disturbances in the laminar blood flow. 2,3,4
Disturbances activate platelets which play an important role of the thrombus formation cascade.2
The impact of recoil on the laminar blood flow was simulated using computational flow dynamics.
1) Schmidt W et al. In vitro performance investigation of bioresorbable scaffolds - Standard tests for vascular stents and beyond.Cardiovascular Revascularization Medicine. 2016; 17(6):375-383.2) Foin N et al. Incomplete Stent Apposition Causes High Shear Flow Disturbances and Delay in Neointimal Coverage as a Function of Strut to Wall Detachment Distance, DOI: 10.1161/CIRCINTERVENTIONS.113.0009313) Kolandaivelu K et al. “Stent Thrombogenicicty Early in High-Risk Interventional Settings Is Drive by Stent design and Deployment and Protected by Polymer-Drug Coatings” DOI:10.1161/CIRCULTATIONAHA.100.0032104) Jiménez J.M., Davies P.F. Hemodynamically Driven Stent Strut Design. Annals of Biomedical Engineering. 2009
Magmaris MagmarisAbsorb Absorb
1
Computed flow dynamics predicted the impact of recoil on the risk of platelet activation
and platelet aggregation Magmaris was simulated with a stable 5% recoil. Absorb was simulated with a 5% and 8% recoil at acute and 1 hour post-
implantation respectively1. Only the results 1-hour post-implantation are shown here.
Computed flow dynamic simulation predicts the lowest risk of platelet activation for Magmaris and the highest for Absorb.2
The activated platelets are transported to the vessel wall. The transport is represented by the platelet convection number, which resulted lowest for Magmaris.2
Finally, the transported platelets aggregate. The risk of platelet aggregation is lowest for Magmaris compared to Absorb.2
1) Schmidt W. et al, Cardiovasc Revasc Med 2016;17(6):375-832) IIB(R)03_2017_Entwurf BIOTRONIK data on file, 3) Pictures from: http://ib.bioninja.com.au/standard-level/topic-6-human-physiology/63-defence-against-infectio/clotting.html
0.11
0.27
0
0.05
0.1
0.15
0.2
0.25
0.3
Magmaris Absorb
Pla
tele
t Sh
ear
N
um
ber
(P
SN)
12.6
14.1
0
5
10
15
Magmaris AbsorbP
late
let
Agg
rega
tio
n
Nu
mb
er (
PAN
)2.34
3.05
0
0.5
1
1.5
2
2.5
3
3.5
Magmaris Absorb
Pla
tele
t C
on
vect
ion
N
um
ber
(P
CN
)
Scaffold Thrombosis Factors
Stent geometry
Late-aquired incomplete device apposition
Delayed or incomplete endothelialisation of device struts
Hypersensitivity or inflammatory reactions to device components
Modified from : Capodanno D, et al., EuroIntervention, 2015;11 Suppl V:V181-4
Stent geometry
Magmaris vs Absorb endothelialisation in rabbitmodel at 28 days
Vessel surface coverage of BRS struts determines pace of re-endothelialisation
Magmaris PLLA BRS
Waksman R. et al., EuroIntervention 2017; published online ahead of print
PLLA BRSMagmaris
p<0.004
p = 0.007
Scaffold Thrombosis Factors
Stent geometry
Late-aquired incomplete device apposition
Delayed or incomplete endothelialisation of device struts
Hypersensitivity or inflammatory reactions to device components
Modified from : Capodanno D, et al., EuroIntervention, 2015;11 Suppl V:V181-4
Stent geometry
Results Shunt Study 1: Magmaris vs. Absorb vs. Orsiro
Immunoflurescence (2) Significantly less Neutrophil (PM1+) adherence in Magmaris and Orsiro compared to Absorb
Significantly less Monocyte (CD14+) adherence in Magmaris compared to Absorb
PM1+ Neutrophil staining: green, CD14+ Monocyte staining: green, DAPI nuclei staining: blue, CD42b/CD61 platelelt staining: red
Waksman R. et al., In press Circulation Cardiovascular Intervention
Results Shunt Study 2: Magmaris vs 316L-Equivalent
Immunofluorescence – Neutrophil Attachment Significantly less Neutrophil (PM1+) adherence in Magmaris compared to 316L-Equivalent
P<0.001
Magmaris
316L-Equivalent
316L-Equivalent
Results Shunt Study 2: Magmaris vs 316L-Equivalent
Immunofluorescence – Monocyte Attachment Significantly less Monocyte (CD14+) adherence in Magmaris compared to 316L-Equivalent
Magmaris
P<0.0001
316L-Equivalent
316L-Equivalent
Conclusions
Geometric design of Magmaris impacts favorably on acutethrombogenicity relative to Absorb and Orsiro
Endothelialization is advanced in Magmaris relative to Absorb in a rabbitmodel at 28 days
Magmaris hemodynamic flow properties and biocompatible coating seemto have favorable effects on platelet aggregation and endothelialisation1
Decreased inflammatory cell attachment in Magmaris relative to Absorband Orsiro is observed 1 hour following AV shunt flow
The BIOlute coating showed reproducible hemocompatibility on variousdesigns
The backbone Magnesium material seems to have a beneficial effect on acute thrombosis risk
1) Malek A.M. et al., Hemodynamic sheer stress and its role in atherosclerosis, JAMA 1999;282:2035-2042
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