Stenting:επαναστένωσηISR (intra stent restenosis)
Μετεκπαιδευτικό Πρόγραμμα στην Αγγειοχειρουργική - Αγγειοχειρουργική - Ενδαγγειακή ΧειρουργικήΕνδαγγειακή Χειρουργική
Κ. Α. ΦίληςΚ. Α. ΦίληςΕπίκ. Καθηγητής ΕΚΠΑΕπίκ. Καθηγητής ΕΚΠΑ
Definitions
ISRISR can be definedcan be defined clinically clinically oror angiographically.angiographically.
Clinically, it is defined as the presentation of recurrent ischaemia
Angiographically, ISR is the presence of >50% diameter stenosis in the stented segment.
50%-70% : moderate 70%-99% : severe
Teirstein PS,
N Engl J Med, 1997
Cellular response to injuryCellular response to injury
• Platelet adherence and degranulation (10-30min)– Subenthothelial collagen exposure
– Platelets adherence (αΙΙb βIΙa, Von Villebrand, Fibronectin)
– ADP, thromboxane A2,
– Platelets recruitment (αΙΙb βΙΙIa)
– Platelets degranulation (PDGF)
• Leukocyte, monocytes, macrophages • SMC proliferation and migration (1day – 3months)
• Endothelial cell regrowth
Diffuse in stent restenosisDiffuse in stent restenosis
Initial role of stents : optionalInitial role of stents : optional
to support the dissected ballooned plaque from further dissection-rupture
to prevent arterial recoil by their radial force
PTA result
PTA result
Το δίλημμα
• Αγγειοπλαστική με μπαλόνι– Constrictive remodeling (αναδιαμόρφωση σύσπασης)– Elastic recoil (ελαστική επαναφορά)
• Αγγειοπλαστική με ενδοπρόθεση– Αυξημένη μυο-ενδοθηλιακή υπερπλασία
Intimal hyperplasia
Various ISR rates @ 1 year according to locations
Time course of ISR
Factors influencing ISRFactors influencing ISR
Cardiovascular factorsCardiovascular factors
Smoking
Diabetes
Hyperlipidemia
Effect of smoking in ISREffect of smoking in ISRCardiovascular factorsCardiovascular factors
Effect of diabetes in ISREffect of diabetes in ISRCardiovascular factorsCardiovascular factors
P=0.89 (NIDM)P=0.04 (IDM)
Genomic
Blood flow
Plaque
GenomicGenomicEndogenous factorsEndogenous factors
Blood flowBlood flowEndogenous factorsEndogenous factors
PlaquePlaqueEndogenous factorsEndogenous factors
Endogenous factorsEndogenous factors
Endogenous factorsEndogenous factors
Endogenous factorsEndogenous factors
Endogenous factorsEndogenous factors
Exogenous factorsExogenous factors
Stent
Exogenous factorsExogenous factors
StentStent
ΕυλυγισίαΠάχοςΕυκολία καθοδήγησης
Ακτινική δύναμη
ΒιοσυμβατότηταΜηχανική αντοχήΑντίσταση στη ρήξη
Stent asymetryStent asymetryExogenous factorsExogenous factors
Self expanding Self expanding VV balloon expanded balloon expandedExogenous factorsExogenous factors
Cell designCell designExogenous factorsExogenous factors
Strut ThicknessStrut ThicknessExogenous factorsExogenous factors
Stent fractureStent fractureExogenous factorsExogenous factors
Restenosis-ThrombosisPharmacologic prevention
ASA & Heparin
ASA & Ticlopidin
Restenosis-ThrombosisPharmacologic prevention
Gold standard : Clopidogrel + aspirin
Σημασία των αντιαιμοπεταλιακών
• Αναστολή αιμοπεταλιακής δραστικότητας με σκοπό την πρόληψη της οξείας θρόμβωσης της αγγειοπλαστικής
• Ανεπαρκή για την επαναστένωση
Prevention of ISR
• Medicines
• Drug eluting stents
• Brachytherapy, Cryoplasty
• Genes
MedicinesMedicines ISR on coronary PTA/stent
PDGF I
antiallergic
Reo pro
Induction of vascular atrophy as a novel approach to treating restenosis. A review
Seung-Kee Min MDa, Richard D. Kenagy PhDb and Alexander W. Clowes MDb, ,
After vascular reconstruction, luminal narrowing is in part caused by
intimal thickeningintimal thickening, the consequence of endothelial injury and endothelial injury and
inflammationinflammation, smooth muscle cell hyperplasiasmooth muscle cell hyperplasia, , and extracellular matrix extracellular matrix
accumulationaccumulation. It may be possible to induce these lesions to shrink.
This novel approach to the treatment of restenosis is supported by animal
experiments and a few clinical observations demonstrating vascular
atrophy in response to drugs such as Gleevec (EDGF I).
A potential limitation to this approach might be the formation of
aneurysms.
Journal of Vascular SurgeryVolume 47, Issue 3, March 2008, Pages 662-670
Drug eluting stents
sirolimus
results from coronary
paclitaxel
DES inhibit smooth muscle cells and endothelial cells
1. They inhibit ISR
2. They are more thrombogenic
Clinical practice : no benefit in survival, no benefit in MACE,
But fewer reinterventions to keep the artery patent
DES in cardiac & peripheral arteries
Drug eluting stents in peripheral Drug eluting stents in peripheral arteriesarteries
J Endovasc Ther. 2009 Jun;16(3):251-60.Infragenicular stent implantation for below-the-knee atherosclerotic disease:clinical evidence from an international collaborative meta-analysis on 640 patients.Biondi-Zoccai GG, Sangiorgi G, Lotrionte M, Feiring A, Commeau P, Fusaro M, Agostoni P, Bosiers M, Peregrin J, Rosales O, Cotroneo AR, Rand T, Sheiban I.
Head-to-head comparisons showed that sirolimus-eluting stents sirolimus-eluting stents were superior to balloon-expandable bare metal stents in were superior to balloon-expandable bare metal stents in preventing restenosis and increasing primary patencypreventing restenosis and increasing primary patency (both p<0.001); sirolimus-eluting stents were also better than paclitaxel-eluting stents in terms of primary patency (p<0.001) and repeat revascularizations (p = 0.014).
BrachytherapyBrachytherapy
Gene therapyGene therapy
• Genetically engineered cells secreting a
thrombolytic enzyme (tPA) which are topically
applied (on the stent).
• Major problem : cells are moving away by the
blood flow.
ConclusionsConclusions
ISR is a stable endothelial reaction to injurySTRATEGIES TO INHIBIT ISRSTRATEGIES TO INHIBIT ISR
systematic topicalsystematic topical Medicines DES, Drug eluting balloonsedicines DES, Drug eluting balloons
Brachytherapy, Brachytherapy, CryoplastyCryoplasty
Photodynamic therapy Photodynamic therapy
GenesGenes