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Stenting: επαναστένωση ISR (intra stent restenosis)

Stenting: επαναστένωση ISR (intra stent restenosis). Μετεκπαιδευτικό Πρόγραμμα στην Αγγειοχειρουργική - Ενδαγγειακή Χειρουργική. Κ. Α. Φίλης Επίκ. Καθηγητής ΕΚΠΑ. Definitions ISR can be defined clinically or angiographically.

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Stenting: επαναστένωση ISR (intra stent restenosis)

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  1. Stenting:επαναστένωσηISR (intra stent restenosis) Μετεκπαιδευτικό Πρόγραμμα στην Αγγειοχειρουργική - Ενδαγγειακή Χειρουργική Κ. Α. Φίλης Επίκ. Καθηγητής ΕΚΠΑ

  2. Definitions ISRcan be defined clinically orangiographically. Clinically, it is defined as the presentation ofrecurrent 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

  3. Cellular 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

  4. Diffuse in stent restenosis

  5. Initial role of stents : optional to support the dissected ballooned plaque from further dissection-rupture to prevent arterial recoil by their radial force

  6. PTA result PTA result

  7. Το δίλημμα • Αγγειοπλαστική με μπαλόνι • Constrictive remodeling (αναδιαμόρφωση σύσπασης) • Elastic recoil (ελαστική επαναφορά) • Αγγειοπλαστική με ενδοπρόθεση • Αυξημένη μυο-ενδοθηλιακή υπερπλασία

  8. Intimal hyperplasia

  9. Various ISR rates @ 1 year according to locations

  10. Time course of ISR

  11. Factors influencing ISR

  12. Cardiovascular factors Smoking Diabetes Hyperlipidemia

  13. Cardiovascular factors Effect of smoking in ISR

  14. Cardiovascular factors Effect of diabetes in ISR P=0.89 (NIDM) P=0.04 (IDM)

  15. Genomic Blood flow Plaque

  16. Endogenous factors Genomic

  17. Endogenous factors Blood flow

  18. Endogenous factors Plaque

  19. Endogenous factors

  20. Endogenous factors

  21. Endogenous factors

  22. Endogenous factors

  23. Exogenous factors Stent

  24. Exogenous factors Stent Ευλυγισία Πάχος Ευκολία καθοδήγησης Ακτινική δύναμη Βιοσυμβατότητα Μηχανική αντοχή Αντίσταση στη ρήξη

  25. Exogenous factors Stent asymetry

  26. Exogenous factors Self expanding V balloon expanded

  27. Exogenous factors Cell design

  28. Exogenous factors Strut Thickness

  29. Exogenous factors Stent fracture

  30. Restenosis-ThrombosisPharmacologic prevention ASA & Heparin ASA & Ticlopidin

  31. Restenosis-ThrombosisPharmacologic prevention

  32. Gold standard : Clopidogrel + aspirin

  33. Σημασία των αντιαιμοπεταλιακών • Αναστολή αιμοπεταλιακής δραστικότητας με σκοπό την πρόληψη της οξείας θρόμβωσης της αγγειοπλαστικής • Ανεπαρκή για την επαναστένωση

  34. Prevention of ISR • Medicines • Drug eluting stents • Brachytherapy, Cryoplasty • Genes

  35. Medicines ISR on coronary PTA/stent Reo pro PDGF I antiallergic

  36. Induction of vascular atrophy as a novel approach to treating restenosis. A review Seung-Kee Min MDa, Richard D. KenagyPhDb and Alexander W. ClowesMDb, , Journal of Vascular SurgeryVolume 47, Issue 3, March 2008, Pages 662-670 After vascular reconstruction, luminal narrowing is in part caused by intimal thickening, the consequence of endothelial injury and inflammation, smooth muscle cell hyperplasia, and extracellular matrix accumulation. 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.

  37. Drug eluting stents sirolimus results from coronary paclitaxel DES inhibit smooth muscle cells and endothelial cells They inhibit ISR They are more thrombogenic Clinical practice : no benefit in survival, no benefit in MACE, But fewer reinterventions to keep the artery patent

  38. DES in cardiac & peripheral arteries

  39. Drug eluting stents in peripheral arteries 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 were superior to balloon-expandable bare metal stents in preventing 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).

  40. Brachytherapy

  41. Gene 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.

  42. Conclusions ISR is a stable endothelial reaction to injury STRATEGIES TO INHIBIT ISR systematic topical Medicines DES, Drug eluting balloons Brachytherapy, Cryoplasty Photodynamic therapy Genes

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