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