Mechanism of late in-stent restenosis after implantation of a paclitaxel derivate-eluting polymer stent system in humans.
BACKGROUND
We recently reported delayed angiographic restenosis in 15 patients who received 7-hexanoyltaxol (QP2)-eluting polymer stents (QuaDS) for the treatment of in-stent restenosis. This study presents the histological findings of atherectomy specimens from a subset of these patients receiving implants.


RESULTS
Between October and December 2001, 5 patients treated with QuaDS-QP2 stents underwent directional coronary atherectomy at 11.2+/-1.0 months for recurrent in-stent restenosis. Restenotic lesion composition was assessed with special stains, immunohistochemistry with quantitative image analysis, and, in one specimen, transmission electron microscopy. Atherectomy specimens contained fibrin interspersed in a smooth muscle cell-rich neointima with proteoglycan matrix. In 2 of 5 specimens, large aggregates of macrophages and T-lymphocytes were noted. These areas of active inflammation demonstrated a relatively high proliferation index by Ki-67 antibody staining, whereas the proliferation index in smooth muscle cell-rich restenotic areas was low.


CONCLUSIONS
Restenotic lesions from QuaDS-QP2-eluting stents at 12 months show persistent fibrin deposition with varying degrees of inflammation. These pathological changes, representing delayed healing, are usually observed up to only 3 months in human coronary arteries with stainless steel balloon-expandable stents. The nonreabsorbable polymer alone may have induced chronic inflammation.
Virmani
Renu
R
Catheterization Laboratories, Ospedale San Raffaele and Emo Centro Cuore Columbus, Milan, Italy. virmani@afip.osd.mil
Liistro
Francesco
F
Stankovic
Goran
G
Di Mario
Carlo
C
Montorfano
Matteo
M
Farb
Andrew
A
Kolodgie
Frank D
FD
Colombo
Antonio
A
D000368:Aged; D017225:Atherectomy, Coronary; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D002908:Chronic Disease; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000473:pathology / Q000601:surgery; D023903:Coronary Restenosis / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D003331:Coronary Vessels / Q000473:pathology / Q000601:surgery; D003692:Delayed-Action Preparations / Q000009:adverse effects*; D004343:Drug Implants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D011108:Polymers / Q000009:adverse effects*; D012008:Recurrence; D012086:Reoperation; D015607:Stents / Q000009:adverse effects*
D001952:Bridged-Ring Compounds; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011108:Polymers; C434083:7-hexanoyltaxol