Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization.
BACKGROUND
Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent placement has emerged as a major concern. Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown.


RESULTS
From a registry totaling 81 human autopsies of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted >30 days. We identified 28 lesions with thrombus and compared those with 34 of similar duration without thrombosis using computer-guided morphometric and histological analyses. LST was defined as an acute thrombus within a coronary artery stent in place >30 days. Multiple logistic generalized estimating equations modeling demonstrated that endothelialization was the best predictor of thrombosis. The morphometric parameter that best correlated with endothelialization was the ratio of uncovered to total stent struts per section. A univariable logistic generalized estimating equations model of occurrence of thrombus in a stent section versus ratio of uncovered to total stent struts per section demonstrated a marked increase in risk for LST as the number of uncovered struts increased. The odds ratio for thrombus in a stent with a ratio of uncovered to total stent struts per section >30% is 9.0 (95% CI, 3.5 to 22).


CONCLUSIONS
The most powerful histological predictor of stent thrombosis was endothelial coverage. The best morphometric predictor of LST was the ratio of uncovered to total stent struts. Heterogeneity of healing is a common finding in drug-eluting stents with evidence of LST and demonstrates the importance of incomplete healing of the stented segment in the pathophysiology of LST.
Finn
Aloke V
AV
Cardiac Unit, Department of Internal Medicine, Massachusetts General Hospital, Boston, USA.
Joner
Michael
M
Nakazawa
Gaku
G
Kolodgie
Frank
F
Newell
John
J
John
Mike C
MC
Gold
Herman K
HK
Virmani
Renu
R
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000886:Anthropometry / Q000379:methods; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D023903:Coronary Restenosis / Q000150:complications; D003328:Coronary Thrombosis / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D004343:Drug Implants; D004363:Drug Utilization / Q000706:statistics & numerical data; D004730:Endothelium, Vascular / Q000473:pathology*; D004867:Equipment Design; D004868:Equipment Failure; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D016017:Odds Ratio; D017239:Paclitaxel / Q000008:administration & dosage; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D020123:Sirolimus / Q000008:administration & dosage; D015607:Stents / Q000009:adverse effects*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D017539:Tunica Intima / Q000473:pathology; D014945:Wound Healing
D004343:Drug Implants; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D017239:Paclitaxel; D001241:Aspirin; D020123:Sirolimus