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(Circulation. 2009;120:391-399.)
© 2009 American Heart Association, Inc.

Interventional Cardiology

Correlation of Intravascular Ultrasound Findings With Histopathological Analysis of Thrombus Aspirates in Patients With Very Late Drug-Eluting Stent Thrombosis

Stéphane Cook, MD^*; Elena Ladich, MD^*; Gaku Nakazawa, MD; Parham Eshtehardi, MD; Michel Neidhart, PhD; Rolf Vogel, MD, PhD; Mario Togni, MD; Peter Wenaweser, MD; Michael Billinger, MD; Christian Seiler, MD; Steffen Gay, MD; Bernhard Meier, MD; Werner J. Pichler, MD; Peter Jüni, MD; Renu Virmani, MD; Stephan Windecker, MD

From the Department of Cardiology, Bern University Hospital, Bern, Switzerland (S.C., P.E., R.V., M.T., P.W., M.B., C.S., B.M., S.W.); CVPath Institute Inc, Gaithersburg, Md (E.L., G.N., R.V.); World Health Organization Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University Hospital Zürich, Zürich, Switzerland (M.N., S.G.); Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland (P.J.); and Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology (W.J.P.), and Clinical Trials Unit (P.J., S.W.), Bern University Hospital, Bern, Switzerland.

Correspondence to Stephan Windecker, MD, Invasive Cardiology, Department of Cardiology, University Hospital Bern, 3010 Bern, Switzerland. E-mail stephan.windecker{at}insel.ch

Received January 30, 2009; accepted May 26, 2009.

Background— Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST.

Methods and Results— The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020±283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2±2.4 mm² and evidence of vessel remodeling (index, 1.6±0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263±149 white blood cells per high-power field) and eosinophils (DES, 20±24 eosinophils per high-power field; sirolimus-eluting stents, 34±28; paclitaxel-eluting stents, 6±6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20±24) than in those from spontaneous acute myocardial infarction (7±10), early bare-metal stent ST (1±1), early DES ST (1±2), and late bare-metal stent ST (2±3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm² increase in ISA cross-sectional area.

Conclusions— Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

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CLINICAL PERSPECTIVE

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