title: Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography.
abstract: BACKGROUND
  The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event.
  
  
  RESULTS
  Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early- and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1-7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82-10.04; P<0.001 and 13.03; 95% confidence interval, 10.13-16.93; P<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55-4.25; versus 1.29 mm; 95% confidence interval, 0.81-1.77; P<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early- and newer-generation drug-eluting stents.
  
  
  CONCLUSIONS
  The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early- and new-generation drug-eluting stents. The longitudinal extension of malapposed and uncovered stent was the most important correlate of thrombus formation in VLST.
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Masanori
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Maria D
authors.initials: MD
authors.lastname: Radu
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Serge
authors.initials: S
authors.lastname: Zaugg
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Amabile
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Hector M
authors.initials: HM
authors.lastname: Garcia-Garcia
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Kyohei
authors.initials: K
authors.lastname: Yamaji
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Erik
authors.initials: E
authors.lastname: Jørgensen
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Henning
authors.initials: H
authors.lastname: Kelbæk
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Pilgrim
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Christophe
authors.initials: C
authors.lastname: Caussin
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Zanchin
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Aurelie
authors.initials: A
authors.lastname: Veugeois
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Ulrik
authors.initials: U
authors.lastname: Abildgaard
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Stephane
authors.initials: S
authors.lastname: Cook
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Konstantinos C
authors.initials: KC
authors.lastname: Koskinas
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.).
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: From Department of Cardiology, Bern University Hospital, Switzerland (M.T., K.Y., T.P., T.Z., K.C.K., S.W., L.R.); Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark (M.D.R., E..J.); Clinical Trials Unit, Bern University, Bern, Switzerland (S.Z.) Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Canada (P.J.); Department of Cardiology, Institut Mutualiste Montsouris, Paris, France (N.A., C.C., A.V.); Interventional Cardilogy, Washington Hospital Center, Washington, DC (H.M.G.-G.); Department of Cardiology, Roskilde Hospital, Denmark (H.K.); Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (U.A.); and Department of Cardiology, Fribourg University and Hospital, Switzerland (S.C.). lorenz.raeber@insel.ch.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
mesh_terms: D000368:Aged; D003331:Coronary Vessels / Q000473:pathology* / Q000601:surgery; D003430:Cross-Sectional Studies; D054855:Drug-Eluting Stents / Q000009:adverse effects* / Q000592:standards / Q000639:trends*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011475:Prosthesis Failure; D013927:Thrombosis / Q000175:diagnosis* / Q000209:etiology*; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods*
keywords: drug-eluting stents; stents; thrombosis; tomography, optical coherence