Revista
Portuguesa
de
Cardiologia
Portuguese
Journal
of
Cardiology
www.revportcardiol.org
CASE
REPORT
Triple,
simultaneous,
very
late
coronary
stent
thrombosis
Miguel
Silva
Vieira
∗,
André
Luz,
Diana
Anjo,
Nuno
Antunes,
Mário
Santos,
Henrique
Carvalho,
Severo
Torres
CardiologyDepartment,SantoAntónioHospital---CentroHospitalardoPorto,Porto,Portugal Received30May2012;accepted4June2012
KEYWORDS
Verylatestent thrombosis; Drug-elutingstents
Abstract Coronary artery stent thrombosis is an uncommon but potentially catastrophic complication. The risk of very late stent thrombosis (VLST) raises important safety issues regardingthe firstgeneration ofdrug-elutingstents (DES).Althoughseveralcomplex mech-anisms for VLST have been suggested and various predictors have been described, its pathophysiologyisnotcompletely understoodanditisnotknownwhetherlonger-termdual antiplatelet therapyreducestherisk.Wepresentarare caseofsimultaneous verylate DES thrombosisinthethreevascularterritories,followingdiscontinuationofantiplatelettherapy sevenyearsafterstentplacement,presentingascardiogenicshock.
© 2012 Sociedade Portuguesa de Cardiologia Published by Elsevier España, S.L. All rights reserved.
PALAVRAS-CHAVE
Trombosemuito tardiadestent; Stentsrevestidos
Trombosetripla,simultânea,muitotardiadestentscoronários
Resumo Atrombosedestentcoronárioéumacomplicac¸ãoraramaspotencialmente catas-trófica.Oriscodetrombosemuitotardiadestent(TMTS)temlevantadoquestõesimportantes sobreaseguranc¸adousodestentsrevestidoscomfármacos(SRF)deprimeiragerac¸ão.Embora sejamváriosecomplexososmecanismosdaTMTSeváriosospreditoresquetêmsidodescritos, asuafisiopatologiaaindanãoestátotalmenteesclarecidaedesconhece-seseoprolongarda terapêuticaantiagreganteduplareduzesserisco.Descrevemosumcasorarodetrombosemuito tardiadeSRFocorrendoemsimultâneonostrêsterritóriosvasculares,apósinterrupc¸ãoda ter-apêuticaantiagregante,seteanosapósimplantac¸ãodosstents,apresentando-secomochoque cardiogénico.
© 2012 Sociedade Portuguesa de Cardiologia.Publicado por Elsevier España, S.L. Todosos direitosreservados.
∗Correspondingauthor.
E-mailaddress:[email protected](M.S.Vieira).
Case
report
Wepresentthecaseof a49-year-oldmanwithapast his-toryofnon-Qwave myocardialinfarction(MI)sevenyears 0870-2551/$–seefrontmatter©2012SociedadePortuguesadeCardiologiaPublishedbyElsevierEspaña,S.L.Allrightsreserved.
2,5 x 33mm 3,0 x 18mm 3,0 x 33mm 2,5 x 18mm
A
B
D
E
C
F
Figure1 Top:Leftanteriorobliqueviewofthemid-rightcoronaryarterycriticalstenosis(PanelA),rightanteriorobliquecranial viewofthemid-left anteriordescendingarterycriticalstenosis(Panel B)andrightanteriorobliquecaudal viewofthesecond obtusemarginalcriticalstenosis(PanelC).Bottom:AngiographicresultafterPCIwithballoonpredilatationandimplantationof sirolimus-elutingstents(arrowheads)(D---F).
before,withthree-vesseldisease (right dominant circula-tion), who underwent complete functional percutaneous revascularization with sirolimus-eluting stents (Figure 1). Hehadan unremarkablefollow-upundermedicaltherapy, having completed12 monthsof dualantiplatelet therapy (DAPT), with no residual angina, normal left ventricular ejection fraction and good functional capacity, although withsuboptimalcontrolofcardiovascularriskfactors (dys-lipidemiaandoverweight).Noin-stentrestenosiswasnoted inelective angiographyatsixmonthsandhehadno resid-ualischemiaonexerciseradionuclidemyocardialperfusion imagingperformedsixyearslater.
Sevenyearslater,thepatientwasadmittedwithacute ST-segmentelevationmyocardialinfarction,eightdaysafter stopping aspirin. Also notable was a gout attack in the week of the cardiac event. He presented with typical severeretrosternalchestpainandST-segmentelevationin anteroseptalandinferiorleads(Figure2).Hewas immedi-atelytransferredtothecardiaccatheterizationlaboratory, witha door-to-balloontimeof 40minutes andKillip class Ionadmission. Simultaneousstentthrombosis (ST)in the threecoronaryarteries wasnoted onfirst contrast
injec-tion(Figure3).Thrombusaspirationandballoonangioplasty
of the left anterior descending coronary artery achieved onlysuboptimalreperfusion.No-reflowandbail-outensued, despite antithrombotic pharmacotherapy (aspirinand clo-pidogrelloadingdoses,unfractionatedheparinandplatelet glycoproteinIIb/IIIa receptorinhibitors)andintracoronary adenosine administration. Right ventricular pacing was needed due tocomplete atrioventricularblock. Advanced cardiovascularlifesupportwasthenstarteddueto hemody-namiccollapseandcardiacasystole.Whilecardiopulmonary resuscitation (CPR) was being performed, right coronary arterycatheterizationwasattemptedthrougha contralat-eral femoral approach with thrombus aspiration, balloon angioplasty and stent implantation. Despite intra-aortic balloon pump placement and prolonged CPR, the patient developed several episodes of ventricular fibrillation and incessant pulselessventriculartachycardia and eventually expired.
Discussion
Coronary artery stent thrombosis is a rare but poten-tial catastrophic complication of percutaneous coronary
I II aVR aVL aVF III V1 V2 V3 V4 V5 V6
Figure2 ElectrocardiogramonadmissionwithST-segmentelevationinanteroseptalandinferiorleads.
Figure3 Dramaticsimultaneous verylatestentthrombosisoftheleft anteriordescending,secondobtusemarginalandright coronaryarteries(AandB).Notetheextensivepositiveremodelingwithseveralaneurysmsinthenon-stentedproximalright coro-naryarteryreferencesegments(BandD).Suboptimalreperfusionandno-reflowphenomenonafterthrombusaspiration,multiple balloondilations,administrationofintracoronaryplateletglycoproteinIIb/IIIareceptorinhibitorsandadenosine,rightventricular endocavitarypacingandintra-aorticballoonpumpcounterpulsation(CandD).
intervention (PCI), usually presenting assudden death or MI.1,2Moreover,patientswhosurvivetheeventhaveaworse
prognosisandareatincreasedriskofanotherSTin follow-up.3
The risk of very late stent thrombosis (VLST) (occur-ring more than one year after stent placement) raises long-termsafetyconcernsregardingthefirstgenerationof DES(sirolimus-eluting and paclitaxel-eluting stents), even though,comparedwithbaremetalstents,theywereamajor breakthrough, consistently being associated withreduced ratesofangiographicrestenosisandischemia-driventarget vesselrevascularization.4Thereportedcumulativeratesof
definitiveVLST,accordingtotheAcademicResearch Consor-tium definition, vary in the literature depending on the durationoffollow-upused,andareslightlyhigherin obser-vationalstudies.3---8
Delayed neointimal coverage and a hypersensitivity reactiontocomponentsofthedrug-polymer-stent combina-tion,together withongoing vesselinflammation, impaired healing and abnormal remodeling leading to late and very late acquired stent malapposition, have been asso-ciated with VLST, but the precise mechanism is still unknown.9---13 Patient-relatedfactors(includingcompliance
withantiplatelettherapy),proceduralandpost-procedural factors(includingtypeanddurationofantiplatelettherapy) probablyinteractandpredisposethepatienttoST.2,3,10
Endothelial dysfunction has also been described as an adverse consequence following coronary DES implanta-tion, although its clinical significance is still unknown.14
In fact, although DES target vascular smooth muscle cell proliferation and migration (neointimal hyperplasia), the key factors in the development of restenosis, they impair re-endothelialization and promote late in-stent neoatherosclerosis, a new concept whose precise mecha-nism is also unknown, that acts as another substrate for VLST.15,16 This alsoinvolves both proximaland distal
non-stentedreferencesegments and leads todelayed arterial healing, impairment of endothelial nitric oxide synthe-sis and imbalance between endothelium-derived relaxing andcontractingfactors,resultingin athrombogenic envi-ronmentandparadoxical vasoconstrictionof theadjacent segments.10,16Moreover,stent-inducedmechanicalchanges
invesselgeometrymodifyitsresponsetoendothelialinjury andhavebeenlinkedtothepathobiologyofST.17
Tothebestofourknowledge,thisisthefirstreportof aVLST,81monthspost-PCI,simultaneouslyoccurringinthe threecoronaryarteryterritories following discontinuation ofantiplatelettherapy.
The peri-stentaneurysmsdepictedonangiography sug-gestextensivelocalpositivevascular remodeling,aknown late complication after DES deployment which has also been linked to very late acquired stent malapposition andST; a review of the initial PCI showedno procedure-related mechanical problems such as residual dissection thatcouldhaveactedasasubstrateforthefinalextensive remodeling.18---20Furthermore,althoughintravascular
ultra-soundwasnotperformedduetothedramaticcourseofthe event,thepronouncedpositiveremodelingsuggeststhe pos-sibilityofverylatestentmalapposition,anidusforthrombus formation. Unfortunately there was no histopathological analysis of thrombus aspirates to search for eosinophilic infiltrates,whicharecommoninthrombifromverylateDES
thrombosisassociatedwithhypersensitivityreactionstothe drug---polymer---stentcombination,andrelatedtotheextent ofstentmalapposition.10
Severalmechanisms have been implicatedin this posi-tivevascular remodeling,suchasprocedure-relatedacute vessel injury,hypersensitivity reactions tothe stent poly-mercoatings,toxiceffectsofantiproliferativedrugsonthe vessel,andevenfocalinfections.14---21
We hypothesize that a complex interplay of several thrombogenicfactorsprobablyactedtogethertocreatethis ‘‘perfect storm’’scenario thatended inadramatic triple stentthrombosis:significantunderlyingendothelial dysfunc-tion provoking an abnormalresponseto endothelialshear stress, abnormal rheological conditions and possible very lateacquiredstentmalapposition;recentdiscontinuationof antiplatelettherapy(probablyplayingapivotalrole);andan inflammatorystate ---arecentgoutattack,whichhasalso beenlinkedtoacuteMI.22
Ourreporthighlightstheseriousconsequencesof discon-tinuing antiplatelet therapy,even several yearsafter DES deployment and for a brief period. Although the optimal duration ofDAPT afterDES implantationis stillunknown, robust data are only available for up to six months of therapy, and there are other mechanisms not related to discontinuation ofdrug therapy implicated in VLST, anec-dotalcaseslikethisdemonstratethattheremaybenotime limit to theoccurrence of this complication, andlifelong antiplatelettherapyismandatory.2,9---12,23,24
Because there is currently no established method to identify patientsat high risk of VLST,a recognized multi-factorialevent,andthereisnodefinitiveevidenceonthe optimal duration of DAPT, careful surveillance for poten-tial late complications in patients with DES is crucial. Medication compliance, optimization of the PCI tech-nique,quantificationofcoronaryarterydiseasecomplexity by the SYNTAX score, shifting toward functional rather than visual guided angioplasty and thus avoiding unnec-essary procedures,usinginvasive (fractionalflowreserve, intravascular ultrasound, optical coherence tomography, and quantitative coronary angiography after intracoro-nary acetylcholine infusion for evaluation of vasomotor dysfunction) and non-invasive advanced coronary imaging techniques for tailored post-procedure monitoring, may helptoreducetheincidenceofthispotentiallydevastating complication.25---27
The multifactorial nature of ST makes it difficult to predict and neither genotyping for reduced-function cytochrome P2C19 nor platelet function testing currently haveadefiniterole.28
Although new anticoagulant and antiplatelet therapies have the potential to influence future clinical decisions regarding the duration of DAPT, the current approved therapies should not be discontinued ahead of the rec-ommendations in the guidelines. The era of personalized antiplatelettherapyisthereforeeagerlyawaited.
Furthermore,althoughthereappearstobeaclasseffect betweenthedifferentantiproliferativedrugs,thedataon new-generationDES(withthinner,morebiocompatibleand even bioabsorbable polymers, different stent alloys with better flexibility, conformability, and deliverability, and alternative drugs) are encouraging and may reduce this complicationfurther.29,30
Finally,long-termfollow-upstudiesarerequiredtoassess thesignificanceandmanagementoflateandverylate vas-cular pathologic changes secondary to DES implantation, particularlyin-stentneoatherosclerosis,abnormal vasomo-tion,acquired verylatestent malapposition andcoronary artery aneurysms, and to improve our understanding of endothelialfunction.
Ethical
disclosures
Protection of human and animal subjects.The authors declarethatnoexperimentswereperformedonhumansor animalsforthisstudy.
Confidentialityofdata.Theauthorsdeclarethattheyhave followedtheprotocolsoftheirworkcenteronthe publica-tionofpatientdataandthatallthepatientsincludedinthe studyreceivedsufficientinformationandgavetheirwritten informedconsenttoparticipateinthestudy.
Righttoprivacyandinformedconsent.The authorshave obtained the written informedconsent ofthe patients or subjectsmentionedinthearticle.Thecorrespondingauthor isinpossessionofthisdocument.
Conflicts
of
interest
Theauthorshavenoconflictsofinteresttodeclare.
Appendix
A.
Supplementary
data
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.repc.2012.
06.019.
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