Case report
Triple, simultaneous, very late coronary stent thrombosis
Trombose tripla, simultânea, muito tardia de stents coronários
Miguel Silva Vieira
, André Luz, Diana Anjo, Nuno Antunes, Mário Santos, Henrique Carvalho, Severo Torres
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Cardiology Department, Santo António Hospital– Centro Hospitalar do Porto, Porto, Portugal
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Note the extensive positive remodeling with several aneurysms in the non-stented proximal right coronary artery reference segments (B and D). Suboptimal reperfusion and no-reflow phenomenon after thrombus aspiration, multiple balloon dilations, administration of intracoronary platelet glycoprotein IIb/IIIa receptor inhibitors and adenosine, right ventricular endocavitary pacing and intra-aortic balloon pump counterpulsation (C and D).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">We present the case of a 49-year-old man with a past history of non-Q wave myocardial infarction (MI) seven years before, with three-vessel disease (right dominant circulation), who underwent complete functional percutaneous revascularization with sirolimus-eluting stents (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). He had an unremarkable follow-up under medical therapy, having completed 12 months of dual antiplatelet therapy (DAPT), with no residual angina, normal left ventricular ejection fraction and good functional capacity, although with suboptimal control of cardiovascular risk factors (dyslipidemia and overweight). No in-stent restenosis was noted in elective angiography at six months and he had no residual ischemia on exercise radionuclide myocardial perfusion imaging performed six years later.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Seven years later, the patient was admitted with acute ST-segment elevation myocardial infarction, eight days after stopping aspirin. Also notable was a gout attack in the week of the cardiac event. He presented with typical severe retrosternal chest pain and ST-segment elevation in anteroseptal and inferior leads (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). He was immediately transferred to the cardiac catheterization laboratory, with a door-to-balloon time of 40 minutes and Killip class I on admission. Simultaneous stent thrombosis (ST) in the three coronary arteries was noted on first contrast injection (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>). Thrombus aspiration and balloon angioplasty of the left anterior descending coronary artery achieved only suboptimal reperfusion. No-reflow and bail-out ensued, despite antithrombotic pharmacotherapy (aspirin and clopidogrel loading doses, unfractionated heparin and platelet glycoprotein IIb/IIIa receptor inhibitors) and intracoronary adenosine administration. Right ventricular pacing was needed due to complete atrioventricular block. Advanced cardiovascular life support was then started due to hemodynamic collapse and cardiac asystole. While cardiopulmonary resuscitation (CPR) was being performed, right coronary artery catheterization was attempted through a contralateral 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 pulseless ventricular tachycardia and eventually expired.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Coronary artery stent thrombosis is a rare but potential catastrophic complication of percutaneous coronary intervention (PCI), usually presenting as sudden death or MI.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Moreover, patients who survive the event have a worse prognosis and are at increased risk of another ST in follow-up.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The risk of very late stent thrombosis (VLST) (occurring more than one year after stent placement) raises long-term safety concerns regarding the first generation of DES (sirolimus-eluting and paclitaxel-eluting stents), even though, compared with bare metal stents, they were a major breakthrough, consistently being associated with reduced rates of angiographic restenosis and ischemia-driven target vessel revascularization.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The reported cumulative rates of definitive VLST, according to the Academic Research Consortium definition, vary in the literature depending on the duration of follow-up used, and are slightly higher in observational studies.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Delayed neointimal coverage and a hypersensitivity reaction to components of the drug-polymer-stent combination, together with ongoing vessel inflammation, impaired healing and abnormal remodeling leading to late and very late acquired stent malapposition, have been associated with VLST, but the precise mechanism is still unknown.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–13</span></a> Patient-related factors (including compliance with antiplatelet therapy), procedural and post-procedural factors (including type and duration of antiplatelet therapy) probably interact and predispose the patient to ST.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3,10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Endothelial dysfunction has also been described as an adverse consequence following coronary DES implantation, although its clinical significance is still unknown.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> 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 mechanism is also unknown, that acts as another substrate for VLST.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> This also involves both proximal and distal non-stented reference segments and leads to delayed arterial healing, impairment of endothelial nitric oxide synthesis and imbalance between endothelium-derived relaxing and contracting factors, resulting in a thrombogenic environment and paradoxical vasoconstriction of the adjacent segments.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,16</span></a> Moreover, stent-induced mechanical changes in vessel geometry modify its response to endothelial injury and have been linked to the pathobiology of ST.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">To the best of our knowledge, this is the first report of a VLST, 81 months post-PCI, simultaneously occurring in the three coronary artery territories following discontinuation of antiplatelet therapy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The peri-stent aneurysms depicted on angiography suggest extensive local positive vascular remodeling, a known late complication after DES deployment which has also been linked to very late acquired stent malapposition and ST; a review of the initial PCI showed no procedure-related mechanical problems such as residual dissection that could have acted as a substrate for the final extensive remodeling.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18–20</span></a> Furthermore, although intravascular ultrasound was not performed due to the dramatic course of the event, the pronounced positive remodeling suggests the possibility of very late stent malapposition, a nidus for thrombus formation. Unfortunately there was no histopathological analysis of thrombus aspirates to search for eosinophilic infiltrates, which are common in thrombi from very late DES thrombosis associated with hypersensitivity reactions to the drug–polymer–stent combination, and related to the extent of stent malapposition.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Several mechanisms have been implicated in this positive vascular remodeling, such as procedure-related acute vessel injury, hypersensitivity reactions to the stent polymer coatings, toxic effects of antiproliferative drugs on the vessel, and even focal infections.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–21</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We hypothesize that a complex interplay of several thrombogenic factors probably acted together to create this “perfect storm” scenario that ended in a dramatic triple stent thrombosis: significant underlying endothelial dysfunction provoking an abnormal response to endothelial shear stress, abnormal rheological conditions and possible very late acquired stent malapposition; recent discontinuation of antiplatelet therapy (probably playing a pivotal role); and an inflammatory state – a recent gout attack, which has also been linked to acute MI.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Our report highlights the serious consequences of discontinuing antiplatelet therapy, even several years after DES deployment and for a brief period. Although the optimal duration of DAPT after DES implantation is still unknown, robust data are only available for up to six months of therapy, and there are other mechanisms not related to discontinuation of drug therapy implicated in VLST, anecdotal cases like this demonstrate that there may be no time limit to the occurrence of this complication, and lifelong antiplatelet therapy is mandatory.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,9–12,23,24</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Because there is currently no established method to identify patients at high risk of VLST, a recognized multifactorial event, and there is no definitive evidence on the optimal duration of DAPT, careful surveillance for potential late complications in patients with DES is crucial. Medication compliance, optimization of the PCI technique, quantification of coronary artery disease complexity by the SYNTAX score, shifting toward functional rather than visual guided angioplasty and thus avoiding unnecessary procedures, using invasive (fractional flow reserve, intravascular ultrasound, optical coherence tomography, and quantitative coronary angiography after intracoronary acetylcholine infusion for evaluation of vasomotor dysfunction) and non-invasive advanced coronary imaging techniques for tailored post-procedure monitoring, may help to reduce the incidence of this potentially devastating complication.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25–27</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The multifactorial nature of ST makes it difficult to predict and neither genotyping for reduced-function cytochrome P2C19 nor platelet function testing currently have a definite role.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">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 recommendations in the guidelines. The era of personalized antiplatelet therapy is therefore eagerly awaited.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Furthermore, although there appears to be a class effect between the different antiproliferative drugs, the data on new-generation DES (with thinner, more biocompatible and even bioabsorbable polymers, different stent alloys with better flexibility, conformability, and deliverability, and alternative drugs) are encouraging and may reduce this complication further.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Finally, long-term follow-up studies are required to assess the significance and management of late and very late vascular pathologic changes secondary to DES implantation, particularly in-stent neoatherosclerosis, abnormal vasomotion, acquired very late stent malapposition and coronary artery aneurysms, and to improve our understanding of endothelial function.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres250701" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec238291" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres250700" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec238292" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Right to privacy and informed consent" ] ] ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-05-30" "fechaAceptado" => "2012-06-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec238291" "palabras" => array:2 [ 0 => "Very late stent thrombosis" 1 => "Drug-eluting stents" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec238292" "palabras" => array:2 [ 0 => "Trombose muito tardia de <span class="elsevierStyleItalic">stent</span>" 1 => "<span class="elsevierStyleItalic">Stents</span> revestidos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Coronary artery stent thrombosis is an uncommon but potentially catastrophic complication. The risk of very late stent thrombosis (VLST) raises important safety issues regarding the first generation of drug-eluting stents (DES). Although several complex mechanisms for VLST have been suggested and various predictors have been described, its pathophysiology is not completely understood and it is not known whether longer-term dual antiplatelet therapy reduces the risk. We present a rare case of simultaneous very late DES thrombosis in the three vascular territories, following discontinuation of antiplatelet therapy seven years after stent placement, presenting as cardiogenic shock.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A trombose de <span class="elsevierStyleItalic">stent</span> coronário é uma complicação rara mas potencialmente catastrófica. O risco de trombose muito tardia de <span class="elsevierStyleItalic">stent</span> (TMTS) tem levantado questões importantes sobre a segurança do uso de <span class="elsevierStyleItalic">stents</span> revestidos com fármacos (SRF) de primeira geração. Embora sejam vários e complexos os mecanismos da TMTS e vários os preditores que têm sido descritos, a sua fisiopatologia ainda não está totalmente esclarecida e desconhece-se se o prolongar da terapêutica antiagregante dupla reduz esse risco. Descrevemos um caso raro de trombose muito tardia de SRF ocorrendo em simultâneo nos três territórios vasculares, após interrupção da terapêutica antiagregante, sete anos após implantação dos <span class="elsevierStyleItalic">stents</span>, apresentando-se como choque cardiogénico.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0095" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia><elsevierMultimedia ident="upi0020"></elsevierMultimedia><elsevierMultimedia ident="upi0025"></elsevierMultimedia><elsevierMultimedia ident="upi0030"></elsevierMultimedia><elsevierMultimedia ident="upi0035"></elsevierMultimedia><elsevierMultimedia ident="upi0040"></elsevierMultimedia><elsevierMultimedia ident="upi0045"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0045" ] ] ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2505 "Ancho" => 3000 "Tamanyo" => 355049 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Top: Left anterior oblique view of the mid-right coronary artery critical stenosis (Panel A), right anterior oblique cranial view of the mid-left anterior descending artery critical stenosis (Panel B) and right anterior oblique caudal view of the second obtuse marginal critical stenosis (Panel C). Bottom: Angiographic result after PCI with balloon predilatation and implantation of sirolimus-eluting stents (arrowheads) (D–F).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 992 "Ancho" => 2998 "Tamanyo" => 212098 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Electrocardiogram on admission with ST-segment elevation in anteroseptal and inferior leads.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1780 "Ancho" => 1300 "Tamanyo" => 251111 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Dramatic simultaneous very late stent thrombosis of the left anterior descending, second obtuse marginal and right coronary arteries (A and B). Note the extensive positive remodeling with several aneurysms in the non-stented proximal right coronary artery reference segments (B and D). Suboptimal reperfusion and no-reflow phenomenon after thrombus aspiration, multiple balloon dilations, administration of intracoronary platelet glycoprotein IIb/IIIa receptor inhibitors and adenosine, right ventricular endocavitary pacing and intra-aortic balloon pump counterpulsation (C and D).</p>" ] ] 3 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc1.avi" "ficheroTamanyo" => 468560 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc1.flv" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc1.m4v" "poster" => "mmc1.jpg" ] ] ] ] 4 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc2.avi" "ficheroTamanyo" => 392196 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc2.flv" "poster" => "mmc2.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc2.m4v" "poster" => "mmc2.jpg" ] ] ] ] 5 => array:5 [ "identificador" => "upi0015" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc3.avi" "ficheroTamanyo" => 1175948 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc3.flv" "poster" => "mmc3.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc3.m4v" "poster" => "mmc3.jpg" ] ] ] ] 6 => array:5 [ "identificador" => "upi0020" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc4.avi" "ficheroTamanyo" => 454172 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc4.flv" "poster" => "mmc4.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc4.m4v" "poster" => "mmc4.jpg" ] ] ] ] 7 => array:5 [ "identificador" => "upi0025" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc5.avi" "ficheroTamanyo" => 462908 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc5.flv" "poster" => "mmc5.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc5.m4v" "poster" => "mmc5.jpg" ] ] ] ] 8 => array:5 [ "identificador" => "upi0030" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc6.avi" "ficheroTamanyo" => 502936 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc6.flv" "poster" => "mmc6.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc6.m4v" "poster" => "mmc6.jpg" ] ] ] ] 9 => array:5 [ "identificador" => "upi0035" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc7.avi" "ficheroTamanyo" => 1589582 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc7.flv" "poster" => "mmc7.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc7.m4v" "poster" => "mmc7.jpg" ] ] ] ] 10 => array:5 [ "identificador" => "upi0040" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc8.avi" "ficheroTamanyo" => 592820 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc8.flv" "poster" => "mmc8.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc8.m4v" "poster" => "mmc8.jpg" ] ] ] ] 11 => array:5 [ "identificador" => "upi0045" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc9.avi" "ficheroTamanyo" => 464602 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc9.flv" "poster" => "mmc9.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:2 [ "fichero" => "mmc9.m4v" "poster" => "mmc9.jpg" ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G.W. 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 11 | 6 | 17 |
| 2024 Outubro | 45 | 28 | 73 |
| 2024 Setembro | 58 | 21 | 79 |
| 2024 Agosto | 64 | 29 | 93 |
| 2024 Julho | 45 | 33 | 78 |
| 2024 Junho | 41 | 30 | 71 |
| 2024 Maio | 60 | 33 | 93 |
| 2024 Abril | 36 | 26 | 62 |
| 2024 Maro | 64 | 18 | 82 |
| 2024 Fevereiro | 46 | 27 | 73 |
| 2024 Janeiro | 34 | 24 | 58 |
| 2023 Dezembro | 37 | 29 | 66 |
| 2023 Novembro | 39 | 21 | 60 |
| 2023 Outubro | 41 | 17 | 58 |
| 2023 Setembro | 32 | 19 | 51 |
| 2023 Agosto | 41 | 15 | 56 |
| 2023 Julho | 45 | 8 | 53 |
| 2023 Junho | 37 | 10 | 47 |
| 2023 Maio | 44 | 24 | 68 |
| 2023 Abril | 21 | 5 | 26 |
| 2023 Maro | 33 | 17 | 50 |
| 2023 Fevereiro | 46 | 15 | 61 |
| 2023 Janeiro | 63 | 14 | 77 |
| 2022 Dezembro | 51 | 14 | 65 |
| 2022 Novembro | 36 | 26 | 62 |
| 2022 Outubro | 39 | 19 | 58 |
| 2022 Setembro | 30 | 25 | 55 |
| 2022 Agosto | 43 | 28 | 71 |
| 2022 Julho | 45 | 34 | 79 |
| 2022 Junho | 36 | 21 | 57 |
| 2022 Maio | 28 | 38 | 66 |
| 2022 Abril | 37 | 20 | 57 |
| 2022 Maro | 40 | 29 | 69 |
| 2022 Fevereiro | 26 | 26 | 52 |
| 2022 Janeiro | 43 | 20 | 63 |
| 2021 Dezembro | 18 | 30 | 48 |
| 2021 Novembro | 42 | 34 | 76 |
| 2021 Outubro | 40 | 40 | 80 |
| 2021 Setembro | 48 | 31 | 79 |
| 2021 Agosto | 53 | 24 | 77 |
| 2021 Julho | 42 | 29 | 71 |
| 2021 Junho | 37 | 13 | 50 |
| 2021 Maio | 63 | 29 | 92 |
| 2021 Abril | 106 | 29 | 135 |
| 2021 Maro | 112 | 17 | 129 |
| 2021 Fevereiro | 70 | 18 | 88 |
| 2021 Janeiro | 40 | 9 | 49 |
| 2020 Dezembro | 42 | 9 | 51 |
| 2020 Novembro | 39 | 16 | 55 |
| 2020 Outubro | 29 | 16 | 45 |
| 2020 Setembro | 39 | 3 | 42 |
| 2020 Agosto | 20 | 8 | 28 |
| 2020 Julho | 36 | 13 | 49 |
| 2020 Junho | 36 | 3 | 39 |
| 2020 Maio | 42 | 4 | 46 |
| 2020 Abril | 27 | 10 | 37 |
| 2020 Maro | 46 | 6 | 52 |
| 2020 Fevereiro | 70 | 25 | 95 |
| 2020 Janeiro | 33 | 9 | 42 |
| 2019 Dezembro | 38 | 7 | 45 |
| 2019 Novembro | 29 | 5 | 34 |
| 2019 Outubro | 39 | 2 | 41 |
| 2019 Setembro | 21 | 8 | 29 |
| 2019 Agosto | 31 | 3 | 34 |
| 2019 Julho | 43 | 10 | 53 |
| 2019 Junho | 28 | 8 | 36 |
| 2019 Maio | 40 | 7 | 47 |
| 2019 Abril | 21 | 11 | 32 |
| 2019 Maro | 63 | 9 | 72 |
| 2019 Fevereiro | 63 | 9 | 72 |
| 2019 Janeiro | 81 | 5 | 86 |
| 2018 Dezembro | 113 | 11 | 124 |
| 2018 Novembro | 95 | 5 | 100 |
| 2018 Outubro | 229 | 18 | 247 |
| 2018 Setembro | 74 | 17 | 91 |
| 2018 Agosto | 58 | 16 | 74 |
| 2018 Julho | 39 | 11 | 50 |
| 2018 Junho | 79 | 8 | 87 |
| 2018 Maio | 107 | 9 | 116 |
| 2018 Abril | 95 | 23 | 118 |
| 2018 Maro | 145 | 11 | 156 |
| 2018 Fevereiro | 58 | 7 | 65 |
| 2018 Janeiro | 105 | 1 | 106 |
| 2017 Dezembro | 167 | 11 | 178 |
| 2017 Novembro | 41 | 7 | 48 |
| 2017 Outubro | 44 | 12 | 56 |
| 2017 Setembro | 52 | 17 | 69 |
| 2017 Agosto | 49 | 10 | 59 |
| 2017 Julho | 37 | 8 | 45 |
| 2017 Junho | 51 | 17 | 68 |
| 2017 Maio | 38 | 10 | 48 |
| 2017 Abril | 34 | 5 | 39 |
| 2017 Maro | 21 | 37 | 58 |
| 2017 Fevereiro | 47 | 16 | 63 |
| 2017 Janeiro | 27 | 5 | 32 |
| 2016 Dezembro | 32 | 12 | 44 |
| 2016 Novembro | 46 | 11 | 57 |
| 2016 Outubro | 24 | 9 | 33 |
| 2016 Setembro | 20 | 11 | 31 |
| 2016 Agosto | 23 | 5 | 28 |
| 2016 Julho | 8 | 8 | 16 |
| 2016 Junho | 6 | 9 | 15 |
| 2016 Maio | 19 | 7 | 26 |
| 2016 Abril | 40 | 2 | 42 |
| 2016 Maro | 46 | 6 | 52 |
| 2016 Fevereiro | 77 | 21 | 98 |
| 2016 Janeiro | 63 | 7 | 70 |
| 2015 Dezembro | 67 | 9 | 76 |
| 2015 Novembro | 48 | 5 | 53 |
| 2015 Outubro | 49 | 9 | 58 |
| 2015 Setembro | 60 | 11 | 71 |
| 2015 Agosto | 60 | 15 | 75 |
| 2015 Julho | 80 | 8 | 88 |
| 2015 Junho | 44 | 2 | 46 |
| 2015 Maio | 57 | 5 | 62 |
| 2015 Abril | 81 | 15 | 96 |
| 2015 Maro | 50 | 3 | 53 |
| 2015 Fevereiro | 52 | 8 | 60 |
| 2015 Janeiro | 44 | 7 | 51 |
| 2014 Dezembro | 57 | 10 | 67 |
| 2014 Novembro | 56 | 7 | 63 |
| 2014 Outubro | 71 | 15 | 86 |
| 2014 Setembro | 63 | 15 | 78 |
| 2014 Agosto | 63 | 8 | 71 |
| 2014 Julho | 58 | 10 | 68 |
| 2014 Junho | 60 | 6 | 66 |
| 2014 Maio | 52 | 11 | 63 |
| 2014 Abril | 52 | 9 | 61 |
| 2014 Maro | 76 | 16 | 92 |
| 2014 Fevereiro | 76 | 15 | 91 |
| 2014 Janeiro | 72 | 15 | 87 |
| 2013 Dezembro | 78 | 12 | 90 |
| 2013 Novembro | 61 | 20 | 81 |
| 2013 Outubro | 64 | 15 | 79 |
| 2013 Setembro | 72 | 19 | 91 |
| 2013 Agosto | 77 | 36 | 113 |
| 2013 Julho | 87 | 23 | 110 |
| 2013 Junho | 59 | 21 | 80 |
| 2013 Maio | 77 | 28 | 105 |
| 2013 Abril | 122 | 51 | 173 |
| 2013 Maro | 51 | 23 | 74 |
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