FUNDAMENTO: A eficácia dos stents farmacológicos em reduzir os índices de eventos cardíacos não é uniforme a todos os subgrupos de lesões ou pacientes. OBJETIVO: Avaliar a evolução clínica tardia dos pacientes submetidos a implante de stents farmacológicos nas lesões ateroscleróticas da artéria descendente anterior e identificar, entre as características clínicas, angiográficas e do ultra-som intravascular, quais as que permitem predizer risco de eventos cardíacos. MÉTODOS: De maio de 2002 a agosto de 2005, foram tratados 205 pacientes com implante de 236 stents farmacológicos guiados pelo ultra-som intravascular. RESULTADOS: Com um acompanhamento médio de 711 dias, a taxa de trombose do stent foi de 0,48%, a mesma observada para infarto agudo do miocárdio ou cirurgia de revascularização. A taxa de revascularização da lesão tratada foi de 7,31% e a taxa global de eventos de 10,24%. Os indicadores de eventos, conforme análise multivariada, foram o implante de mais de um stent na mesma artéria, lesões concêntricas e área mínima intra-stent medida pelo ultra-som intravascular menor que 3,88 mm². CONCLUSÃO: Baseados nos dados obtidos, concluímos que a revascularização da artéria descendente anterior com implante de stents farmacológicos escolhidos e otimizados pelo ultra-som intravascular apresenta baixo índice de eventos tardios. O implante de dois stents farmacológicos para o tratamento das lesões longas foi o principal fator independente para a ocorrência de eventos tardios. A área luminal final maior que 3,88 mm² obtidos nos segmentos de pequenos diâmetros de referência é um indicador independente de evolução livre de eventos.
Implante de
IHospital Cardiológico Costantini - Brasil
IIFaculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP - Brasil
Os
A boa evolução da revascularização da artéria descendente anterior é um indicador independente de sobrevida nos principais estudos cirúrgicos comparativos de pacientes receptores ou não de enxerto de artéria mamária. Essa técnica de revascularização é indicada de modo extensivo principalmente nos pacientes com lesões complexas na artéria descendente anterior - lesões que envolvem os ramos diagonais, lesões longas (>20 mm), vasos finos (<2,75 mm de diâmetro) ou por associação com o diabete melito. Esses subgrupos foram incluídos em muitos estudos randomizados para o uso dos
Alguns estudos sugerem que o uso de ultra-som intravascular, como método-guia do implante dos
São os seguintes os objetivos desta pesquisa:
Avaliar a evolução clínica (eventos cardíacos) tardia dos pacientes submetidos a tratamento de lesões ateroscleróticas da artéria descendente anterior com implante de
Identificar, entre as características clínicas, angiográficas e do ultra-som, quais as que permitem indicar risco de eventos cardíacos.
Todos os pacientes submetidos ao procedimento intervencionista apresentaram previamente uma cinecoronariografia diagnóstica. No dia que antecedeu o procedimento, seguindo uma padronização do serviço, foram submetidos à avaliação clínica, eletrocardiográfica e laboratorial - hemograma, creatinina e glicemia de jejum. A medicação prescrita foi aspirina (200 mg), clopidogrel (300 mg) e uma estatina de escolha do médico assistente. Foram mantidas as outras medicações habituais do paciente, com exceção dos anticoagulantes e hipoglicemiantes orais. Jejum foi prescrito para as seis horas anteriores ao encaminhamento à sala de hemodinâmica.
Antes da liberação dos
Os
Foi usado cateter transdutor Atlantis de 40 MHz, que contém na extremidade um espelho angulado rotatório com velocidade de 1.800 rpm na frente do cristal emissor das ondas sonoras. As ondas sonoras emitidas eram recebidas e transformadas em imagens do interior do vaso pelo aparelho de ultra-som Galaxy ou Clearview, da empresa Boston Scientific, que as disponibilizava para a tela em tempo real e as armazenava em fita de videocassete. A análise pré-implante do
Os cálculos da avaliação do IVUS pós-implante foram realizados com o programa Echoplaque 2, versão 2.5.x, da empresa Indec Systems Inc, Califórnia, USA.
Os pacientes foram acompanhados por seus clínicos durante todo o processo. Nos meses de maio e junho de 2006, fez-se levantamento, por meio de contacto telefônico, dos eventos cardíacos maiores.
Deu-se ênfase aos eventos tardios:
óbito;
infarto agudo do miocárdio;
trombose do
taxa de revascularização da lesão tratada (TLR) caracterizada como qualquer nova revascularização cirúrgica ou percutânea decorrente de uma restenose angiográfica das lesões previamente dilatadas;
taxa de revascularização do vaso alvo (TVR) caracterizada como qualquer nova revascularização cirúrgica ou percutânea decorrente de restenose ou de uma nova lesão no vaso previamente tratado.
Participaram do estudo pacientes com idade superior a 18 anos, independentemente do sexo, de fatores de risco e da síndrome clínica no momento da admissão, com indicação de tratamento intervencionista somente da artéria descendente anterior associada ou não aos ramos septais ou diagonais. Em todos os pacientes, a fração de ejeção do ventrículo esquerdo era maior que 30%, e o diâmetro de referência da artéria descendente anterior maior ou igual a 2,25 mm. Foram englobados os pacientes uniarterial ou multiarterial, com todos os tipos de lesão aterosclerótica "de novo" (nomenclatura da força tarefa AHA/ACC9) e com todos os tipos de restenose de
Foram excluídos deste estudo os indivíduos submetidos à intervenção cirúrgica ou percutânea de outros vasos, além do sistema da artéria descendente anterior, nos três meses precedentes. Excluíram-se também os pacientes com implante de
Neste estudo, a variável resposta considerada foi pelo menos um evento (presente ou não). Para avaliação da associação entre variáveis dicotômicas e a variável resposta, considerou-se o teste exato de Fisher. Variáveis contínuas foram avaliadas pelo teste
Foram incluídas no modelo de forma dicotomizada as variáveis contínuas - idade, diâmetro do balão usado para expandir os
Foram considerados aceitáveis os seguintes pontos de corte:
idade: 57 anos;
área luminal mínima intra-
2;
diâmetro do balão usado para expandir os
A análise foi realizada com o
Constituíram a casuística desta pesquisa os pacientes com doença coronariana aterosclerótica obstrutiva da artéria descendente anterior, diagnosticada mediante coronariografia invasiva. As lesões obstrutivas apresentavam comprometimento estenótico da luz arterial maior que 70%, daí a indicação do implante de
Foram tratados com implante de
Em 153 indivíduos (74,63%), a doença aterosclerótica estava restrita à artéria descendente anterior (pacientes uniarteriais), enquanto em 52 (25,36%) a doença comprometia outros vasos, além da artéria descendente anterior (pacientes multiarteriais). As lesões da artéria descendente anterior envolviam em 56,61% a origem de ramos diagonais maiores de 2,25 mm, lesão em bifurcação.
Nos 205 pacientes, foram tratadas 242 lesões da artéria descendente anterior (média de 1,18 lesão por paciente), assim classificadas de acordo com a Força-tarefa AHA/ACC9:
tipo A: 6 lesões (2,47%);
tipo B1: 23 lesões (9,50%);
tipo B2: 96 lesões (39,66%);
tipo C: 80 lesões (33,57%).
Não seguiam a classificação da Força-tarefa AHA/ACC, por serem restenóticas, 37 lesões.
As características isoladas das lesões estão apresentadas na
Na artéria descendente anterior, foram implantados 240
As diferenças nas características dos
A extensão média do
67 DA (32,6%) receberam entre 8 e 20 mm;
55 DA (26,8%) receberam entre 21 e 30 mm;
57 DA (27,8%) receberam entre 31 e 40 mm;
10 DA (4,8%) receberam entre 41 e 50 mm;
16 DA (7,8%) receberam entre 51 e 65 mm.
No segmento de referência proximal, a área do vaso era de 15,13 ± 4,36 mm2, a área do lúmen era de 7,62 ± 2,55 mm2, a porcentagem de estenose de 48,68 ± 11,47% e o diâmetro de referência de 3,10 ± 0,51mm. No segmento de referência distal, a área do vaso era de 9,94 ± 3,51 mm2, a área do lúmem era de 6,27 ± 1,98 mm2, a porcentagem de estenose de 35,39 ± 13,31% e o diâmetro de referência de 2,82 ± 0,43 mm.
Área luminal mínima (mm
2): 5,13 ± 1,53.
Diâmetro luminal mínimo (mm): 2,55 ± 0,37.
Assimetria: 0,86 ± 0,86.
Volume: 190,79 ± 93,14.
O acompanhamento dos 205 pacientes teve o período médio de 711±306 dias (23,3±10 meses), mais de 8 meses de evolução do último paciente desta casuística. As taxas de ocorrência de trombose de
A taxa de 1,46% de óbito corresponde a três pacientes do sexo feminino:
® 3,0/18 mm. O procedimento foi realizado em maio de 2002 e o óbito ocorreu em junho de 2005. Óbito súbito, domiciliar.
® 2,5/28 mm e 2,5/18 mm. O procedimento foi realizado em dezembro de 2002 e o óbito ocorreu em outubro de 2005. Óbito por infarto agudo, na cidade de origem.
® 2,75/32 mm. O procedimento foi realizado em fevereiro de 2004 e o óbito ocorreu em agosto de 2005. Óbito súbito, domiciliar, por provável acidente isquêmico cerebral.
A taxa de revascularização da lesão tratada foi de 7,31% (15 pacientes), desses pacientes 9 receberam um novo
Neste estudo, a variável resposta considerada foi pelo menos um evento cardíaco (presente ou não) (
Na
Este estudo visou ao acompanhamento clínico, em longo prazo (23,3±10 meses de média), de pacientes submetidos à angioplastia da artéria descendente anterior com implante de um ou mais
Os dados apresentados impõem algumas questões:
Se a seleção da extensão dos
Apesar de reconhecidos os baixos índices de restenose intra-
Essas são perguntas difíceis de responder porque implicam muitos vieses da técnica do implante dos
O ultra-som intravascular foi usado na avaliação pré-implante do
Todos os
Com a evolução dos
Neste estudo, a taxa global de (pelo menos um) eventos cardíacos foi de 10,24%. Eventos como óbito, cirurgia de revascularização e infarto agudo do miocárdio foram poucos, e entre eles a revascularização da lesão tratada teve a taxa mais elevada (7,31%), correspondente a 9/ pacientes que receberam um novo
A taxa de trombose tardia foi de 0,48% por paciente ou de 0,33% por
Nesta série, foram tratados todos os tipos de lesões ateroscleróticas ou de síndromes clínicas que envolviam a artéria descendente anterior, e os resultados mostram que é alta (98,54%) a taxa de sobrevida desses pacientes. A restenose clínica (taxa de revascularização da lesão tratada) foi o principal evento tardio observado em nossos pacientes (7,31%). Entretanto, a taxa de revascularização da lesão tratada foi aqui inferior às taxas descritas em muitos estudos clínicos.
Os principais fatores indicadores de eventos tardios foram a área luminal final avaliada pelo ultra-som e o número de
Na análise univariada realizada na presente pesquisa, observou-se que a área luminal intra-
Trinta e um pacientes receberam mais de um
Um fato muito curioso verificou-se aqui: a única característica angiográfica com p menor que 0,25 mm foi a excentricidade das lesões (p = 0,18). As lesões concêntricas foram preditivas independentes de eventos, do mesmo modo que as lesões excêntricas apresentaram
Nesta casuística, as lesões excêntricas foram um indicativo protetor contra eventos (p = 0,012,
A análise multivariada demonstrou tendência estatística do diabetes como indicador independente de eventos cardíacos; os não-diabéticos apresentaram um
Muitos estudos clínicos demonstraram a boa evolução obtida com
A casuística estudada representa a experiência de um único grupo, que tem como característica o uso rotineiro do ultra-som intracoronariano para guiar o implante dos
Baseados nos dados obtidos, concluímos que a revascularização da artéria descendente anterior com implante de
Declaro não haver conflito de interesses pertinentes.
O presente estudo não teve fontes de financiamento externas.
Este artigo é parte de tese de Doutorado de Marcelo de Freitas Santos pela Faculdade de Ciências Médicas da Santa Casa de São Paulo.
Correspondência: Marcelo de Freitas Santos Rua Monsenhor Ivo Zanlorenzi, 2546/1901 Mossungue, 81210-000, Curitiba, PR - Brasil E-mail:
Artigo recebido em 12/03/07; revisado recebido em 04/11/07; aceito em 14/04/08.
BACKGROUND: The efficacy of pharmacological stents in decreasing the incidence of cardiac events is not homogeneous for all lesions or patient subgroups. OBJECTIVE: 1) To evaluate the late clinical evolution of patients submitted to pharmacological stent implantation in atherosclerotic lesions of the left anterior descending artery; 2) to identify, among the clinical, angiographic and intravascular ultrasonographic characteristics, the ones predictive of cardiac event risk. METHODS: From May 2002 to August 2005, 205 patients were treated with 236 pharmacological stent implants, guided by the intravascular US (IVUS). RESULTS: After a mean follow-up period of 711 days, the rate of stent thrombosis was 0.48%, the same observed for acute myocardial infarction or revascularization surgery. The revascularization rate of the treated lesion was 7.31% and the general event rate was 10.24%. The event indicators, according to the multivariate analysis were the implant of more than one stent in the same artery, concentric lesions and the minimal intra-stent area measured by IVUS < 3.88 mm². CONCLUSION: Based on the data obtained, we conclude that the revascularization of the left anterior descending artery with pharmacological stent implant, chosen and optimized by IVUS, presents a low incidence of late events. The implant of two pharmacological stents for the treatment of long lesions was the main independent factor for the occurrence of late events. The final luminal area > 3.88 mm² obtained in the small reference-diameter segments is an independent indicator of event-free evolution.
IHospital Cardiológico Costantini
IIFaculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP - Brasil
Mailing address
The pharmacological stents with antiproliferative agents have as target the suppression of neointimal hyperplasia. The pharmacological actions of these agents directly block the cell cycle in its initial phase (cytostatic phase) or in its final phase (cytotoxic phase). The sirolimus-coated (rapamycin) or paclitaxel-coated pharmacological stents - the most extensively studied pharmacological prosthesis with long-term evolution - have presented a significant decrease in late events, especially due to the decrease in the re-stenosis, when compared to non-pharmacological (metallic) stents1-4.
The good evolution of the anterior descending artery revascularization is an independent indicator of survival in the main comparative surgical studies of patients receiving or not mammary artery grafts.
This revascularization technique is extensively indicated, mainly in patients with complex lesions in the anterior descending artery - lesions that involve the diagonal branches, long lesions (> 20 mm), thin vessels (< 2.75 mm of diameter) or due to association with diabetes mellitus.
These subgroups were included in many studies that were randomized for the use of pharmacological stents3,5-7; however, they were not specific for the anterior descending artery (ADA). The acknowledged benefit of the pharmacological stents in selected groups, in the several aforementioned randomized studies, allows a good evolution of the ADA revascularization, regardless of the complexity of the atherosclerotic lesion or its present clinical characteristic.
Some studies have suggested that the use of IVUS to guide non-pharmacological stent implants could reduce the incidence of late re-stenosis in some subgroups of patients8. Regarding the participation of this resource to guide pharmacological stents, however, the published studies have been scarce.
The aims of the present study are:
1) To evaluate the late clinical evolution (cardiac events) of patients submitted to the treatment of atherosclerotic lesions of the ADA with pharmacological stent implants;
2) To identify, among the clinical, angiographic and intravascular ultrasonographic characteristics, the ones that allow us to predict the risk of cardiac events.
All patients submitted to the intervention procedure had presented a previous diagnostic coronary angiography. On the day before the procedure, following the standard operations of the Service, they were submitted to clinical evaluation, electrocardiographic and laboratory assessment - complete blood count, creatinine and fasting glycemia. The prescribed medication was aspirin 200 mg, clopidogrel 300 mg and the attending physician's statin of choice. The patients' other usual medications were maintained, except anticoagulants and oral hypoglycemic drugs. A six-hour fasting, prior to entering the hemodynamic room, was prescribed.
Before the release of the pharmacological stents, the pre-dilation of the lesions was carried out using the conventional balloons with a diameter between 2.0 mm and 3.5 mm or through atheroabrasive techniques. A direct implant without pre-dilation was performed when conditions favorable for its expansion were seen to be present.
The pharmacological stents were released with a pressure between 4 and 18 ATM and the complementary dilation was carried out with a balloon that was shorter than the stent length, which allows the expansion of the latter without injuring its borders. After the adequate angiographic result of stent release (residual lesion < 10% by the subject analysis of the operator) and based on the measurements obtained post-implant with IVUS, the necessity of new dilations was assessed.
A transducer catheter Atlantis of 40 MHz was used, which has a rotating angulated mirror in its extremity that rotates at 1,800 rpm in the front of the sound-wave emitting crystal. The emitted sound waves were received and transformed into images of the interior of the vessel by the Galaxy or Clearview ultrasound device, by Boston Scientific, which projected them on the screen in real-time and stored them in video cassette tapes. The pre-implant analysis of the pharmacological stent aimed at evaluating the proximal and distal reference diameters, as well as the extension of the atherosclerotic plaque in order to select the ideal pharmacological stent (in diameter as well as in extension). In the post-implant control, a good apposition of the stent rods to the vessel walls and a correlation between intra-stent minimal luminal areas and the reference areas were sought.
The calculations of the assessment of the post-implant IVUS were carried out with the Echoplaque 2 program, version 2.5.x, by Indec Systems Inc, California, USA.
The patients were followed by their clinicians throughout the entire process. In May and June 2006, the occurrence of major cardiac events was verified by telephone contact.
The late events that were emphasized were:
- death;
- acute myocardial infarction;
- thrombosis of the pharmacological stent, defined as acute or late angiographic occlusion of the stents;
- target lesion revascularization (TLR), characterized as any new surgical or percutaneous revascularization caused by an angiographic re-stenosis of previously dilated lesions;
- target vessel revascularization (TVR), characterized by any new surgical or percutaneous revascularization caused by a re-stenosis or a new lesion in the previously dilated vessel.
Patients aged 18 years or older, regardless of gender, risk factors and clinical syndrome at the moment of admission; with indication of interventionist treatment only for the ADA, associated or not to the septal or diagonal branches. Left ventricular ejection fraction (EF) was > 30% in all patients and the reference diameter of the ADA was e" 2.25 mm. The uniarterial and multiarterial patients were joined, with all types of
To have been submitted to surgical or percutaneous intervention of other vessels other than the ADA system during the prior three months; patients with stent implant in the left coronary trunk or circumflex artery, caused by ostial lesion of the descending artery; pregnant patients those with concomitant severe disease, with high probability of death within 12 months and patients with economic or clinic limitations to receive the association of the platelet antiaggregants clopidogrel and acetylsalicylic acid for at least three months.
In the present study, the considered response variable was at least one event (present or not). To evaluate the association between dichotomous variables and the response variable, Fisher exact test was considered. Continuous variables were assessed by the Student's
The continuous variables age, diameter of the balloon used to expand the post-implant stents and minimal intra-stent luminal area were included in the model in the dichotomized form; an acceptable cutoff was found according to the adjustment of the ROC curve (area below the curve significantly > 0.5 mm).
The following cutoffs were considered acceptable:
- age: 57 years;
- minimal intra-stent luminal area: 3.88 mm2;
- diameter of the balloon used to expand the post-implant stents: 3 mm.
The statistical analysis was carried out using the software SPSS 11.0. Statistical significance was set at p<0.05.
This sample consisted of patients with obstructive atherosclerotic coronary disease of the anterior descending artery (ADA), diagnosed by invasive coronary angiography.
The obstructive lesions presented stenotic involvement of the arterial lumen > 70%, thus the indication of the pharmacological stent implant as the interventionist treatment, based on the clinical and angiographic findings.
The patients were treated with sirolimus-eluting (Cypher™ stent) or paclitaxel-eluting stent implant (Taxus™ stent). All the prostheses were selected through the measurements obtained at the ultrasonographic assessment in the pre-implant phase and optimized in their expansion with post-dilation guided by US. Patient inclusion started in May 2002 and finished in August 2005. The procedures were carried out in
A total of 205 patients were treated with pharmacological stent implant, whose clinical characteristics are shown in
In 153 individuals (74.63%) the atherosclerotic disease was restricted to the anterior descending artery (ADA), whereas in 52 (23.36%), the disease involved other vessels rather than the ADA (multiarterial patients). The lesions in the ADA involved, in 56.61% of the cases, the origin of the diagonal branches larger than 2.25 mm, bifurcation lesion.
A total of 242 lesions of the ADA were treated in the 205 patients (mean of 1.18 lesions per patient), thus classified according to the AHA/ACC task force9:
- type A: 6 lesions (2.47%);
- type B1: 23 lesions (9.50%);
- type B2: 96 lesions (39.66%);
- type C: 80 lesions (33.57%).
Thirty-seven lesions did not follow the classification by the AHA/ACC task force, as they were re-stenotic lesions. The isolated characteristics of the lesions are shown in
The characteristic differences between the implanted Cypher™ and Taxus™ stents are shown in
The mean extension of the pharmacological stents per vessel was 27.74±11.59/ mm. In the studied sample, according to the addition of the extensions of the pharmacological stents implanted in a same anterior descending artery (ADA), the following data was observed:
- 67 ADAs (32.6%) received between 8 and 20 mm;
- 55 ADAs (26.8%) received between 21 and 30 mm;
- 57 ADAs (27.8%) received between 31 and 40 mm;
- 10 ADAs (4.8%) received between 41 and 50 mm;
- 16 ADAs (7.8%) received between 51 and 65 mm.
These measurements were obtained through the analysis of the intravascular US
In the proximal reference segment, the vessel area was 15.13 ± 4.36 mm2, the lumen area was 7.62 ± 2.55mm2, the percentage of stenosis was 48.68 ± 11.47% and the reference diameter was 3.10 ± 0.51mm. In the distal reference segment, the vessel area was 9.94 ± 3.51 mm2, the lumen area was 6.27 ± 1.98mm2, the percentage of stenosis was 35.39 ± 13.31% and the reference diameter was 2.82 ± 0.43mm.
The measurements of the intravascular US of the stent segment were:
- Minimal luminal area (mm2) of 5.13±1.53;
- Minimal luminal diameter (mm) 2.55±0.37;
- Asymmetry 0.86±0.86;
- Volume 190;79±93;14.
The mean follow-up period of the 205 patients was 711±306 days (23.3±10 months), more than 8 months of evolution of the last patient in this series. The incidence rates of stent thrombosis, acute myocardial infarction or revascularization surgery or TVR were similar: 1/205 - 0.48% for each outcome. The only patient with thrombosis was a 43 year-old male that had been submitted to one Taxus™ implant 3.0/16 mm (re-stenotic stent lesion). The reintervention with conventional angioplasty occurred 4 months after the pharmacological stent implant and 15 days after clopidogrel withdrawal.
The 1.46% death rate corresponds to three female patients:
The incidence of TVR was 7.31% (15 patients), of which 9 received a new pharmacological stent and the others were treated with angioplasty with balloon-catheter with titanium blades.
In the present study, the considered response variable was at least 1 cardiac event (present or not,
This study aimed the long-term follow-up (mean of 23.3±10 months) of patients submitted to the angioplasty of the anterior descending artery (ADA) with the implant of one or more pharmacological stents guided by intravascular ultrasound (IVUS). The association of the IVUS technique as a guide to implant the non-pharmacological stent allows its optimization, decreasing the late re-stenosis8. As for the implant of pharmacological stents, the use of IVUS to select and optimize the stent expansion needs to be validated by scientific studies.
Randomized studies with the implant of pharmacological stents present distinct late outcomes, which are directly related to the characteristics of the treated lesions. The Sirius3 study allowed the inclusion of long lesions and thin vessels, raising the incidence of late stenosis to 8.9%, located mainly in the stent borders, considering that the incidence of intra-stent re-stenosis was low (3.2%).
The data presented raise some questions: If the selection of the extension of stents were guided by ultrasound, prioritizing the lining of the entire extension of the target plaque, would the rates of stent border re-stenosis be the same? Although the rates of intra-stent re-stenosis of pharmacological stents are known to be low, would the optimization of the stent expansion have a positive late effect?
These are difficult questions to answer, as they involve many biases of the stent implant technique, as well as of the personal interpretation of the IVUS images.
The intravascular ultrasound was used in the pre-implant assessment of the stent to analyze the extension of the obstructive atherosclerotic plaque, which would allow the chosen stent to recover the entire segment of the plaque, with its borders in a segment with a lower plaque load or without atherosclerotic lesion.
All stents implanted in anterior descending artery had their expansion optimized according to the IVUS assessment. Regardless of an optimal angiographic image, if the ultrasound assessment showed that the prostheses were not adequately expanded, the stents were dilated again.
With the development of the pharmacological stents - which allowed a good control of the neointimal proliferation - it was observed that the later loss of the intra-stent luminal diameter was low not only in the short stents (shorter than 20 mm), but was very low in long stents, as well11. Due to this action of long pharmacological stents observed in scientific studies and in clinical practice, the importance of the assessment of the atherosclerotic plaque by ultrasound in the selection of the length of the stents, so that the entire injured segment could be covered, increased even more.
In this study, the general rate of (at least one) cardiac events was 10.24%. Events such as death, revascularization surgery and acute myocardial infarction were scarce and among them, the rates of TVR were the highest (7.31%), corresponding to 9 patients that received a new pharmacological stent and other 6 patients submitted to dilation with catheter-balloon with titanium blades.
The incidence of late thrombosis was 0.48% per patient or 0.33% per stent, even when including patients with complex lesions, long stents, multiple stents and bifurcation lesions; this is a very low incidence, similar to the one found in studies with non-pharmacological stents12.
Thrombosis occurred in only one patient that withdrew the use of clopidogrel in the fourth month, developing an intra-stent thrombosis 15 days later.
In this series, all types of atherosclerotic lesions or clinical syndromes that involved the ADA were treated, and the results show that the survival rate among these patients is high (98.54%). The clinical re-stenosis (target vessel revascularization rate) was the main late event observed in our series (7.31%). However, the TVR rate observed here was lower than the ones described in many clinical studies.
The main factors that indicated late events were the final luminal area evaluated by ultrasound and the number of stents implanted in the ADA. The reference diameter of the vessel, bifurcation lesion, stents implanted in thin vessels (d" 2.75) or the type of stent implanted (Cypher™ or Taxus™) did not show any statistical difference at the uni- or multivariate analysis.
The univariate analysis carried out in the present study showed that the intra-stent luminal area < 3.88 mm2 was an event predictor, with a significant p value (p=0.0107). The patients with an intra-stent luminal area < 3.88 mm2 at the final ultrasound assessment presented a higher incidence of events when compared to patients with intra-stent luminal area > 3.88 mm2 (21.28 %
Thirty-one patients had more than 1 pharmacological stent implanted in the ADA; of these, 7 (22.58%) presented at least one event. The implant of long stents (mean length of stents implanted in this series: 24.11) was not a late event risk increase factor; however, the implant of two prostheses was an independent event factor. This finding supports the importance of the availability of long stents, with more 30 mm of length, indicating to the interventionist the use of these stents, instead of the implant of two prostheses for the treatment of long lesions.
A noteworthy fact observed herein was that the only angiographic characteristic with a p value < 0.25 was lesion eccentricity (p=0.18). The concentric lesions were independent predictors of events, similarly to the eccentric lesions that had an OR = 0.24 (95%CI: 0.07-0.81). The fact might be related to the distribution of the stent rods, which usually separate close to the wall with less resistance, i.e., with less plaque, and gather on the side with lower expansion, which is the segment with more plaque.
The multivariate analysis showed a statistical tendency of diabetes to be an independent indicator of cardiac events; non-diabetic individuals presented an odds ratio of 0.31 (95%CI: 0.10-1.02; p=0.0536), thus diabetes was not a strong predictor of events as shown in the literature; this fact might be related to the characteristic of the group of non-diabetic patients that also received long stents, equaling the extension of the metallic net per vessel between the groups. The advent of pharmacological stents showed that the protective effects of the drugs also extend to the diabetic patients, who present evolution that is very similar to that of non-diabetic patients. However, one cannot affirm that it is possible to fully control late events in diabetic patients.
Many clinical studies have demonstrated the good evolution with pharmacological stents in vessels < 2.75 mm (thin vessels). In this series, the rate of events was 13.12% with the use of stents < 3mm and 9.03% (p=0.45) with longer stents. This variable was studied in the logistic regression due to its relevance as an indicative factor in studies with metallic stents. The multivariate analysis showed a non-significant p (p=0.14).
The studied series represents the experience of a single group that has as its characteristic, the routine use of intracoronary ultrasound to guide the implant of pharmacological stents. This study shows mainly which patients are event-free (percentage of exactness of 99.5% by the adjusted model of logistic regression).
Based on the obtained data, we conclude that the revascularization of the anterior descending artery with the implant of pharmacological stents chosen and optimized by the use of intravascular ultrasound presents a low incidence of late events. The implant of pharmacological stents for the treatment of long lesions was the main independent factor for the occurrence of late events. The final luminal area > 3.88 mm2, obtained in segments of small reference diameters is an independent indicator of event-free evolution.
No potential conflict of interest relevant to this article was reported.
There were no external funding sources for this study.
This article is part of the thesis of doctoral submitted by Marcelo de Freitas Santos, from
FUNDAMENTO: La eficacia de los stents farmacológicos para reducir los índices de eventos cardiacos no es la misma para todos los subgrupos de lesiones o pacientes. OBJETIVO: Evaluar la evolución clínica tardía de los pacientes sometidos a implante de stents farmacológicos en las lesiones ateroscleróticas de la arteria descendente anterior e identificar, entre las características clínicas, angiográficas y de ultrasonido intravascular, cuales son las que permiten predecir riesgos de eventos cardiacos MÉTODOS: De mayo de 2002 a agosto de 2005, se trataron a 205 pacientes con implante de 236 stents farmacológicos guiados por ultrasonido intravascular. RESULTADOS: Con un seguimiento promedio de 711 días, la tasa de trombosis del stent fue del 0,48%, la misma que se observó para infarto agudo de miocardio o cirugía de revascularización. La tasa de revascularización de la lesión tratada fue del 7,31% y la tasa global de eventos fue del 10,24%. Los indicadores de eventos, conforme análisis multivariada, fueron el implante de más de un stent en la misma arteria, lesiones concéntricas y área mínima intrastent medida por el ultrasonido intravascular menor que 3,88 mm². CONCLUSIÓN: Tomando como base los datos obtenidos con esta investigación, concluimos que la revascularización de la arteria descendente anterior con implante de stents farmacológicos, elegidos y optimizados por el ultrasonido intravascular, presenta un bajo índice de eventos tardíos. El implante de dos stents farmacológicos para el tratamiento de las lesiones largas fue el principal factor independiente para la ocurrencia de eventos tardíos. El área luminal final mayor que 3,88 mm², obtenida en los segmentos de pequeños diámetros de referencia es un indicador independiente de evolución libre de eventos.
IHospital Cardiológico Costantini, São Paulo, SP - Brazil
IIFaculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP - Brazil
Correspondencia
Los
La buena evolución de la revascularización de la arteria descendente anterior es un indicador independiente de sobrevida en los principales estudios quirúrgicos comparativos de pacientes receptores o no de injerto de arteria mamaria. Se indica la realización de esa técnica de revascularización, de modo extensivo, principalmente en los pacientes con lesiones complejas en la arteria descendente anterior —lesiones que implican las ramas diagonales, lesiones largas (>20/ mm), vasos finos (<2,75/ mm de diámetro) o por asociación a la diabetes mellitus. Muchos estudios randomizados incluyeron esos subgrupos para la utilización de los
Algunos estudios sugieren que la utilización de ultrasonido intravascular (IVUS), como método guía del implante de los
Siguen a continuación los objetivos de esta investigación:
Evaluar la evolución clínica (eventos cardiacos) tardía de los pacientes sometidos a tratamiento de lesiones de la arteria descendente anterior con implante de
Identificar, entre las características clínicas, angiográficas y de ultrasonido intravascular, cuales son las que permiten indicar riesgos de eventos cardiacos.
Todos los pacientes sometidos al procedimiento intervencionista presentaron previamente una cinecoronariografía diagnóstica. El día anterior al procedimiento, bajo una estandarización del servicio, se los sometieron a evaluación clínica, electrocardio-gráfica y laboratorial —hemograma, creatinina y glicemia de ayuno. La medicación prescrita fue aspirina (200/ mg), clopidogrel (300/ mg) y una estatina de elección del médico asistente. Los pacientes siguieron tomando las otras medicaciones habituales, a excepción de los anticoagulantes y hipoglucemiantes orales. Se prescribió ayuno a los pacientes, seis horas antes de que fueran a la sala de hemodinámica.
Antes de la liberación de los
Se liberaron los
Se utilizó el catéter transductor Atlantis de 40 MHz, cuya extremidad lleva un espejo angulado rotatorio con velocidad de 1.800 rpm, frente al cristal emisor de las ondas sonoras. El aparato de ultrasonido Galaxy o Clearview (de la empresa Boston Scientific) emitía las ondas sonoras, que tras recibidas, se transformaban en imágenes del interior del vaso; el aparato disponía las imágenes en la pantalla en tiempo real y las almacenaba en cinta de videocasete. El análisis pre implante del
Los cálculos de la evaluación del IVUS post implante se realizaron con el programa Echoplaque 2, versión 2.5.x, de la empresa Indec Systems Inc, California, USA.
Los pacientes fueron seguidos por sus médicos durante todo el proceso. En los meses de mayo y junio de 2006, se hizo un levantamiento, por medio de llamada telefónica, de los eventos cardiacos mayores.
Se puso énfasis a los eventos tardíos a continuación:
Óbito;
Infarto agudo de miocardio;
Trombosis del
Tasa de revascularización de la lesión tratada (TLR), caracterizada como cualquier nueva revascularización quirúrgica o percutánea, resultante de una restenosis angiográfica de las lesiones previamente dilatadas;
Tasa de revascularización del vaso blanco (TVR), caracterizada como cualquier nueva revascularización quirúrgica o percutánea, resultante de una restenosis o de una nueva lesión en el vaso previamente tratado.
Participaron del estudio pacientes con edad superior a los 18 años, independientemente del sexo, de factores de riesgo y del síndrome clínico al ingreso, con indicación de tratamiento intervencionista solamente de la arteria descendente ante-rior asociada o no a las ramas septales o diagonales. En todos los pacientes, la fracción de eyección del ventrículo izquierdo era mayor que el 30%, y el diámetro de referencia de la arteria descendente anterior mayor o igual a 2,25/ mm. Se implicaron a los pacientes uniarteriales o multiarteriales, con todos los tipos de lesión aterosclerótica "de nuevo" (nomenclatura de la fuerza de tarea AHA/ACC9) y con todos los tipos de restenosis de
Se excluyeron de este estudio a los individuos sometidos a la intervención quirúrgica o percutánea de otros vasos, además del sistema de la arteria descendente anterior, en los tres meses precedentes. Se excluyeron también a los pacientes con implante de
En este estudio, se consideró al menos un evento (presente o no) como la variable respuesta. Para evaluación de la asociación entre las variables dicotómicas y la variable respuesta, se tomó en cuenta la prueba exacta de Fisher. Variables continúas fueron evaluadas por la prueba t de Student para muestras independientes —tomándose en consideración la homogeneidad o no de las variancias—, o por la prueba no paramétrica de Mann-Whitney. Se realizó el análisis multivariado con el ajuste de un modelo de regresión logística en el cual se incluyeron todas las variables que tuvieran valor de p < 0,2510. Además de esas variables, se incluyeron otras con relevancia clínica (sexo, lesión larga >20 mm, tabaquismo y diámetro del
El modelo incluyó, de forma dicotomizada, las variables continúas —edad, diámetro del balón utilizado para expandir los
Se tomaron en cuenta los puntos de corte que siguen a continuación:
• Edad: 57 años;
• Área luminal mínima intrastent: 3,88/ mm2;
• Diámetro del balón utilizado para expandir los
El análisis se realizó con el
Formaron parte de la casuística de esta investigación los pacientes con enfermedad coronaria aterosclerótica obstructiva de la arteria descendente anterior, diagnosticada mediante coronario-grafía invasiva. Las lesiones obstructivas presentaban compromiso estenótico de la luz arterial mayor que el 70%. Ello justificó la indicación del implante de
Se trataron con implante de
En 153 individuos (74,63%), la enfermedad aterosclerótica estaba restricta a la arteria descen-dente anterior (pacientes uniarteriales), mientras que en 52 pacientes (25,36%) la enfermedad comprometía otros vasos, además de la arteria descendente anterior (pacientes multiarteriales). Las lesiones de la arteria descendente anterior implicaban en el 56,61% el origen de ramas diagonales mayores de 2,25 mm, lesión en bifurcación.
En los 205 pacientes, se trataron 242 lesiones de la arteria descendente anterior (promedio de 1,18 lesión por paciente), así clasificadas de acuerdo con la Fuerza de Tarea AHA/ACC9:
Clase A: 6 lesiones (2,47%);
Clase B1: 23 lesiones (9,50%);
Clase B2: 96 lesiones (39,66%);
Clase C: 80 lesiones (33,57%);
Un total de 37 lesiones no seguía la clasificación de la Fuerza de Tarea AHA/ACC, por su condición restenótica.
Las características aisladas de las lesiones están presentadas en la
En la arteria descendente anterior, se implantaron 240
Las diferencias en las características de los
La extensión promedio del
67 DA (32,6%) recibieron entre 8 y 20/ mm;
55 DA (26,8%) recibieron entre 21 y 30/ mm;
57 DA (27,8%) recibieron entre 31 y 40/ mm;
10 DA (4,8%) recibieron entre 41 y 50/ mm;
16 DA (7,8%) recibieron entre 51 y 65/ mm;
En el segmento de referencia proximal, el área del vaso era de 15,13
Área luminal mínima (mm
2): 5,13
Diámetro luminal mínimo (mm): 2,55
Asimetría: 0,86
Volumen: 190,79
El seguimiento de los 205 pacientes tuvo la duración promedio de 711
La tasa del 1,46% de óbito corresponde a tres pacientes del sexo femenino:
® 3,0/18/ mm. El procedimiento se reali-zó en mayo de 2002 y el óbito tuvo lugar en junio de 2005. Óbito súbito, domiciliar.
® 2,5/28/ mm y 2,5/18/ mm. El procedimiento tuvo lugar en diciembre de 2002 y el óbito ocurrió en octu-bre de 2005. Óbito por infarto agudo, en la ciudad de origen.
® 2,75/32/ mm. El procedimiento se realizó en febrero de 2004 y el óbito ocurrió en agosto de 2005. Óbito súbito, domiciliar, por probable accidente isquémico cerebral.
La tasa de revascularización de la lesión tratada fue de 7,31% (15 pacientes). De esos pacientes 9 recibieron un nuevo
En este estudio, la variable respuesta considerada fue de al menos un evento cardíaco (presente o no) (
En la
Este estudio buscó el seguimiento clínico, a largo plazo (23,3±10 meses de promedio), de pacientes sometidos a la angioplastia de la arteria descendente anterior con implante de un o más
Los datos presentados plantean algunas cuestiones:
Si la elección de la extensión de los
Pese al reconocimiento de los bajos índices de restenosis intrastent de los
Esas son preguntas difíciles de ersponder porque implican muchas vías de la técnica del implante de los
El ultrasonido intravascular se utilizó en la evaluación pre implante del
Todos los
Con la evolución de los
En este estudio, la tasa global de (como mínimo uno) eventos cardíacos fue del 10,24%. Eventos como óbito, cirugía de revascularización e infarto agudo de miocardio fueron pocos, siendo que entre ellos la revascularización de la lesión tratada tuvo la tasa más elevada (7,31%), correspondiente a 9/ pacientes que recibieron un nuevo
La tasa de trombosis tardía fue del 0,48% por paciente ó del 0,33% por
En esta serie, se trataron todas las clases de lesiones ateroscleróticas o de síndromes clínicas que implicaban la arteria descendente anterior, y los resultados evidenciaron que la tasa de sobrevida de esos pacientes es alta (98,54%). La restenosis clínica (tasa de revascularización de la lesión tratada) fue el principal evento tardío observado en nuestros pacientes (7,31%). Sin embargo, la tasa de revascularización de la lesión tratada en esta investigación fue inferior a las tasas descritas en muchos estudios clínicos.
Los principales factores indicadores de eventos tardíos fueron el area final evaluada por el ultrasonido y el número de
En el análisis univariado realizado en la presente investigación, se observó que el área luminal intrastent menor que 3,88/ mm2 fue predictiva de eventos, con valor significativo de p (p = 0,0107). Los pacientes con área luminal intrastent menor que 3,88 mm2 en la evaluación final al ultrasonido presentaron mayor índice de eventos, cuando comparados a los pacientes con áreas luminales intrastent mayores que 3,88 mm2 (21,28% vs. 6,96%, respectivamente, con p = 0,01). El tratamiento de lesiones largas implica la ubicación de los
Observamos que los
Un total de 31 pacientes recibió más de un
Un hecho muy curioso se verificó en este estudio: la única característica angiográfica con p menor que 0,25/ mm fue la excentricidad de las lesiones (p = 0,18). Las lesiones concéntricas fueron predictivas independientes de eventos, a la vez que las lesiones excéntricas presentaron
En esta casuística, las lesiones excéntricas se mostraron como un indicativo protector contra eventos (p = 0,012,
El análisis multivariado presentó tendencia estadística de la diabetes como indicador independiente de eventos cardiacos; los no diabéticos presentaron un
Muchos estudios clínicos demostraron la buena evolución obtenida con
La casuística estudiada representa la experiencia de un único grupo, que tiene como característica el uso frecuente del ultrasonido intracoronariano para guiar el implante de los
Tomando como base los datos obtenidos con esta investigación, concluimos que la revascularización de la arteria descendente anterior con implante de
Declaro no haber conflicto de intereses pertinentes.
El presente estudio no tuvo fuentes de financiación externas.
Este artículo forma parte de tesis de Doctorado de Marcelo de Freitas Santos, por la
Facultad de Ciencias Médicas de la Santa Casa de São Paulo.