FUNDAMENTO: A Intervenção Coronariana Percutânea (ICP) vem aumentando na doença arterial coronariana crônica. Consequentemente, cada vez mais pacientes submetidos a Cirurgia de Revascularização Miocárdica (CRM) apresentam stent coronariano. OBJETIVO: Avaliar a influência do antecedente de stent coronariano na mortalidade hospitalar após CRM. MÉTODOS: Análise prospectiva com 1.099 pacientes consecutivos submetidos a CRM com circulação extracorpórea, entre maio/2007 e junho/2009. Pacientes sem ICP prévia (n = 938; 85,3%) foram comparados com pacientes com ICP prévia (n = 161; 14,6%), utilizando modelos de regressão logística e análise de pareamento de amostras. RESULTADOS: Ambos os grupos apresentavam semelhança em relação aos fatores de risco, exceto pela maior presença de pacientes com angina instável no grupo com ICP prévia (16,1% vs. 9,9%; p = 0,019). A mortalidade hospitalar após CRM foi maior entre os pacientes com ICP prévia (9,3% vs. 5,1%, p = 0,034), e foi semelhante à esperada em relação ao EuroSCORE e ao 2000 Bernstein-Parsonnet score. Na análise com regressão logística multivariada a ICP prévia emergiu como fator de risco independente para mortalidade hospitalar pós-operatória (odds ratio 1,94; IC 95% 1,02-3,68; p = 0,044) tão forte quanto diabetes (odds ratio 1,86; IC 95% 1,07-3,24; p = 0,028). Após o pareamento dos grupos, a mortalidade hospitalar continuou sendo maior entre os pacientes com ICP prévia, com odds ratio 3,46 ; IC 95% 1,10-10,93; p = 0,034. CONCLUSÃO: A ICP prévia em pacientes com doença coronariana multiarterial é fator de risco independente para mortalidade hospitalar após CRM. Tal fato deve ser considerado quando a ICP for indicada como alternativa inicial em pacientes com doença arterial coronariana mais avançada. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)
Intervenção Coronariana Percutânea prévia como fator de risco para Revascularização Miocárdica
Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP - Brasil
Apesar de todas as evidências científicas e diretrizes para o tratamento da doença arterial coronariana crônica, demonstrando os benefícios da Cirurgia de Revascularização Miocárdica (CRM), especialmente em pacientes com doença multiarterial, tem havido um crescimento exponencial da Intervenção Coronariana Percutânea (ICP) com
Na chamada "era do
O objetivo do presente estudo é avaliar o impacto da ICP com
Foi realizado um estudo observacional prospectivo. Todos os pacientes submetidos por primeira vez a CRM isolada, com circulação extracorpórea, entre maio de 2007 e julho de 2009, foram incluídos neste estudo. O grupo de estudo consistiu de 1.099 pacientes consecutivos com idade média de 63,6 ± 12,6 anos, submetidos a CRM de forma eletiva, ou de urgência ou emergência. Todos os pacientes tinham doença coronariana aterosclerótica multiarterial. Pacientes com cirurgia cardíaca marcada foram excluídos. CRM sem circulação extracorpórea e reoperações foram excluídos para minimizar interferências técnicas cirúrgicas. Os pacientes submetidos a ICP anterior na mesma hospitalização que a cirurgia também foram excluídos. Todos os pacientes foram operados no Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo, referência nacional terciária, e os dados foram coletados prospectivamente, criando um banco de dados.
As características dos pacientes e fatores de risco pré-operatórios foram analisados, seguindo o Sistema Europeu para Avaliação de Risco em Cirurgia Cardíaca (EuroSCORE) aditivo e o modelo Bernstein-Parsonnet 200016,17. A correlação entre mortalidade prevista e observada foi comparada com esses dois modelos, para uma melhor avaliação. O resultado foi mortalidade cirúrgica intra-hospitalar, definida como a morte ocorrida no intervalo de tempo entre a cirurgia e a alta hospitalar.
Este estudo foi aprovado pela Comissão Científica e Ética do Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo.
A CRM foi realizada com circulação extracorpórea, utilizando a técnica clássica por esternotomia mediana em todos os pacientes. Foram utilizados 500 UI/kg de heparina para obter um tempo de coagulação ativada maior do que 400 segundos. A proteção miocárdica foi obtida com infusão anterógrada intermitente de solução cardioplégica sanguínea hipercalêmica normotérmica ou com pinçamento intermitente da aorta. A protamina foi utilizada para a reversão da heparina na proporção de 1:1. No final da cirurgia, os pacientes foram transferidos para a unidade de cuidados intensivos e atendidos de acordo com o protocolo de unidade.
Os pacientes que recebiam terapia antiplaquetária dupla, com ácido acetilsalicílico e clopidogrel, antes da cirurgia, foram tratados da seguinte forma: o ácido acetilsalicílico foi interrompido no dia da cirurgia e reintroduzido no dia seguinte à cirurgia; o clopidogrel foi descontinuado no mínimo de dois a cinco dias antes da cirurgia e, quando necessário, foi reintroduzido pelo menos dois dias após a cirurgia.
As variáveis são apresentadas em tabelas de contingência com frequências absoluta (n) e relativa (%). As associações entre elas, levando em consideração os grupos com e sem ICP prévia, foram avaliadas pelo teste do qui-quadrado, o teste da razão de verossimilhança, ou pelo teste exato de Fisher.
As variáveis quantitativas foram apresentadas em tabelas incluindo os valores da mediana e do 1º e 3 º quartis. A distribuição das variáveis foi avaliada pelo teste de Mann-Whitney.
O teste de bondade de ajuste de Hosmer-Lemeshow foi utilizado para comparar a mortalidade observada e a prevista com intervalos de confiança de 95%. Um modelo bem calibrado corresponde a um p > 0,05.
Modelos de regressão logística univariada e multivariada foram utilizados para identificar fatores associados e independentes preditores pré-operatórios para mortalidade intra-hospitalar. As variáveis identificadas pela análise univariada com valor de p ≤ 0,10 foram utilizadas para o ajuste do modelo de regressão logística multivariada (
Em um esforço adicional para minimizar a influência de um estudo não randomizado, uma segunda análise foi realizada mediante o pareamento por escore de propensão. Pacientes com ICP prévia (grupo de estudo) foram combinados com os pacientes sem ICP prévia (grupo controle), na proporção de 1:1. Após o pareamento, a mortalidade intra-hospitalar foi comparada entre os dois grupos. As amostras pareadas também foram reavaliadas usando testes de regressão logística uni e multivariados, a fim de controlar o eventual risco de viés de seleção.
A análise foi feita usando testes bicaudais e p < 0,05 foi considerado estatisticamente significativo. Para a análise estatística foi utilizada a versão 18.0 do software SPSS (SPSS Inc, Chicago, Illinois).
De maio de 2007 a julho de 2009, um total de 1.551 pacientes foi submetido a CRM isolada, pela primeira vez, no Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo. Foram excluídos 429 pacientes porque foram operados sem circulação extracorpórea ou porque foram submetidos a ICP na mesma hospitalização que o tratamento cirúrgico; 15 pacientes foram excluídos porque foram submetidos a procedimentos vasculares associadas a CRM; e 8 pacientes foram excluídos por informações incompletas referentes à angioplastia prévia. Os restantes 1.099 pacientes foram a população final do estudo.
Dos 1.099 pacientes incluídos no estudo, 938 (85,3%) pacientes foram submetidos a CRM sem ICP anterior e 161 (14,6%) pacientes apresentavam ICP anterior. Desses, 147 (91,3%) haviam sido submetidos a ICP utilizando
No intraoperatório, os pacientes com ICP prévia apresentaram uma menor média de artérias coronarianas revascularizadas (3,0
A mortalidade global de acordo com o EuroSCORE aditivo e o modelo de risco Bernstein-Parsonnet 2000 são exibidas, respectivamente, nas
O pareamento por escore de propensão foi realizado levando em consideração fatores pré-operatórios com maior impacto sobre a cirurgia, para coincidir com grupo de estudo (pacientes com ICP prévia) e grupo controle (pacientes sem ICP prévia). Os seguintes parâmetros foram selecionados: sexo, idade, diabetes, hipertensão arterial sistêmica, insuficiência cardíaca congestiva, angina instável, infarto do miocárdio recente. Para essa análise, 161 pacientes do grupo de estudo foram pareados com 161 controles correspondentes, na proporção de 1:1 (
Cirurgiões cardiovasculares recebem, com cada vez maior frequência, pacientes encaminhados para CRM após uma ICP prévia bem-sucedida. Este estudo mostrou claramente, com base em um banco de dados criado para uma análise prospectiva, com ajuste de fatores de risco, que a ICP prévia é fator de risco independente para mortalidade intra-hospitalar após a CRM.
Os fatores de risco para mortalidade após a cirurgia cardíaca têm sido estudados desde os anos 1980. Inicialmente, só usando associações e mais tarde com modelos de estratificação de risco18,19. Uma série de variáveis, incluindo a ICP na mesma hospitalização, tem sido estudada e são conhecidas há muito tempo como preditores de mortalidade intra-hospitalar após a CRM16,17,20. A influência da ICP prévia na CRM tem sido observada pelos cirurgiões cardíacos na prática diária. No entanto, não tem sido extensivamente estudada e só recentemente é que foi levada mais a sério.
Em 1995, Johnson e cols.21 observaram um impacto negativo de uma ICP prévia na CRM. Comparando 234 pacientes submetidos com sucesso a angioplastia, os quais mais tarde precisaram CRM, eles observaram que o risco cirúrgico no momento da cirurgia foi significativamente maior, 4,0%, que o 2,8% antes da angioplastia (p = 0,04).Em 1996, Jones e cols.22, numa extensiva análise de sete grandes bases de dados com 172.184 pacientes que tinham sido submetidos a CRM, foram os primeiros a identificar a ICP prévia como um fator de risco. No momento foi classificada como nível 2, ou seja, não claramente relacionada com a mortalidade após a cirurgia. Em 1998, Kalaycioğlu e cols.23, em um pareamento por escore de propensão com 80 pacientes submetidos a CRM, observaram piores resultados no grupo de pacientes com angioplastia coronariana prévia. Mais recentemente, Hassan e cols.8, em um amplo estudo com 6.504 pacientes submetidos a CRM (919 pacientes com ICP prévia), demonstraram claramente que a ICP prévia é preditor independente de mortalidade intra-hospitalar após a CRM, razão de chances de 1,93 (p = 0,003). No entanto, hoje em dia ainda restam dúvidas se a ICP prévia é um fator de risco para pacientes submetidos a CRM.
Nos últimos anos houve um número crescente de intervenções utilizando
Em um relatório recente, com análise
No presente estudo, na análise de 1.099 pacientes consecutivos submetidos à CRM com circulação extracorpórea, a mortalidade hospitalar global foi de 5,7%. Essa mortalidade observada reflete a alta complexidade apresentada no serviço terciário de referência nacional, e era comparável com a mortalidade prevista com base no EuroSCORE aditivo e no modelo de risco logístico Bernstein-Parsonnet 200027,28. A mortalidade foi maior em pacientes com história de ICP prévia (9,3%
Embora diversos estudos tenham demonstrado que a ICP prévia usando
Há várias causas possíveis que podem explicar o impacto negativo da ICP prévia, utilizando
1 - Uma delas pode ser a trombose do
2 - Outra causa pode ser o número de anastomoses coronarianas ou de revascularização incompleta nesse grupo de pacientes. Os motivos mais comuns são as artérias coronarianas obstruídas ou com múltiplos
3 - A necessidade de executar a anastomose coronariana mais distalmente do habitual (como consequência da presença de
4 - A quarta causa pode ser a presença de múltiplas intervenções coronarianas, prejudicando o fluxo sanguíneo normal por colaterais causando microinfartos do miocárdio. Como consequência, há maior resistência ao fluxo nos enxertos e menor irrigação do miocárdio9,34. Na nossa experiência, a maioria dos pacientes (84,5%) teve apenas uma ICP prévia e esse fato pode ser a causa em só 15% dos pacientes.
5 - A gravidade da progressão da doença aterosclerótica coronariana pode justificar maior mortalidade. Atualmente, os pacientes submetidos a ICP com
6 - Mais recentemente, foram estudadas as anormalidades endoteliais causadas pela presença de
Se, por um lado, há evidências de que os
O mecanismo associado com um pior prognóstico após a CRM em pacientes com ICP prévia é multifatorial e provavelmente é causado por uma reação inflamatória crônica, disfunção endotelial, processos isquêmicos miocárdicos e mudanças ou dificuldade da técnica cirúrgica15,36. Uma análise crítica e estudos maiores e mais abrangentes devem ser realizados para estabelecer essa associação e os seus respectivos mecanismos.
Esse tipo de estudo não pode ser aleatório e a comparação entre os grupos com e sem ICP prévia tem claras limitações, especialmente em relação aos diferentes tamanhos de amostra. Mesmo se o pareamento por escore de propensão é utilizado, a análise não é a ideal, já que depende das variáveis selecionadas para o pareamento. O tipo de ICP prévia também não foi detalhado. Não se sabe se houve qualquer outro procedimento, além de implante de
A ICP prévia é fator de risco independente para mortalidade intra-hospitalar em pacientes com doença coronariana multiarterial, que exigem mais tarde CRM para o tratamento de doença arterial coronariana. Os cirurgiões cardíacos têm que estar cientes desse, assim como dos outros fatores, tais como insuficiência renal e diabetes.
Declaro não haver conflito de interesses pertinentes.
O presente estudo não teve fontes de financiamento externas.
Este artigo é parte de tese de livre-docência de Luiz Augusto Ferreira Lisboa, pela Faculdade de Medicina - Universidade de São Paulo.
: Luiz Augusto Ferreira Lisboa Rua Philipp Lohbauer, 446, Jardim dos Estados. CEP 04642-060, São Paulo, SP - Brasil E-mail:
Artigo recebido em 09/02/12
Revisado em 14/02/12
Aceito em 27/02/12.
BACKGROUND: Percutaneous coronary intervention (PCI) has increased as the initial revascularization strategy in chronic coronary artery disease. Consequently, more patients undergoing coronary artery bypass grafting (CABG) have history of coronary stent. OBJECTIVE: Evaluate the impact of previous PCI on in-hospital mortality after CABG in patients with multivessel coronary artery disease. METHODS: Between May/2007 and June/2009, 1099 consecutive patients underwent CABG on cardiopulmonary bypass. Patients with no PCI (n=938, 85.3%) were compared with patients with previous PCI (n=161, 14.6%). Logistic regression models and propensity score matching analysis were used to assess the risk-adjusted impact of previous PCI on in-hospital mortality. RESULTS: Both groups were similar, except for the fact that patients with previous PCI were more likely to have unstable angina (16.1% x 9.9%, P=0.019). In-hospital mortality after CABG was higher in patients with previous PCI (9.3% x 5.1%, P=0.034) and it was comparable with EuroSCORE and 2000 Bernstein-Parsonnet risk score. Using multivariate logistic regression analysis, previous PCI emerged as an independent predictor of postoperative in-hospital mortality (odds ratio 1.94, 95% CI 1.02-3.68, P=0.044) as strong as diabetes (odds ratio 1.86, 95% CI 1.07-3.24, P=0.028). After computed propensity score matching based on preoperative risk factors, in-hospital mortality remained higher among patients with previous PCI (odds ratio 3.46, 95% CI 1.10-10.93, P=0.034). CONCLUSIONS: Previous PCI in patients with multivessel coronary artery disease is an independent risk factor for in-hospital mortality after CABG.This fact must be considered when PCI is indicated as initial alternative in patients with more severe coronary artery disease. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)
Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP - Brazil
Mailing Address
Despite all scientific evidences and the guidelines for the treatment of chronic coronary artery disease demonstrating the benefits of coronary artery bypass grafting (CABG), especially in patients with multivessel disease, there has been an exponential growth in percutaneous coronary intervention (PCI) with stents1,2. With technological advances and the experience accumulated over the years, the indication for PCI has expanded and procedures in multivessel coronary disease have become more common3,4.
In this so-called "stent era", patients with coronary artery disease and class I indication for CABG are frequently submitted to PCI as initial alternative, before being convinced to surgical treatment5. Some studies have shown restenosis rates after PCI with stent, with need of reintervention due to symptom recurrence, ranging from 20% to 40%6,7. More recently, it has been discussed whether previous PCI is a risk factor with negative impact on the outcomes of CABG8-10. A significant inflammatory process and endothelial function abnormalities in the coronary arteries have been related to the treatment with stent, especially when drug-eluting stents were used11-13. However, the actual clinical impact of the presence of stents in the coronary artery in the prognosis of CABG has not been clearly established and it is controversy14,15. The increase in mortality is the main event that can influence changes in the guidelines.
The objective of this study is to assess the impact of previous PCI with stent as risk factor for in-hospital mortality in patients with multivessel chronic coronary artery disease who requiring later surgical treatment for myocardial revascularization.
A prospective observational design was used. All patients who underwent first-time isolated CABG surgery on cardiopulmonary bypass between May 2007 and July 2009 were included in this study. The study group consisted of 1,099 consecutive patients of mean age 63.6 ± 12.6 years who underwent elective, urgent or emergency CABG surgery. All patients had multivessel atherosclerotic coronary disease. Patients with combined cardiac surgery were excluded. CABG without cardiopulmonary bypass and reoperations were excluded to minimize surgical technique interferences. Patients underwent previous PCI in the same hospitalization as the surgery, were also excluded. All patients were operated at Heart Institute University of Sao Paulo Medical School, a tertiary referral national center and data were prospectively collected, creating a database.
Patient characteristics and preoperative risk factors were analyzed, following the additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) and 2000 Bernstein-Parsonnet logistic risk model16,17. The correlation of predicted and observed mortality was compared with these two models, for better evaluation. The outcome was in-hospital surgical mortality, defined as death occurring in the time interval between surgery and hospital discharge.
This study was approved by the Scientific and Ethics Committee of Heart Institute, University of São Paulo Medical School.
CABG was performed with cardiopulmonary bypass, using the classic technique by median sternotomy in all patients. Five hundred UI/Kg of heparin was used to obtain an activated coagulation time greater than 400 seconds. Myocardial protection was achieved with intermittent hyperkalemic antegrade warm blood cardioplegia or with intermittent aortic clamping. Protamine was used for heparin reversal at a ratio of 1:1. At the end of surgery, patients were transferred to the intensive care unit and managed according to the unit protocol.
Patients receiving dual anti-platelet therapy with acetylsalicylic acid and clopidogrel prior surgery were treated as follows: acetylsalicylic acid was discontinued on surgery day and was reintroduced the day following surgery, clopidogrel was discontinued at least 2 to 5 days prior surgery and, if required, it was reintroduced within at least 2 days after surgery.
Variables are shown in contingency tables with absolute (n) and relative (%) frequencies. Association among them, taking into consideration the groups with and without prior PCI, was evaluated by the chi-squared test, the likelihood ratio test or Fisher’s exact test.
Quantitative variables were shown in tables including the median, and 1st and 3rd quartile values. The distribution of variables was evaluated by Mann-Whitney’s test.
The Hosmer–Lemeshow goodness-of-fit statistic test was used to compare the observed and predicted mortality with 95% confidence intervals. A well-calibrated model gives corresponding p > 0.05.
Univariate and multivariate logistic regression models were used to identify associated factors and independent preoperative predictors for in-hospital mortality. The variables identified by the univariate analysis with a p value ≤ 0.10 were used to the adjustment of the multivariate logistic regression model (forward procedure).
In an additional effort to minimize the influence from a non-randomized study, a second analysis was performed using the propensity score matching. Patients with prior PCI (study group) were matched with patients without prior PCI (control group), at a 1:1 ratio. After matching, in-hospital mortality was compared between the two groups. Paired samples were also reevaluated using the univariate and multivariate logistic regression tests, in order to control eventual risk factor selection bias.
The analysis was done using two-tailed tests and p <0.05 was considered statistically significant. The SPSS software version 18.0 was used for statistical analysis (SPSS Inc, Chicago, Illinois).
From May 2007 to July 2009, 1551 patients were submitted to first time isolated CABG at the Heart Institute University of Sao Paulo Medical School. Four hundred and twenty-nine patients were excluded because they were operated without cardiopulmonary bypass or because they were submitted to PCI during the same hospitalization as the surgical treatment, 15 patients were excluded because they were submitted to vascular procedures associated to CABG and 8 patients were excluded due to incomplete information regarding prior angioplasty. The other 1099 patients were the final study population.
Of the 1099 patients included in the study, 938 (85.3%) patients underwent CABG without previous PCI and 161 (14.6%) patients had previous PCI. Of these, 147 (91.3%) had been submitted to PCI using bare metal stents and 14 (8.7%) using drug-eluting stents. The comparison of patients with and without prior PCI taking into consideration clinical manifestation and preoperative risk factors showed that patients with prior PCI had a more frequent unstable angina (16.1% vs. 9.9%, p=0.019) at the time of hospitalization. There were no others statistical differences between the two groups as to the remaining clinical manifestations and preoperative cardiovascular risk factors (
In the intraoperative, patients with prior PCI had lower mean number of revascularized coronary arteries (3.0 vs 3.2 – p=0.446), longer aortic clamping time (76.1 vs. 74.8 minutes, p=0.673) and longer cardiopulmonary bypass time (90.7 vs 85.3 minutes, p=0.584), however, there was no statistical significance. There were also no differences between the two groups regarding the use of left internal thoracic artery (95.2% vs 97.3%, p=0.386).
The overall mortality according to the additive EuroSCORE and 2000 Bernstein-Parsonnet risk model are showing, respectively, in
Propensity score matching was performed taking into consideration preoperative factors with a greater impact on surgery to match study group (patients with previous PCI) and control group (patients without previous PCI). The following parameters were selected: gender, age, diabetes, systemic hypertension, congestive heart failure, unstable angina, recent myocardial infarction. For this analysis, 161 study group patients were successfully paired with 161 corresponding controls at a ratio of 1;1 (
Cardiovascular surgeons have more and more often been faced with patients referred for CABG after a successful previous PCI. This study clearly showed, based on a database created for a prospective analysis with adjustment of risk factors, that previous PCI is an independent risk factor for in-hospital mortality after CABG.
Mortality risk factors after cardiac surgery have been studied since the late 80s. Initially only using associations and later with risk stratification models18,19. Many variables, including PCI at the same hospitalization, have been studied and known for a long time as in-hospital mortality predictors after CABG16,17,20. The influence of previous PCI on CABG has been observed for cardiac surgeons in daily practice. However, it has not been extensively studied and only recently, it has been taken into account more seriously.
In 1995, Johnson et al21 observed negative impact of a previous PCI on CABG. Comparing 234 patients successfully submitted to angioplasty who later required CABG, they observed that surgical risk at the time of surgery was 4.0%, significantly higher than the 2.8% prior angioplasty (p=0.04).In 1996, Jones et al22 in extensive review of seven large databases with 172,184 patients underwent CABG were the first to identify previous PCI as a risk factor. At the time, it was classified as level 2, i.e., not clearly related to mortality after surgery. In 1998, Kalaycioglu et al23 in a propensity score matching with 80 patients underwent CABG observed worse outcomes in the group of patients with previous coronary angioplasty. More recently, Hassan et al8 in a large study with 6504 patients underwent CABG (919 patients with a previous PCI), clearly demonstrated that previous PCI is an independent predictor for in-hospital mortality after CABG, odds ratio of 1.93 (p=0.003). However, nowadays still have doubt if previous PCI is a risk factor for patients who undergoing CABG.
In the last years, there is an increasing number of interventional procedures using stents in intermediate risk patients as well as in patients with more severe multivessel coronary disease, which used to be considered inadequate for PCI3,4,24. As consequence, there are an increasing number of patients who have been submitted to PCI with stents before being finally referred for CABG. In the literature, this incidence ranges from 10% to 20%8-10. From our study group, 161 patients (14.6%) had previous PCI. In this context, it is important to reassess the clinical relevance of previous PCI and the prognostic value of risks in patients who may require later CABG.
Recent report, with post hoc analysis, patients with history of PCI had worse prognosis after CABG and an increase in cardiovascular events during clinical follow-up25. Bonaros et al26 confirmed these data in study with 306 patients with previous PCI who were matched with similar group without PCI prior to CABG. Patients with previous PCI had higher in-hospital mortality (4.4% vs. 2.4%, p<0.001).
In the present study, the analysis of 1099 consecutive patients underwent CABG on cardiopulmonary bypass the overall hospital mortality was 5.7%. This observed mortality reflect the high complexity presented in tertiary service of national reference and it was comparable with predicted mortality based on the additive EuroSCORE and 2000 Bernstein-Parsonnet logistic risk model27,28. The mortality was greater in patients with a history of previous PCI (9.3% vs 5.1%, p<0.034). Logistic regression models indicated that previous PCI with stent was an independent predictor for in-hospital mortality after CABG with an odds ratio of 1.94 (p=0.044). Propensity score matching confirmed previous PCI as a risk factor for in-hospital mortality after CABG (odds ratio of 3.46, p=0.034).
Even though several studies have shown that the previous PCI using stents is risk factor for in-hospital mortality after CABG, this correlation is still controversial. Some groups believe there is no correlation between previous PCI and subsequent CABG14. Others have found this correlation only in patients receiving multiple coronary interventions or in diabetic patients9,29-31. Yap et al14 analyzed 13,184 patients (1,457 with history of PCI) underwent CABG and did not find an association between previous PCI and early or mid term mortality (odds ratio of 1.11, p=0.41). Thielmann et al29 analyzed 2626 patients undergoing CABG and found an association between previous PCI and hospital mortality, however, it was only significant in the presence of multiple previous PCIs (odds ratio of 2.24; p<0.001). Massoud et al9 in multicenter study with almost 30,000 patients confirmed the history of multiple previous PCIs as risk factor for hospital mortality after CABG (odds ratio of 2.02; p=0.0005). In a sub-analysis with 749 diabetic patients, Thielmann et al31, observed the association of hospital mortality after CABG with odds ratio of 2.87 (p=0.03) for diabetic patients with a history of previous PCI. In our study group (with previous PCI), 90 patients (56.0%) did not have diabetes and 136 patients (84.5%) had only one previous PCI, even so previous PCI was an independent risk factor. This risk had similar impact as diabetes (odds ratio of 1.86, p=0.028) and chronic renal failure (odds ratio of 4.80, p=0.029), risk factors which have long been known and accepted by the medical community.
There are several possible causes that may explain the negative impact of previous PCI using stents on CABG:
1- One of them might be stent thrombosis, which takes place more frequently in the first six months after the procedure, and mainly when antiplatelet drugs are discontinued early on to carry out surgery. This thrombotic risk is greater when more than one stent is used, with long stents, stents placed in bifurcations, drug-eluting stents, diabetic patients and in renal failure32. In our casuistic, this could explain the cause of approximately 1/3 of the patients operated on within less than 12 months of the PCI.
2 – Another cause might be the number of coronary anastomoses or incomplete revascularization in this group of patients. The most common reasons are occluded coronary arteries or those with multiple stents. Incomplete revascularization may lead to postoperative events such as myocardial infarct and death33. In our casuistic, patients with previous PCI had a lower number of coronary anastomosis per patient (3.0 vs. 3.2 in the group without a previous intervention), however there was no statistical difference.
3 – The need to perform coronary anastomosis more distally than usual (as a result of the presence of stents in the mid third of the arteries) may also affect surgery. In this region, arteries have a smaller diameter, greater flow resistance and it is more difficulty to perform coronary anastomosis. This is a mechanic cause, related to the surgical technique, which is difficult to quantify and assess, but definitely plays a major role in the early outcomes of the surgical treatment.
4 - A fourth cause may be the presence of multiple coronary interventions, impairing native blood flow by collaterals causing micro myocardial infarctions. As a consequence, there is more flow resistance of the grafts and lower myocardial irrigation9,34. In our experience, most of the patients (84.5%) had only one previous PCI and this fact could be the cause of only 15% of the patients.
5 – The severity of the progression of coronary atherosclerotic disease may justify the greater mortality. Currently, patients undergoing PCI with a stent have more severe atherosclerotic disease, but not as severe as those undergoing surgical treatment. When treatment fails, these patients are referred for surgical revascularization, however the atherosclerotic disease is then more severe and diffuse35. In our casuistic, preoperative clinical factors and the presence of left main lesion were similar between the two groups, which leads to the conclusion that the presence of the stent may have worsened the progression of atherosclerotic disease and delayed the optimal time for surgical treatment.
6 – More recently, endothelial abnormalities caused by the presence of stents have been studied. There is evidence indicating the coronary stents cause lesions in the arterial wall, leading to endothelial dysfunction with a chronic inflammatory response and platelet and neutrophil activation. The inflammatory and proliferative abnormalities are not limited to the treated coronary. It affects other coronary arteries, surrounding tissues, including the myocardium, causing adverse cardiovascular effects. Endothelial abnormalities may also render coronary anastomosis more difficult, affecting the perviousness of the grafts11-13. This is common in bare metal stents and is even more intense in drug-eluting stents13. In our casuistic, only 8% of the patients had a previous intervention with drug-eluting stents. If on one hand, there are evidences that drug-eluting stents cause greater inflammatory and chronic response and therefore may further increase surgical risk, on the other hand they may reduce the need of reinterventions and decrease the number of patients requiring CABG after PCI. This association should be further studied.
The mechanism associated with worse prognostic after CABG in patients with previous PCI is multifactorial and probably is caused by a chronic inflammatory reaction, endothelial dysfunction, myocardial ischemic events and changes or difficulty of the surgical technique15,36. Critical analysis and larger and more comprehensive studies should be carried out to establish this association and its respective mechanisms.
This type of study cannot be randomized and the comparison between groups with and without previous PCI has clear limitations, especially regarding the different sample sizes. Even if the propensity score matching is used, the analysis is not ideal, since it depends on selected variables for matching. The type of previous PCI was also not detailed. It was not known whether there was any other procedure in addition to stent implantation or whether there was any other complication. Different causes for surgical treatment indication were also not separated among patients with a previous PCI, such as restenosis, occlusion, thrombosis or disease progression.
Previous PCI is an independent risk factor for in-hospital mortality in patients with multivessel coronary artery disease who requiring later CABG for coronary artery disease. The cardiac surgeons have to be mindful of this, just as they are already had with other factors, such as renal failure and diabetes.
No potential conflict of interest relevant to this article was reported.
There were no external funding sources for this study.
This study is part of the thesis of full professor the submitted by Luiz Augusto Ferreira Lisboa, from Faculdade de Medicina - Universidade de São Paulo.