Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC FpZM9XtZBMBnnxvkHZnDHgb S0066-782X2017000200149 10.5935/abc.20170003 S0066-782X2017005002105 Original Articles Which Coronary Lesions Are More Prone to Cause Acute Myocardial Infarction? Sen Taner 1 Astarcioglu Mehmet Ali 1 Beton Osman 2 Asarcikli Lale Dinc 3 Kilit Celal 1 Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital Kutahya Turkey Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital, Kutahya - Turkey Dumlupinar University Sivas Cumhuriyet University Sivas Turkey Sivas Cumhuriyet University, Sivas - Turkey Diskapi Education and Research Hospital Ankara Turkey Diskapi Education and Research Hospital, Ankara - Turkey Mailing Address: Taner, Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital. Kutahya - Turkey. E-mail: medicineman_tr@hotmail.com, tanersen1980@gmail.com

Author contributions

Conception and design of the research, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Sen T; Acquisition of data: Sen T, Astarcioglu MA, Beton O, Asarcikli LD, Kilit C; Analysis and interpretation of the data: Sen T, Astarcioglu MA, Beton O; Statistical analysis: Sen T, Beton O.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

 16 01 2017 02 2017 108 2 149 153 03 03 2016 21 06 2016 13 09 2016 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background:

According to common belief, most myocardial infarctions (MIs) are due to the rupture of nonsevere, vulnerable plaques with < 70% obstruction. Data from recent trials challenge this belief, suggesting that the risk of coronary occlusion is, in fact, much higher after severe stenosis. The aim of this study was to investigate whether or not acute ST-elevation MIs result from high-grade stenoses by evaluating the presence of coronary collateral circulation (CCC).

 Methods:

We retrospectively included 207 consecutive patients who had undergone primary percutaneous coronary intervention for acute ST-elevation MI. Collateral blood flow distal to the culprit lesion was assessed by two investigators using the Rentrop scoring system.

 Results:

Out of the 207 patients included in the study, 153 (73.9%) had coronary collateral vessels (Rentrop 1-3). The Rentrop scores were 0, 1, 2, and 3 in 54 (26.1%), 50 (24.2%), 51 (24.6%), and 52 (25.1%) patients, respectively. Triglycerides, mean platelet volume (MPV), white cell (WBC) count, and neutrophil count were significantly lower in the group with good collateral vessels (p = 0.013, p = 0.002, p = 0.003, and p = 0.021, respectively).

 Conclusion:

More than 70% of the patients with acute MI had CCC with Rentrop scores of 1-3 during primary coronary angiography. This shows that most cases of acute MI in our study originated from underlying high-grade stenoses, challenging the common believe. Higher serum triglycerides levels, greater MPV, and increased WBC and neutrophil counts were independently associated with impaired development of collateral vessels.

 Keywords: Plaque, Atherosclerotic Rupture Myocardial Infarction Coronary Restenosis Collateral Circulation Introduction

An ST-segment myocardial infarction (STEMI) is the result of an abrupt rupture of a coronary atherosclerotic plaque and subsequent thrombosis. Most myocardial infarctions (MIs) are thought to follow the rupture of vulnerable plaques deemed nonsevere and with less than 70% obstruction.1-3 This belief has been mostly founded on old studies and, as a result, has been debated in recent years. In these older trials, the time between the angiography and the index case was long; this may be problematic since noncritical lesions may progress to a more severe stenosis with time. Reflecting this issue, Alderman et al. published in 1993 a 5-year, prospective, follow-up study (the CASS trial) in which they suggested that the risk of coronary occlusion was much higher in severe compared with nonsevere stenoses.4

Collateral vessels develop distally from the ischemic area to compensate for the decreased blood supply distal to the lesions. These collateral vessels may preserve the myocardial function in the case of severe stenosis. In this study, we used the presence of coronary collateral circulation (CCC) as a marker of severe stenosis. Our hypothesis was that the finding of coronary collaterals distal to the culprit lesion would mean that the lesion responsible for the acute occlusion was already severe prior to the episode of acute MI. The aim of this study was to investigate in patients with an episode of acute STEMI whether this episode originated or not from high-grade stenoses.

 Methods

We included retrospectively 207 patients who had undergone primary percutaneous coronary intervention (PCI) due to an acute STEMI at the Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital during a 6 month-period between January 2012 and June 2012. The patients were selected from our catheter laboratory database. At least two physicians double-checked the database to guarantee the accuracy of the data.

The definition of STEMI comprised an ST-segment elevation greater than 1 mm in two or more contiguous precordial leads, or two or more adjacent limb leads, or new or presumed new left bundle-branch block with angina. The culprit lesion was defined as the lesion that received the intervention. Collateral blood flow distal to the culprit lesion was measured by two investigators using the Rentrop grading system:5

Rentrop 0 - No visible filling of collateral vessels;

Rentrop 1 - Filling of collateral vessels without any epicardial filling of the artery to be dilated;

Rentrop 2 - Partial epicardial filling by collateral vessels of the artery to be dilated;

Rentrop 3 - Complete epicardial filling by collateral vessels of the artery to be dilated.

Only patients who had undergone primary PCI for acute STEMI were included in the study. Patients with acute coronary syndromes without ST elevation and those who did not undergo primary PCI were excluded.

The number and percentages of the patients who had CCC according to the Rentrop scoring system were calculated. We then divided the patients into two groups according to the rating of the collateral vessels and the Rentrop scores: patients with collateral vessels deemed "poor" (Rentrop 0-1) were included in group 1 and those with collateral vessels deemed "good" (Rentrop 1-3) were included in group 2.

Statistical analysis

Continuous variables are expressed as mean ± standard deviation (SD) and categorical variables are presented as numbers and percentages. The normality of the data was tested with the Kolmogorov-Smirnov test. Numerical predictors were estimated with the Mann-Whitney U test, whereas categorical predictors were estimated with Pearson's chi-square test. Differences were considered statistically significant when p < 0.05. The variables with a p value below 0.1 were included in a multiple logistic regression analysis.

 Results

Out of the 207 patients included in the study, 138 were males (67%) and 69 were females (33%). The mean age of the patients was 63 ± 11 years. In total, 153 patients (73.9%) presented CCC (Rentrop 1-3). The Rentrop scores were 0, 1, 2, and 3 in 54 (26.1%), 50 (24.2%), 51 (24.6%), and 52 (25.1%) patients, respectively (Table 1). The left anterior descending artery was the most common culprit artery (48.3%), followed by the right coronary artery (30.9%), and the circumflex artery (20.8%). The most common acute STEMI type was inferior MI (52%).

Distribution of the patients according to Rentrop scores
Rentrop score Number of patients %
0 54 26,1
1 50 24,2
2 51 24,6
3 52 25,1
1-3 153 73,9

When we grouped the patients according to the adequacy of collateral vessel development as "poor" (Rentrop 0-1) and "good" (Rentrop 2-3), we found no significant differences between these groups in terms of baseline demographic and clinical characteristics. Triglycerides, mean platelet volume (MPV), white cell (WBC) count, and neutrophil count were significantly lower in the group with "good" collateral vessel development (p = 0.013, p = 0.002, p = 0.003 and p = 0.021, respectively).

Multiple logistic regression analysis showed that triglycerides levels (odds ratio [OR] 1.005, 95% confidence interval [95%CI] 1.001-1.008), MPV (OR 1.271, 95%CI 1.084-1.490), WBC count (OR 1.142, 95%CI 1.020-1.278), and neutrophil count (OR 1.159, 95%CI 1.040-1.292) were independent predictors of CCC (Table 2).

Univariate and multivariate predictors of inadequate coronary collateral circulation (CCC, Rentrop 0 and 1)
Variable Univariate analysis Multivariate analysis
OR p 95%CI OR p 95%CI
Triglycerides (TG) (TG) 0.006 1.001-1.008 1.004 0.018 1.001-1.008
Mean platelet volume (MPV) 1.271 0.003 1.084-1.490 1.215 0.021 1.030-1.434
Neutrophil count 1.159 0.007 1.040-1.292
White cell (WBC) count 1.142 0.022 1.020-1.278 1.142 0.020 1.021-1.278

TG, MPV, and neutrophil and WBC count were analyzed with forward stepwise multiple logistic regression. CI: confidence interval; OR: odds ratio.

 Discussion

Our study showed that the majority of the acute STEMIs originated from severe stenotic segments of coronary arteries. A total of 73.9% of our patients had coronary collateral vessels, indicating that the majority of the acute MIs originated from previous severe stenotic lesions. This finding challenges the historical belief that acute MI occurs as a result of abrupt rupture of nonsignificant (< 50% obstruction) coronary lesions.

This is a field with many controversies. Older studies supported the idea that coronary occlusion and acute STEMI due to sudden plaque rupture occur from nonsignificant coronary stenotic lesions.6,7 Little et al.1 conducted one such study in which they monitored 29 patients after coronary angiography until they presented MI. The mean follow-up time was 706 days. As a result, the initial stenosis was below 70% in 97% of the patients. They concluded that the majority of the cases of MI arose from nonsignificant coronary stenosis.1 The major limitation of their study was that the time from the initial angiography to the acute MI was so long that nonsignificant coronary lesions could have progressed to high-grade stenosis during follow-up. In another study by Hackett et al.,8 the authors found that the mean residual stenosis was below 70% in patients with acute MI after successful thrombolytic therapy. In 1993, Alderman et al. reported results of a prospective study showing that severe lesions were more likely to progress to total occlusion than mild ones after a follow-up period of 5 years.4

Results of more recent studies dispute these findings. Frobert et al.9 conducted a study in 156 patients with MI who had spontaneous reflow or reflow after uncomplicated wiring at the first angioplasty. Using quantitative coronary analysis (QCA) programs to measure the severity of the culprit lesion, they found that the severity of the underlying lesion was > 50% in 151 (96%) patients and > 70% in 103 (66%) of them.9 However, the main disadvantage of this method is that it excludes the presence of thrombus, since the presence of thrombi makes the lesion appear more severe than they really are. Manoharan et al.10 performed thrombus aspiration after wiring the culprit lesions in patients with STEMI undergoing primary coronary angioplasty. They then measured the severity of the underlying coronary stenosis with QCA and found that only 11% of the culprit stenoses were below 50%.10

In our study, we used the presence of CCC and the Rentrop scoring system to assess the severity of the underlying lesions, instead of using thrombolytic application, thrombus aspiration, and recanalization (spontaneous or wiring), as done in other previous studies.

In a study similar to ours, Khoo et al.11 investigated the development of collateral vessels using the Rentrop grading system in 159 patients with acute MI. Of all patients, 95 (60%) had collateral vessels.11 Their study supports our findings and was the first trial using CCC as a surrogate marker for underlying lesion severity. Our study is the second trial using this method but our sample size is larger than that in the study by Khoo et al. 11

Collateral vessels are vascular connections from one coronary vessel to other high-grade, stenotic vessels.12 This is an adaptation to ischemia. Although the exact mechanism for this occurrence is unknown, it has been suggested to be through the release of some growth factors in response to ischemia.13 Collateral vessels have some beneficial effects, including reduced infarct size, preservation of ejection function, and reduction of postinfarction complications like rupture and aneurysm.14-16 While coronary collaterals may supply enough blood flow during rest, they may not supply sufficient flow during exercise.17

The degree of collateral development varies among patients. It is not clear why some patients have a Rentrop score of 3 for collateral vessels, while others have a Rentrop 1 score. Several factors and markers have been identified as contributors to the development of coronary collateral vessels. The severity of the underlying coronary stenosis, proximal location of the lesion, symptom duration, and slow heart rates are described as clinical factors that influence the development of collaterals.18-20 Granulocyte-monocyte-colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), physical exercise, and external counterpulsation have also been found to positively affect the development of collaterals, whereas aging, obesity, and levels of uric acid and C-reactive protein have been found to have negative effects.21-28

We found in our study that higher levels of serum triglycerides, greater MPV, and increased WBC and neutrophil counts were independently associated with impairment of collateral vessel development. Akın et al.29 reported that the level of serum triglycerides and ratio of neutrophil / lymphocyte (N/L) were independently associated with poor CCC development after multivariate regression analysis. MPV and WBC count were not different between the groups with poor and good CCC in their study. In our study, we did not find any significant association between N/L ratio and CCC, expect for the neutrophil count.

The association between MPV and CCC is unclear. Ege et al.30 reported that MPV levels were significantly higher in patients with poor CCC and coronary artery disease (CAD). In contrast, Duran et al. reported that elevated MPV levels were independent predictors of a good CCC development in patients with acute coronary syndrome.31 While Kadı et al. found that levels of high-density cholesterol (HDL-C) were associated with good CCC development,32 we found that serum triglycerides level was positively associated with CCC development.

The presence of coronary collateral vessels may imply that the underlying stenosis is severe. In our study, we regarded patients with Rentrop 1-3 coronary collateral vessel development as having underlying high-grade ischemia causing stenosis. Our use of collateral vessel development as a surrogate marker of ischemia may reflect more reliably the physiological reality than methods to measure the anatomical calculation of lesion severity used in previous studies.

Study limitations

Collateral vessels of small caliber may not have been visible during coronary angiography. With that, we may have underestimated the presence of coronary collateral vessels.

The Rentrop scoring system is a subjective method to evaluate collateral vessel development. Coronary flow index is a better method for this evaluation, as it is a more objective and sensitive technique to determine the development of CCC. However, while it may evaluate CCC more accurately than Rentrop, it is an invasive technique and not easy to incorporate into routine clinical practice.

 Conclusion

Most cases of acute myocardial ischemia originated from underlying high-grade stenoses, contrary to older belief. More than 70% of the patients with acute MI had CCC with Rentrop scores of 1-3 during primary coronary angioplasty. Higher serum triglycerides level, greater MPV, and increased WBC and neutrophil counts were independently associated with impairment of collateral vessel development.

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any thesis or dissertation work.

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Ege MR Acıkgoz S Zorlu A Sıncer I Guray Y Guray U Mean platelet volume: an important predictor of coronary collateral development Platelets 2013 24 3 200 204 31 Duran M, Gunebakmaz O, Uysal OK, Ocak A, Yilmaz Y, Arinc H, et al. Relation between mean platelet volume and coronary collateral vessels in patients with acute coronary syndromes. J Cardiol. 2013;61(4):295-8. Duran M Gunebakmaz O Uysal OK Ocak A Yilmaz Y Arinc H Relation between mean platelet volume and coronary collateral vessels in patients with acute coronary syndromes J Cardiol 2013 61 4 295 298 32 Kadı H, Özyurt H, Ceyhan K, Koç F, Çelik A, Burucu T. The relationship between high-density lipoprotein cholesterol and coronary collateral circulation in patients with coronary artery disease. J Investig Med. 2012;60(5):808-12. Kadı H Özyurt H Ceyhan K Koç F Çelik A Burucu T The relationship between high-density lipoprotein cholesterol and coronary collateral circulation in patients with coronary artery disease J Investig Med 2012 60 5 808 812 Artigos Originais Quais Lesões Coronarianas São Mais Propensas a Causar Infarto Agudo do Miocárdio? Sen Taner 1 Astarcioglu Mehmet Ali 1 Beton Osman 2 Asarcikli Lale Dinc 3 Kilit Celal 1 Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital, Kutahya - Turquia Sivas Cumhuriyet University, Sivas - Turquia Diskapi Education and Research Hospital, Kutahya - Turquia Correspondência: Taner, Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital. Kutahya - Turquia. E-mail: medicineman_tr@hotmail.com, tanersen1980@gmail.com

Contribuição dos autores

Concepção e desenho da pesquisa, Redação do manuscrito e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Sen T; Obtenção de dados: Sen T, Astarcioglu MA, Beton O, Asarcikli LD, Kilit C; Análise e interpretação dos dados: Sen T, Astarcioglu MA, Beton O; Análise estatística: Sen T, Beton O.

Potencial conflito de interesse

Declaro não haver conflito de interesses pertinentes.

 Resumo Fundamento:

Há uma crença geral de que a maioria dos infartos agudos do miocárdio (IAM) ocorrem devido à ruptura de placas vulneráveis, não graves, com obstrução < 70%. Dados de ensaios recentes desafiam esta crença, sugerindo que o risco de oclusão coronariana é, na realidade, muito maior após estenose grave. O objetivo deste estudo foi investigar se a presença ou não de IAM com supradesnível do segmento ST resulta de estenoses de alto grau através da avaliação da presença de circulação colateral coronariana (CCC).

 Métodos:

Nós incluímos retrospectivamente 207 pacientes consecutivos submetidos à intervenção coronariana percutânea primária devido à ocorrência de IAM com supradesnível do segmento ST. O fluxo sanguíneo colateral distal à lesão culpada foi avaliado por dois investigadores com utilização do sistema de escores de Rentrop.

 Resultados:

Dos 207 pacientes incluídos no estudo, 153 (73,9%) apresentavam vasos coronarianos colaterais (Rentrop 1-3). Os escores Rentrop foram de 0, 1, 2 e 3 em 54 (26,1%), 50 (24,2%), 51 (24,6%) e 52 (25,1%) pacientes, respectivamente. Triglicérides, volume plaquetário médio (VPM), contagem de células brancas (CCB) e contagem de neutrófilos estiveram significativamente mais baixos no grupo com bons vasos colaterais (p = 0,013, p = 0,002, p = 0,003 e p = 0,021, respectivamente).

 Conclusão:

Mais de 70% dos pacientes com IAM apresentaram CCC com escores de Rentrop de 1-3 durante angiografia coronariana primária. Isto demonstra que a maioria dos casos de IAM em nosso estudo originou a partir de estenoses subjacentes de alto grau, contrariamente à sabedoria comum. Níveis séricos mais elevados de triglicérides, maior VPM e elevação na CCB e na contagem de neutrófilos estiveram independentemente associados com comprometimento no desenvolvimento de vasos colaterais.

 Palavras-chave: Placa Aterosclerótica Ruptura Infarto do Miocárdio Reestenose da Coronária Circulação Colateral Introdução

O infarto agudo do miocárdio (IAM) com supradesnível do segmento ST (IAMCSST) resulta de uma ruptura abrupta de uma placa aterosclerótica coronariana e subsequente trombose. Considera-se que a maioria dos IAMs ocorra após uma ruptura de placas vulneráveis consideradas não severas e com menos de 70% de obstrução.1-3 Esta crença encontra fundamento principalmente em estudos antigos e, como resultado, tem sido debatida nos últimos anos. Nesses ensaios mais antigos, o tempo entre a angiografia e o caso índice foi longo; isso pode ser problemático, já que lesões não críticas podem progredir para estenoses mais graves com o tempo. Refletindo esta questão, Alderman et al.4 publicaram em 1993 um estudo prospectivo com seguimento de 5 anos (ensaio CASS) no qual sugeriram que o risco de oclusão coronariana foi muito maior para estenoses graves em comparação às não graves.

Vasos colaterais se desenvolvem distalmente à área de isquemia para compensar a diminuição do suprimento sanguíneo distal às lesões. Esses vasos colaterais podem preservar a função miocárdica no caso de estenose grave. Neste estudo, nós utilizamos a circulação colateral coronariana (CCC) como um marcador de estenose grave. Nossa hipótese foi de que o encontro de colaterais coronarianas distais à lesão culpada significaria que a lesão responsável pela oclusão aguda já era grave antes do IAM. O objetivo deste estudo foi investigar em pacientes com um episódio de IAMCSST se este episódio originou ou não de estenoses de alto grau.

 Métodos

Nós incluímos retrospectivamente 207 pacientes que haviam sido submetidos à intervenção coronariana percutânea (ICP) primária por IAMCSST no Dumlupinar University Kutahya Evliya Celebi Education and Research Hospital durante um período de 6 meses entre janeiro de 2012 e junho de 2012. Os pacientes foram selecionados a partir do banco de dados do nosso laboratório de hemodinâmica. Ao menos dois médicos verificaram duas vezes o banco de dados para garantir a acurácia dos dados.

A definição de IAMCSST incluiu a presença de supradesnível do segmento ST maior que 1 mm em duas ou mais derivações precordiais contíguas, ou duas ou mais derivações adjacentes de membros, ou um novo ou presumidamente novo bloqueio de ramo esquerdo com angina. A lesão culpada foi definida como a lesão que recebeu a intervenção. O fluxo sanguíneo colateral distal à lesão culpada foi avaliado por dois investigadores utilizando o sistema de escores de Rentrop.5

Rentrop 0 - Sem enchimento visível dos vasos colaterais;

Rentrop 1 - Enchimento dos vasos colaterais sem qualquer enchimento epicárdico da artéria a ser dilatada;

Rentrop 2 - Enchimento epicárdico parcial por vasos colaterais da artéria a ser dilatada;

Rentrop 3 - Enchimento epicárdico completo por vasos colaterais da artéria a ser dilatada.

Apenas os pacientes que haviam sido submetidos à ICP primária devido à ocorrência de IAMCSST foram incluídos no estudo. Pacientes com síndromes coronarianas agudas sem supradesnível de ST e pacientes não submetidos à ICP primária foram excluídos.

O número e a porcentagem de pacientes que apresentaram CCC de acordo com o sistema de escores de Rentrop foram calculados. Em seguida, dividimos os pacientes em dois grupos de acordo com a classificação dos vasos colaterais e os escores de Rentrop: pacientes com vasos colaterais considerados "pobres" (Rentrop 0-1) foram incluídos no grupo 1 e aqueles com vasos colaterais considerados "bons" (Rentrop 1-3) foram incluídos no grupo 2.

Análise estatística

As variáveis contínuas estão expressas como média ± desvio padrão (DP) e as variáveis categóricas são apresentadas como números e porcentagens. A normalidade dos dados foi analisada com o teste de Kolmogorov-Smirnov. Os preditores numéricos foram estimados com o teste U de Mann-Whitney, enquanto preditores categóricos foram estimados com o teste do qui-quadrado de Pearson. As diferenças foram consideradas estatisticamente significativas quando p < 0,05. As variáveis com um valor de p menor que 0,1 foram incluídas em uma análise de regressão logística múltipla.

 Resultados

Dos 207 pacientes incluídos no estudo, 138 eram do sexo masculino (67%) e 69 eram do sexo feminino (33%). A média de idade dos pacientes foi de 63 ± 11 anos. No total, 153 pacientes (73,9%) apresentaram CCC (Rentrop 1-3). Os escores de Rentrop foram de 0, 1, 2 e 3 em 54 (26,1%), 50 (24,2%), 51 (24,6%) e 52 (25,1%) pacientes, respectivamente (Tabela 1). A artéria descendente anterior foi a artéria culpada mais comum (48,3%), seguida pelas artérias coronária direita (30,9%) e circunflexa (20,8%). O tipo mais comum de IAMCSST foi o IAM inferior (52%).

Distribuição dos pacientes de acordo com os escores de Rentrop
Escore de Rentrop Número de pacientes %
0 54 26,1
1 50 24,2
2 51 24,6
3 52 25,1
1-3 153 73,9

Quando agrupamos os pacientes de acordo com a adequação do desenvolvimento de vasos colaterais em "pobre" (Rentrop 0-1) e "bom" (Rentrop 2-3), não encontramos diferenças significativas entre os grupos em relação às características basais demográficas e clínicas. Triglicérides, volume plaquetário médio (VPM), contagem de células brancas (CCB) e contagem de neutrófilos se mostraram significativamente inferiores no grupo com "bom" desenvolvimento de vasos colaterais (p = 0,013, p = 0,002, p = 0,003 e p = 0,021, respectivamente).

A análise de regressão logística múltipla mostrou que os níveis de triglicérides (odds ratio [OR] 1,005, intervalo de confiança de 95% [IC95%] 1,001-1,008), VPM (OR 1,271, IC95% 1,084-1,490), CCB (OR 1,142, IC95% 1,020-1,278) e contagem de neutrófilos (OR 1,159, IC95% 1,040-1,292) foram preditores independentes de CCC (Tabela 2).

Preditores univariados e multivariados de circulação colateral coronariana (CCC) inadequada (Rentrop 0 e 1)
Variável Análise univariada Análise multivariada
OR p IC95% OR p IC95%
Triglicérides (TG) 1,005 0,006 1,001-1,008 1,004 0,018 1,001-1,008
Volume plaquetário médio (VPM) 1,271 0,003 1,084-1,490 1,215 0,021 1,030-1,434
Contagem de neutrófilos 1,159 0,007 1,040-1,292
Contagem de células brancas (CCB) 1,142 0,022 1,020-1,278 1,142 0,020 1,021-1,278

TG, VPM, contagem de neutrófilos e CCB foram analisados com análise regressão logística múltipla com método stepwise forward. IC: intervalo de confiança; OR: odds ratio.

 Discussão

Nosso estudo mostrou que a maioria dos episódios de IAMCSST se originaram a partir de segmentos de artérias coronárias com estenose grave. No total, 73,9% dos nossos pacientes apresentavam vasos colaterais coronarianos, indicando que a maioria dos IAMs se originaram a partir de lesões estenóticas graves. Este achado desafia a crença histórica de que o IAM ocorre como resultado da ruptura abrupta de lesões coronarianas não significativas (< 50% de obstrução).

Esta é uma área com muitas controvérsias. Estudos mais antigos apoiam a ideia de que lesões estenóticas coronarianas não significativas dão origem à oclusão coronariana e ao IAMCSST devido à ruptura súbita de placas.6,7 Little et al.1 realizaram um desses estudos, no qual monitoraram 29 pacientes após angiografia coronariana até que apresentassem IAM. O tempo médio de seguimento foi de 706 dias. Como resultado, a estenose inicial era inferior a 70% em 97% dos pacientes. Os autores concluíram que a maioria dos casos de IAM surgiu de estenoses coronarianas não significativas.1 A principal limitação do estudo desses autores foi o fato de que o tempo entre a angiografia inicial e o IAM foi tão longo que lesões coronarianas não significativas podem ter evoluído para estenoses de alto grau durante o seguimento. Em um outro estudo realizado por Hackett et al.,8 os autores encontraram que a média de estenose residual esteve abaixo de 70% em pacientes com IAM após uma terapia trombolítica bem-sucedida. Em 1993, Alderman et al.4 relataram resultados de um estudo prospectivo mostrando que as lesões graves foram as mais prováveis de progredir para oclusão total do que as lesões leves após um período de seguimento de 5 anos.

Resultados de estudos mais recentes disputam esses achados. Frobert et al.9 realizaram um estudo com 156 pacientes com IAM que apresentaram recanalização espontânea ou após passagem do fio-guia na primeira angioplastia. Utilizando programas de análise coronariana quantitativa (ACQ) para medir a gravidade da lesão culpada, esses autores encontraram que a gravidade da lesão subjacente foi > 50% em 151 (96%) pacientes e > 70% em 103 (66%) deles.9 No entanto, a principal desvantagem desse método é a exclusão da presença de trombo, já que a presença destes mostra as lesões como sendo mais graves do que realmente são. Manoharan et al.10 realizaram aspiração do trombo após passagem do fio-guia em lesões culpadas em pacientes com IAMCSST submetidos à angioplastia coronariana primária. Eles mediram com ACQ a gravidade da estenose coronariana subjacente e verificaram que apenas 11% das estenoses de lesões culpadas estiveram abaixo de 50%.10

Em nosso estudo, utilizamos a CCC e o sistema de escores de Rentrop para avaliar a gravidade da lesão subjacente, ao invés de utilizarmos aplicação de trombolítico, aspiração de trombo e recanalização (espontânea ou após passagem do fio-guia), como outros estudos anteriores.

Em um estudo semelhante ao nosso, Khoo et al.11 investigaram o desenvolvimento de vasos colaterais utilizando o sistema de escores de Rentrop em 159 pacientes com IAM. De todos os pacientes, 95 (60%) apresentavam vasos colaterais.11 O estudo desses autores apoia os nossos achados e foi o primeiro ensaio com utilização da CCC como um marcador substituto de gravidade de lesão subjacente. Nosso estudo é o segundo ensaio utilizando este método, mas o tamanho de nossa amostra é maior do que a do estudo de Khoo et al.11

Vasos colaterais são conexões vasculares de um vaso coronariano para outros vasos com estenose de alto grau.12 Esta é uma adaptação à isquemia. Embora o mecanismo exato para essa ocorrência seja desconhecido, tem sido sugerido que possa ocorrer através da liberação de alguns fatores de crescimento em resposta à isquemia.13 Os vasos colaterais têm alguns efeitos benéficos, incluindo a redução do tamanho do infarto, preservação da função de ejeção e redução de complicações pós-infarto, como ruptura e aneurisma.14-16 Enquanto o fluxo de sangue fornecido por essas colaterais coronarianas possa ser suficiente durante o repouso, pode ser insuficiente durante o exercício.17

O grau de desenvolvimento de colaterais varia entre pacientes. Não está claro o porquê de alguns pacientes terem um escore de Rentrop de 3 para vasos colaterais, enquanto outros têm Rentrop 1. Vários fatores e marcadores têm sido identificados como contribuintes para o desenvolvimento de vasos colaterais coronarianos. A gravidade da estenose coronariana subjacente, proximal à localização da lesão, a duração dos sintomas e um batimento cardíaco lento são descritos como fatores clínicos que influenciam o desenvolvimento de colaterais.18-20 O fator estimulador de colônias de granulócitos-monócitos (GM-CSF) e o fator estimulador de colônias de granulócitos (G-CSF), o exercício físico e a contrapulsação externa também têm sido considerados como afetando positivamente o desenvolvimento de colaterais, enquanto o envelhecimento, a obesidade e os níveis de ácido úrico e proteína C reativa foram descritos como tendo efeitos negativos.21-28

Encontramos em nosso estudo que concentrações séricas mais elevadas de triglicérides, maior VPM, e aumento do CCB e contagem de neutrófilos estiveram independentemente associados com comprometimento no desenvolvimento de vasos colaterais. Akın et al.29 relataram que o nível sérico de triglicérides e a relação de neutrófilos / linfócitos (N/L) estiveram independentemente associados com um desenvolvimento pobre de CCC após análise de regressão multivariada. O VPM e o CCB não diferiram entre os grupos com desenvolvimento pobre ou bom de CCC em seu estudo. Em nosso estudo, não encontramos uma associação significativa entre a relação N/L e a CCC, exceto em relação à contagem de neutrófilos.

A associação entre VPM e CCC não é clara. Ege et al.30 relataram que os níveis de VPM estiveram significativamente mais altos em pacientes com CCC pobre e doença arterial coronariana (DAC). Por outro lado, Duran et al.31 relataram que os níveis elevados de VPM foram preditores independentes de um bom desenvolvimento de CCC em pacientes com síndrome coronariana aguda. Enquanto Kadı et al.32 encontraram que os níveis de colesterol de lipoproteína de alta densidade (HDL-C) estiveram relacionados com um bom desenvolvimento de CCC, nós observamos que o nível sérico de triglicérides esteve positivamente associado com o desenvolvimento de CCC.

A presença de vasos coronarianos colaterais pode sugerir que a estenose subjacente é grave. Em nosso estudo, consideramos pacientes com desenvolvimento de vasos colaterais coronarianos Rentrop 1-3 como tendo isquemia subjacente de alto grau causando estenose. A nossa utilização do desenvolvimento de vasos colaterais como um marcador substituto de isquemia pode refletir mais fielmente a realidade fisiológica do que os métodos para medir o cálculo da gravidade da lesão anatômica utilizado em estudos anteriores.

Limitações do estudo

Vasos colaterais de pequeno calibre podem não ter estado visíveis durante a angiografia coronariana. Com isso, podemos ter subestimado a presença de vasos coronarianos colaterais.

O sistema de escores de Rentrop é um método subjetivo de avaliação do desenvolvimento de vasos colaterais. O índice de fluxo coronariano é um método melhor para esta estimativa, por ser uma técnica mais objetiva e sensível na determinação da CCC, mas enquanto pode permitir uma avaliação mais precisa da CCC do que o Rentrop, é uma técnica invasiva e de difícil incorporação na prática clínica rotineira.

 Conclusão

A maioria dos casos de isquemia miocárdica aguda se origina a partir de estenoses subjacentes de alto grau, contrariamente à crença antiga. Mais de 70% dos pacientes com IAM apresentaram CCC com escores de Rentrop de 1-3 durante angioplastia coronariana primária. Níveis séricos mais elevados de triglicérides, maior VPM, e elevação na CCB e na contagem de neutrófilos se mostraram independentemente associados com comprometimento no desenvolvimento de vasos colaterais.

Fontes de financiamento

O presente estudo não teve fontes de financiamento externas.

Vinculação acadêmica

Não há vinculação deste estudo a programas de pós-graduação.