Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC 9t5ZSQhBsqYL9My6T4wVgnQ S0066-782X2022001300938 abc.20220732 10.36660/abc.20220732 Minieditorial Macrófagos e Neovascularização na Neoaterosclerose Intra-Stent: um Fenótipo Inflamatório Acelerado por OCT com Implicações Terapêuticas Izar Maria Cristina Oliveira 1 0000-0002-9911-4598 Fonseca Francisco A. H. 1 Universidade Federal de São Paulo Escola Paulista de Medicina São Paulo SP Brasil Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP – Brasil Correspondência: Maria Cristina Oliveira Izar • Disciplina de Cardiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo - Rua Loefgren, 1350. CEP 04040-001, Vila Clementino, São Paulo, SP - Brasil, E-mail: mcoizar@cardiol.br 19 12 2022 12 2022 119 6 938 939 This is an open-access article distributed under the terms of the Creative Commons Attribution License Palavras-chave: Reestenose Coronária Fenótipo/inflamação Intervenção Coronária Percutânea Aterosclerose Diagnóstico por Imagem/métodos

Nesta edição dos Arquivos Brasileiros de Cardiologia, Pinheiro et al.,1 apresentam dados de tomografia de coerência óptica (OCT) com diferenças claras de inflamação e neovascularização entre aterosclerose de novo, reestenose intra-stent por hiperplasia intimal e neoaterosclerose intra-stent.

Pacientes submetidos à intervenção coronária percutânea com implante de stent podem apresentar sintomas recorrentes de doença coronariana devido à reestenose intra-stent por lesão vascular que desencadeia uma resposta proliferativa na íntima,2 minimizada pelas técnicas atuais e stents de nova geração.3 No entanto, a lesão neointimal secundária a um atraso na neoendotelização pode levar à recorrência dos sintomas, geralmente durante o primeiro ano de intervenção coronariana.4

Em pacientes com síndromes coronarianas agudas, respostas inflamatórias pronunciadas podem ser detectadas por semanas,5 contribuindo para a instabilidade da placa6 e massa infartada e remodelação ventricular após infarto do miocárdio.7 Além disso, o implante de stent também promove inflamação sistêmica e local.8

Russel Ross9 definiu a aterosclerose como uma doença inflamatória.9 Pinheiro et al.,1 relataram aumento da atividade inflamatória e neovascularização entre lesões de novo e neoaterosclerose intra-stent. Essas duas formas de aterosclerose podem ter diferenças importantes na fisiopatologia. A aterosclerose em artérias nativas está relacionada a fatores de risco cardiovascular e leva muito tempo para se desenvolver, mas após síndromes coronarianas agudas e/ou implante de stents, a inflamação sistêmica pode acelerar sua progressão,6 A neoaterosclerose intra-stent é uma forma nova e rápida de aterosclerose relacionada à lesão e inflamação vascular.4

Complicações como a ruptura da placa aterosclerótica parecem estar associadas não apenas à expansão da placa,10 mas também a características de maior vulnerabilidade (conteúdo inflamatório, capa fibrosa fina e maior teor lipídico).11 A OCT abordou adequadamente todos esses aspectos. As descobertas do artigo têm implicações importantes:

1) A necessidade de terapia apropriada (incluindo terapias hipolipemiantes altamente eficazes) para prevenir o desenvolvimento de aterosclerose em artérias coronárias nativas e possivelmente na aterosclerose intra-stent.12,13

2) O estudo levanta o debate sobre a relevância do risco inflamatório residual e a oportunidade do uso de anti-inflamatórios.14,15

3) Mais estudos são necessários para entender melhor a neoaterosclerose intra-stent e a necessidade de estratégias mais abrangentes, para prevenir esta forma de falha do stent.

Minieditorial referente ao artigo: Fenótipo Inflamatório por Imagem de OCT Coronária: Características Específicas Entre Lesões De Novo, Hiperplasia Intimal e Neoaterosclerose Intra-Stent

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Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs:a 12-week follow-up of coronary reactivity in vivo and in vitro.Atherosclerosis 2001;154(1):61-9. DOI: 10.1016/s0021-9150(00)00458-5 Park SJ Kang SJ Virmani R Nakano M Ueda Y In-stent neoatherosclerosis: a final common pathway of late stent failure J Am Coll Cardiol 2012 59 23 2051 2057 10.1016/j.jacc.2011.10.909 3 Park SJ, Kang SJ, Virmani R, Nakano M, Ueda Y. In-stent neoatherosclerosis: a final common pathway of late stent failure. J Am Coll Cardiol. 2012;59(23):2051-7. DOI: 10.1016/j.jacc.2011.10.909 Giustino G Colombo A Camaj A Yasumura K Mehran R Stone GW Coronary In-Stent Restenosis: JACC State-of-the-Art Review J Am Coll Cardiol 2022 80 4 348 372 10.1016/j.jacc.2022.05.017 4 Giustino G, Colombo A, Camaj A, Yasumura K, Mehran R, Stone GW, et al. Coronary In-Stent Restenosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;80(4):348-72. DOI: 10.1016/j.jacc.2022.05.017 Hilgendorf I Gerhardt LM Tan TC Winter C Holderried TA Chousterman BG Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium Circ Res 2014 114 10 1611 1622 10.1161/CIRCRESAHA.114.303204 5 Hilgendorf I, Gerhardt LM, Tan TC, Winter C, Holderried TA, Chousterman BG, et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res. 2014;114(10):1611-22. DOI: 10.1161/CIRCRESAHA.114.303204 Dutta P Courties G Wei Y Leuschner F Gorbatov R Robbins CS Myocardial infarction accelerates atherosclerosis Nature 2012 487 7407 325 329 10.1038/nature11260 6 Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487(7407)325-9. DOI: 10.1038/nature11260 Fonseca FA Izar MC Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction Front Physiol 2022 13 927163 927163 10.3389/fphys.2022.927163 7 Fonseca FA, Izar MC. Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction. Front Physiol. 2022;13:927163. DOI: 10.3389/fphys.2022.927163 Farsky PS Hirata MH Arnoni RT Almeida AFS Issa M Lima PHO Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent Arq Bras Cardiol 2018 111 2 134 141 10.5935/abc.20180119 8 Farsky PS, Hirata MH, Arnoni RT, Almeida AFS, Issa M, Lima PHO. Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent. Arq Bras Cardiol. 2018;111(2):134–41. DOI: 10.5935/abc.20180119 Ross R Atherosclerosis - an inflammatory disease N Engl J Med 1999 340 2 115 126 10.1056/NEJM199901143400207 9 Ross R. Atherosclerosis - an inflammatory disease. 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Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41(42):4092-9. DOI: 10.1056/NEJMoa1707914 Short Editorial Macrophages and Neovascularization in In-Stent Neoatherosclerosis: An Accelerated Inflammatory Phenotype by OCT with Therapeutic Implications Izar Maria Cristina Oliveira 1 0000-0002-9911-4598 Fonseca Francisco A. H. 1 São Paulo SP Brazil Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP – Brazil Mailing Address: Maria Cristina Oliveira Izar • Disciplina de Cardiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo - Rua Loefgren, 1350. Postal Code 04040-001, Vila Clementino, São Paulo, SP - Brazil, E-mail: mcoizar@cardiol.br Keywords: Coronary Restenosis Phenotype/inflammation Percutaneous Coronary Intervention Atherosclerosis Diagnostic, Imaging/methods

In this edition of Arquivos Brasileiros de Cardiologia, Pinheiro et al.1 show optical coherence tomography (OCT) data with clear differences in inflammation and neovascularization among de novo atherosclerosis, in-stent restenosis due to intimal hyperplasia, and in-stent neoatherosclerosis.

Patients undergoing percutaneous coronary intervention with stent implantation may have recurrent symptoms of coronary heart disease due to in-stent restenosis due to vascular injury that triggers an intimal proliferative response,2 minimized by current techniques and stents of new generation.3 However, the neointimal lesion secondary to a delay in neoendothelialization can lead to symptom recurrence, usually during the first year of coronary intervention.4

In patients with acute coronary syndromes, pronounced inflammatory responses can be detected for weeks,5 contributing to plaque instability6 and infarcted mass and ventricular remodeling after myocardial infarction.7 In addition, stent implantation also promotes systemic and local inflammation.8

Russel Ross9 defined atherosclerosis as an inflammatory disease.9 Pinheiro et al.1 reported increased inflammatory activity and neovascularization among de novo lesions and intra-stent neoatherosclerosis. These two forms of atherosclerosis may have important differences in pathophysiology. Atherosclerosis in native arteries is related to cardiovascular risk factors, and it takes a long time to develop, but after acute coronary syndromes and/or stent implantation, systemic inflammation may accelerate its progression.6 Intra-stent neoatherosclerosis is a new and fast form of atherosclerosis-related to vascular injury and inflammation.4

Complications such as atherosclerotic plaque rupture seem to be associated not only with plaque expansion10 but also with characteristics of greater vulnerability (inflammatory content, thin fibrous cap, and higher lipid content).11 OCT has properly addressed all these aspects. The article’s findings have important implications:

The need for appropriate therapy (including highly-effective lipid-lowering therapies) to prevent the development of atherosclerosis in native coronary arteries and possibly in the intra-stent atherosclerosis.12,13

The study raises the debate about the relevance of residual inflammatory risk and the opportunity to use anti-inflammatory drugs.14,15

More studies are necessary to understand better intra-stent neoatherosclerosis and the need for more comprehensive strategies, to prevent this form of stent failure.

Short Editorial related to the article: Inflammatory Phenotype by OCT Coronary Imaging: Specific Features Among De Novo Lesions, In-Stent Neointima, and In-Stent Neo-Atherosclerosis