Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC rq4sgqx4w7ytXB6Zg5YrSsw S0066-782X2024000200204 00204 10.36660/abc.20240117 Minieditorial O Papel dos Marcadores Hemodinâmicos, Metabólicos e Biomarcadores na Previsão da Mortalidade após a Cirurgia de Revascularização do Miocárdio: Já Chegamos Lá? 0000-0002-1270-8618 Hossne Nelson Americo Junior 1 Universidade Federal de São Paulo Escola Paulista de Medicina Disciplina de Cirurgia Cardiovascular São Paulo SP Brasil Disciplina de Cirurgia Cardiovascular, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP – Brasil Correspondência: Nelson Americo Hossne Junior • Universidade Federal de São Paulo Escola Paulista de Medicina – Cirurgia Cardiovascular – Rua Napoleão de Barros, 715 3º andar. CEP 04023-062, São Paulo, SP – Brasil E-mail: nelson.hossne@unifesp.br 26 04 2024 2024 121 2 e20240117 24 02 2024 20 03 2024 20 03 2024 This is an open-access article distributed under the terms of the Creative Commons Attribution License Palavras-chave Revascularização Miocárdica/cirurgia Mortalidade Biomarcadores/análise Inflamação

A cirurgia de revascularização do miocárdio (CRM) é o procedimento cirúrgico cardíaco mais realizado no Brasil1 e em todo o mundo2 e tem sido um dos procedimentos mais estudados. Os aspectos pós-procedimento têm sido amplamente investigados e os escores de risco pré-operatório desenvolvidos. Vários marcadores e índices pós-operatórios, incluindo hemodinâmicos, metabólicos e biomarcadores, foram identificados e propostos, com o objetivo de prever com precisão os maus resultados dos pacientes. 3-5

Dr. Yamaguti et al.6 realizaram um estudo observacional prospectivo no qual foram analisados biomarcadores hemodinâmicos, metabólicos e de hipoperfusão tecidual em 183 pacientes (idades entre 35 e 83 anos) com disfunção ventricular esquerda (fração de ejeção entre 40% e 42,5%) submetidos à cirurgia de revascularização do miocárdio com circulação extracorpórea, conforme evolução clínica pós-operatória (complicada ou não complicada). Os pacientes com evolução clínica complicada (definida como morte dentro de 30 dias após a cirurgia ou mais de 4 dias de internação na UTI) eram mais velhos (66,3 vs 59,7; p = 0,002) e tinham um EuroSCORE mais alto (6 vs 3; p < 0,001). Os autores também constataram que o EuroSCORE, os níveis de lactato 6 horas após admissão na UTI, a diferença de pressão parcial de dióxido de carbono venoarterial (ΔPCO2) e o quociente respiratório estimado (eRQ = ΔPCO2/Ca-vO2) 12 horas após a admissão na UTI foram preditores independentes de evolução pós-operatória complicada, por análise de regressão logística multivariada.

Outros fatores contribuem de forma independente para piores resultados após a CRM. Os escores EuroSCORE II e STS têm bom poder de discriminação para prever mortalidade hospitalar de pacientes submetidos a CRM.7 Os níveis de proteína C reativa4 e lactato no pós-operatório8 estão diretamente correlacionados com maiores taxas de mortalidade hospitalar e complicações. Os níveis de troponina e CK-MB são fortes preditores de mortalidade em curto e longo prazo, independentemente do uso de circulação extracorpórea.9

Vários estudos e registros demonstraram que o tempo prolongado de pinçamento aórtico tem impacto prognóstico nesses pacientes,10,11 aumentando a mortalidade hospitalar e tardia. Além disso, as transfusões de sangue aumentam inadvertidamente os biomarcadores inflamatórios e de hipoperfusão, levando a um maior tempo de internação pós-operatória e maior morbimortalidade.12,13

Identificar parâmetros hemodinâmicos e metabólicos, bem como biomarcadores, muitos dos quais estão prontamente disponíveis e acessíveis em um ambiente de UTI, e compreender seu papel e correlação com os resultados pós-operatórios do paciente é de suma importância para melhorar o atendimento ao paciente, otimizando a perfusão tecidual e a extração de oxigênio.

No entanto, a resposta inflamatória após cirurgia cardíaca é heterogênea, mediada por uma rede complexa, e deve-se reconhecer o papel da imunidade inata na lesão de tecidos e órgãos após o procedimento. Uma revisão sistemática de ensaios clínicos randomizados sobre intervenções de proteção de órgãos visando a ativação do sistema imunológico inato não elucidou a incerteza quanto à eficácia desses tratamentos em cirurgia cardíaca.14

Nenhum biomarcador único como lesão tecidual relacionada especificamente a alterações inflamatórias intraoperatórias foi identificado,15 nem devemos visar um único caminho. A melhor abordagem hoje continua sendo a análise abrangente de diversos biomarcadores, juntamente com parâmetros hemodinâmicos e metabólicos.

Minieditorial referente ao artigo: Marcadores de Perfusão Tecidual como Preditores de Desfechos Adversos em Pacientes com Disfunção Ventricular Esquerda Submetidos à Revascularização Miocárdica (Bypass Coronário)

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J Am Coll Cardiol. 2021;78(4):365-83. doi: 10.1016/j.jacc.2021.04.099 Shahian DM Grover FL Biomarkers and risk models in cardiac surgery Circulation 2014 130 12 932 935 10.1161/CIRCULATIONAHA.114.0119834 3 Shahian DM, Grover FL. Biomarkers and risk models in cardiac surgery. Circulation. 2014;130(12):932-35. doi: 10.1161/CIRCULATIONAHA.114.0119834. Heo RH Wang MK Meyre PB Birchenough L Park L Vuong K Associations of inflammatory biomarkers with the risk of morbidity and mortality after cardiac surgery: a systematic review and meta-analysis Can J Cardiol 2023 39 11 1686 1694 10.1016/j.cjca.2023.07.021 4 Heo RH, Wang MK, Meyre PB, Birchenough L, Park L, Vuong K, et al. Associations of inflammatory biomarkers with the risk of morbidity and mortality after cardiac surgery: a systematic review and meta-analysis. Can J Cardiol. 2023;39(11):1686-94. doi: 10.1016/j.cjca.2023.07.021 Ramkumar N Jacobs JP Berman RB Parker DM MacKenzie TA Likosky DS Cardiac biomarkers predict long-term survival after cardiac surgery Ann Thorac Surg 2019 108 6 1776 1782 10.1016/j.athoracsur.2019.04.123 5 Ramkumar N, Jacobs JP, Berman RB, Parker DM, MacKenzie TA, Likosky DS, et al. Cardiac biomarkers predict long-term survival after cardiac surgery. Ann Thorac Surg. 2019;108(6):1776-82. doi: 10.1016/j.athoracsur.2019.04.123 Yamaguti T Auler JOC Junior Dallan LAO Galas FRBG Cunha LGC Piccioni MA Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery Arq Bras Cardiol 2024 121 2 e20230247 DOI: https://doi.org/10.36660/abc.20230247 6 Yamaguti T, Auler Junior JOC, Dallan LAO, Galas FRBG, Cunha LGC, Piccioni MA. Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery. Arq Bras Cardiol. 2024; 121(2):e20230247. DOI: https://doi.org/10.36660/abc.20230247 Gao F Shan L Wang C Meng X Chen J Han L Predictive Ability of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) Score for in-Hospital and Medium-Term mortality of patients undergoing coronary artery by-pass grafting Int J Gen Med 2021 14 8509 8519 10.2147/IJGM.S338819 7 Gao F, Shan L, Wang C, Meng X, Chen J, Han L, et al. Predictive Ability of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) Score for in-Hospital and Medium-Term mortality of patients undergoing coronary artery by-pass grafting. 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Ann Thorac Surg. 2009;87(6):1981-92. doi: 10.1016/j.athoracsur.2008.12.063 Ruggieri VG Bounader K Verhoye JP Onorati F Rubino AS Gatti G Prognostic impacto f prolonged cross-clamp time in coronary artery by-pass grafting Heart Lung Circ 2018 27 12 1476 1482 10.1016/j.hlc.2017.09.006 10 Ruggieri VG, Bounader K, Verhoye JP, Onorati F, Rubino AS, Gatti G, et al. Prognostic impacto f prolonged cross-clamp time in coronary artery by-pass grafting. Heart Lung Circ. 2018;27(12):1476-82. doi: 10.1016/j.hlc.2017.09.006 Doenst T Borger MA Weisel RD Yau TM Maganti M Rao V Relation between aortic cross-clamp time and mortality - not as straightforward as expected Eur J Cardio Thorac Surg 2008 33 4 660 665 10.1016/j.ejcts.2008.01.001 11 Doenst T, Borger MA, Weisel RD, Yau TM, Maganti M, Rao V. Relation between aortic cross-clamp time and mortality – not as straightforward as expected. Eur J Cardio Thorac Surg. 2008;33(4):660-5. doi: 10.1016/j.ejcts.2008.01.001 Santos AA Sousa AG Thomé HO Machado RL Piotto RF Impacto n eraly and late mortality after blood transfusion in coronary artery bypass graft surgery Rev Bras Cir Cardiovasc 2013 28 1 1 9 10.5935/1678-9741.20130003 12 Santos AA, Sousa AG, Thomé HO, Machado RL, Piotto RF. Impacto n eraly and late mortality after blood transfusion in coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2013;28(1):1-9. doi: 10.5935/1678-9741.20130003 Murphy GJ Reeves BC Rogers CA Rizvi SI Culliford L Angelini GD Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery Circulation 2007 116 22 2544 2552 10.1161/CIRCULATIONAHA.107.698977 13 Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116(22):2544-52. doi: 10.1161/CIRCULATIONAHA.107.698977 Abbasciano RG Tomassini S Roman MA Rizzello A Pathak S Ramzi J Effects of interventions targeting the systemic inflammatory response to cardiac surgery on clinical outcomes in adults Cochrane Database Sys Rev 2023 10 10 CD013584 CD013584 10.1002/14651858.CD013584.pub2 14 Abbasciano RG, Tomassini S, Roman MA, Rizzello A, Pathak S, Ramzi J, et al. Effects of interventions targeting the systemic inflammatory response to cardiac surgery on clinical outcomes in adults. Cochrane Database Sys Rev. 2023;10(10):CD013584. doi: 10.1002/14651858.CD013584.pub2 Aljure OD Fabbro II Cardiopulmonary bypass and inflammation: The Hidden Enemy J Cardiotor Vasc Anest 2019 33 2 346 347 10.1053/j.jvca.2018.05.030 15 Aljure OD, Fabbro II. Cardiopulmonary bypass and inflammation: The Hidden Enemy. J Cardiotor Vasc Anest. 2019;33(2):346-7. doi: 10.1053/j.jvca.2018.05.030 Short Editorial The Role of Hemodynamic, Metabolic, and Biomarkers in Predicting Mortality after Coronary Artery Bypass Grafting: Are we there yet? 0000-0002-1270-8618 Hossne Nelson Americo Junior 1 São Paulo SP Brazil Disciplina de Cirurgia Cardiovascular, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP – Brazil Mailing Address: Nelson Americo Hossne Junior • Universidade Federal de São Paulo Escola Paulista de Medicina – Cirurgia Cardiovascular – Rua Napoleão de Barros, 715 3º andar. Postal Code 04023-062, São Paulo, SP – Brasil E-mail: nelson.hossne@unifesp.br Keywords Myocardial Revascularization/surgery Mortality Biomarkers/analysis Inflammation

Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure performed in Brazil1 and worldwide2 and has been one of the most studied procedures. Postprocedural aspects have been widely investigated and preoperative risk scores have been developed. Several postoperative markers and indexes, including hemodynamic, metabolic, and biomarkers, have been identified and proposed, aiming to accurately predict poor patient outcomes.3-5

Dr. Yamaguti et al.6 conducted a prospective observational study in which hemodynamic, metabolic, and tissue hypoperfusion biomarkers were analyzed in 183 patients (ages between 35 and 83 years) with left ventricular dysfunction (ejection fraction between 40% and 42,5%) who underwent coronary artery bypass surgery with cardiopulmonary bypass, according to postoperative clinical course (complicated or uncomplicated). Patients with a complicated clinical course (defined as death within 30 days after surgery or more than 4 days of ICU stay) were older (66,3 vs 59,7; p=0.002) and had a higher EuroSCORE (6 vs 3; p<0.001). The authors also found that EuroSCORE, the lactate levels 6 hours after ICU admission, the venoarterial carbon dioxide partial pressure difference (ΔPCO2), and estimated respiratory quotient (eRQ = ΔPCO2/ Ca-vO2) 12 hours after ICU admission were independent predictors of complicated postoperative course, by multivariate logistic regression analysis.

Other factors independently contribute to worse outcomes after CABG. EuroSCORE II and STS scores have good discrimination power to predict in-hospital mortality of patients undergoing CABG.7 Postoperative C-reactive protein4 and lactate levels8 are directly correlated to higher in-hospital mortality rates and complications. Troponin and CK-MB levels are stronger predictors of short and long-term mortality, regardless of the use of cardiopulmonary bypass.9

Several studies and registries demonstrated that a prolonged aortic cross-clamp time has a prognostic impact on these patients,10,11 increasing in-hospital and late mortality. Moreover, blood transfusions inadvertently increase inflammatory and hypoperfusion biomarkers, leading to longer postoperative length of stay and higher morbimortality.12,13

Identifying hemodynamic and metabolic parameters, as well as biomarkers, most of which are readily available and accessible in a regular ICU setting, and understanding their role and correlation to patient postoperative outcomes is of paramount importance to improving patient care, by optimizing tissue perfusion and oxygen extraction.

Nevertheless, inflammatory response after cardiac surgery is intricate, mediated by a complex network, and one should acknowledge the role of innate immunity in tissue and organ injury following the procedure. A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments in cardiac surgery.14

No single biomarker as tissue injury related specifically to intraoperative inflammatory changes has been identified,15 nor we should target a single pathway. The best approach nowadays remains the comprehensive analysis of several biomarkers, along with hemodynamic and metabolic parameters.

Short Editorial related to the article: Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery