Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC zCdK3sKC7NXz8xgn65VDmrd 01193 S0066-782X2020001401193 abc.20201194 10.36660/abc.20201194 Carta Científica Tópicos Emergentes em Insuficiência Cardíaca: Abordagem Contemporânea da Insuficiência Cardíaca Avançada 0000-0002-2533-5638 Marcondes-Braga Fabiana G. 1 * 0000-0001-5982-8847 Vieira Jefferson L. 2 * 0000-0002-6767-4785 Souza João David de Neto 2 0000-0001-5647-2961 Calado Gustavo 3 0000-0002-9271-8233 Ayub-Ferreira Silvia Moreira 1 0000-0001-7603-2752 Bacal Fernando 1 0000-0003-4207-3809 Clausell Nadine 4 Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo São Paulo SP Brasil Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HCFMUSP),São Paulo, SP - Brasil Hospital do Coração de Messejana Fortaleza CE Brasil Hospital do Coração de Messejana, Fortaleza, CE - Brasil Pontifícia Universidade Católica de Campinas Campinas SP Brasil Pontifícia Universidade Católica de Campinas (PUCC), Campinas, SP - Brasil Hospital de Clínicas de Porto Alegre Porto Alegre RS Brasil Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brasil Correspondência: Nadine Clausell • Serviço de Cardiologia - Hospital de Clinicas de Porto Alegre - Rua Ramiro Barcelos, 2360. CEP 90035-903, Porto Alegre, RS – Brasil E-mail: nclausell07@gmail.com

Os autores Fabiana G. Marcondes-Braga e Jefferson Luís Vieira contribuíram igualmente para este trabalho como primeiro autores

Contribuição dos Autores

Concepção e desenho da pesquisa: Marcondes-Braga FG, Clausell N; Obtenção de dados e Redação do manuscrito: Marcondes-Braga FG, Vieira JL, Souza Neto JD, Calado G, Bacal F, Clausell N; Análise e interpretação dos dados: Marcondes-Braga FG, Vieira JL, Souza Neto JD, Calado G, Bacal F, Clausell N; Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Marcondes-Braga FG, Vieira JL, Ayub-Ferreira SM, Bacal F, Clausell N

Potencial Conflito de Interesses

Os autores declaram não haver conflito de interesses pertinentes.

 18 01 2021 12 2020 115 6 1193 1196 27 10 2020 27 10 2020 27 10 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Insuficiência Cardíaca Avançada Terapias Avançadas Transplante Cardíaco Suporte Circulatório Mecânico Cuidados Paliativos Definição

O termo insuficiência cardíaca (IC) avançada define um perfil de pacientes com sintomas graves, descompensações recorrentes e disfunção cardíaca progressiva a despeito da máxima terapêutica instituída.1 Pacientes que permanecem gravemente sintomáticos ou em classe funcional (CF) IV persistente podem ser candidatos a terapias avançadas, como transplante cardíaco (TC), assistência circulatória mecânica (ACM) ou cuidados paliativos. Vale ressaltar que algumas comorbidades, como as doenças pulmonar, renal e hepática, também são consideradas determinantes de pior prognóstico na IC crônica grave; na presença de alguma delas, os pacientes devem ser avaliados para possível indicação de terapias avançadas da IC.

Avaliação prognóstica

Existem diversos escores de risco na IC ( Figura 1 ); cada escore foi desenvolvido a partir de coortes específicas, incluindo aquelas com IC aguda, IC com fração de ejeção reduzida e/ou IC com fração de ejeção preservada. Dentre os escores CHARM ( Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity ), GISSI-HF ( Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure ), MAGGIC ( Meta-Analysis Global Group in Chronic Heart Failure ) e SHFM ( Seattle Heart Failure Model ), o MAGGIC parece apresentar o melhor poder discriminatório para mortalidade em um ano.2 Outros escores de risco propostos para ACM de curta e longa permanência, como o SAVE ( Survival After Veno-Arterial Extracorporeal Membrane Oxygenation ) e o Escore de Risco HeartMate II, respectivamente, são úteis na seleção de pacientes, embora restritos a dispositivos específicos. Recentemente, o escore PREDICT-HF ( Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure ) foi criado com dados do estudo PARADIGM-HF ( Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure ) buscando retratar o manejo contemporâneo da IC e aguarda validação prospectiva.3

– Escores de risco para insuficiência cardíaca. ADHERE CART: Acute Decompensated Heart Failure National Registry Classification and Regression Tree Analysis; ARIC: Atherosclerosis Risk in Communities; BCN bio-HF: Barcelona Bio-Heart Failure; CHARM: Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity; CORONA: Controlled Rosuvastatin Multinational; EFFECT: Enhanced Feedback for Effective Cardiac Treatment; ESCAPE: Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness; GISSI-HF: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure; GWTG-HF: Get With the Guidelines–Heart Failure; I-PRESERVE: Predicting death for severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation; IC: insuficiência cardíaca; ICFEP: insuficiência cardíaca com fração de ejeção preservada; ICFER: insuficiência cardíaca com fração de ejeção reduzida; MAGGIC: Meta-Analysis Global Group in Chronic Heart Failure; OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; OPTIMIZE-HF: Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure; PREDICT-HF: Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure; PROTECT HF: Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function.

Manejo da IC avançada no cenário agudo Manejo da congestão

O manejo da congestão continua sendo um desafio e exige a associação de diferentes estratégias: diurético endovenoso em doses elevadas; associação de diferentes classes de diuréticos; solução salina hipertônica; ultrafiltração e diálise peritoneal.4

Embora poucas inovações tenham surgido nesse campo, evidências recentes apontam um impacto da monitorização da congestão no prognóstico de pacientes com IC. Estudos de monitorização não-invasiva por telemonitoramento mostraram benefício sobre tempo de hospitalização e morte por todas as causas;5 resultados similares foram observados com o dispositivo implantável CardioMEMS™ HF System, que fornece monitorização direta da artéria pulmonar. O CardioMEMS™ mostrou-se eficaz e seguro em estudos de “vida real”, de custo-efetividade e de pós-comercialização,6 com achados semelhantes em centros europeus;7 trata-se de uma estratégia promissora com potencial a ser acrescentada à prática clínica.

 Manejo do choque cardiogênico

Recentemente, a Sociedade de Angiografia Cardiovascular e Intervenção (SCAI) propôs uma classificação do choque cardiogênico (CC) visando estabelecer uma linguagem comum para facilitar a identificação das diferentes fases do choque e planejar o manejo apropriado. As cinco fases dessa classificação permitem uma definição hemodinâmica simples, oportunizando maior discriminação dos estágios da classificação INTERMACS ( Interagency Registry for Mechanically Assisted Circulatory Support ).8 ( Figura 2 )

– Algoritmo de tratamento do paciente com insuficiência cardíaca avançada. *Classificação clínica de pacientes com insuficiência cardíaca avançada da Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Perfil 1: choque cardiogênico grave; Perfil 2: declínio progressivo, apesar do uso de inotrópico; Perfil 3: estável às custas de inotrópico endovenoso; Perfil 4: internações frequentes; Perfil 5: em casa, intolerante aos esforços; Perfil 6: limitação aos esforços; Perfil 7: NYHA III. **Classificação de choque cardiogênico proposta pela Society for Cardiovascular Angiography and Interventions (SCAI). Estágio A: “sob risco “ de choque; Estágio B: “início” do choque; Estágio C: choque “clássico”; Estágio D: choque em “deterioração”; Estágio E: “extremo”. Adaptado de Baran DA, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock. Catheter Cardiovasc Interv. 2019; 94: 29– 37. doi:10.1002/ccd.28329. <italic>CDI: cardiodesfibrilador implantável; CF: classe funcional; DACM: dispositivos de assistência circulatória mecânica; DAV: dispositivo de assistência ventricular implantável; ECMO-VA: circuito de oxigenação por membrana extracorpórea venoarterial; IC: insuficiência cardíaca; NYHA: New York Heart Association.</italic>

Nos últimos anos, estratégias focadas em atuação precoce no curso do CC, envolvendo avaliação multidisciplinar ( shock team ), têm destacado o papel do especialista em IC avançada coordenando as decisões terapêuticas com agilidade.9 As drogas vasoativas (DVAs) devem ser usadas de maneira a suportar minimamente o perfil hemodinâmico/metabólico, com a recomendação ainda vigente de uso de terapia combinada em baixa dose, com vistas a reduzir dano tecidual. Uma revisão sistemática recente sugere não haver superioridade entre as DVAs, mas sinaliza a importância da estratégia precoce focada em objetivo específico ( early goal-directed strategy ) buscando estabilização hemodinâmica dentro de tempos predeterminados.10 O escalonamento de drogas deve servir de alerta para a mudança de estratégia em direção ao uso de ACM para evitar a espiral de dano hemodinâmico/metabólico.

Os dispositivos de curta permanência fornecem suporte uni ou biventricular para situações clínicas, como CC, IC aguda, intervenção coronária de alto risco ou parada cardíaca.11 Os dispositivos mais utilizados são o balão intra-aórtico (BIA), o Impella®, o TandemHeart® e o circuito de oxigenação por membrana extracorpórea venoarterial (ECMO-VA).4 Embora esses dispositivos previnam a espiral de dano hemodinâmico/metabólico com sucesso, não há evidência de benefício sobre a mortalidade no CC.12 Além disso, estudos observacionais recentes sugeriram maiores taxas de eventos adversos e custos com o Impella® do que com o BIA.13 Apesar das limitações, o BIA ainda é o dispositivo de curta permanência mais utilizado no CC.

No campo da pesquisa clínica, o sistema de assistência ventricular intravascular NuPulseCV (iVAS) é um dispositivo minimamente invasivo que fornece contrapulsação ambulatorial de longa permanência por meio de um balão implantável inserido pela artéria subclávia e controlado por uma unidade externa.14 O iVAS supera muitas limitações do BIA, sendo uma opção promissora na IC avançada.

 Terapias avançadas

As características dos candidatos a terapias avançadas para IC, como TC e dispositivos de assistência ventricular implantáveis (DAV), mudaram muito ao longo dos anos, tornando o processo de seleção mais complexo. A seguir, abordaremos progressos e desafios no campo das terapias avançadas para IC.

Com relação ao TC, que é o tratamento de escolha para IC avançada,15 estratégias para aumentar o número de doadores efetivos tem sido aventadas; de fato, nos Estados Unidos, a UNOS recentemente mudou sua política de alocação de órgãos.16 Considerando que a sobrevida pós-transplante é pior com ECMO-VA pré-operatória do que com DAV, o novo sistema atribui maior prioridade aos pacientes com ACM de curta duração, enquanto aqueles com DAV ou inotrópicos são priorizados em um status inferior. No Brasil, mudanças semelhantes também estão sendo adotadas em alguns estados. Outra proposta recente é de substituir o peso corporal por massa cardíaca prevista ( predicted heart mass , PHM) como ferramenta ideal na avaliação da desproporção de tamanho entre doador-receptor. Estudos têm demonstrado a superioridade da PHM na predição de disfunção primária do enxerto e mortalidade pós-transplante comparada com peso, altura ou índice de massa corporal,17 além de predizer recuperação do acoplamento ventrículo-arterial pulmonar após TC.18 Por fim, o advento de antivirais de ação direta no tratamento da hepatite C crônica, como o Sofosbuvir, agora permite a alocação de órgãos de doadores infectados em receptores não infectados.19

No campo dos DAVs, a incorporação do HeartMate 3™ resultou em benefício clínico expressivo, com redução significativa nas taxas de arritmia ventricular, reinternações e eventos adversos de hemocompatibilidade (sangramento, trombose e acidente vascular cerebral).20 Futuros avanços devem envolver a miniaturização dos DAVs e a criação de um sistema totalmente intracorpóreo.

Finalmente, os cuidados paliativos têm se mostrado uma estratégia indispensável no manejo da IC avançada, assumindo protagonismo maior nos casos inelegíveis para TC ou DAVs. O uso intermitente de ultrafiltração, diálise peritoneal ou inotrópicos são estratégias possíveis em regime hospitalar, hospital-dia ou mesmo domiciliar visando ao alívio de sintomas.1

 Lista de Participantes do Heart Failure Summit Brazil 2020 / Departamento de Insuficiência Cardíaca - DEIC/SBC

Aguinaldo Freitas Junior, Andréia Biolo, Antonio Carlos Pereira Barretto, Antônio Lagoeiro Jorge, Bruno Biselli, Carlos Eduardo Montenegro, Denilson Campos de Albuquerque, Dirceu Rodrigues de Almeida, Edimar Alcides Bocchi, Edval Gomes dos Santos Júnior, Estêvão Lanna Figueiredo, Evandro Tinoco Mesquita, Fabiana G. Marcondes-Braga, Fábio Fernandes, Fabio Serra Silveira, Felix José Alvarez Ramires, Fernando Atik, Fernando Bacal, Flávio de Souza Brito, Germano Emilio Conceição Souza, Gustavo Calado de Aguiar Ribeiro, Humberto Villacorta Jr., Jefferson Luis Vieira, João David de Souza Neto, João Manoel Rossi Neto, José Albuquerque de Figueiredo Neto, Lídia Ana Zytynski Moura, Livia Adams Goldraich, Luís Beck-da- Silva, Luís Eduardo Paim Rohde, Luiz Claudio Danzmann, Manoel Fernandes Canesin, Marcelo Bittencourt, Marcelo Westerlund Montera, Marcely Gimenes Bonatto, Marcus Vinicius Simões, Maria da Consolação Vieira Moreira, Miguel Morita Fernandes da Silva, Monica Samuel Avila, Mucio Tavares de Oliveira Junior, Nadine Clausell, Odilson Marcos Silvestre, Otavio Rizzi Coelho Filho, Pedro Vellosa Schwartzmann, Reinaldo Bulgarelli Bestetti, Ricardo Mourilhe Rocha, Sabrina Bernadez Pereira, Salvador Rassi, Sandrigo Mangini, Silvia Marinho Martins, Silvia Moreira Ayub Ferreira, Victor Sarli Issa.

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Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure. JAMA Cardiol. 2020. Simpson J Jhund PS Lund LH Padmanabhan S Claggett BL Shen L et al Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure JAMA Cardiol 2020 4. Rohde LEP, Montera MW, Bocchi EA, Clausell NO, Albuquerque DCd, Rassi S, et al. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arquivos Brasileiros de Cardiologia. 2018;111:436-539. Rohde LEP Montera MW Bocchi EA Clausell NO DCd Albuquerque Rassi S et al Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda Arquivos Brasileiros de Cardiologia 2018 111 436 539 5. Koehler F, Koehler K, Deckwart O, Prescher S, Wegscheider K, Kirwan BA, et al. Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial. Lancet. 2018;392(10152):1047-57. Koehler F Koehler K Deckwart O Prescher S Wegscheider K Kirwan BA et al Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial Lancet 2018 392 10152 1047 1057 6. Shavelle DM, Desai AS, Abraham WT, Bourge RC, Raval N, Rathman LD, et al. Lower Rates of Heart Failure and All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy for Ambulatory Heart Failure: One-Year Outcomes From the CardioMEMS Post-Approval Study. Circ Heart Fail. 2020;13(8):e006863. Shavelle DM Desai AS Abraham WT Bourge RC Raval N Rathman LD et al Lower Rates of Heart Failure and All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy for Ambulatory Heart Failure: One-Year Outcomes From the CardioMEMS Post-Approval Study Circ Heart Fail 2020 13 8 e006863 7. Angermann CE, Assmus B, Anker SD, Asselbergs FW, Brachmann J, Brett ME, et al. Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Eur J Heart Fail. 2020. Angermann CE Assmus B Anker SD Asselbergs FW Brachmann J Brett ME et al Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) Eur J Heart Fail 2020 8. Baran DA, Grines CL, Bailey S, Burkhoff D, Hall SA, Henry TD, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheter Cardiovasc Interv. 2019;94(1):29-37. Baran DA Grines CL Bailey S Burkhoff D Hall SA Henry TD et al SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019 Catheter Cardiovasc Interv 2019 94 1 29 37 9. Chioncel O, Parissis J, Mebazaa A, Thiele H, Desch S, Bauersachs J, et al. Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020. Chioncel O Parissis J Mebazaa A Thiele H Desch S Bauersachs J et al Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology Eur J Heart Fail 2020 10. Schumann J, Henrich EC, Strobl H, Prondzinsky R, Weiche S, Thiele H, et al. Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev. 2018;1:CD009669. Schumann J Henrich EC Strobl H Prondzinsky R Weiche S Thiele H et al Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome Cochrane Database Syst Rev 2018 1 CD009669 11. Vieira J, Ventura HO, Mehra MR. Mechanical circulatory support devices in advanced heart failure: 2020 and beyond. Prog Cardiovasc Dis. 2020. Vieira J Ventura HO Mehra MR Mechanical circulatory support devices in advanced heart failure: 2020 and beyond Prog Cardiovasc Dis 2020 12. Ni hIci T, Boardman HM, Baig K, Stafford JL, Cernei C, Bodger O, et al. Mechanical assist devices for acute cardiogenic shock. Cochrane Database Syst Rev. 2020;6:CD013002. Ni hIci T Boardman HM Baig K Stafford JL Cernei C Bodger O et al Mechanical assist devices for acute cardiogenic shock Cochrane Database Syst Rev 2020 6 CD013002 13. Amin AP, Spertus JA, Curtis JP, Desai N, Masoudi FA, Bach RG, et al. The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support. Circulation. 2020;141(4):273-84. Amin AP Spertus JA Curtis JP Desai N Masoudi FA Bach RG et al The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support Circulation 2020 141 4 273 284 14. Uriel N, Jeevanandam V, Imamura T, Onsager D, Song T, Ota T, et al. Clinical Outcomes and Quality of Life With an Ambulatory Counterpulsation Pump in Advanced Heart Failure Patients: Results of the Multicenter Feasibility Trial. Circ Heart Fail. 2020;13(4):e006666. Uriel N Jeevanandam V Imamura T Onsager D Song T Ota T et al Clinical Outcomes and Quality of Life With an Ambulatory Counterpulsation Pump in Advanced Heart Failure Patients: Results of the Multicenter Feasibility Trial Circ Heart Fail 2020 13 4 e006666 15. Bacal F, Marcondes-Braga FG, Rohde LEP, Xavier Júnior JL, Brito FdS, Moura LAZ, et al. 3ª Diretriz Brasileira de Transplante Cardíaco. Arquivos Brasileiros de Cardiologia. 2018;111:230-89. Bacal F Marcondes-Braga FG Rohde LEP Xavier JL Júnior FdS Brito Moura LAZ et al 3ª Diretriz Brasileira de Transplante Cardíaco Arquivos Brasileiros de Cardiologia 2018 111 230 289 16. Jawitz OK, Fudim M, Raman V, Bryner BS, DeVore AD, Mentz RJ, et al. Reassessing Recipient Mortality Under the New Heart Allocation System: An Updated UNOS Registry Analysis. JACC Heart Fail. 2020;8(7):548-56. Jawitz OK Fudim M Raman V Bryner BS DeVore AD Mentz RJ et al Reassessing Recipient Mortality Under the New Heart Allocation System: An Updated UNOS Registry Analysis JACC Heart Fail 2020 8 7 548 556 17. Kransdorf EP, Kittleson MM, Benck LR, Patel JK, Chung JS, Esmailian F, et al. Predicted heart mass is the optimal metric for size match in heart transplantation. J Heart Lung Transplant. 2019;38(2):156-65. Kransdorf EP Kittleson MM Benck LR Patel JK Chung JS Esmailian F et al Predicted heart mass is the optimal metric for size match in heart transplantation J Heart Lung Transplant 2019 38 2 156 165 18. Nazario RA, Goldraich LA, Hastenteufel LCT, Santos ABS, Carrion L, Clausell N. Donor–recipient predicted heart mass ratio and right ventricular– pulmonary arterial coupling in heart transplant. Eur J Cardio-Thoracic Surgery. DOi 10.1093/ejcts/ezaa391. Nazario RA Goldraich LA Hastenteufel LCT Santos ABS Carrion L Clausell N Donor–recipient predicted heart mass ratio and right ventricular– pulmonary arterial coupling in heart transplant Eur J Cardio-Thoracic Surgery 10.1093/ejcts/ezaa391. 19. Aslam S, Grossi P, Schlendorf KH, Holm AM, Woolley AE, Blumberg E, et al. Utilization of hepatitis C virus-infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement. J Heart Lung Transplant. 2020;39(5):418-32. Aslam S Grossi P Schlendorf KH Holm AM Woolley AE Blumberg E et al Utilization of hepatitis C virus-infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement J Heart Lung Transplant 2020 39 5 418 432 20. Mehra MR, Uriel N, Naka Y, Cleveland JC, Yuzefpolskaya M, Salerno CT, et al. A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report. N Engl J Med. 2019;380(17):1618-27. Mehra MR Uriel N Naka Y Cleveland JC Yuzefpolskaya M Salerno CT et al A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report N Engl J Med 2019 380 17 1618 1627

Carta científica referente ao Heart Failure Summit Brazil 2020 – Departamento de Insuficiência Cardíaca da Sociedade Brasileira de Cardiologia (DEIC/SBC)

Vinculação Acadêmica

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

Fontes de Financiamento .O presente estudo não contou com fontes de financiamento externas.

 Research Letter Emerging Topics in Heart Failure: Contemporaneous Management of Advanced Heart Failure 0000-0002-2533-5638 Marcondes-Braga Fabiana G. 1 * 0000-0001-5982-8847 Vieira Jefferson L. 2 * 0000-0002-6767-4785 Souza João David de Neto 2 0000-0001-5647-2961 Calado Gustavo 3 0000-0002-9271-8233 Ayub-Ferreira Silvia Moreira 1 0000-0001-7603-2752 Bacal Fernando 1 0000-0003-4207-3809 Clausell Nadine 4 Brazil Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HCFMUSP), São Paulo, SP - Brazil Brazil Hospital do Coração de Messejana, Fortaleza, CE - Brazil Brazil Pontifícia Universidade Católica de Campinas (PUCC), Campinas, SP - Brazil Brazil Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil Mailing Address: Nadine Clausell • Serviço de Cardiologia - Hospital de Clinicas de Porto Alegre - Rua Ramiro Barcelos, 2360. Postal Code 90035-903, Porto Alegre, RS – Brazil E-mail: nclausell07@gmail.com

The authors Fabiana G. Marcondes-Braga e Jefferson Luís Vieira contributed equally to this work and are co-first authors

Author Contributions

Conception and design of the research: Marcondes-Braga FG, Clausell N; Data acquisition and Writing of the manuscript: Marcondes-Braga FG, Vieira JL, Souza Neto JD, Calado G, Bacal F, Clausell N; Analysis and interpretation of the data: Marcondes-Braga FG, Vieira JL, Souza Neto JD, Calado G, Bacal F, Clausell N; Critical revision of the manuscript for intellectual content: Marcondes-Braga FG, Vieira JL, Ayub-Ferreira SM, Bacal F, Clausell N.

Potential Conflict of Interest

The authors report no conflict of interest concerning the materials and methods used in this study or the findings specified in this paper.

 Advanced Heart Failure Advanced Therapies Heart Transplant Mechanical Circulatory Support Paliative Care Definition

Advanced heart failure (HF) is a condition characterized by persistent severe HF symptoms, frequent episodes of decompensation, and progressive cardiac dysfunction despite optimal evidence-based treatment.1 These patients may be candidates for advanced therapies, such as heart transplantation (HT), mechanical circulatory support (MCS), and/or palliative care. It should be pointed out that some comorbidities, including pulmonary disease and liver and kidney dysfunction, are now included as possible major determinants of poor prognosis and should be considered during patient evaluation for advanced HF therapies.

Prognosis and risk scores

There are several risk scores for predicting outcomes in HF populations ( Figure 1 ); each model has been developed for use in specific cohorts, including those with acute HF, HF with reduced ejection fraction, and/or HF with preserved ejection fraction. The MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score seems to have better accuracy than the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure), and SHFM (Seattle Heart Failure Model) scores for predicting 1-year mortality.2 Other risk stratification tools for short- and long-term MCS, such as the SAVE (Survival After Veno-Arterial Extracorporeal Membrane Oxygenation) and HeartMate II risk scores, respectively, may be helpful in patient selection, but are restricted to specific devices. Recently, the PREDICT-HF (Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure) score used data from the PARADIGM-HF (Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure) trial to develop a prognostic model for patients receiving contemporary evidence-based therapies for HF. It has yet to be validated.3

– Risk scores for heart failure. ADHERE CART: Acute Decompensated Heart Failure National Registry Classification and Regression Tree Analysis; ARIC: Atherosclerosis Risk in Communities; BCN bio-HF: Barcelona Bio-Heart Failure; CHARM: Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity; CORONA: Controlled Rosuvastatin Multinational; EFFECT: Enhanced Feedback for Effective Cardiac Treatment; ESCAPE: Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness; GISSI-HF: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure; GWTG-HF: Get With the Guidelines–Heart Failure; HF: heart failure; HFPEF: heart failure with preserved ejection fraction; HFREF: heart failure with reduced ejection fraction; I-PRESERVE: Predicting death for severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation; MAGGIC: Meta-Analysis Global Group in Chronic Heart Failure; OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; OPTIMIZE-HF: Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure; PREDICT-HF: Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure; PROTECT HF: Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function.

Treatment of advanced HF in the acute setting Congestion management

Volume overload management remains clinically challenging and may require a combination of several strategies, including higher doses of intravenous loop diuretics, combined diuretic therapy, hypertonic saline, ultrafiltration and peritoneal dialysis.4

Although there has been relatively little innovation in this field, recent evidence suggests that remote patient HF monitoring may have potential benefits. Studies of non-invasive home telemonitoring have shown improvements in hospital length of stay and all-cause mortality.5 Similar results were observed with the implantable CardioMEMS™ HF System, which provides direct pulmonary artery pressure monitoring. CardioMEMS™ proved safe and effective in real-life and post-marketing studies and was also found cost-effective,6 with reproducible findings across European centers.7 This promising strategy has translation potential for clinical practice.

 Cardiogenic shock

Recently, the Society for Cardiovascular Angiography and Intervention (SCAI) has proposed a new consensus statement on the classification of cardiogenic shock (CS) to provide collective language for the different stages and appropriate management of CS. The 5-stage classification allows for a simple hemodynamic definition, providing granularity for the INTERMACS classification.8 ( Figure 2 )

– Decision-making algorithm for patients with advanced heart failure. * Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles of advanced heart failure. Profile 1: critical cardiogenic shock; Profile 2: progressive decline on inotropic support; Profile 3: stable but IV inotrope dependent; Profile 4: resting symptoms home on oral therapy; Profile 5: exertion intolerant; Profile 6: exertion limited Profile 7: advanced NYHA Class III symptoms. **Cardiogenic shock classification scheme proposed by the Society for Cardiovascular Angiography and Intervention (SCAI). Stage A is “at risk” for cardiogenic shock; stage B is “beginning” shock; stage C is “classic” cardiogenic shock; stage D is “deteriorating”; stage E is “extremis”. Baran, DA, Grines, CL, Bailey, S, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock. Catheter Cardiovasc Interv. 2019; 94: 29– 37. dooi:10.1002/ccd.28329. IABP: intra-aortic balloon pump; ICD: implantable cardioverter-defibrillator; IV: intravenous; LVAD: left ventricular assist device; MCS: mechanical circulatory support; VA-ECMO: veno-arterial extracorporeal membrane oxygenation; NYHA: New York Heart Association.

In recent years, strategies associated with early intervention in CS, including multidisciplinary team-based management (Shock Team), have highlighted the role of advanced HF specialists in coordinating timely therapeutic decisions.9 Vasoactive agents are often used to provide hemodynamic and metabolic support, but low-dose combination therapies should be prioritized to avoid further tissue damage. A recent systematic review found no significant difference between vasoactive agents but stressed the importance of early goal-directed therapy, including early hemodynamic stabilization within predefined timelines.10 Escalating doses of vasoactive agents should prompt consideration of MCS candidacy to prevent irreversible hemodynamic/metabolic derangements of the CS spiral.

Short-term MCS devices are designed to provide uni- or biventricular support for a wide range of conditions, including CS, acute HF, high-risk percutaneous coronary intervention, and cardiac arrest.11 The most commonly used percutaneous assist systems include intra-aortic balloon pumps (IABP), Impella®, TandemHeart® and veno-arterial extracorporeal membrane oxygenation (VA-ECMO).4 Despite the preemptive improvement in hemodynamics with these devices, randomized trials have not demonstrated significant reduction in CS mortality.12 Moreover, recent observational studies hinted at higher rates of adverse events and costs with Impella than IABP.13 Despite certain limitations, the IABP remains the most widely used MCS device in CS.

In clinical research, the NuPulseCV intravascular ventricular assist system (iVAS) is a novel minimally invasive device that provides long-term ambulatory counterpulsation via a durable pump placed through the subclavian artery and controlled by an external drive unit.14 The iVAS overcomes many limitations of the IABP and may be a promising option for patients with advanced HF.

 Advanced therapies for HF

The characteristics of candidates for advanced HF therapies, such as HT and left ventricular assist device (LVAD), have changed dramatically over the years, leading to a more complex selection process. Below, we highlight some advances and challenges in the field.

Regarding HT, the treatment of choice for patients with advanced HF,15 strategies to increase the donor organ pool have been suggested; in fact, in the United States, the United Network for Organ Sharing (UNOS) recently changed its donor organ allocation policy.16 Given that post-transplant survival is worse with pre-operative VA-ECMO than LVAD, the new system assigns high priority to patients supported with short-tem MCS devices, while stable patients supported with LVAD or inotropes alone are assigned a lower status. In Brazil, some states are making similar changes. Another recent suggestion is the use of predicted heart mass (PHM), rather than body weight as an ideal metric for donor-recipient size matching. Studies have shown that PHM mismatch is a better predictor of primary graft dysfunction and 1-year mortality after HT than weight, height, or body mass index mismatch,17 and it also predicts right ventricular-pulmonary arterial coupling after HT.18 Finally, the advent of direct-acting antiviral agents (e.g. sofosbuvir) for treating hepatitis C virus infection has enabled allocation of organs from hepatitis C virus-infected donors to uninfected recipients.19

In the field of LVAD, the HeartMate 3™ has been associated with meaningful clinical benefit, with a significant reduction in the rates of ventricular arrhythmias, readmissions, and hemocompatibility-related adverse events (bleeding, thrombosis and stroke).20 Further technological advances are needed, such as the miniaturization of devices and the development of a truly internalized power system.

Finally, palliative care has proven indispensable in advanced HF management, playing a central role in cases that are not considered eligible for HT or LVAD. Intermittent use of ultrafiltration, peritoneal dialysis, or inotropic infusions can be considered in the hospital, the hospice, or even at home to control symptoms.1

 List of participants of the Heart Failure Summit Brazil 2020 / Heart Failure Department - Brazilian Society of Cardiology

Aguinaldo Freitas Junior, Andréia Biolo, Antonio Carlos Pereira Barretto, Antônio Lagoeiro Jorge, Bruno Biselli, Carlos Eduardo Montenegro, Denilson Campos de Albuquerque, Dirceu Rodrigues de Almeida, Edimar Alcides Bocchi, Edval Gomes dos Santos Júnior, Estêvão Lanna Figueiredo, Evandro Tinoco Mesquita, Fabiana G. Marcondes-Braga, Fábio Fernandes, Fabio Serra Silveira, Felix José Alvarez Ramires, Fernando Atik, Fernando Bacal, Flávio de Souza Brito, Germano Emilio Conceição Souza, Gustavo Calado de Aguiar Ribeiro, Humberto Villacorta Jr., Jefferson Luis Vieira, João David de Souza Neto, João Manoel Rossi Neto, José Albuquerque de Figueiredo Neto, Lídia Ana Zytynski Moura, Livia Adams Goldraich, Luís Beck-da- Silva, Luís Eduardo Paim Rohde, Luiz Claudio Danzmann, Manoel Fernandes Canesin, Marcelo Bittencourt, Marcelo Westerlund Montera, Marcely Gimenes Bonatto, Marcus Vinicius Simões, Maria da Consolação Vieira Moreira, Miguel Morita Fernandes da Silva, Monica Samuel Avila, Mucio Tavares de Oliveira Junior, Nadine Clausell, Odilson Marcos Silvestre, Otavio Rizzi Coelho Filho, Pedro Vellosa Schwartzmann, Reinaldo Bulgarelli Bestetti, Ricardo Mourilhe Rocha, Sabrina Bernadez Pereira, Salvador Rassi, Sandrigo Mangini, Silvia Marinho Martins, Silvia Moreira Ayub Ferreira, Victor Sarli Issa.

Research letter related to Heart Failure Summit Brazil 2020 / Heart Failure Department - Brazilian Society of Cardiology

Study Association

This study is not associated with any thesis or dissertation.

Sources of Funding .There was no external funding source for this study.