COVID-19 in heart transplant patients: Case reports from Brazil

ABSTRACT: The COVID-19 pandemic continues, with a late hyperinflammatory phase. The immunosuppressive therapy used in heart transplant patients, in theory, could reduce inflammation thus benefitting patients with COVID-19. So far, however, there is still very little literature on this subject. METHODS: This is a single-center retrospective study. We described laboratory parameters and clinical outcomes from 11 heart transplant patients with COVID-19 assisted at Dante Pazzanese Institute of Cardiology between March and July 2020. RESULTS: Patients with ages between 35 to 79 years, and heart transplantation occurred from 3 to 264 months. The main comorbidities were diabetes mellitus (9/11; 81.8%), hypertension (10/11; 90.9%), and chronic renal disease (6/11; 54.5%). Cyclosporine A was used in 10 (90.9%) patients, mycophenolate mofetil in 9 (81.8%), and mTOR inhibitor in 5 (45.5%). Fever and cough were observed in 8 (72.7%) patients, and dyspnea and gastrointestinal symptoms in 5 (45.5%). Lymphopenia was observed in 10 (90.9%) and thrombocytopenia in 5 (45.5%). The higher level of troponin associated with chest tomography above 50% infiltrates of ground-glass opacity (GGO) was observed in those with the worst outcomes. Nine patients needed intensive care, and hospital stay ranged from 4 to 21 days, with 2 (18.2%) patients requiring vasopressor drugs and mechanical ventilation, and three patients (27.3%) dying due to COVID-19 complications. CONCLUSION: Heart transplant patients had the similar symptoms and outcomes as general population; immunosuppressive therapy seems not to have protected them. Patients who presented higher levels of troponin and D-dimer, associated to greater GGO pulmonary infiltrates had worse outcomes. More studies with larger cohorts may clarify immunosuppressive effects on COVID-19 outcomes.

Covid-19 em Receptores de Transplante de Coração em São Paulo: Uma Série de Casos / Covid-19 in Heart Transplant Recipients in São Paulo: A Case Series

Introdução A doença causada pelo novo coronavírus (Covid-19), o SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), foi declarada uma pandemia pela Organização Mundial da Saúde (OMS) em 11 de março de 2020.1 Por analogia a outras infecções respiratórias, principalmente com base na pandemia de 2009 do vírus influenza H1N1,2,3 esperava-se um aumento de casos de pneumonia e progressão para choque séptico com síndrome do desconforto respiratório agudo entre os receptores de transplante de órgão sólido com Covid-19 em comparação com a população não transplantada.4 Porém, a imunossupressão no transplante poderia teoricamente revogar a síndrome hiperinflamatória secundária à tempestade de citocinas, responsável pela maioria das mortes pela Covid-19.5,6 Dados sobre a imunossupressão que potencialmente poderiam levar a apresentações clínicas atípicas ou aumentar o risco de eventos adversos na presença de Covid-19 são conflitantes.7,8 Relatamos nossa experiência com transplantados de coração (TxC) diagnosticados com Covid-19 em uma instituição com programa de TxC desde 1992 em São Paulo, Brasil.

Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long -term heart transplantation

INTRODUCTION: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently verify the way in which it affects the outcome of the allograft. METHODS: In this retrospective study, 300 archives paraffin embedded endomyocardial biopsies from 63 heart allograft recipients were assessed. Cellular rejection and vasculitis were diagnosed through histological analysis, and antibody mediated rejection was performed with immunohistochemical C4d staining. The transcripts of ICAM, VCAM, VEGF, CCL2, IFNG, TGFB, TNF, ADIPOR1, and ADIPOR2 genes were examined through quantitative real -time polymerase chain reaction using B2M for normalization. RESULTS: We observed a higher prevalence of severe vasculitis in the early period of post transplant, and recovery was observed to take place around one year post the transplant. Additionally, vasculitis was found to be directly associated with acute cellular rejection and antibody -mediated rejection. The intense C4d capillary positivity predicts higher long -term cardiovascular disease mortality. In comparison to the vasculitis free group, the group with severe vasculitis displayed reduced left ventricular ejection fraction, and an up -regulation of VCAM and IFNG associated to the down -regulation of VEGF, ADIPOR1, and ADIPOR2. CONCLUSION: The vasculitis associated with the presence of C4d and the change of intragraft gene expression profile may contribute to poor allograft outcomes.

Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda

INTRODUÇÃO: A organização de uma diretriz clínica é tarefa complexa, que necessariamente deve envolver planejamento prévio, coordenação apropriada, revisão aprofundada da literatura científica, com envolvimento de múltiplos profissionais da área da saúde com notório reconhecimento. A elaboração de uma diretriz clínica de insuficiência cardíaca é ainda mais difícil, por conta da complexidade da síndrome, da amplitude das evidências científicas que permeiam o tópico e do grande impacto que as recomendações propostas têm sobre os pacientes, a comunidade médica e a sociedade como um todo. No presente documento, o Departamento de Insuficiência Cardíaca (DEIC) da Sociedade Brasileira de Cardiologia (SBC) apresenta uma revisão e uma atualização detalhadas de sua Diretriz de Insuficiência Cardíaca Crônica. Os trabalhos se iniciaram em setembro de 2017, com a definição da Comissão Coordenadora, que estabeleceu prioridades, dividiu grupos de trabalho e definiu o cronograma das atividades. Os grupos de trabalho, compostos por três a cinco participantes, deram início a intensas discussões virtuais, que culminaram com a redação de tabelas preliminares, sendo posteriormente amplamente divulgadas e revisadas pelos 34 participantes da diretriz. As discussões finais foram realizadas em reunião presencial em março de 2018, com a participação de todos os colaboradores, nas quais as principais recomendações foram votadas individualmente. As decisões quanto à classe das recomendações foram definidas por maioria plena (concordância de mais de 75% dos participantes). As recomendações terapêuticas propostas no presente documento se embasam nas evidências científicas mais atuais, considerando não apenas aspectos de eficácia clínica demonstrados em grandes ensaios clínicos, mas também contextualizando seus achados para o cenário de saúde brasileiro e incorporando aspectos econômicos definidos em estudos de custo-efetividade. Buscamos sumarizar as principais recomendações em fluxogramas e algoritmos de fácil entendimento e grande aplicabilidade clínica, propondo abordagens para o diagnóstico e o tratamento da síndrome em formato moderno, atualizado e didático. Na última seção da diretriz, o que não podemos deixar de fazer e o que não devemos fazer no diagnóstico, prevenção e tratamento da síndrome foram sumarizados em apenas três tabelas. Em especial, destacamos seis intervenções que foram consideradas de alta prioridade, por apresentarem relações de custo-efetividade altamente favoráveis. Sobretudo, esperamos que a publicação deste documento possa auxiliar na redução das elevadas taxas de mortalidade que ainda estão associadas com a insuficiência cardíaca no Brasil, além de minimizar o cruel impacto que a síndrome causa na qualidade de vida de nossos pacientes. Acreditamos que esta diretriz apresenta, de forma hierarquizada, a linha mestra que deve nortear a prática clínica em diferentes níveis de atenção à saúde, permitindo reconhecimento precoce de pacientes em risco, diagnóstico apropriado e implementação de tratamento de forma escalonada, eficaz e coerente com nossa realidade.

Summary of the II Brazilian Guideline update on Acute Heart Failure 2009/2011.

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Risk factors for myocardial infarction in Brazil.

BACKGROUND: Approximately three-quarters of cardiovascular disease deaths in the world come from developing countries, and acute myocardial infarction (AMI) is an important cause of death. Brazil is one of the largest countries in Latin America and the contemporary evaluation of risk factors for AMI is crucial for a more efficacious disease management. METHODS: The Acute Myocardial Infarction Risk Factor Assessment in Brazil (AFIRMAR) study is a case-control, hospital-based study involving 104 hospitals in 51 cities in Brazil, designed to evaluate risk factors for a first ST-segment elevation AMI. RESULTS: A total of 1279 pairs, matched by age (+/- 5 years) and sex, were enrolled. The conditional multivariable analysis of 33 variables showed the following independent risk factors for AMI: > or =5 cigarettes per day (odds ratio [OR] 4.90, P <.00001); glucose > or =126 mg/dL (OR 2.82, P <.00001); waist/hip ratio > or =0.94 (OR 2.45, P <.00001); family history of CAD (OR 2.29, P <.00001), low-density lipoprotein-cholesterol 100 to 120 mg/dL (OR 2.10, P <.00001); reported hypertension (OR 2.09, P <.00001); <5 cigarettes per day (OR 2.07, P =.0171); low-density lipoprotein-cholesterol >120 mg/dL (OR 1.75, P <.00001); reported diabetes mellitus (OR 1.70, P =.0069); waist/hip ratio 0.90 to 0.93 (OR 1.52, P =.0212); alcohol intake (up to 2 days/week) (OR 0.75, P <.0309); alcohol intake (3-7 days/week) (OR 0.60, P =.0085); family income R$600 to R$1200 and college education (OR 2.92, P =.0499); family income >R$1200 and college education (OR 0.68, P = 0.0239) CONCLUSIONS: The independent risk factors for AMI in Brazil showed a conventional distribution pattern (smoking, diabetes mellitus and central obesity among others) with different strengths of association; most of them being preventable by implementation of adequate policies.