Perfis clínicos e genéticos de pacientes com amiloidose transtiretina hereditária e do tipo selvagem: o registro de amiloidose cardíaca transtiretina no Estado de São Paulo, Brasil (REACT-SP) / Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the transthyretin cardiac amyloidosis registry in the State of São Paulo, Brazil (REACT-SP)

INTRODUÇÃO: A amiloidose transtiretina (ATTR) é uma doença multissistêmica causada pela deposição de proteína fibrilar em órgãos e tecidos. Os genótipos e fenótipos da ATTR são altamente heterogêneos. MÉTODOS: Apresentamos dados sobre sinais e sintomas físicos, avaliações cardíacas e neurológicas, e genética em pacientes incluídos no Registro de Amiloidose Cardíaca Transtiretina no Estado de São Paulo (REACT-SP), Brasil. RESULTADOS: Foram incluídos 644 pacientes, sendo 505 com a forma variante (ATTRv) e 139 com a forma selvagem (ATTRwt). Dezesseis mutações diferentes foram detectadas, sendo as mais comuns Val50Met (48,3%) e V142Ile (40,8%). No geral, mais da metade dos pacientes apresentou envolvimento cardíaco, e a diferença nessa proporção entre os grupos ATTRv e ATTRwt foi significativa (43,9 vs. 89,9%; p<0,001). O fenótipo neurológico também diferiu entre ATTRv e ATTRwt (56,8 vs. 31,7%; p<0,001). O fenótipo misto foi encontrado em 25,6% da população, sem diferença significativa entre as formas de amiloidose. Um grupo de pacientes permaneceu assintomático (10,4%), com uma proporção menor de pacientes assintomáticos no grupo ATTRwt. CONCLUSÕES: Este estudo detalha o espectro clínico e genético de pacientes com ATTR em São Paulo, Brasil. Esta análise preliminar destaca a considerável heterogeneidade fenotípica das manifestações neurológicas e cardíacas em pacientes com ATTR variante e ATTR do tipo selvagem.

Registry of transthyretin amyloidosis in the state of São Paulo (REACT-SP) / Registro em amiloidose transtirretina do estado de São Paulo (REACT-SP)

BACKGROUND: Amyloidosis is a systemic disease that involves multiple organs, characterized by the deposition of amyloid fibrils. Knowledge regarding the epidemiological, clinical, and genetic profile of the population affected by amyloidosis throughout the country is of fundamental importance for establishing diagnostic and therapeutic strategies. OBJECTIVE: To evaluate the epidemiological, clinical, laboratory, imaging, and treatment variables of patients with TTR cardiac amyloidosis. MATERIALS AND METHODS: A multicenter, retrospective, prospective, and observational study based on collection of data on the natural history of patients with TTR amyloidosis, followed in the state of São Paulo. RESULTS: To make it possible to map the regional distribution of the disease, increasing knowledge about the disease among clinicians and specialists in different areas. To evaluate patients with hereditary and wild-type TTR amyloidosis, in addition to following individuals with positive genotype and negative phenotype.

FUNDAMENTO: A amiloidose é uma doença sistêmica com envolvimento de diversos órgãos caracterizada pela deposição de fibrilas amiloides. O conhecimento do perfil epidemiológico, clínico e genético da população acometida por amiloidose no país é de fundamental importância em estratégias para estabelecer o diagnóstico bem como as estratégias terapêuticas. OBJETIVO: Avaliar as variáveis epidemiológicas, clínicas, laboratoriais, de imagem e tratamento dos pacientes com amiloidose cardíaca por transtirretina (TTR). MATERIAL E MÉTODOS: Estudo multicêntrico, retrospectivo, prospectivo e observacional baseado na coleta de dados da história natural dos pacientes com amiloidose TTR seguidos no estado de São Paulo. RESULTADOS: Permitir um mapa da distribuição regional da doença, aumentando o conhecimento da doença entre clínicos e especialistas nas diversas especialidades. Avaliar pacientes com amiloidose por TTR formas familiar e selvagem além de acompanhar indivíduos com genótipo positivo e fenótipo negativo. CONCLUSÃO: As informações coletadas poderão evidenciar uma maior conscientização da doença, criação de novos fluxogramas diagnósticos e de tratamento com impacto direto no conhecimento da história natural da doença e prognóstico dos pacientes.

Recommendations for the management of cardiovascular risk in patients with chronic myeloid leukemia on tyrosine kinase inhibitors: risk assessment, stratification, treatment and monitoring

ABSTRACT This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation.In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low).Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion.The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.

Implications for clinical practice from a multicenter survey of heart failure management centers

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Sociedade brasileira de cardiologia a carta das mulheres / Brazilian society of cardiology the women's letter

O objetivo primordial desse documento é estimular a melhoria das condições de saúde das mulheres brasileiras, com foco na doença cardiovascular (DCV). A DCV é responsável por 17,5 milhões de mortes prematuras/ano no mundo, com previsão de aumento para 23 milhões em 2030. As DCV são responsáveis por um terço de todas as mortes no Brasil, com semelhança entre homens e mulheres após a menopausa. Esses dados revestem-se de maior importância quando consideramos que 80% das mortes prematura. (AU)

Left Ventricular Regional Wall Motion Abnormality is a Strong Predictor of Cardiotoxicity in Breast Cancer Patients Undergoing Chemotherapy / Alteração Contrátil Segmentar Ventricular Esquerda é Preditor Independente de Cardiotoxicidade em Pacientes com Câncer de Mama em Tratamento Quimioterápico

Abstract Background: Chemotherapeutic agents of anthracyclines class and humanized monoclonal antibodies are effective treatments for breast cancer, however, they present a potential risk of cardiotoxicity. Several predictors have been recognized as predictors in the development of cardiac toxicity, and the evaluation of left ventricular segmental wall motion abnormalities (LVSWMA) has not been studied. Objective: To analyze prospectively the role of LVSWMA among echocardiographic parameters in the prediction of development of cardiotoxicity in breast cancer patients undergoing treatment with chemotherapy. Methods: Prospective cohort of patients diagnosed with breast cancer and in chemotherapy treatment with potential cardiotoxicity medications including doxorubicin and trastuzumab. Transthoracic echocardiograms including speckle tracking strain echocardiography were performed at standard times before, during and after the treatment to assess the presence (or lack thereof) of cardiotoxicity. Cardiotoxicity was defined by a 10% decrease in the left ventricular ejection fraction, on at least one echocardiogram. Multivariate logistic regression models were used to verify the predictors related to the occurrence of cardiotoxicity over time. Results: Of the 112 patients selected (mean age 51,3 ± 12,9 years), 18 participants (16.1%) had cardiotoxicity. In the multivariate analysis using the logistic regression model, those with LVWMA (OR = 6.25 [CI 95%: 1.03; 37.95], p < 0,05), LV systolic dimension (1.34 [CI 95%: 1.01; 1.79], p < 0,05) and global longitudinal strain by speckle tracking (1.48 [CI 95%: 1.02; 2.12], p < 0,05) were strongly associated with cardiotoxicity. Conclusion: In the present study, we showed that LVWMA, in addition to global longitudinal strains, were strong predictors of cardiotoxicity and could be useful in the risk stratification of these patients.

Resumo Fundamento: Os agentes quimioterápicos da classe das antraciclinas e dos anticorpos monoclonais humanizados são tratamentos eficazes para o câncer de mama, entretanto, apresentam alto risco de cardiotoxicidade. Diversos parâmetros têm sido reconhecidos como preditores no desenvolvimento de toxicidade cardíaca, sendo que a avaliação da alteração contrátil segmentar ventricular esquerda (ACSVE) ainda não foi estudada. Objetivo: Analisar a associação entre o surgimento de ACSVE e o desenvolvimento de cardiotoxicidade em pacientes com câncer de mama em tratamento com quimioterapia. Métodos: Coorte prospectiva de pacientes diagnosticados com câncer de mama e em tratamento quimioterápico com doxorrubicina e/ou trastuzumab. Foram realizados ecocardiogramas transtorácicos antes, durante e depois do tratamento para avaliar a presença ou não de cardiotoxicidade. A cardiotoxicidade foi definida por um decréscimo de 10% na fração de ejeção do ventrículo esquerdo, em pelo menos um ecocardiograma. Modelos de regressão logística multivariada foram utilizados para verificar os fatores preditores na ocorrência de cardiotoxicidade ao longo do tempo. Resultados: Dos 112 pacientes selecionados (idade média = 51,3 ± 12,9 anos), 18 (16,1%) apresentaram cardiotoxicidade. Na análise multivariada os pacientes com ACSVE (OR = 6,25 [IC 95%: 1,03; 37,95], p < 0,05), diâmetro sistólico do VE (OR = 1,34 [IC 95%:1,01; 1,79], p < 0,05) e strain longitudinal global pela técnica de speckle tracking (OR = 1,48 [IC 95%: 1,02; 2,12], p < 0,05) foram preditores significativos e independentes na predição de cardiotoxidade. Conclusão: Mostramos que ACSVE, bem como a redução do strain longitudinal global foram preditores independentes para cardiotoxicidade, podendo ser úteis na estratificação de risco destes pacientes.

Antiplatelet Therapy in Breast Cancer Patients Using Hormonal Therapy: Myths, Evidence and Potentialities - Systematic Review / Terapia Antiplaquetária em Pacientes com Câncer de Mama em Uso de Terapia Hormonal: Mitos, Evidências e Potencialidades - Revisão Sistemática

Abstract Breast cancer is the most frequently diagnosed tumor in women worldwide, with a significant impact on morbidity and mortality. Chemotherapy and hormone therapy have significantly reduced mortality; however, the adverse effects are significant. Aspirin has been incorporated into clinical practice for over 100 years at a low cost, making it particularly attractive as a potential agent in breast cancer prevention and as an adjunct treatment to endocrine therapy in the prophylaxis of cardiovascular complications. The objective of this study was to evaluate the role of aspirin in reducing the incidence of breast cancer and to evaluate the impact of its use on morbidity and mortality and reduction of cardiovascular events as adjuvant therapy during breast cancer treatment with selective estrogen receptor modulators. A systematic review was performed using the PRISMA methodology and PICO criteria, based on the MEDLINE, EMBASE and LILACS databases. The original articles of clinical trials, cohort, case-control studies and meta-analyses published from January 1998 to June 2017, were considered. Most studies showed an association between the use of selective estrogen receptor modulators and the increase in thromboembolic events. The studies suggest a protective effect of aspirin for cardiovascular events during its concomitant use with selective estrogen receptor modulators and in the prevention of breast cancer. This systematic review suggests that aspirin therapy combines the benefit of protection against cardiovascular events with the potential reduction in breast cancer risk, and that the evaluation of the benefits of the interaction of endocrine therapy with aspirin should be further investigated.

Resumo O câncer de mama é o tumor mais frequentemente diagnosticado em mulheres de todo o mundo, com impacto importante na morbimortalidade. A quimioterapia e a terapia hormonal reduziram significativamente a mortalidade, mas os efeitos adversos são consideráveis. A aspirina está incorporada à prática clínica há mais de 100 anos, com baixo custo, tornando-a particularmente atraente como potencial agente na prevenção do câncer de mama e auxiliar durante o tratamento endócrino, na profilaxia de complicações cardiovasculares. Objetivou-se avaliar o papel da aspirina na redução da incidência do câncer de mama e avaliar o impacto de seu uso na morbimortalidade e na redução de eventos cardiovasculares como terapia adjuvante durante o tratamento do câncer de mama com moduladores seletivos do receptor do estrogênio. Procedeu-se à revisão sistemática utilizando-se a metodologia PRISMA e os critérios PICO, nas bases MEDLINE, EMBASE e LILACS. Foram considerados os artigos originais do tipo ensaio clínico, coorte, caso-controle e metanálises, publicados no período de janeiro de 1998 até junho de 2017. Na maioria dos estudos, houve relação entre o uso dos moduladores seletivos do receptor do estrogênio e o aumento de eventos tromboembólicos. Os estudos sugerem efeito protetor da aspirina para eventos cardiovasculares em uso concomitante aos moduladores seletivos do receptor do estrogênio e na prevenção do câncer de mama. Esta revisão sistemática sugere que o tratamento com aspirina combina o benefício da proteção contra eventos cardiovasculares com a potencial redução do risco de câncer de mama, e que a avaliação dos benefícios da interação da terapia endócrina com a aspirina deve ser melhor investigada.

Cardioproteção durante o tratamento oncológico / Cardioprotection during cancer treatment

O primeiro passo para a prevenção de cardiotoxicidade é avaliar o indivíduo quanto ao risco cardiovascular basal e identificar os pacientes de alto risco. É essencial a abordagem proativa, otimizando o tratamento das doenças cardiovasculares existentes e reduzindo os fatores que contribuem para o aumento do risco cardiovascular. Essa avaliação é um processo contínuo, que deve acontecer durante todo o tratamento. Nos pacientes candidatos a altas doses de antraciclina, algumas estratégias possíveis para mitigar a cardiotoxicidade são o uso de infusão contínua de antraciclina em vez de infusão em bolus, uso de doxorrubicina lipossomal em substituição a doxorrubicina tradicional e uso de dexrazoxano antes da infusão de antracíclico. As evidências atuais ainda não corroboram o uso rotineiro de bloqueadores neuro-hormonais ou estatinas como agentes cardioprotetores em todos os pacientes tratados com quimioterapia potencialmente cardiotóxica

he first step in preventing cardiotoxicity is to evaluate the baseline cardiovascular risk in the individual, and to identify high-risk patients. A proactive approach is essential, optimizing the treatment of existing cardiovascular patients and reducing the factors that contribute to the increase in cardiovascular risk. This evaluation is a continuous process that should occur throughout the treatment. In candidate patients for high-dose anthracycline, some possible strategies to mitigate cardiotoxicity are the use of continuous anthracycline infusion instead of as a bolus, the use of liposomal doxorubicin to replace traditional doxorubicin, and the use of dexrazoxane prior to anthracycline infusion. Current evidence does not support the routine use of neurohormonal blockers or statins as cardioprotective agents in all patients treated with potentially cardiotoxic chemotherapy