Importance of genetic testing in dilated cardiomyopathy : applications and challenges in clinical practice

A miocardiopatia dilatada (MCD) é uma síndrome caracterizada por dilatação ventricular esquerda e disfunção contrátil, sendo considerada a causa mais comum de insuficiência cardíaca em adultos jovens. O uso do sequenciamento de nova geração tem contribuído com a descoberta de uma grande quantidade de dados genômicos relacionados à MCD, identificando mutações que envolvem genes que codificam proteínas do citoesqueleto, sarcômero e canais iônicos, os quais são responsáveis por aproximadamente 40% dos casos classificados como MCD idiopática. Nesse cenário, geneticistas e especialistas em genética cardiovascular passaram a atuar em conjunto, agregando conhecimento e estabelecendo diagnósticos mais precisos. No entanto, é fundamental interpretar corretamente os resultados genéticos, sendo necessário criar e fomentar equipes multidisciplinares dedicadas à gestão e análise das informações coletadas. Nesta revisão, abordamos os fatores genéticos associados à MCD, aspectos prognósticos, além de discutirmos como o emprego dos testes genéticos, quando bem indicados, pode ser útil na tomada de decisão na prática clínica dos cardiologistas.Dilated cardiomyopathy (DCM) is a clinical syndrome characterized by left ventricular dilatation and contractile dysfunction. It is the most common cause of heart failure in young adults. The advent of next-generation sequencing has contributed to the discovery of a large amount of genomic data related to DCM. Mutations involving genes that encode cytoskeletal proteins, the sarcomere, and ion channels account for approximately 40% of cases previously classified as idiopathic DCM. In this scenario, geneticists and cardiovascular genetics specialists have begun to work together, building knowledge and establishing more accurate diagnoses. However, proper interpretation of genetic results is essential and multidisciplinary teams dedicated to the management and analysis of the obtained information should be considered. In this review, we approach genetic factors associated with DCM and their prognostic relevance and discuss how the use of genetic testing, when well recommended, can help cardiologists in the decision-making process

Baixa concordância entre a classificação da NYHA e as variáveis do teste de exercício cardiopulmonar em pacientes com insuficiência cardíaca e fração de ejeção reduzida

FUNDAMENTO: A classificação funcional da New York Heart Association (NYHA) é o sistema de classificação mais utilizado para a insuficiência cardíaca (IC), enquanto o teste de exercício cardiopulmonar (TECP) é o padrão ouro para a avaliação do estado funcional na IC. OBJETIVO: Analisar a correlação e a concordância entre as classes da NYHA e as variáveis do TECP. MÉTODOS: Foram selecionados pacientes com IC com indicação clínica para TECP e fração de ejeção (FE) < 50%. A correlação (coeficiente de Spearman) e a concordância (kappa) entre a classificação da NYHA e as classificações baseadas no TECP foram analisadas. Um valor de p < 0,05 foi considerado significativo. RESULTADOS: No total, foram incluídos 244 pacientes no estudo. A idade média foi de 56±14 anos, e a FE média foi de 35,5%±10%. A distribuição de pacientes de acordo com a classificação da NYHA foi a seguinte: classe I (31,2%), classe II (48,3%), classe III (19,2%) e classe IV (1,3%). A correlação (r) entre as classes da NYHA e de Weber foi de 0,489 (p < 0,001), e a concordância foi de 0,231 (p < 0,001). A correlação (r) entre as classes da NYHA e ventilatórias (inclinação da ventilação minuto/produção de dióxido de carbono [VE/VCO(2)]) foi de 0,218 (p < 0,001), e a concordância foi de 0,002 (p = 0,959). A correlação de Spearman entre as classes da NYHA e do escore TECP foi de 0,223 (p = 0,004), e a concordância kappa foi de 0,027 (p = 0,606). CONCLUSÃO: Foi identificada uma associação moderada entre as classes da NYHA e de Webber, embora a concordância tenha sido baixa. As classes ventilatórias (inclinação VE/VCO(2)) e do escore TECP apresentaram uma associação fraca e uma baixa concordância com as classes da NYHA

Classification system for cardiorespiratory fitness based on a sample of the Brazilian population

Background: Peak oxygen consumption (VO2peak) is an important prognostic marker and its classification helps the cardiologist in the therapeutic decision-making process. The most commonly used cardiorespiratory fitness (CRF) classification has not been validated for the Brazilian population. Objective: To elaborate a CRF classification using a Brazilian sample and to compare it with the American Heart Association (AHA), Cooper and UNIFESP classifications. Methods: A total of 6,568 healthy subjects were analyzed through cardiopulmonary exercise testing (CPET). They were distributed by sex and the following age groups (years): 7-12, 13-19, 20-79 (per decades) and > 80 years. After measurement of the VO2peak, participants were distributed into quintiles of CRF in very poor, poor, moderate, high and very high (AEMA Table). The CRF classifications by AEMA, AHA, Cooper, and UNIFESP were compared using the Wilcoxon, Kappa and concordance percentages. Results: VO2peak presented an inverse and moderate correlation with age considering both sexes (R = -0.488, p < 0.001). All paired comparisons between CRF classification systems showed differences (p < 0.001) and disagreement percentage - AEMA versus AHA (k = 0.291, 56.7%), AEMA versus Cooper (k = 0.220, 62.4%) and AEMA versus UNIFESP (k = 0.201, 63.9 %). Conclusion: The AEMA table showed important discrepancies in the classification of CRF when compared to other tables widely used in our setting. Because it was obtained from a large sample of the Brazilian population, the AEMA table should be preferred over other classification systems in our population

Cardiopulmonary exercise and 6-min walk tests as predictors of quality of life and long-term mortality among patients with heart failure due to Chagas disease

Universidade Federal de São Paulo, Div Cardiol, São Paulo, BrazilSanta Izabel Hosp, Div Cardiol, Salvador, BrazilBrazilian Clin Res Inst, São Paulo, BrazilDuke Clin Res Inst, Durham, NC USAUniversidade Federal de São Paulo, Div Cardiol, São Paulo, BrazilWeb of Scienc

The six-minute step test as a predictor of functional capacity according to peak VO2 in cardiac patients

Fundamento: O teste do degrau de seis minutos (TD6) é uma forma simples de avaliar a capacidade funcional, embora tenha sido pouco estudado em pacientes com doença arterial coronariana (DAC) ou insuficiência cardíaca (IC). Objetivo: Analisar a associação entre o TD6 e o consumo de oxigênio de pico (VO2pico) e desenvolver uma equação que estime o VO2pico com base no TD6, bem como determinar um ponto de corte para o TD6 que preveja um VO2pico ≥ 20 mL. kg-1.min-1 Métodos: Nos 171 pacientes submetidos ao TD6 e a um teste de exercício cardiopulmonar, análises da curva ROC, de regressão e de correlação foram usadas, e um p 105 passos [área sob a curva 0,85; intervalo de confiança de 95% 0,79 - 0,90; p 105 passos.Background: Six-minute step test (6MST) is a simple way to evaluate functional capacity, although it has not been well studied in patients with coronary artery disease (CAD) or heart failure (HF). Objective: Analyze the association between the 6MST and peak oxygen uptake (VO2peak) and develop an equation for estimating VO2peak based on the 6MST, as well as to determine a cutoff point for the 6MST that predicts a VO2peak ≥20 mL.Kg-1.min-1 Methods: In 171 patients who underwent the 6MST and a cardiopulmonary exercise test, correlation, regression, and ROC analysis were used and a p 105 steps (AUC 0.85; 95% CI 0.79 -0.90; p 105 steps

Cardiopulmonary Exercise Test: Background, Applicability and Interpretation

Cardiopulmonary exercise test (CPET) has been gaining importance as a method of functional assessment in Brazil and worldwide. In its most frequent applications, CPET consists in applying a gradually increasing intensity exercise until exhaustion or until the appearance of limiting symptoms and/or signs. The following parameters are measured: ventilation; oxygen consumption (VO2); carbon dioxide production (VCO2); and the other variables of conventional exercise testing. In addition, in specific situations, pulse oximetry and flow-volume loops during and after exertion are measured. The CPET provides joint data analysis that allows complete assessment of the cardiovascular, respiratory, muscular and metabolic systems during exertion, being considered gold standard for cardiorespiratory functional assessment.1-6 The CPET allows defining mechanisms related to low functional capacity that can cause symptoms, such as dyspnea, and correlate them with changes in the cardiovascular, pulmonary and skeletal muscle systems. Furthermore, it can be used to provide the prognostic assessment of patients with heart or lung diseases, and in the preoperative period, in addition to aiding in a more careful exercise prescription to healthy subjects, athletes and patients with heart or lung diseases. Similarly to CPET clinical use, its research also increases, with the publication of several scientific contributions from Brazilian researchers in high-impact journals. Therefore, this study aimed at providing a comprehensive review on the applicability of CPET to different clinical situations, in addition to serving as a practical guide for the interpretation of that test

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Estatinas na sepse: nova arma terapêutica no arsenal da medicina intensiva?

JUSTIFICATIVA E OBJETIVOS: Sepse é uma síndrome de base inflamatória; diversos fármacos que -atuam sobre as vias de ativação da inflamação vêm sendo observados. As estatinas, além do conhecido efeito hipolipemiante detêm capacidades antiinflamatórias chamados pleiotrópicas. Essa ação pode ser benéfica no tratamento da sepse. O objetivo deste estudo foi revisar as principais publicações abordando o seu uso na sepse. MÉTODO: Busca por artigos originais cruzando os unitermos sepse e estatina no MedLine entre 1990 e 2006. RESULTADOS: Diversos estudos experimentais e retrospectivos investigaram o uso de estatinas em sepse, até o momento, em sua maioria mostraram melhora de mortalidade e morbidade. Não existem estudos prospectivos, aleatórios, placebo-controlados ou metanálises, o que demonstrou que a falta de evidências sólidas e comprovadas para indicação de uso desta conduta ainda é prevalente. Portanto ainda com seu beneficio questionável, são necessários estudos clínicos aleatórios que possam comprovar a teoria em questão. CONCLUSÕES: Diversos estudos experimentais e retrospectivos têm investigado o uso de estatinas em pacientes sépticos, porém, apesar da literatura demonstrar ser esta teoria promissora, ainda necessita-se de estudos clínicos abordando maior número de pacientes, de forma aleatória, para estar-se apto a entender e, possivelmente, recomendar o uso desta medicação no tratamento de pacientes com sepse