Testes Ergométricos em Pacientes com Anemia Falciforme: Segurança, Viabilidade e Possíveis Implicações no Prognóstico / Exercise Testing In Patients with Sickle Cell Disease: Safety, Feasibility and Potential Prognostic Implication

Resumo Fundamento Pacientes com anemia falciforme (AF) têm risco aumentado de complicações cardiovasculares. O teste ergométrico é usado como marcador de prognóstico em uma série de doenças cardiovasculares. Entretanto, há uma escassez de evidências sobre exercícios em pacientes com AF, especialmente em relação à sua segurança, viabilidade e possível função prognóstica. Objetivos Usamos o teste em esteira máximo para determinar a segurança e a viabilidade do teste ergométrico em pacientes com AF. Além disso, os fatores associados à duração do exercício, bem como o impacto das alterações causadas pelo exercício em resultados clínicos, também foram avaliados. Métodos 113 pacientes com AF que passaram pelo teste ergométrico e por uma avaliação cardiovascular abrangente incluindo um ecocardiograma e os níveis do peptídeo natriurético do tipo B (BNP). O desfecho de longo prazo foi uma combinação de eventos incluindo morte, crises álgicas graves, síndrome torácica aguda ou internações hospitalares por outras complicações associadas â doença falciforme. A análise de regressão de Cox foi realizada para identificar as variáveis associadas ao resultado. Um p valor <0,05 foi considerado estatisticamente significativo. Resultados A média de idade foi de 36 ± 12 anos (intervalo, 18-65 anos), e 62 pacientes eram do sexo feminino (52%). A presença de alterações isquêmicas ao esforço e resposta pressórica anormal ao exercício foram detectadas em 17% e 9 % da´população estudada respectivamente. Dois pacientes apresentaram crise álgica com necessidade de internação hospitalar no período de 48 horas da realização do exame. Fatores associados à duração do exercício foram idade, sexo, velocidade máxima de regurgitação tricúspide (RT), e relação E/e', após a padronização quanto aos marcadores da gravidade da doença. Durante o período médio de acompanhamento de 10,1 meses (variando de 1,2 a 26), 27 pacientes (23%) apresentaram desfechos clínicos adversos. Preditores independentes de eventos adversos foram a concentração de hemoglobina, velocidade do fluxo transmitral tardio (onda A), e a resposta da PA ao exercício. Conclusões A realização de testes ergométricos em pacientes com AF, clinicamente estáveis, é viável. A duração do exercício estava associada à função diastólica e a pressão arterial pulmonar. A resposta anormal da PA foi um preditor independente de eventos adversos.

Abstract Background Patients with sickle cell disease (SCD) are at increased risk for cardiovascular complications. Exercise testing is used as a prognostic marker in a variety of cardiovascular diseases. However, there is a lack of evidence on exercise in SCD patients, particularly regarding its safety, feasibility, and possible prognostic role. Objectives We used the maximal treadmill test to determine safety and feasibility of the exercise testing in SCD patients. Additionally, the factors associated with exercise duration, as well as the impact of exercise-induced changes on clinical outcome, were also assessed. Methods One-hundred thirteen patients with SCD, who underwent exercise testing, were prospectively enrolled. A comprehensive cardiovascular evaluation, including echocardiography and B-type natriuretic peptide (BNP) levels, were obtained. The long-term outcome was a composite endpoint of death, severe acute painful episodes, acute chest syndrome, or hospitalization for other SCD-related complications. Cox regression analysis was performed to identify the variables associated with the outcome. A p-value<0.05 was considered to be statistically significant. Results The mean age was 36 ± 12 years (range, 18-65 years), and 62 patients were women (52%). Ischemic electrocardiogram and abnormal blood pressure (BP) response to exercise were detected in 17% and 9%, respectively. Two patients experienced pain crises within 48 hours that required hospitalization. Factors associated with exercise duration were age, sex, tricuspid regurgitation (TR) maximal velocity, and E/e' ratio, after adjustment for markers of disease severity. During the mean follow-up of 10.1 months (ranging from 1.2 to 26), the endpoint was reached in 27 patients (23%). Independent predictors of adverse events were hemoglobin concentration, late transmitral flow velocity (A wave), and BP response to exercise. Conclusions Exercise testing in SCD patients who were clinically stable is feasible. Exercise duration was associated with diastolic function and pulmonary artery pressure. Abnormal BP response was an independent predictor of adverse events.

Caracterização Histológica das Lesões da Valva Mitral de Pacientes com Cardiopatia Reumática / Histopathological Characterization of Mitral Valvular Lesions from Patients with Rheumatic Heart Disease

Resumo Fundamentos: Os mecanismos subjacentes pelos quais a doença cardíaca reumática (DCR) levam à disfunção valvar grave não são totalmente compreendidos. Objetivo: O presente estudo avaliou as alterações histopatológicas nas valvas mitrais (VM) buscando uma associação entre o padrão de disfunção valvar predominante e os achados histopatológicos. Métodos: Em 40 pacientes submetidos à troca da VM devido a DCR e em 20 controles submetidos a transplante cardíaco, foram analisados os aspectos histológicos da VM excisada. Dados clínicos e ecocardiográficos também foram coletados. As análises histológicas foram realizadas usando coloração com hematoxilina-eosina. Determinou-se inflamação, fibrose, neoangiogênese, calcificação e metaplasia adiposa. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados: A idade média dos pacientes com DCR foi de 53±13 anos, sendo 36 (90%) do sexo feminino, enquanto a idade média dos controles foi de 50±12 anos, semelhante aos casos, sendo a maioria do sexo masculino (70%). O endocárdio valvar reumático apresentou espessura maior que os controles (1,3±0,5 mm versus 0,90±0,4 mm, p=0,003, respectivamente), e infiltrado inflamatório mais intenso no endocárdio (78% versus 36%; p=0,004), com predominância de células mononucleares. Ocorreu fibrose moderada a acentuada mais frequentemente em válvulas reumáticas do que em válvulas controle (100% vs. 29%; p<0,001). Ocorreu calcificação em 35% das valvas reumáticas, principalmente entre as valvas estenóticas, associada à área valvar mitral (p=0,003). Conclusões: Apesar do intenso grau de fibrose, o processo inflamatório permanece ativo na valva mitral reumática, mesmo em doença tardia com disfunção valvar. A calcificação predominou em valvas estenóticas e em pacientes com disfunção ventricular direita.

Abstract Background: The underlying mechanisms by which rheumatic heart disease (RHD) lead to severe valve dysfunction are not completely understood. Objective: The present study evaluated the histopathological changes in mitral valves (MV) seeking an association between the pattern of predominant valvular dysfunction and histopathological findings. Methods: In 40 patients who underwent MV replacement due to RHD, and in 20 controls that underwent heart transplant, histological aspects of the excised MV were analyzed. Clinical and echocardiographic data were also collected. Histological analyses were performed using hematoxylin-eosin staining. Inflammation, fibrosis, neoangiogenesis, calcification and adipose metaplasia were determined. A p value<0.05 was considered to be statistically significant. Results: The mean age of RHD patients was 53±13 years, 36 (90%) were female, whereas the mean age of controls was 50±12 years, similar to the cases, with the majority of males (70%). The rheumatic valve endocardium presented greater thickness than the controls (1.3±0.5 mm versus 0.90±0.4 mm, p=0.003, respectively), and a more intense inflammatory infiltrate in the endocardium (78% versus 36%; p=0.004), with predominance of mononuclear cells. Moderate to marked fibrosis occurred more frequently in rheumatic valves than in control valves (100% vs. 29%; p<0.001). Calcification occurred in 35% of rheumatic valves, especially among stenotic valves, which was associated with the mitral valve area (p=0.003). Conclusions: Despite intense degree of fibrosis, the inflammatory process remains active in the rheumatic mitral valve, even at late disease with valve dysfunction. Calcification predominated in stenotic valves and in patients with right ventricular dysfunction.

Morbidity and prognostic factors in chronic chagasic cardiopathy

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.