Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study).

AIMS: Pre-clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells (BMNC) improves heart function in dilated cardiomyopathies. Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction (LVEF) of patients with non-ischaemic dilated cardiomyopathy (NIDCM). METHODS AND RESULTS: This study was a multicentre, randomized, double-blind, placebo controlled trial with a follow-up of 12 months. Patients with NIDCM and LVEF <35% were recruited at heart failure ambulatories in specialized hospitals around Brazil. One hundred and sixty subjects were randomized to intracoronary injection of BMNC or placebo (1:1). The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography. One hundred and fifteen patients completed the study. Left ventricular ejection fraction decreased from 24.0% (21.6-26.3) to 19.9% (15.4-24.4) in the BMNC group and from 24.3% (22.1-26.5) to 22.1% (17.4-26.8) in the placebo group. There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction. Mortality rate was 20.37% in placebo and 21.31% in BMNC. CONCLUSION: Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00333827.

O valor do Doppler tecidual no diagnóstico diferencial da hipertrofia do atleta e da cardiomiopatia hipertrófica / The value of tissue Doppler in the differential diagnosis of athlete's heart and hypertrophic cardiomyopathy

Introdução: A cardiomiopatia hipertrófica é a responsável pelo maior número de mortes súbitas ou inesperadas por problemas cardíacos, em atletas jovens, e, quando tentamos esclarecer o diagnóstico pela ecocardiografia tradicional, a simples presença de hipertrofia, muitas vezes, não permite distinguir a sua etiologia, como a hipertrofia dos atletas e a hipertrofia secundária à hipertensão arterial. O Doppler tecidual (DTI) pode auxiliar na diferenciação das referidas hipertrofias. Objetivo: Avaliar os valores do Doppler tecidual (TDI) no anel mitral, em pacientes com cardiomiopatia hipertrófica, hipertrofia hipertensiva e hipertrofia, induzida pelo exercício, em atletas saudáveis de alta performance. Métodos: Foram estudados 147 pacientes: 30 voluntários saudáveis (grupo controle); 49 atletas de alta performance, jogadores de futebol profissionais do fluminense Futebol Clube , da cidade do rio de Janeiro-RJ (grupo dos atletas), avaliados na classe 1 de weber pela ergoespirometria; 40 portadores de hipertensão arterial sistêmica moderada controlada, com hipertrofia ventricular esquerda e função ventricular preservada (grupo dos hipertensos)...

Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study.

BACKGROUND: Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. METHOD/DESIGN: We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. DISCUSSION: Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

Doença arterial coronariana e mixoma cardíaco: prevalência e associação com os fatores de risco convencionais / Coronary artery disease and cardiac myxoma: prevalence and association with conventional risk factors

Analisar a prevalência de doença arterial coronariana(DAC) em pacientes com mixoma cardíaco e sua correlação com fatores de risco para aterosclerose. Métodos: Estudo retrospectivo, transversal, no qual foram selecionados todos os pacientes com diagnóstico de mixoma cardíaco, encaminhados para tratamento cirúrgico em uma única instituição, entre janeiro de 1998 e dezembro de 2005. Nesse período, 21 pacientes com mixoma foram identificados por meio de consulta ao banco de dados da cirurgia cardíaca do Instituto. Foram excluídos três pacientes que não realizaram coronariografia pré-operatória. Resultados: A idade média dos pacientes foi de 59 mais ou menos 10 anos, sendo 83 por cento mulheres. Foi encontrada DAC em 3 pacientes (16,7 por cento). A presença de fatores de risco tradicionais para aterosclerose não foi estatisticamente diferente entre os pacientes operados por mixoma com e sem DAC na coronariografia. Conclusão: Preditores clínicos não são capazes de diferenciar, com segurança, pacientes com e sem DAC no pré-operatório de cirurgia de mixoma, sendo sugerida a realização de coronariografia em todos os casos.

[Cell therapy in dilated cardiomyopathy]. / Terapia celular na cardiomiopatia dilatada.

A forty-one-year-old male with systolic heart failure, FC-III NYHA, clinical stage C due to dilated cardiomyopathy was submitted to an autologous transplant of the mononuclear fraction of bone marrow via coronary artery system through heart catheterism. Two months after the procedure, there was a decrease in plasma BNP and cardiac area reduction at the thorax X-ray and nuclear magnetic resonance. The echocardiogram showed decrease of the secondary regurgitation and mitral ring dilatation. There was a better performance at the ergospirometry, with increase of the maximum oxygen consumption and consequent reduction in drug therapy. The absence of adverse events characterized by clinical/hemodynamic instability, enzymatic alteration or electrocardiogram demonstrate the safety and feasibility of this procedure carried out and described with pioneering spirit in dilated cardiomyopathy.

Terapia celular na cardiomiopatia dilatada / Cell therapy in dilated cardiomyopathy

Homem de 41 anos em insuficiência cardíaca sistólica, CF III NYHA, estágio clínico C, por cardiomiopatia dilatada, foi submetido ao transplante autólogo da fração mononuclear da medula óssea, via sistema arterial coronariano, através de cateterismo cardíaco. Dois meses após o procedimento, houve diminuição do BNP plasmático, diminuição da área cardíaca ao estudo radiológico do tórax e à ressonância nuclear magnética. O ecocardiograma demonstrou diminuição do fluxo regurgitante secundário a dilatação do anel mitral. Na ergoespirometria houve melhor desempenho, com aumento do consumo máximo de oxigênio, sendo possível redução da terapêutica medicamentosa. A ausência de eventos adversos caracterizados por: instabilidade clínica/hemodinâmica, alteração enzimática ou eletrocardiográfica apontam para segurança e exeqüibilidade deste procedimento realizado e descrito com pioneirismo na cardiomiopatia dilatada.

Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits.

Autoantibodies against muscarinic and adrenergic receptors have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDC) and Chagas disease, but it is still unclear whether they can functionally interact with their respective receptors to modulate cardiac functions. In this study, our goal was to detect the presence of those antibodies in the sera of patients with IDC and characterize their electrophysiological effects on cardiomyocytes from rabbits. By using ELISA immunoassays, we detected high titers of antibodies against muscarinic M2 receptors in the sera of all IDC patients, whereas the detection of antibodies against the beta1-receptor occurred in 50% of them. Electrophysiological experiments using the whole cell configuration of the patch-clamp technique showed that sera from 43% of IDC patients induced a significant decrease (approximately 26%) in isoproterenol-stimulated L-type Ca2+ currents in rabbit ventricular myocytes, whereas the sera from healthy blood donors failed to do so. As expected, IDC sera also decreased the action potential duration (by 10.5%) due to a shortening of the plateau phase. Sera that reduced isoproterenol-stimulated L-type Ca2+ currents did not cause any effect on K+ currents. We conclude that sera from IDC patients have autoantibodies, which interact with muscarinic M2 receptors of rabbit cardiomyocytes, acting in an agonist-like fashion. This action results in changes in electrogenesis, which, as often observed in patients with IDC, could initiate ventricular arrhythmias that lead to sudden death.