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.

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years.

BACKGROUND: Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. OBJECTIVE: This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. METHODS: Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. RESULTS: The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. CONCLUSIONS: Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

BACKGROUND Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. OBJECTIVE This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. METHODS Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. RESULTS The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. CONCLUSIONS Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Predictors of all-cause 1-year mortality in implantable cardioverter defibrillator patients with chronic Chagas' cardiomyopathy.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) have been used in the treatment of either sustained ventricular tachycardia or ventricular fibrillation in patients with Chagas' cardiomyopathy. This study aimed at determining mortality rate and risk factors of all-cause 1-year mortality in primary and secondary ICD patients with Chagas' cardiomyopathy. METHODS: One hundred and forty-eight Chagas' patients with ICDs were included from the Medtronic ICD Registry Latin America. All patients were followed for 1 year. RESULTS: At implant, mean age was 60.1 ± 9.4 years and 72.9% were male. Mean left ventricular ejection fraction (LVEF) was 40.1 ± 11%. Mean follow-up was 12 ± 7 months. During the follow-up, 15 patients died (10.2%). Patients who died were older (64 ±10.8 years vs 59 ± 9.1; P = 0.04), had more atrial fibrillation (13.3% vs 3.8%; P = 0.02), had lower LVEF (33.4%± 9.8 vs 40.9%± 11.3; P = 0.01), and worse functional class (III/IV 40% vs 21.8%; P = 0.03). The multivariate analysis showed that two independent predictors of all-cause 1-year mortality remained statistically significant: age more than 65 (hazard ratio [HR] = 2.85, 95% confidence interval [CI] 1.77-3.92; P = 0.03) and LVEF less than 30% (HR = 2.68, 95% CI 1.57-3.79; P = 0.04). CONCLUSION: This analysis showed that patients older than 65 years of age and with LVEF less than 30% were independent predictors of all-cause 1-year mortality in patients with chronic Chagas' cardiomyopathy.

Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema.

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009).

Estudo multicêntrico de pacientes submetidos a implante de cardioversor-desfibrilador implantável (CDI) na America Latina / Multi-center study of patients who underwent implants of implantable cardioverter-defibrillator (ICD) in Latin America / Estudio multicéntrico de pacientes sometidos a implante de cardioversor-desfibrilador implantable(CDI) en Latinoamérica

O ICD Register da Medtronic foi introduzido na América Latina com a finalidade de coletar dados relacionados à indicação de implantes de CDI para prevenção primária e secundária de morte súbita e ao acompanhamento de pacientes originários de Porto Rico, Caribe. México e América do Sul. Além dessa ampla variedade geográfica, também foram incluídos detalhes referentes aos cuidados de saúde recebidos como parte do tratamento. O presente estudo apresenta as características de desfecho de 910 portadores de cardiopatias tratados para prevenção primária, em comparação com aqueles nos quais o implante destinou-se à prevenção secundária.

The ICD Register was introduced to Latin America to collect data related to implant indication of ICD for the prevention of primary and secondary deaths and for the follow-up of patients from Puerto Rico, the Caribbean, Mexico and South America. In addition to this vast geographic variety, information related to the health care as part of the treatment has also been included. This study shows the characteristics of the outcome of 910 cardiopathy patients treated for primary prevention, incomparison to those whose implants were meant for secondary prevention.

El ICD Register de Medtronic fue introducido en América Latina a fin de recoger datos relacionados a la indicación de implantes de CDI para la prevención primaria y secundaria de muerte súbita y a la remisión de pacientes provenientes de Puerto Rico, Caribe, México y Sudamérica. Ademásde esa amplia variedad geográfica, también se incluyeron detalles referentes a los cuidados de saludrecibidos como parte del tratamiento. El presente estudio presenta las características de solución de 910 portadores de cardiopatías tratados para la prevención primaria, en comparación con aquellos cuyo implante se destinó a la prevención secundaria.

Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study.

BACKGROUND: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. METHODS AND RESULTS: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2 max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2 max) were not significantly different. Death occurred more frequently with RVP. CONCLUSION: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode.

Apnéia obstrutiva do sono e arritmias cardíacas: [revisão] / Obstructive sleep apnea and cardiac arrythmias: [review] / Apnea obstructiva del sueño y arritmias cardiacas: [revisión]

A síndrome da apnéia obstrutiva do sono (SAOS) é uma condição prevalente, frequentemente não diagnosticada, associada à elevação do risco cardiovascular, incluindo as arritmias. O reconhecimento da síndrome requer avaliação clínica detalhada, realizada por cardiologistas, e pode ser confirmada por meio da polissonografia. Arritmias que ocorrem durante o sono foram relatadas pela primeira vez em 1965, em pacientes com Síndrome de Pickwick. Desde então, diversos estudos foram realizados sobre incidência, fatores de risco, tratamentos, bem sobre sua importância clínica. Este artigo aborda a fisiopatologia e os aspectos clínicos das arritmias durante a apnéia do sono, por meio de uma revisão dos principais artigos sobre o assunto.

ABSTRACT: The syndrome of obstructive sleep apnea (OSA) is a prevailing condition in the population associated with increased cardiovascular risk, often undiagnosed, including arrhythmias. Therecognition of the syndrome requires a high degree of clinical suspicion, particularly by cardiologists, and it can be confirmed by polysomnography. Arrhythmias that occur during sleep have been reported since 1965 in patients with syndrome of Pickwick. Since then there have been several studies to analyze the frequency, risk factors, treatments, as well as the clinical importance. This article coversthe physiopathology and clinical aspects of arrhythmias during sleep apnea, through a review of the main articles on the subject.

RESUMEN: El síndrome de la apnea obstructiva del sueño (SAOS) es una condición prevalente en la población, asociada con el mayor riesgo cardiovascular, a menudo no diagnosticada, incluyéndose las arritmias. El reconocimiento del síndrome requiere alto grado de sospecha clínica, especialmentepor cardiólogos, y se la puede confirmar por medio de la polisonografia. Las arritmias que ocurren durante el sueño se relatan desde 1965 en pacientes con Síndrome de Pickwick. Desde esa época, se han llevado a cabo diversos estudios a fin de analizar su frecuencia, factores de riesgo, tratamientos, así como su importancia clínica. Este artículo aborda la fisiopatología y los aspectos clínicos de las arritmias durante la apnea del sueño, a través de una revisión de los principales artículos sobre el tema.

Bloqueio atrioventricular total pós- correção cirúrgica de defeito do septo atrioventricular parcial em paciente com associação charge / Total atrioventricular block after septum defect correction surgery partial atrioventricular in patients with charge association / Bloqueo aurículoventricular total post-corrección quirúrgica de defecto del septo aurículoventricular parcial en paciente con asociación charge

Descreveremos o caso de uma paciente com uma síndrome rara (Associação Charge), que evoluiu para uma complicação bastante temida, o bloqueio atrioventricular total, no pós-operatório de correção do defeito do septo atrioventricular parcial.

We will describe a woman’s case with a rare syndrome (Charge Association) with a quite feared complication evolution, the total atrioventricular block, in the postoperative of partialatrioventricular defect correction.

Describiremos el caso de una paciente con un síndrome raro (Asociación Charge), que evolucionó hacia una complicación bastante temida, el bloqueo aurículoventricular total, en el postoperatorio de corrección del defecto del septo aurículoventricular parcial.

Taquicardia mediada por marcapasso ou por reentrada eletrônica - uma revisão / Pacemaker mediated tachycadia - a revision / Taquicardia mediada por marcapasos o por reentrada electrónica - una revisión

A estimulação cardíaca artificial constitui-se em um dos grandes avanços tecnológicos na área da cardiologia para o tratamento das bradiarritmias, contudo não está livre de complicações. A implantação de marcapassos bicamerais trouxe uma nova e importante condição: a Taquicardia Mediada por Marcapasso ou também denominada Taquicardia por Reentrada Eletrônica. Nesse artigo, procuramos atualizar o estado da arte sobre essa condição, suas causas e possíveis formas de prevenção.

The artificial cardiac stimulation constitutes one of the great advances thechnological in the cardiology for the treatment of bradyarrhythmias. However it is not free of complications. The implantation of bicameral pacemakers brought a new and important condition, the Pacemaker Mediated Tachycrdia. In this article, we look for to bring up to date the state of the art on this condition, its causesand possible forms of prevention.

La estimulación cardiaca artificial se constituye en uno de los grandes avances tecnológicos en el área de la cardiología para el tratamiento de las bradiarritmias, sin embargo no estálibre de complicaciones. La implantación de marcapasos bicamerales trajo una nueva e importante condición: la Taquicardia Mediada por Marcapasos o también denominada Taquicardia por Reentrada Electrónica. En este artículo, tratamos de actualizar el estado del arte sobre esa condición, sus causasy posibles formas de prevención.

Journal impact factor: this editorial, academic and scientific influence.

In this report the authors present information on the bibliometric instruments and their importance in measuring the quality of scientific journals and researchers. They in particular the history and deployment of the impact factor of the existing Institute for Scientific Information since 1955. Are presented and discussed the criticism regarding the inadequacy of the impact factor for evaluation of scientific production, misuse and strategies editorial handling of the bibliometric index. It is presented to the new classification CAPES for the journals, based on various criteria and the impact factor and its influence on national scientific and academic life. The authors conclude that, despite all obstacles and discussions, the impact factor of the Institute for Scientific Information is still an useful tool and the only isolation available to assess the scientific and intellectual productivity.

Importância e influência do fator de impacto nos meios editorial, acadêmico e científico / Impact factor confirms nature is top research journal

Os autores descrevem os instrumentos bibliométricos utilizados atualmente para aferir a qualidade de periódicos científicos, pesquisadores e docentes. apresentam a história de criação do fator de impcto (FI) do Institute for Scientific Information (ISI), existente desde 1955. Discutem as críticas referentes ao instrumento, entre elas sua inadequação para avaliação da produção científica, seu uso indevido e as estratégias editoriais de manipulação desse índice. Apresentam a nova classificação CAPES para periódicos científicos, baseada no FI em outros critérios, destacando sua influência na vida acadêmica e científica nacional. Concluem que, apesar de seus limites, o FI ainda é uma ferramenta útil para avaliar os periódicos científicos e a produtividade intelectual.

Benefícios da programação dos intervalos AV e VV na estimulação biventricular / The AV and VV interval program in the biventricular stimulation and its benefits

A insuficiência cardíaca crônica está frequentemente associada a distúbios de condução intra e interventricular, o que resulta em uma síndrome de baixo débito sistêmica. Para promover melhora dessa disfunção miocárdica, tanto nas formas agudas como crônica, é crucial restaurar a sincronia por meio do ajuste dos estímulos entre átrios e ventrículos, entre ventrículos e dentro do próprio ventrículo. Benefícios hemodinâmicos adicionais têm relação direta com a otimização dos intervalos AV e VV, medidas que devem ser individualizadas e programadas por meio do ecocardiograma (doppler pulsado). O objetivo desse artigo é discutir a importância dessa programação para o paciente submetido a TRC e como executá-la.

Fator de impacto: importância e influência no meio editorial, acadêmico e científico / Journal impact factor: this editorial, academic and scientific influence

Neste relato, os autores apresentam informações sobre os instrumentos bibliométricos e a sua importância na aferição da qualidade dos periódicos científicos, pesquisadores e docentes. Apresentam em particular a história e a implantação do fator de impacto do Institute for Scientific Information existente desde 1955. São apresentadas e discutidas as críticas referentes à inadequação do fator de impacto para avaliação da produção científica, uso indevido e estratégias editoriais de manipulação deste índice bibliométrico. É apresentada a nova classificação CAPES para os periódicos, baseada em vários critérios e no Fator de impacto, em especial, e a sua influência na vida acadêmica e científica nacional. Conclui que, apesar de todos os óbices e discussões, o Fator de Impacto do Institute for Scientific Information ainda é uma ferramenta útil e, isoladamente, a única existente para avaliar os periódicos científicos e a produtividade intelectual

In this report the authors present information on the bibliometric instruments and their importance in measuring the quality of scientific journals and researchers. They in particular the history and deployment of the impact factor of the existing Institute for Scientific Information since 1955. Are presented and discussed the criticism regarding the inadequacy of the impact factor for evaluation of scientific production, misuse and strategies editorial handling of the bibliometric index. It is presented to the new classification CAPES for the journals, based on various criteria and the impact factor and its influence on national scientific and academic life. The authors conclude that, despite all obstacles and discussions, the impact factor of the Institute for Scientific Information is still an useful tool and the only isolation available to assess the scientific and intellectual productivity

Registro latino-americano de cardiodesfibriladores do ICD registry: aspectos demográficos / Latin american cardiodefribrillator registry ICD registry: demographic aspects

Apresenta-se pela primeira vez na literatura mundial uma avaliação do acompanhamento de pacientes que receberam implante de cardiodesfibriladores na américa latina(ICD Registry - Medtronic Latin America). O resgistro é de vital importância para orientar condutas em cardiopatias de diferentes etiologias, tais como doença de chagas, miocardiopatia dilatada idiopática e coronariopatias...