Down regulation of protective genes is associated with cellular and antibody-mediated rejection.

Despite advances in immunosuppressive therapy, rejection still remains the main obstacle to a successful transplant. This study aims to explore the gene expression profile of the rejection process in order to decrease the number of unnecessary endomyocardial biopsies in stable patients. METHODS: A total of 300 formalin-fixed and paraffin-embedded (FFPE) endomyocardial biopsies sampled from 63 heart allograft recipients were included in this study. Acute cellular rejection (ACR) and antibody-mediated rejection (AMR) were diagnosed by histological analysis and immunohistochemical C4d staining, respectively. Analysis of gene expression was performed by quantitative real-time polymerase chain reaction. The samples were grouped according to the ISHLT rejection classification, aiming the statistical analysis. RESULTS: There was a significant decrease in the HMOX1, AIF1, and CCL2 transcript over the post-transplantation period in non-rejection group (P<.001). Furthermore, the ADIPOR1, ADIPOR2, BCL2L1, and VEGFA protective genes were significantly downregulated in the ACR group (P<.05). ADIPOR2, BCL2L1, IL6, and NOS2 genes were also significantly downregulated in the AMR group than in the non-rejection group (P<.05). CONCLUSION: The downregulations of the protective genes contribute to the allograft rejection, and the archived FFPE samples are useful for the gene expression analysis aiming the allograft rejection surveillance.

Septal Ablation with Radiofrequency Catheters Guided by Echocardiography for Treatment of Patients with Obstructive Hypertrophic Cardiomyopathy: Initial Experience. / Ablação Septal com Cateteres e Radiofrequência Guiada pela Ecocardiografia para Tratamento de Pacientes com Cardiomiopatia Hipertrófica Obstrutiva: Experiência Inicial.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can cause obstruction in the left ventricular outflow tract (LVOT), and be responsible for the onset of limiting symptoms, such as tiredness. When such symptoms are refractory to pharmacological treatment, interventionist alternative therapies can be useful, such as septal ablation through the infusion of alcohol in the coronary artery or through myectomy. Recently, the use of a radiofrequency (RF) catheter for endocardial septal ablation guided by electroanatomic mapping has proven to be efficient, despite the high incidence of complete atrioventricular block. An alternative would be the application of RF at the beginning point of the septal gradient guided by the transesophageal echocardiography (TEE). The echocardiography is an imaging method with high accuracy to determine septal anatomy. OBJECTIVE: To assess the long term effect of septal ablation for the relief of ventricular-arterial gradient, using TEE to help place the catheter in the area of larger septal obstruction. Besides, to assess the effects of ablation on the functional class and echocardiographic parameters. METHODS: Twelve asymptomatic patients, with LVOT obstruction, refractory to pharmacological therapy, underwent endocardial septal ablation with 8mm-tip catheters, whose placement was oriented in the region of larger obstruction, assisted by the TEE. Temperature-controlled and staggered RF applications were performed. After each application, the gradient was reassessed and a new application was performed according to the clinical criterion. The effects of RF applications were assessed both for the gradient at rest and for that provoked by the Valsalva maneuver, and considering the gradient. The differences were significant when p-value was lower than or equal to 0.05. RESULTS: It was possible to observe that the mean reduction of the maximum gradients was from 96.8±34.7 mmHg to 62.7±25.4 mmHg three months after the procedure (p=0.0036). After one year, the mean of maximum gradient was 36.1±23.8 mmHg (p=0.0001). The procedure was well tolerated, without records of complete atrioventricular block nor severe complications. CONCLUSION: The TEE-guided septal ablation was efficient and safe, and the results were maintained during the clinical follow-up period. It is a reasonable option for the interventionist treatment of LVOT obstruction in HCM.

FUNDAMENTOS: A cardiomiopatia hipertrófica (CMH) pode causar obstrução da via de saída do ventrículo esquerdo (VSVE) e ser responsável pelo surgimento de sintomas limitantes, como cansaço físico. Quando tais sintomas são refratários ao tratamento farmacológico, os tratamentos alternativos intervencionistas podem ser úteis, como a ablação septal por meio da infusão de álcool na artéria coronária ou por meio da miectomia cirúrgica. Recentemente, o uso de cateter de radiofrequência (RF) para ablação do septo endocárdico guiado por mapeamento eletroanatômico mostrou-se eficaz apesar da elevada incidência de bloqueio atrioventricular total. Uma alternativa seria a aplicação de radiofrequência no ponto de início do gradiente septal guiada pelo ecocardiograma transesofágico (ETE). O ecocardiograma é um método de imagem com elevada acurácia para determinação da anatomia septal. OBJETIVO: Avaliar o efeito em longo prazo da ablação septal para alívio do gradiente ventrículo-arterial, utilizando o ETE para auxiliar no posicionamento do cateter na área de maior obstrução septal. Avaliar também os efeitos da ablação na classe funcional e parâmetros ecocardiográficos. MÉTODOS: Doze pacientes sintomáticos com obstrução da VSVE, refratários à terapia farmacológica, foram submetidos à ablação endocárdica septal com cateteres com ponta de 8 mm, cujo posicionamento foi orientado na região de maior obstrução com auxílio do ETE. Foram realizadas aplicações de radiofrequência (RF) termocontrolada e escalonadas sobre a área alvo. Após cada aplicação, o gradiente era reavaliado e nova aplicação era realizada de acordo com critério clínico. Foram avaliados os efeitos das aplicações de RF tanto para o gradiente em repouso como para o provocado por meio da manobra de Valsalva, e considerado o gradiente. As diferenças foram significativas quando o valor de p foi menor ou igual a 0,05. RESULTADOS: Observou-se que a redução da média dos gradientes máximos obtidos foi de 96,8±34,7 mmHg para 62,7±25,4 mmHg ao final de três meses do procedimento (p=0,0036). Após um ano, a média dos gradientes máximos obtidos foi de 36,1±23,8 mmHg (p=0,0001). O procedimento foi bem tolerado e não houve registro de bloqueio atrioventricular total e nem complicações graves. CONCLUSÃO: A ablação septal guiada pelo ETE foi eficaz e segura, com resultados mantidos durante o período de seguimento clínico. É uma opção razoável para o tratamento intervencionista da obstrução da VSVE em CMH.

Safety and Efficacy of Aerobic Exercise Training Associated to Non-Invasive Ventilation in Patients with Acute Heart Failure.

BACKGROUND: Exercise training (ET) improves functional capacity in chronic heart failure (HF). However, ET effects in acute HF are unknown. OBJECTIVE: To investigate the effects of ET alone or combined with noninvasive ventilation (NIV) compared with standard medical treatment during hospitalization in acute HF patients. METHODS: Twenty-nine patients (systolic HF) were randomized into three groups: control (Control - only standard medical treatment); ET with placebo NIV (ET+Sham) and ET+NIV (NIV with 14 and 8 cmH2O of inspiratory and expiratory pressure, respectively). The 6MWT was performed on day 1 and day 10 of hospitalization and the ET was performed on an unloaded cycle ergometer until patients' tolerance limit (20 min or less) for eight consecutive days. For all analyses, statistical significance was set at 5% (p < 0.05). RESULTS: None of the patients in either exercise groups had adverse events or required exercise interruption. The 6MWT distance was greater in ET+NIV (Δ120 ± 72 m) than in ET+Sham (Δ73 ± 26 m) and Control (Δ45 ± 32 m; p < 0.05). Total exercise time was greater (128 ± 10 vs. 92 ± 8 min; p < 0.05) and dyspnea was lower (3 ± 1 vs. 4 ± 1; p < 0.05) in ET+NIV than ET+Sham. The ET+NIV group had a shorter hospital stay (17 ± 10 days) than ET+Sham (23 ± 8 days) and Control (39 ± 15 days) groups (p < 0.05). Total exercise time in ET+Sham and ET+NIV had significant correlation with length of hospital stay (r = -0.75; p = 0.01). CONCLUSION: Exercise training in acute HF was safe, had no adverse events and, when combined with NIV, improved 6MWT and reduce dyspnea and length of stay.

Ablação septal com cateteres e radiofrequência guiada pela ecocardiografia para tratamento de pacientes com cardiomiopatia hipertrófica obstrutiva: experiência inicial / Septal ablation with radiofrequency catheters guided by echocardiography for treatment of patients with obstructive hypertrophic cardiomyopathy: initial experience

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can cause obstruction in the left ventricular outflow tract (LVOT), and be responsible for the onset of limiting symptoms, such as tiredness. When such symptoms are refractory to pharmacological treatment, interventionist alternative therapies can be useful, such as septal ablation through the infusion of alcohol in the coronary artery or through myectomy. Recently, the use of a radiofrequency (RF) catheter for endocardial septal ablation guided by electroanatomic mapping has proven to be efficient, despite the high incidence of complete atrioventricular block. An alternative would be the application of RF at the beginning point of the septal gradient guided by the transesophageal echocardiography (TEE). The echocardiography is an imaging method with high accuracy to determine septal anatomy. OBJECTIVE: To assess the long term effect of septal ablation for the relief of ventricular-arterial gradient, using TEE to help place the catheter in the area of larger septal obstruction. Besides, to assess the effects of ablation on the functional class and echocardiographic parameters. METHODS: Twelve asymptomatic patients, with LVOT obstruction, refractory to pharmacological therapy, underwent endocardial septal ablation with 8mm-tip catheters, whose placement was oriented in the region of larger obstruction, assisted by the TEE. Temperature-controlled and staggered RF applications were performed. After each application, the gradient was reassessed and a new application was performed according to the clinical criterion. The effects of RF applications were assessed both for the gradient at rest and for that provoked by the Valsalva maneuver, and considering the gradient. The differences were significant when p-value was lower than or equal to 0.05. RESULTS: It was possible to observe that the mean reduction of the maximum gradients was from 96.8±34.7 mmHg to 62.7±25.4 mmHg three months after the procedure (p=0.0036). After one year, the mean of maximum gradient was 36.1±23.8 mmHg (p=0.0001). The procedure was well tolerated, without records of complete atrioventricular block nor severe complications. CONCLUSION: The TEE-guided septal ablation was efficient and safe, and the results were maintained during the clinical follow-up period. It is a reasonable option for the interventionist treatment of LVOT obstruction in HCM.

FUNDAMENTOS: A cardiomiopatia hipertrófica (CMH) pode causar obstrução da via de saída do ventrículo esquerdo (VSVE) e ser responsável pelo surgimento de sintomas limitantes, como cansaço físico. Quando tais sintomas são refratários ao tratamento farmacológico, os tratamentos alternativos intervencionistas podem ser úteis, como a ablação septal por meio da infusão de álcool na artéria coronária ou por meio da miectomia cirúrgica. Recentemente, o uso de cateter de radiofrequência (RF) para ablação do septo endocárdico guiado por mapeamento eletroanatômico mostrou-se eficaz apesar da elevada incidência de bloqueio atrioventricular total. Uma alternativa seria a aplicação de radiofrequência no ponto de início do gradiente septal guiada pelo ecocardiograma transesofágico (ETE). O ecocardiograma é um método de imagem com elevada acurácia para determinação da anatomia septal. OBJETIVO: Avaliar o efeito em longo prazo da ablação septal para alívio do gradiente ventrículo-arterial, utilizando o ETE para auxiliar no posicionamento do cateter na área de maior obstrução septal. Avaliar também os efeitos da ablação na classe funcional e parâmetros ecocardiográficos. MÉTODOS: Doze pacientes sintomáticos com obstrução da VSVE, refratários à terapia farmacológica, foram submetidos à ablação endocárdica septal com cateteres com ponta de 8 mm, cujo posicionamento foi orientado na região de maior obstrução com auxílio do ETE. Foram realizadas aplicações de radiofrequência (RF) termocontrolada e escalonadas sobre a área alvo. Após cada aplicação, o gradiente era reavaliado e nova aplicação era realizada de acordo com critério clínico. Foram avaliados os efeitos das aplicações de RF tanto para o gradiente em repouso como para o provocado por meio da manobra de Valsalva, e considerado o gradiente. As diferenças foram significativas quando o valor de p foi menor ou igual a 0,05. RESULTADOS: Observou-se que a redução da média dos gradientes máximos obtidos foi de 96,8±34,7 mmHg para 62,7±25,4 mmHg ao final de três meses do procedimento (p=0,0036). Após um ano, a média dos gradientes máximos obtidos foi de 36,1±23,8 mmHg (p=0,0001). O procedimento foi bem tolerado e não houve registro de bloqueio atrioventricular total e nem complicações graves. CONCLUSÃO: A ablação septal guiada pelo ETE foi eficaz e segura, com resultados mantidos durante o período de seguimento clínico. É uma opção razoável para o tratamento intervencionista da obstrução da VSVE em CMH.

Estimation of right ventricular mass by two-dimensional echocardiography.

BACKGROUND: This report describes two original echocardiographic approaches to measure right ventricular (RV) mass (RVM). METHODS: In the bullet formula (5/24 pi D1 D2 L), where D1 and D2 are short axes and L the log axis, the RVM is obtained by subtracting the cavity volume from the RV total volume and subsequently multiplying the difference by myocardium density. The second method uses 3 endocardium segments measured at: (1) short axis plane of the aortic valve and left atrium (b1); (2) short axis plane at the midpoint between the tricuspid valve annulus and the apex (b2); and (3) 4-chamber view (h). Those segment lengths are applying in the formula A = [(b1 + b2)/2] x h. The result is multiplied by the wall thickness and by myocardium density. RESULTS: Both formulas were primarily tested in 30 mongrel dogs and have shown good correlation with the true mass ( r = 0.869 with the segments formula and r = 0.819 with the bullet formula). The same method was used in 20 human patients before heart transplant with similar results ( r = 0.810 with the segments formula and r = 0.836 with the bullet formula). CONCLUSIONS: The RVM can be satisfactorily estimated by 2-dimensional echocardiography. The linear regression between the calculated mass (using the smoothest and thinner myocardium thickness) and the actual mass may provide the correction factor for the RVM calculation. Two echocardiographic methods were used to measure right ventricular mass. One of them used a bullet formula variant (5/24 pi D1 D2 L). The second method used 3 endocardium segments measured in 3 2-dimensional echocardiographic planes (short axis of aortic valve and left ventricle, and 4-chamber view), and applied in the formula A = [(b1 + b2)/2] x h. Both formulas have shown good correlation with the true mass in 30 mongrel dogs ( r = 0.869 with the segments formula and r = 0.819 with the bullet formula) and in 20 human patients before heart transplant ( r = 0.810 and r = 0.836, respectively).

Safety and Efficacy of Aerobic Exercise Training Associated to Non-Invasive Ventilation in Patients with Acute Heart Failure / Segurança e Eficácia do Treinamento Aeróbio Combinado à Ventilação Não-Invasiva em Pacientes com Insuficiência Cardíaca Aguda

Abstract Background: Exercise training (ET) improves functional capacity in chronic heart failure (HF). However, ET effects in acute HF are unknown. Objective: To investigate the effects of ET alone or combined with noninvasive ventilation (NIV) compared with standard medical treatment during hospitalization in acute HF patients. Methods: Twenty-nine patients (systolic HF) were randomized into three groups: control (Control - only standard medical treatment); ET with placebo NIV (ET+Sham) and ET+NIV (NIV with 14 and 8 cmH2O of inspiratory and expiratory pressure, respectively). The 6MWT was performed on day 1 and day 10 of hospitalization and the ET was performed on an unloaded cycle ergometer until patients' tolerance limit (20 min or less) for eight consecutive days. For all analyses, statistical significance was set at 5% (p < 0.05). Results: None of the patients in either exercise groups had adverse events or required exercise interruption. The 6MWT distance was greater in ET+NIV (Δ120 ± 72 m) than in ET+Sham (Δ73 ± 26 m) and Control (Δ45 ± 32 m; p < 0.05). Total exercise time was greater (128 ± 10 vs. 92 ± 8 min; p < 0.05) and dyspnea was lower (3 ± 1 vs. 4 ± 1; p < 0.05) in ET+NIV than ET+Sham. The ET+NIV group had a shorter hospital stay (17 ± 10 days) than ET+Sham (23 ± 8 days) and Control (39 ± 15 days) groups (p < 0.05). Total exercise time in ET+Sham and ET+NIV had significant correlation with length of hospital stay (r = -0.75; p = 0.01). Conclusion: Exercise training in acute HF was safe, had no adverse events and, when combined with NIV, improved 6MWT and reduce dyspnea and length of stay.

Resumo Fundamento: O exercício físico melhora a capacidade funcional em pacientes com insuficiência cardíaca (IC) crônica. Entretanto, os efeitos do exercício na IC aguda são desconhecidos. Objetivo: Investigar os efeitos do exercício físico isolado ou associado à ventilação não-invasiva (VNI) em comparação ao tratamento convencional em pacientes com IC durante internação. Métodos: Vinte e nove pacientes (IC sistólica) foram randomizados em três grupos: Controle (tratamento clínico convencional); exercício com ventilação placebo (EX+Sham) e EX+VNI (VNI com 14 e 8 cmH2O de pressão inspiratória e expiratória, respectivamente).O TC6M foi realizado no primeiro e no décimo dia de internação e o exercício realizado em cicloergômetro até o limite de tolerância (20 minutos ou menos) por oito dias consecutivos. Para todas as análises, foi considerado p < 0,05 estatisticamente significante. Resultados: Nenhum paciente dos grupos EX+Sham e EX+VNI apresentou complicações ou necessitou interromper o exercício. O grupo EX+VNI apresentou melhor desempenho no TC6M (Δ120 ± 72 m) que os grupos EX+Sham (Δ73 ± 26 m) e Controle (Δ45 ± 32 m; p < 0,05). O tempo total de exercício foi maior (128 ± 10 vs. 92 ± 8 min; p < 0,05) e a dispneia menor (3 ± 1 vs. 4 ± 1; p < 0,05) no EX+VNI em relação ao EX+Sham. O grupo EX+VNI apresentou menor tempo de internação (17 ± 10 dias) comparado ao EX+Sham (23 ± 8 dias) e Controle (39 ± 15 dias; p < 0,05). O tempo total de exercício nos grupos EX+Sham e EX+VNI correlacionou-se com o tempo de internação hospitalar (r = -0,75; p = 0,01). Conclusão: O exercício físico foi seguro em pacientes com IC aguda, não houve complicações hospitalares e, quando associada à VNI, melhorou o desempenho no TC6M, dispneia e o tempo de internação.

Eficacia de la estrategia de control del ritmo en pacientes con miocardiopatía hipertrófica y fibrilación o flutter auricular, sometidos a cardioversión eléctrica / Efficacy of rhythm control strategy in patients with hypertrophic cardiomyopathy and atrial fibrillation or flutter, undergoing electrical cardioversion

Contexto: la fibrilación y el flutter auricular son arritmias frecuentes en pacientes con miocardiopatía hipertrófica e incrementan su morbilidad. La cardioversión de la arritmia mejora la calidad de vida del paciente, sin embargo, no existe información sobre la eficacia o predictores de esta terapia en la literatura. Objetivo: identificar en pacientes que presentan miocardiopatía hipertrófica asociada a fibrilación o flutter auricular que fueron sometidos a cardioversión eléctrica, las variables relacionadas con la evolución de la arritmia después de esta terapia. Métodos: se analizaron los datos de 37 pacientes con diagnóstico de miocardiopatía hipertrófica asociada a fibrilación auricular (n=21) y flutter auricular (n=16), sometidos a cardioversión eléctrica, en lo relativo a éxito inmediato (reversión después del choque), recurrencia (reaparición del problema después de la cardioversión eléctrica) y éxito tardío (ritmo sinusal observado en la última consulta registrada). Resultados: el éxito inmediato se produjo en el 96% de procedimientos de cardioversión eléctrica en pacientes con fibrilación auricular y en el 100% de pacientes con flutter auricular. La recurrencia se produjo en el 76,9% de los pacientes con fibrilación auricular sometidos a cardioversión eléctrica después de un tiempo medio de 630 días y en el 57,1% de los pacientes con flutter auricular luego de un seguimiento de 1.138 días. Conclusión: se evaluó la eficacia de la cardioversión eléctrica mediante los resultados clínicos observados en pacientes con miocardiopatía hipertrófica asociada a fibrilación o flutter auricular; además se identificaron las variables relacionadas con la recurrencia y el éxito tardío después de la cardioversión eléctrica. (AU)

Background: fibrillation and atrial flutter are frequent arrhythmias in patients with hypertrophic cardiomyopathy and increase their morbidity. Cardioversion of arrhythmia improves the quality of life of the patient; however, there is no information on the efficacy or predictors of this therapy in the literature. Aim: to identify the variables related to the evolution of the arrhythmia after therapy in patients with hypertrophic cardiomyopathy associated with atrial fibrillation or flutter were underwent electrical cardioversion. Methods: data from 37 patients with atrophic cardiomyopathy associated with atrial fibrillation (n = 21) and atrial flutter (n = 16), submitted to electrical cardioversion, were analyzed for immediate success (reversion after shock), Recurrence (recurrence of the problem after electrical cardioversion) and late success (sinus rhythm observed at the last recorded visit). Results: immediate success occurred in 96% of electrical cardioversion procedures in patients with atrial fibrillation and in 100% of patients with atrial flutter. Recurrence occurred in 76.9% of patients with atrial