Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

Detoxification of cardiotoxic traditional Chinese medicine and traditional Chinese medicine for prevention of cardiotoxicity: a review / 中国中药杂志

Cardiotoxicity is smong the main safety problems of drugs in clinical application. In recent years, traditional Chinese medicine has been gradually emphasized and studies on the evaluation of cardiac safety and prevention of cardiotoxicity of Chinese medicine have been on the rise, particularly the cardiotoxic Chinese medicine or the Chinese medicine components targeting cardiotoxicity. As for the research methods for cardiac safety evaluation of Chinese medicine, this review introduces the related clinical indexes and cell and animal models. As to the improvement of heart safety, this study reviews the material basis and mechanism of cardiotoxic Chinese medicines as well as the alleviation of cardiotoxicity by controlling the content of toxic compounds and changing dosage form, processing method, and compatibility of Chinese medicine. In addition, the effective components and mechanisms of prescriptions and active compounds in Chinese medicine for preventing and treating cardiotoxicity induced by chemotherapeutic drugs in recent years were summarized. This review is expected to serve as a reference for cardiac safety evaluation and clinical rational application of Chinese medicine.

Enfermedad cardíaca inducida por radiación: Implicaciones prácticas en su prevención, diagnóstico y tratamiento / Radiation-Induced Heart Disease: Practical Implications for Its Prevention, Diagnosis, and Treatment

Resumen La radioterapia representa una herramienta terapéutica de gran utilidad en el tratamiento de varios tipos de cáncer. Cuando se emplea a lesiones en tórax existe el riesgo de aplicar determinada radiación en el corazón y consecuentemente presentar complicaciones cardíacas. Los efectos adversos se pueden observar en los distintos componentes del corazón y las manifestaciones pueden apreciarse principalmente a largo plazo. Mediante una evaluación integral del riesgo cardiovascular, la identificación de las terapias concomitantes con potencial cardiotóxico, la aplicación de técnicas de radioterapia con función protectora del corazón y el control con estudios cardiológicos se intenta optimizar el desenlace oncológico y cardiovascular de los pacientes. En aquellos pacientes que se presenten con complicaciones cardíacas, existen varias opciones terapéuticas tanto quirúrgicas como percutáneas, que implican un desafío dado la complejidad de los casos. Finalmente, existen distintas consideraciones de manejo para los pacientes con dispositivos electrónicos cardíacos implantables. Estrategia de búsqueda: Se realizó una búsqueda en Pubmed de artículos bajo el criterio de radioterapia y corazón, con un intervalo de tiempo de los últimos 5 años hasta agosto 2020, escritos en inglés. Además, se buscaron referencias cruzadas y se incluyeron documentos de consenso de parte de sociedades de cardiología internacionales.

Abstract Radiation-Induced Heart Disease: Practical Implications for Its Prevention, Diagnosis, and Treatment The radiotherapy represents a very useful therapeutic tool for the treatment of different types of cancer. When it is used to treat thoracic lesions there is a risk of appliying a determined radiation dose to the heart and consequently develop cardiac complications. The adverse effects can be seen in distinct heart components and the manifestations can be appreciated mainly in the long term. Through an integral evaluation of the cardiovascular risk, the identification of concomitant therapies with cardiotoxic potential, the application of heart sparing radiotherapy techniques and the control with cardiac tests, it is intended to optimize the oncologic and cardiovascular outcomes of the patients. In those patients who present with cardiac complications, there are several therapeutic options ranging from chirurgic to percutaneous, which are challenging given the complexity of the cases. Finally, there are different considerations in regard to the management of patients with electronically implantable cardiaca devices. Search strategy: A search was carried out in Pubmed for articles under the criteria of radiotherapy and heart, with a time interval of the last 5 years until August 2020, written in English. In addition, cross-references were searched and consensus documents from international cardiology societies were included.

Cardiotoxicidad por irradiación en pediatría / Cardiotoxicity by irradiation in Pediatrics

Introducción: La cardiotoxicidad depende de varios factores y se manifiesta por las alteraciones cardiovasculares inducidas por los tratamientos oncoespecíficos en la función y morfología del corazón. Objetivo: Determinar las manifestaciones de cardiotoxicidad en pacientes pediátricos. Métodos: Estudio descriptivo transversal en el que se incluyeron 79 pacientes tratados en el Instituto de Oncología y Radiobiología de Cuba con irradiación tórax-mediastino, entre enero 2008 a diciembre 2014. La enfermedad de Hodgkin estaba presente en 54 pacientes y en 25, tumores del sistema nervioso central: meduloblastomas en 19 y tumores primarios neuroectodérmicos en 6 pacientes. A todos se les hizo historia clínica con examen físico, electrocardiograma de 12 derivaciones y ecocardiograma 2D pre- y postratamientos. Se analizaron las características demográficas y clínicas. Los enfermos con Hodgkin recibieron irradiación con intensidad de 2 400 centigray y de 2 340 los pacientes con tumores del sistema nervoso central; la poliquimioterapia se realizó con antraciclinas, vincristina, vinblastina y otros. Resultados: La edad promedio de todos los pacientes fue de 7 años con predominio del sexo masculino. No se registraron síntomas o signos de cardiotoxicidad. Conclusiones: En nuestra serie de pacientes la irradiación del área cardiaca aparentemente es bien tolerada, sin aparición temprana de cardiotoxicidad, ni en periodos de seguimiento de hasta 9 años. Aparecieron naúseas y leucopenias transitorias en algunos casos. No existió diferencias en las toxicidades en los grupos de tumores estudiados Es necesario mantener un seguimiento estrecho para descartar la aparición de cardiotoxicidad en años siguientes(AU)

Introduction: Cardiotoxicity depends on various factors and it is evident in cardiovascular alterations induced by oncologic treatments directed to the heart´s function and morphology. Objective: To determine the symptoms of cardiotoxicity in pediatric patients. Methods: Descriptive and cross-sectional study in which there were included 79 patients treated in the Cuban Institute of Oncology and Radiobiology with thorax-mediastine irradiation from January 2008 to December 2014. Hodgkin disease was present in 54 patients, tumors of the central nervous system in 25, medulloblastomas in 19, and neuroectodermic primary tumors in 6. All the patients underwent physical examination, 12 -lead electrocardiogram and pre- and post-treatment 2D echocardiograms to include in the clinical records. The demographic and clinic characteristics were analyzed. Hodgkin disease's patients received irradiation with 2 400 cGy intensity and the patients presenting tumors in the central nervous system with 2 340 cGy. Polychemotherapy was carried out with antracyclines, vincristine, vinblastine and others. Results: Average age of all patients was 7 years with predominance of male sex. Symptoms of cardiotoxicity were not recorded. Conclusions: In the serie of analyzed patients, irradiation in the heart area was apparently well beared by the patients, without early appearance of cardiotoxicity, not even in follow up periods of 9 years. Transitory nausea and leucopenia appeared in some cases. There are no differences in the toxicities of the different tumour's groups studied. It is necessary to keep the regular follow up to rule out the appearence of cardiotoxicity in the next years(AU)

La cardiooncología pediátrica como disciplina emergente en Cuba / Pediatric cardio-oncology as an emergent discipline in Cuba

El reconocimiento inicial de la disfunción cardíaca ocasionada por estrategias terapéuticas aplicadas contra el cáncer fue realizado en la sexta década del siglo xx. La Cardiooncología es una nueva disciplina horizontal dirigida a la identificación de los pacientes en riesgo elevado para el desarrollo de toxicidad cardíaca. El eficaz desempeño inherente a la Cardiooncología pediátrica radica en la adecuada selección del medio diagnóstico capaz de identificar y evaluar los indicios de cardiotoxicidad mediante la detección de cambios precoces en la funcionalidad del miocardio tras la aplicación de terapias antitumorales y, sobre todo, la predicción a largo plazo de estos eventos en niños sobrevivientes de cáncer. La cardiotoxicidad secundaria a la terapéutica aplicada sobre estos pacientes es un problema de salud latente en nuestro país que precisa la adopción de medidas organizativas concebidas para su enfrentamiento. Se persigue contribuir a la estructuración de la atención integral correspondiente al niño con cáncer y afectado por cardiotoxicidad en Cuba(AU)

The initial recognition of cardiac dysfunction caused by therapeutic strategies applied against cancer was performed in the sixth decade of the twentieth century. Cardio-Oncology is a new horizontal discipline aimed at the identification of patients at high risk for the development of cardiac toxicity. The effective performance inherent in Pediatric cardio-oncology lies in the appropriate selection of the diagnostic mean which can be capable of identifying and evaluating the indications of heart toxicity by detecting early changes in myocardial functionality after the application of anti-tumour therapies and, above all, the long-term prediction of these events in children survivors of cancer. Cardiac toxicity secondary to the therapies applied on these patients is a latent health problem in our country that requires the adoption of organisational measures conceived for their confrontation. It is pursued to contribute to the structuring of the comprehensive care corresponding to children with cancer and affected by cardiotoxicity in Cuba(AU)

Avaliação econômica do uso de dexrazoxano na profilaxia de cardiotoxicidade em crianças em tratamento quimioterápico com antraciclinas / Economic assessment of dexrazoxane in prophylaxis of cardiotoxicity in children undergoing chemotherapy with anthracyclines / Evaluación económica del uso del dexrazoxano en la profilaxia de cardiotoxicidad en niños en tratamiento quimioterápico con antraciclinas

Resumo: O câncer em indivíduos de 0 a 19 anos é considerado raro, quando comparado à incidência em faixas etárias maiores, sendo estimado entre 2% e 3% de todos os tumores malignos registrados no Brasil. O uso de antraciclinas está frequentemente associado ao aparecimento de cardiotoxicidade e faz parte de aproximadamente 60% dos protocolos terapêuticos em oncologia pediátrica. Dentre as estratégias existentes para a prevenção de cardiotoxicidade, o dexrazoxano obteve resultados favoráveis pautados em desfechos intermediários (marcadores bioquímicos e medidas ecocardiográficas). Foi desenvolvida, neste trabalho, uma avaliação de custo-efetividade que compare o uso do dexrazoxano em diferentes populações, além de uma avaliação do impacto orçamentário causado pela possível incorporação da tecnologia. Foi utilizado o horizonte temporal de toda a vida do paciente e a perspectiva de análise do Sistema Único de Saúde. Uma análise de impacto orçamentário para cada tecnologia também foi construída. Após uma busca na literatura, foi desenvolvido um modelo de Markov capaz de comparar o uso do dexrazoxano em seis perfis de pacientes com risco de desenvolver cardiotoxicidade. Usar o medicamento nas crianças menores de cinco anos de idade se mostrou a alternativa mais custo-efetiva (razão de custo-efetividade incremental - RCEI de R$ 6.156,96), seguida de usar em todos os pacientes (RCEI de R$ 58.968,70). Caso o preço diminua a um valor menor que R$ 250,00 por frasco, a alternativa de usar em todas as crianças se torna a mais custo-efetiva. O impacto orçamentário ao final de cinco anos foi de R$ 30.622.404,81 para uso apenas nas crianças menores de cinco anos. Usar a tecnologia em todas as crianças produziria um impacto incremental de R$ 94.352.898,77.

Abstract: Cancer in individuals 0 to 19 years of age is considered rare when compared to incidence in older age brackets, and is estimated at 2% to 3% of all malignant tumors recorded in Brazil. The use of anthracyclines is frequently associated with cardiotoxicity, and these drugs are part of approximately 60% of treatment protocols in pediatric oncology. Among the existing strategies for the prevention of cardiotoxicity, dexrazoxane obtained favorable results based on intermediate outcomes (biochemical markers and echocardiographic parameters). This study was based on a cost-effectiveness assessment comparing the use of dexrazoxane in different populations, besides an assessment of the budget impact from the technology's potential incorporation. The patient's lifetime was used as the timeline, and the analysis was performed from the perspective of the Brazilian Unified National Health System (SUS). A budget impact analysis was also performed for each technology. After a literature search, a Markov model was developed, capable of comparing the use of dexrazoxane in six profiles of patients at risk of developing cardiotoxicity. Use of the drug in children under 5 years of age proved to be the most cost-effective alternative (incremental cost effectiveness ratio - ICER of BRL 6,156.96), followed by use in all patients (ICER of BRL 58,968.70). If the price decreased to less than BRL 250.00 per vial, the alternative of using the drug in all children would become the most cost-effective. The budget impact at 5 years was BRL 30,622,404.81 for use only in children under 5 years of age. Using the technology in all the children could produce an incremental impact of BRL 94,352,898.77.

Resumen: El cáncer en individuos de 0 a 19 años está considerado raro, cuando se compara la incidencia en franjas etarias mayores, estimándose entre 2% y 3% de todos los tumores malignos registrados en Brasil. El uso antraciclinas está frecuentemente asociado a la aparición de cardiotoxicidad y forma parte de aproximadamente un 60% de los protocolos terapéuticos en oncología pediátrica. Entre las estrategias existentes para la prevención de cardiotoxicidad, el dexrazoxano obtuvo resultados favorables pautados en desenlaces intermedios (marcadores bioquímicos y medidas ecocardiográficas). Se desarrolló en este trabajo, una evaluación de costo efectividad que compare el uso del dexrazoxano en diferentes poblaciones, además de una evaluación del impacto presupuestario causado por la posible incorporación de la tecnología. Se utilizó el horizonte temporal de toda la vida del paciente y la perspectiva de análisis del SUS. También se realizó un análisis del impacto presupuestario para cada tecnología. Tras una búsqueda en la literatura, se desarrolló un modelo de Markov capaz de comparar el uso del dexrazoxano en 6 perfiles de pacientes con riesgo de desarrollar cardiotoxicidad. Usar el medicamento en los niños menores de 5 años de edad se mostró la alternativa más costo-efectiva (relación costo-efectividad incremental - RCEI de BRL 6.156,96), seguido de usarlo en todos los pacientes (RCEI de BRL 58.968,7). En caso de que el precio disminuya a un valor inferior a BRL 250,00 por frasco, la alternativa de usarlo en todos los niños se convierte en la más costo-efectiva. El impacto presupuestario tras 5 años fue de BRL 30.622.404,81 para su uso exclusivo en niños menores de 5 años. Usar esta tecnología en todos los niños, tendría un impacto presupuestario incrementándolo hasta los BRL 94.352.898,77.

Importância da Prática de Atividade Física para Prevenção do Risco de Cardiotoxicidade: Revisão Sistemática / Importance of Physical Activity Practice for Cardiotoxicity Risk Prevention: Systematic Review / Importancia de la Práctica de Actividad Física para la Prevención del Riesgo de Cardiotoxicidad: Revisión Sistemática

Introdução: A cardiotoxicidade pode afetar de forma direta a capacidade funcional, a ventilação pulmonar e a força muscular e, também, de forma indireta, outros órgãos e sistemas. O exercício físico é sugerido como uma estratégia não farmacológica efetiva e de baixo custo para minimizar ou prevenir dano miocárdico associado ao tratamento com antraciclinas. Objetivo: Discutir os efeitos do exercício físico em pacientes com risco para cardiotoxicidade pós-tratamento oncológico com quimioterapia e/ou radioterapia. Método: Realizada pesquisa nas bases de dados SciELO, PEDro e PubMed, nos idiomas português e inglês, por artigos científicos publicados entre 2007 e 2018. Resultados: Foram encontrados 256 abstracts, 34 foram selecionados para uma leitura na integra por atenderem aos critérios de inclusão, 25 artigos foram excluídos por não se enquadrarem nos critérios de inclusão e somente nove apresentaram associação dos efeitos do exercício na presença de cardiotoxicidade. Conclusão: A melhora do consumo máximo de oxigênio (VO2max/pico) e da distância percorrida em 6 minutos (DP6M) foi mais evidente no treinamento contínuo e, assim como no exercício resistido, permaneceu por médio e longo prazo. As medidas da DP6M e do VO2max/pico e de ausência foram os parâmetros indicativos de melhora.

Introduction: Cardiotoxicity can directly affect functional capacity, pulmonary ventilation and muscle strength, as well as indirectly affect other organs and systems. Exercise is suggested as an effective and inexpensive non-pharmacological strategy to minimize or prevent myocardial damage associated with anthracycline treatment. Objective: To discuss the effects of physical exercise in patients with cardiotoxicity following cancer treatment with chemotherapy and/or radiotherapy. Method: Scielo, PEDro and PubMed databases were researched, in Portuguese and English, for scientific articles published between 2007 and 2018. Results: We found 256 abstracts, 34 were selected for full reading because they met the inclusion criteria, 25 articles were excluded because they did not meet the inclusion criteria and only 9 presented the association of exercise effects in the presence of cardiotoxicity. Conclusion: The improvement in maximal oxygen uptake (VO2 max/peak) and 6-minute walk distance (6MWD) were more evident in continuous training and, as in resistance exercise, remained in the medium and long term. Measurements of 6WMD and maximal oxygen uptake VO2 max/peak and dyspnea were the indicative parameters for improvement.

Introducción: la cardiotoxicidad puede afectar directamente la capacidad funcional, la ventilación pulmonar y la fuerza muscular, así como afectar indirectamente a otros órganos y sistemas. El ejercicio se sugiere como una estrategia no farmacológica efectiva y económica para minimizar o prevenir el daño miocárdico asociado con el tratamiento con antraciclina. Objetivo: Discutir los efectos del ejercicio físico en pacientes con cardiotoxicidad después del tratamiento del cáncer con quimioterapia y/radioterapia. Método: Se investigaron las bases de datos SciELO, PEDro y PubMed, en portugués e inglés, para artículos científicos publicados entre 2007 y 2018. Resultados: Encontramos 256 resúmenes, 34 fueron seleccionados para lectura completa porque cumplían con los criterios de inclusión, 25 artículos fueron excluidos porque no cumplían los criterios de inclusión y solo 9 presentaron la asociación de los efectos del ejercicio en presencia de cardiotoxicidad. Conclusión: La mejora en lo consumo máximo de oxígeno (VO2 max/pico) y la distancia de caminata de 6 minutos (6MWD) fue más evidente en el entrenamiento continuo y, como en el ejercicio de resistencia, se mantuvo en mediano y largo plazo. Las mediciones de 6MWD y VO2 max/pico y disnea fueron los parámetros indicativos para la mejora.

Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers

SUMMARY OBJECTIVES This study aimed at assessing the role of beta-blockers on preventing anthracycline-induced cardiotoxicity in adults. METHODS A systematic review was performed on electronic databases, including relevant studies that analysed beta-blockers as cardioprotective agents before the use of anthracyclines by adult oncologic patients. RESULTS After application of eligibility and selection criteria, eight articles were considered as high quality, complying with the proposed theme; all eight clinical trials, four of them placebo-controlled, with a total number of 655 patients included. From this sample, 281 (42.9%) used beta-blocker as intervention, and carvedilol was the most frequent (167 patients - 25.5%). Six studies were considered positive regarding the cardioprotection role played by beta-blockers, although only four demonstrated significant difference on left ventricle ejection fraction after chemotherapy on groups that used beta-blockers compared to control groups. Carvedilol and nebivolol, but not metoprolol, had positive results regarding cardioprotection. Other beta-blockers were not analysed in the selected studies. CONCLUSIONS Despite the potential cardioprotective effect of beta-blockers, as demonstrated in small and unicentric clinical trials, its routine use on prevention of anthracycline-associated cardiotoxicity demands greater scientific evidence.

RESUMO OBJETIVO Este estudo teve como objetivo analisar o papel dos betabloqueadores na prevenção da cardiotoxicidade induzida pelas antraciclinas em adultos. MÉTODOS Foi realizada uma revisão sistemática em bases de dados eletrônicos, incluindo os estudos relevantes que analisaram fármacos betabloqueadores como agentes cardioprotetores antes do início do uso de antraciclinas por pacientes oncológicos adultos. RESULTADOS Após aplicação dos critérios de elegibilidade e seleção, foram obtidos oito artigos considerados de boa qualidade, que se adequavam à temática proposta, sendo todos ensaios clínicos, quatro placebo-controlados, totalizando 655 pacientes incluídos. Destes, 281 (42,9%) fizeram uso de algum betabloqueador como intervenção, sendo o carvedilol o mais utilizado (167 pacientes - 25,5%). Seis estudos foram considerados positivos quanto à cardioproteção exercida pelos betabloqueadores, porém apenas quatro demonstraram diferença na fração de ejeção do ventrículo esquerdo após a quimioterapia nos grupos que usaram betabloqueadores em relação aos grupos controle. O carvedilol e o nebivolol, mas não o metoprolol, tiveram resultados positivos quanto à cardioproteção. Outros betabloqueadores não foram avaliados nos estudos incluídos. CONCLUSÕES Apesar de haver um potencial efeito cardioprotetor dos betabloqueadores, conforme demonstrado em ensaios clínicos pequenos e unicêntricos, sua utilização rotineira na prevenção da cardiotoxicidade associada às antraciclinas requer maiores comprovações científicas.

Cardiotoxicidad inducida por tratamientos oncológicos: fundamentos para la implementación de equipos de Cardio-Oncología / Cardiotoxicity of anticancer therapies: towards the implementation of cardio-oncology units

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Evaluación ecocardiográfica longitudinal en pacientes con leucemia linfoide aguda que recibieron antraciclinas durante la edad pediátrica / Longitudinal ecocardiographic assesment in patients with acute lymphoid leukemia that received anthracyclines during childhood

Introducción: La cardiotoxicidad tardía causada por el tratamiento del cáncer puede ser un problema frecuente en los sobrevivientes por lo que se decidió realizar un estudio ecocardiográfico longitudinal de la función cardiovascular con el objetivo de detectar las alteraciones causadas por la administración de antraciclinas en pacientes que tuvieron una leucemia linfoide aguda en la edad pediátrica. Métodos: se incluyeron todos los pacientes atendidos por esta leucemia en el Servicio de Pediatría del Instituto de Hematología e Inmunología ,desde abril de 2002 hasta febrero de 2015, que además debían tener al menos 2 evaluaciones ecocardiográficas posteriores a la conclusión del tratamiento. A todos se les realizó examen físico, se tomaron datos generales de las historias clínicas, se les calculó la dosis acumulativa de antraciclinas y el tiempo transcurrido hasta la realización de la evaluación. De los ecocardiogramas realizados se tomaron las medidas de aurícula izquierda, ventrículo derecho, fracción de eyección y fracción de acortamiento. Resultados : predominaron los signos de cardiotoxicidad tardía subclínica con una media de 9 años después de suspendido el tratamiento y estuvieron afectados ambos sexos por igual. En el primer ecocardiograma realizado, tres años después de la suspensión, la mayor frecuencia de alteraciones estuvieron en las medidas de aurícula izquierda y ventrículo derecho. Los estudios se repitieron cada tres años y en el tercer estudio fue más frecuente la afectación de las fracciones de eyección y de acortamiento. Se encontró que había relación estadísticamente significativa entre el uso de mayores dosis de antraciclinas y las alteraciones ecocardiográficas. Conclusiones: las afectaciones de la función cardiovascular fueron ligeras y aumentaron durante el seguimiento(AU)

Introduction Cancer therapy could cause frequent cardiac toxicity, so we decided to perform an echocardiographic longitudinal study of the late effects caused by anthracyclines administration in patients that were treated for acute lymphoid leukemia during childhood. Methods All the patients admitted in the Pediatric Service of Institute of Hematology and Immunology, with acute lymphoid leukemia since april 2002 until february 2015 and that have at least two echocardiographic studies after finishing therapy. A complete physical exammination was performed to all of them and the cumulative dose of anthracyclines received was calculated and also time until evaluation. From the echocardiograms were taken the measurements of left auricle, right ventricle, ejection fraction and shortening fraction. Results: the main findings were signs of late subclinical cardiotoxicity with a mean of 9 years after therapy completion and there were no sex predominance. In the first echocardiogram performed three years after stopping therapy there were more alterations in the measures of left auricle and right ventricle. The studies were repeated every three years and in the third one there were more alterations in ejection fraction and shortening fraction and there also were a statiscally significative relation between cumulative anthracyclines doses and echocardiographic findings. Conclusions: There were found subclinical cardiac dysfunction that increases as time goes by(AU)

Dexrazoxano na prevenção de cardiotoxicidade causada por antraciclinas em crianças / Dexrazoxane in the prevention of anthracycline cardiotoxicity in children

Contexto: O tratamento do câncer com medicamentos da classe das antraciclinas está frequentemente associado ao aparecimento de cardiotoxicidade. Esse grupo de medicamentos faz parte de aproximadamente 60% dos protocolos terapêuticos em oncologia pediátrica. No SUS, não existem protocolos que pautem a prevenção de cardiotoxicidade no uso de antraciclinas. Dentre as estratégias existentes, o dexrazoxano obteve resultados favoráveis pautados em desfechos intermediários (marcadores bioquímicos e medidas ecocardiográficas). Desfechos clínicos finalísticos (internações evitadas) não foram avaliados. Pergunta: O uso de dexrazoxano associado à antraciclinas para o tratamento do câncer em pacientes pediátricos é eficaz, seguro e custo-efetivo na prevenção de cardiotoxicidade geradora de insuficiência cardíaca e outras doenças do coração quando comparado à quimioterapia isolada? Evidências científicas: Dentre as melhores evidências recuperadas, encontram-se 5 estudos que avaliaram eficácia e segurança, dentre eles ensaios clínicos e estudos de coorte nos Estados Unidos e Coréia do Sul respectivamente. Os grupos de pacientes em sua maioria tinham idade inferior a 18 anos, com leucemia linfoblástica aguda e linfoma de Hodking, e em tratamento com antraciclinas, em doses que variaram de 110 a 410mg/m2. Os desfechos analisados pelos estudos são bastante heterogêneos. Em sua maioria, os estudos usaram marcadores bioquímicos e medidas ecocardiográficas para prever cardiotoxicidade tardia, mortalidade, e sobrevida livre de eventos. Como resultado, o dexrazoxano se mostrou eficaz na prevenção da alteração de marcadores bioquímicos e medidas ecocardiográficas preditoras de cardiotoxicidade tardia. No que diz respeito à mortalidade e ao surgimento de neoplasias secundárias, não houve diferença estatisticamente significativa entre os braços de análise dos estudos. No âmbito da segurança do medicamento, medidas de toxicidade hematológica se apresentaram desfavoráveis ao uso do dexrazoxano. Discussão: As interpretações dos resultados dos estudos devem ser observadas com cautela, pois nenhum deles, com os tempos de acompanhamento propostos, foram capazes de avaliar desfechos clínicos importantes e conclusivos como insuficiência cardíaca ou internação. Apesar disso, são algumas evidências apontam que desfechos intermediários (marcadores bioquímicos) podem ser bons preditores de problemas cardíacos sintomáticos no futuro. Decisão: Não incorporar o dexrazoxano para prevenção de cardiotoxicidade causada por antraciclinas em crianças, como procedimento específico, no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria SCTIE-MS nº 25 publicada no Diário Oficial da União (D.O.U.) nº 110, de 10 de junho de 2016.

Effects of thymoquinone against cisplatin-induced cardiac injury in rats

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.