Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Arrhythmia:innovative understanding from traditional Chinese medicine and treatment by classic herbal formulas / 中国中药杂志

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit / 中国中药杂志

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of "trembling and shivering" may be the clinical manifestation of heart failure, which is an upgraded version of "trembling and shaking" treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury / 中华医学杂志(英文版)

BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

Index of cardiac-electrophysiological balance and the effects of thrombolytic therapy on the electrocardiogram of patients with pulmonary embolism

SUMMARY OBJECTIVE: Different parameters on electrocardiograms (ECG) have been investigated to predict arrhythmia and mortality in patients with acute pulmonary embolism (APE). The acute effect of thrombolytic therapy (TT) on these parameters has not been investigated yet. METHODS: We examined the data of 83 patients who were evaluated as high-risk APE and discharged from the hospital after TT. First, the high-risk APE patients' ECGs were compared with healthy control subjects (n = 55). After their admission and 24 hours later, the ECGs of patients with APE were compared. Heart rate, P-wave morphology, QRS duration, QT distance, Tp-e, and the index of cardiac electrophysiological balance (iCEB) were analyzed. RESULTS: Although P maximum was not different between the groups' ECGs, heart rate, QT, QTc (corrected QT) interval, Tp-e intervals, Tp-e/QT ratio, and P wave dispersion were significantly higher in the APE group ( P values < 0.031). iCEB or iCEBc (corrected iCEB) values were lower in APE group ( P < 0.001). After TT, we determined a decrease in heart rate, Tp-e interval, and Tp-e/QT ratio ( P < 0.001). Although we detected a decrease in the QT and QTc interval and QT dispersion (QTd), QTd had no statistical significance (respectively P -value 0.013, 0.029, and 0.096). The iCEB and iCEBc levels were lower after TT ( P -value was 0.035 and 0.044 respectively). CONCLUSION: The QT, QTc, Tp-e interval, Tp-e/QTc ratio, iCEB, and iCEBc values significantly decreased after TT. It may be thought that effective TT causes partial improvement in ventricular repolarization in an early period.

RESUMO OBJETIVO: Diferentes parâmetros de eletrocardiograma (ECG) têm sido investigados para predizer mortalidade e arritmia em pacientes com embolia pulmonar aguda (EPA). O efeito agudo da terapia trombolítica (TT) nesses parâmetros ainda não foi investigado. MÉTODOS: Examinamos os dados de 83 pacientes avaliados com EPA de alto risco e que receberam alta hospitalar após TT. Primeiramente, comparamos os ECGs dos pacientes com EPA de alto risco com os de indivíduos saudáveis (n = 55). Os ECGs dos pacientes com EPA foram comparados logo após a internação e 24 horas mais tarde. A frequência cardíaca, a morfologia da onda P, a duração do QRS, o intervalo QT, Tp-e e o índice de equilíbrio eletrofisiológico cardíaco (iCEB) foram analisados. RESULTADOS: Embora o valor máximo de P não tenha sido diferente entre os grupos no ECG, a frequência cardíaca, QT, intervalo QTc (QT corrigido), intervalos Tpe, razão TP-e/QT e dispersão da onda P foram significativamente mais elevados no grupo de EPA (valores de P < 0,031). Os valores do iCEB ou iCEBc (iCEB corrigido) foram inferiores no grupo de APE (P < 0,001). Após a TT, observamos uma diminuição da frequência cardíaca, do intervalo TP-e e da razão TP-e/QT ( P < 0,001). Apesar de termos observado uma diminuição do intervalo QT e QTc e da dispersão do QT (QTd), o valor de QTd não apresentou uma diferença estatisticamente significativa (respectivamente, valor de P 0,013, 0,029 e 0,096). Os níveis do iCEB e iCEBc foram menores após a TT (valor de P 0,035 e 0,044, respectivamente). CONCLUSÃO: Os valores de QT, QTc, intervalo Tp-e, razão Tp-e/QTc, iCEB e iCEBc diminuíram significativamente após TT. Pode-se concluir que a TT eficaz causa uma melhora parcial da repolarização ventricular no período inicial.

Translational Approach for Percutaneous Interventions for the Treatment of Cardiac Arrhythmias

Abstract New translational concepts on cellular and tissue substrate of cardiac arrhythmias have been responsible for the development of non-pharmacological interventions, with important achievements compared to the conventional approach with antiarrhythmic drugs. In addition, the increasing knowledge of anatomical and electrophysiological studies, sophisticated mapping methods, special catheters, and controlled clinical trials have favored the progression of ablation of tachyarrhythmias, particularly of ventricular tachyarrhythmias and atrial fibrillation.

Prescription to reduce heart palpitations, a mid-18th century prescription in the New Kingdom of Granada / Formulación para reducir las palpitaciones cardiacas, una receta médica de mediados del siglo xviii en el Nuevo Reino de Granada

Abstract The human being, throughout history, has used plants to prevent and cure diseases. It is important to know that for a long time, the mechanism through which those plants worked was unknown, making herbal medicine a purely empirical science. Medical prescriptions in the 19th century in the Kingdom of Nueva Granada were considered a significant medical advance as a result of knowledge and medical practices in the old continent. Medical literature of the time achieved, despite the lack of studies, the development of new schemes with exact dosages and new therapeutic possibilities. The medical prescription presented in this article was used in the management of heart palpitations, a frequent symptom nowadays, described as thoracic and/or neck beating, underlying various cardiac and non-cardiac diseases. The recipe for the palpitations of the historical archive "Cipriano Rodríguez Santa María" is a mixture of herbal agents that, as reviewed in the medical literature, showed to have anti-inflammatory, anxiolytic, and antioxidant effects, among others, allowing a beneficial effect on cardiac palpitations. Due to the lack of information on the posology, safety in its use, contraindications, and possible adverse effects, its potential use should have been underestimated at that time for the control of palpitations or as phytochemical agents directed to treat diseases causing this symptom.

Resumen A lo largo de la historia, el ser humano ha utilizado plantas para prevenir, aliviar y curar enfermedades. Cabe destacar que durante mucho tiempo se desconoció el mecanismo por el cual su uso era beneficioso, lo que hacía de la fitoterapia una ciencia netamente empírica. Las recetas médicas eran consideradas un avance médico significativo, resultado de conocimientos y prácticas traídas desde el viejo continente. Pese a la carencia de estudios locales, la literatura médica de la época permitió utilizar la biodiversidad de América para el desarrollo, investigación y uso de nuevos esquemas fitoterapéuticos con dosificaciones establecidas e indicaciones de uso, incluso un lugar específico de dispensación, ampliando aún más las posibilidades terapéuticas. La receta médica que se expone en este artículo era empleada en el manejo de las palpitaciones cardiacas, síntoma frecuente aún en la actualidad, descrito como golpes en tórax y/o cuello, subyacente en diversas enfermedades cardiacas y no cardiacas. La receta para las palpitaciones del archivo histórico Cipriano Rodríguez Santa María es una mezcla de agentes herbarios que, al realizar una revisión en la literatura médica, evidencian efectos antiinflamatorios, ansiolíticos y antioxidantes entre otros, sustentando un posible efecto beneficioso en las palpitaciones cardiacas. Debido a la ausencia de información sobre la posología, seguridad en su uso, contraindicaciones y posibles efectos adversos, es subestimado su potencial uso en aquel entonces para el control de las palpitaciones o como unos agentes fitoquímicos dirigidos para tratar enfermedades causantes de dicho síntoma.

Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3 / Inotropic and Antiarrhythmic Transmural Actions of Ranolazine in a Cellular Model of Type 3 Long QT Syndrome

Resumo A Ranolazina (RANO), conhecida na clínica como Ranexa, é um fármaco que previne a arritmia cardíaca através da inibição da corrente de sódio tardia (INaT). Um gradiente de voltagem transmural do canal Nav1.5 encontra-se na parede ventricular esquerda do coração. Assim, investigamos os efeitos da RANO em cardiomiócitos saudáveis e em modelo celular da Síndrome do QT longo tipo 3 (SQTL tipo 3). Usamos células isoladas do endocárdio (ENDO) e do epicárdio (EPI) e um software de medição com detecção de bordas por vídeo e microscopia de fluorescência para monitorar os transientes de cálcio. A RANO (0,1, 1, 10 e 30 uM, a 25OC) em uma série de frequências de estimulação teve impacto pouco significativo sobre ambos os tipos de células, mas a RANO (30uM) a 35OC minimizou o encurtamento dos sarcômeros em ~21% para células do endocárdio. Em seguida, para simular a SQTL tipo 3, as células do ENDO e EPI foram expostas à toxina ATX-II da anêmona do mar, que aumenta a INaT. As arritmias celulares induzidas por ATX-II foram suprimidas com o uso da RANO (30 µM) a 35OC. Com base nesses resultados, podemos concluir que a RANO tem um impacto pouco significativo sobre o encurtamento dos sarcômeros de células saudáveis do ENDO e EPI. Além disso, ela suprime as arritmias induzidas por INaT para níveis semelhantes nas células do ENDO e EPI.

Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

Tratamiento de la embarazada con fibrilación auricular y compromiso hemodinámico / Treatment of pregnant women with atrial fibrillation and hemodynamic disorders

Las arritmias cardiacas son complicaciones frecuentes en el embarazo, son más frecuentes las supraventriculares, con gran importancia la fibrilación auricular con compromiso hemodinámico, que pone en peligro al binomio madre hijo, asociado al efecto dañino de los medicamentos antiarrítmicos. El autor se propone analizar los elementos del consenso científico al tratar la fibrilación auricular de forma más adecuada para el binomio madre hijo, así como la protocolización del tratamiento. A partir de la experiencia del tratamiento de dos embarazadas con fibrilación auricular, con formas y desenlaces totalmente diferentes, en discusión del colectivo multidisciplinario, se busca y analiza una protocolización actualizada, en la conducta a seguir con madre hijo, en caso de arritmia. Las arritmias en la embarazada representan un riesgo para eventos fetales adversos, además de los riesgos potenciales de los medicamentos usados para el tratamiento. La cardioversión eléctrica, sincronizada, parece ser claramente idónea en el tratamiento(AU)

Cardiac arrhythmias are frequent complications in pregnancy, supra ventricular diseases are more frequent, with great importance atrial fibrillation with hemodynamic disorders, which puts the child mother binomial in danger, associated with the harmful effect of antiarrhythmic drugs. The author proposes to analyze the elements of the scientific consensus when treating atrial fibrillation in a more adequate way for the child mother binomial, as well as the protocolization of the treatment. From the experience of the treatment of two pregnant women with atrial fibrillation, with completely different forms and outcomes, in discussion of the multidisciplinary group, an updated protocol is searched and analyzed, in the behavior to be followed with the mother, in case of arrhythmia. Arrhythmias in the pregnant woman represent a risk for adverse fetal events, in addition to the potential risks of the medications used for the treatment. The synchronized electrical cardioversion seems to be clearly suitable in the treatment(AU)

Efecto electromecánico de los antiarrítmicos clase Ic durante el tratamiento de arritmias auriculares en cardiopatías congénitas / Electromechanical effect of Ic class antiarrhythmic drugs during the treatment of atrial arrhythmias in congenital heart diseases

Introducción: los fármacos antiarrítmicos son la primera línea de tratamiento para el control de las taquiarritmias en el paciente pediátrico. La terapéutica con drogas clase Ic en los pacientes con cardiopatías congénitas ha sido limitada, por los reportes que demostraron incremento de la mortalidad en los sujetos con cardiopatías estructurales. Objetivo: valorar el efecto de los antiarrítmicos clase Ic sobre los fenómenos electro-mecánicos cardiacos en los niños con cardiopatías congénitas con arritmias auriculares. Métodos: se realizó un estudio analítico, observacional, longitudinal y prospectivo en los pacientes con cardiopatías congénitas que desarrollaron arritmias auriculares, tratados con antiarrítmicos clase Ic en el Cardiocentro Pediátrico William Soler . Se analizaron variables electrocardiográficas, así como estimación de la función sistodiastólica mediante el ecocardiograma. Resultados: fueron evaluados 46 pacientes, 25 tratados con flecainida (grupo I) y 21 con propafenona (grupo II) durante 4,57±0,86 años. La taquicardia por reentrada intraatrial fue la arritmia de mayor incidencia (58,69 por ciento), mientras que, la tetralogía de Fallot, el defecto cardiaco más común (36,9 por ciento). Las variables electrocardiográficas no sufrieron variaciones nítidas durante el seguimiento. El análisis comparativo intragrupal demostró la preservación de la función sistólica en la totalidad de los sujetos (I, p= 0,275; II, p= 0,262). Comportamiento análogo exhibió la función diastólica, expresada en el índice de Tei (I, p= 0,244; II, p= 0,286). Conclusiones: la utilización de antiarrítmicos clase Ic en los pacientes pediátricos con cardiopatías congénitas no se asocia a largo plazo con alteraciones electrocardiográficas significativas ni compromiso de la función sistodiastólica, por lo que se recomienda su uso en esta población(AU)

Introduction: antiarrhythmic drugs are the first line of treatment for the control of tachyarrhythmias in pediatric patients. Therapy with Ic class drugs in patients with congenital heart disease has been limited, mainly due to reports that showed an increase in mortality in patients with structural heart disease. Objective: to assess the effect of Ic class antiarrhythmic drugs on cardiac electro-mechanical phenomena in children with congenital heart disease with atrial arrhythmias. Methods: an analytical, observational, longitudinal and prospective study was performed in patients with congenital heart diseases who developed atrial arrhythmias treated with Ic class antiarrhythmic drugs in William Soler Pediatric Cardiocenter. Electrocardiographic variables were analyzed, as well as the estimation of systo-diastolic function by echocardiography. Results: 46 patients were evaluated, 25 treated with flecainide (group I) and 21 with propafenone (group II) during 4.57 ± 0.86 years. The intra-atrial reentrant tachycardia was the arrhythmia with the highest incidence (58.69 percent); while tetralogy of Fallot was the most common cardiac defect (36.9 percent). The electrocardiographic variables did not undergo sharp variations during the follow-up. The intergroup comparative analysis showed the preservation of systolic function in all subjects (I, p= 0.275; II, p= 0.262). Analogous behavior showed diastolic function, that was expressed in the Tei index (I, p= 0.244; II, p= 0.286). Conclusions: the use of Ic class antiarrhythmic drugs in pediatric patients with congenital heart disease is not associated in the long term with significant electrocardiographic alterations or compromise of systo-diastolic function, so its use is recommended in this population(AU)

Disfunción tiroidea inducida por amiodarona en pacientes portadores de arritmias / Thyroid dysfunction induced by Amiodarone in patient with arrhythmias

Evaluar la presencia de disfunción tiroidea en pacientes con arritmias cardíacas tratados con Amiodarona (AMD) Métodos: se realizó el estudio en 24 pacientes que presentaron arritmias supraventriculares o ventriculares tratados con AMD, atendidos en el Servicio de Medicina Interna de la Ciudad Hospitalaria "Dr. Enrique Tejera" durante el período julio 2015 ­ abril 2016. Se les determinaron T3L, T4L y TSH a manera de tamizaje previo a la administración de AMD y fueron citados y divididos en 3 grupos de 3, 6 y 12 meses de tratmiento de AMD con determinación del perfil tiroideo en la consulta. Resultados: El hipotiroidismo inducido por AMD (HIA) se presentó en 20,83% (n=5), siendo más frecuente en aquellos pacientes asculinos que tenían 3 meses de tratamiento y que recibían una dosis de 1400 mg/semanal. La tirotoxicosis inducida por AMD (TIA) se presentó en 8,33% (n=2) ambos masculinos con dosis de 1400 mg/semanal. No se encontró asociación entre HIA y TIA con el tiempo, dosis, grupo etario ni género (P>0,05). T3L, T4L y TSH registraron el mayor y menor promedio a los 12 y 3 meses (P < 0,05); 12 y 6 meses; 3 y 12 meses respectivamente. Conclusión: La frecuencia de HIA fue de 20,83 % y TIA de 8,33 %. No hubo asociación estadísticamente significativa entre la HIA o TIA con la duración de consumo, dosis, grupo etario ni género. La TSH presentó el mayor promedio a los 3 meses, la T3L y T4L a los 12 meses (AU)

to evaluate the presence of thyroid dysfunction in patients with cardiac arrhythmia who were treated with Amiodarone (AMD). Methods: the study was done in 24 patients who were treated for supraventricular or ventricular arrhythmia at the Department of Internal Medicine of Hospital "Dr. Enrique Tejera" in Valencia, Venezuela from July 2015 to April 2016. FT3, FT4 and TSH were measured to the administration of AMD. The patients were divided in 3 groups according to time of use of the drug as follows: 3, 6 and 12 months, and their thyroid function was measured at each of these periods. Results: 20.83 % (n=5) presented Amiodarone induced hypothyroidism (AIH), which was more frequent in males at 3 months of treatment and who received 1400 mg weekly. Amiodarone induced thyrotoxicosis (AIT) was found in 8.33% (n=2) also in male patients using 1400mg weekly. There was no association between AIH or AIT and duration, dose of AMD, age or gender. (p>0.05) FT3, FT4 and TSH registered their higher and lower averages on 12 and 3 months (P < 0,05); 12 and 6 months; 3 and 12 months respectively. Conclusion: AIH's frequency was 20.83 % and 8.33% for AIT. There was no statistically significant association between AIH or AIT and duration, dose of AMD, age or gender TSH average measure was higher at 3 months and the FT3 and FT4 at 12 months(AU)

Chronic Heart Disease after Treatment of Oral Acute Chagas Disease / Cardiopatia Crônica após Tratamento de Doença de Chagas Aguda Oral

Abstract We describe the recurrence of cardiac abnormalities in a patient treated during the acute phase of Chagas disease after outpatient follow-up of 5 years.

Resumo Descreve-se a recorrência de alterações cardíacas em paciente tratado na fase aguda de doença de Chagas, após seguimento ambulatorial de 5 anos.

Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment / Remodelação Cardíaca: Conceitos, Impacto Clínico, Mecanismos Fisiopatológicos e Tratamento Farmacológico

Abstract Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies.

Resumo A remodelação cardíaca é definida como um conjunto de mudanças moleculares, celulares e intersticiais cardíacas, que se manifestam clinicamente por alterações no tamanho, massa, geometria e função do coração, em resposta à determinada agressão. Esse processo resulta em mal prognóstico, pois está associado com a progressão da disfunção ventricular e arritmias malignas. Nessa revisão, são discutidos os conceitos e as implicações clínicas da remodelação, além do papel fisiopatológico de diferentes fatores, incluindo morte celular, metabolismo energético, estresse oxidativo, inflamação, colágeno, proteínas contráteis, transporte de cálcio, geometria e ativação neurohormonal. Finalmente, o artigo apresenta o tratamento farmacológico, que pode ser dividido em três estágios: estratégias consolidadas, promissoras e potenciais.

Brugada Syndrome: A Major Cause of Sudden Cardiac Death.

In 1992 a new syndrome was described consisting of syncopal episodes or sudden death in patients with a structurally normal heart and an electrocardiogram characteristic of right bundle branch block with ST segment elevation in leads V1 to V3. Brugada syndrome is an autosomal dominant disorder. It has been shown to be associated with mutations in the gene (SCN5A) that encodes for the sodium ion channel in cardiac myocyte. Over 160 mutations of gene SCN5A have been identifi ed. Th e incidence of the disease is diffi cult to estimate, but it causes sudden deaths of 5 per 10,000 inhabitants per year and involved much more frequently in people of Asian ancestry. Diagnosis can be easily made by means of genetic analysis and ECG. Recent data suggest that loss of the action potential dome in the right ventricular epicardium underlies ST segment elevation seen in this syndrome. Right ventricular epicardium is preferentially aff ected because of the predominance of transient outward current in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent death in symptomatic or asymptomatic individuals. Th ough Implantation of an automatic cardioverter–defi brillator is the only recently proven eff ective therapy; Quinidine has been found to decrease Ventricular fi brillation and could prove to be a secured option of implantable cardioverter–defi brillator. However, researcher set focus on gene therapy that may off er an enduring cure in future years. Th e purpose of this brief review is to record the past highlights that have brought us to our present understanding of Brugada syndrome.

The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice

BACKGROUND/AIMS: Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. METHODS: Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response. RESULTS: The mean daily dose of amiodarone was 227 +/- 126 mg, and the mean duration was 490 +/- 812 days. During the mean follow-up duration of 982 +/- 1,137 days, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year). CONCLUSIONS: Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.