Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

Efecto de los fármacos en la prolongación del QT y la aparición de muerte súbita en la COVID-19 / Effect of Drugs on QT Prolongation and Sudden Death in COVID-19

Introducción: Las evidencias científicas han demostrado que durante el período pandémico por la COVID-19 ha existido un incremento de la incidencia de muerte súbita cardiovascular, proporcional al incremento de los casos y a la letalidad por la enfermedad. Objetivos: Compilar información sobre los fármacos empleados en el tratamiento de la COVID-19 y sus posibles efectos en la prolongación del intervalo QT y la aparición de muerte súbita. Métodos: Se realizó una búsqueda de información a partir de las bases de datos PubMed, Medline y SciELO, en los idiomas español e inglés en el período de enero de 2020 a enero de 2023. Resultados: Los hallazgos más recientes sugieren que los factores relacionados con el tratamiento médico del paciente para sus enfermedades cardiovasculares previas, el empleo concomitante de drogas para otras comorbilidades, el ensayo de nuevas drogas que se investigan en la actualidad para el tratamiento de la enfermedad y el uso inadecuado de fármacos en complicaciones graves por la COVID-19, pueden ocasionar prolongación del intervalo QT y arritmias ventriculares tipo torsades de pointes, lo que puede conllevar a la aparición de muerte súbita. Conclusiones: Ha sido demostrado el efecto deletéreo de los fármacos en el tratamiento de la COVID-19 y sus posibles asociaciones a la terapéutica del paciente, en la prolongación del tiempo de repolarización ventricular cardíaca, cuya traducción eléctrica es un intervalo QT prolongado y su contribución a la génesis de arritmias malignas potencialmente fatales capaces de desencadenar un paro cardíaco y evolucionar a la muerte súbita(AU)

Scientific evidence has shown an increase in the incidence of sudden cardiovascular death during the COVID-19 pandemic period. This has been proportional to the increase in cases and mortality from the disease. Direct and indirect injury to the myocardium and vascular system allow to partially explain the statistics. Among the factors related to the medical treatment of the patient for previous cardiovascular diseases, it is the concomitant use of drugs for other comorbidities. The trial of new drugs for the treatment of this condition and the inappropriate use of drugs in serious complications from COVID-19 are currently being investigated. These can cause QT prolongation and torsades de pointes ventricular arrhythmias, which can lead to sudden death. Monitoring the QT interval is recommended, before and during treatment, in patients who come to the emergency room with a clinical condition suggestive of COVID-19. Additionally, modifiable factors favoring its prolongation should be evaluated. Decision-making in the application of therapeutic protocols in patients with COVID-19 with prolonged QTc at baseline, or with increased QTc after starting treatment, must go through the analysis of the risk/benefit ratio defined by a multi- and interdisciplinary team(AU)

Desfibrilador subcutáneo. Primeros casos en el Instituto Nacional de Cardiología, incluyendo dos pacientes pediátricos / Use of subcutaneous cardioverter-defibrillator. First cases reported from National Institute of Cardiology Ignacio Chávez-Mexico

Resumen Introducción: El desfibrilador automático implantable (DAI) transvenoso es el tratamiento de elección para la prevención de muerte súbita (MS) cardiaca por arritmias ventriculares malignas. Su uso se puede ver limitado cuando existe infección del sistema de estimulación o en población pediátrica donde representa un reto por diversas razones, incluyendo: las mínimas dimensiones del sistema venoso de los niños, la longitud de los electrodos, el tamaño del generador, así como por la complejidad anatómica en casos de cardiopatía congénita asociada. Objetivo: El presente artículo tiene por objetivo presentar la primera serie de casos de pacientes mexicanos a los cuales se les implantó un DAI subcutáneo (DAI-SC) como terapia para la prevención de MS. Métodos: Se presentan los cuatro primeros casos que fueron implantados en el Instituto Nacional de Cardiología Ignacio Chávez con un DAI-SC (Emblem, Boston Scientific, EE.UU.), tres de ellos eran pacientes pediátricos, incluyendo el primer implante de este tipo de dispositivo en un paciente pediátrico en América Latina. Las técnicas de tres y dos incisiones fueron empleadas bajo anestesia general. Resultados: Se realizó el implante exitoso con técnica de tres incisiones en los dos primeros casos y con técnica de dos incisiones en los dos últimos casos. Se corroboró el adecuado funcionamiento del dispositivo en sala, con la verificación de terapia apropiada (65 J) de la fibrilación ventricular inducida mediante estimulación a 50 Hz. No hubo complicaciones inmediatas. Un paciente presentó descargas apropiadas a los dos meses del implante. En el seguimiento, un niño desarrolló erosión de la piel a nivel de la curva del electrodo en el esternón, sin datos de infección. En quirófano se resecó la piel dañada, se retiró el barril y la seda de fijación, se realizó lavado quirúrgico y se volvió a cerrar la piel, logrando así evitar el retiro del sistema. Conclusiones: El DAI-SC es una terapia alternativa al DAI endovenoso y puede ser considerado de primera elección en aquellos casos que no requieran de estimulación ventricular, incluyendo pacientes pediátricos. Pueden ocurrir complicaciones cutáneas, pero no representan una amenaza como las complicaciones venosas de los DAI convencionales.

Abstract Introduction: The transvenous implantable cardioverter defibrillator (ICD) is the treatment of choice for the prevention of sudden cardiac death (SCD). Its use could be restricted when device-related infections occurs or in the pediatric population. In the later, an ICD represents a challenge, due to the minimal dimensions of the venous system in children, the length of the electrodes, the size of the generator, as well as the anatomical complexity in cases with associated congenital heart disease. Objective: This article presents the first Mexican patients with a subcutaneous ICD (SC-ICD) implant as a therapy for the prevention of SCD. Methods: The first four cases were implanted at the Ignacio Chávez National Institute of Cardiology with a SC-ICD (Emblem, Boston Scientific, USA), three of them were pediatric patients, including the first implant of this type of device in a pediatric patient in Latin America. The 3-incision and 2-incision techniques were used under general anesthesia. Results: A successful implantation was obtained with the 3-incision technique in the first 2 cases and the last 2 with the 2-incision technique. Proper functioning of the device was corroborated in the operating room with proof of appropriate therapy (65 J) for ventricular fibrillation induced with 50 Hz stimulation. No immediate complications were observed. One patient had appropriate shocks two months after the implant. During follow-up, one child developed skin erosion at the level of the curve of the electrode on the sternum, with no signs of infection. In the operating room, the damaged skin was resected, the barrel and the fixation silk were removed, surgical lavage was performed, and the skin was closed again, thus avoiding removal of the system. Conclusions: The SC-ICD is an alternative therapy to the transvenous ICD. It can be considered first choice in subjects who do not require ventricular pacing, including pediatric patients. Skin complications can occur but do not pose a threat as venous complications of conventional ICDs.

Taquicardia ventricular polimórfica tipo torsadess de pointes secundaria a estimulación por marcapasos / Polymorphic ventricular taquicardia "torsades de pointes" associated to abnormal pacemaker stimulation

La taquicardia ventricular polimórfica se origina en los ventrículos, cuyos complejos QRS son de morfología, amplitud y dirección variable, con frecuencias que oscilan entre 200 y 250 lpm, pudiendo ser autolimitadas o degenerar en una fibrilación ventricular. La TdP es un tipo de taquicardia ventricular polimórfica caracterizada por complejos con un eje eléctrico que gira alrededor de la línea isoeléctrica y que está asociada a QT largo. Se presenta el caso de una paciente portadora de marcapaso que presenta episodios de taquicardia ventricular polimórfica, con una morfología típica de TdP, sin documentación de QT prolongado previo ni actual, generada por la estimulación ventricular sobre onda T, de forma accidental por desplazamiento del electrodo auricular a Ventrículo Derecho (VD).

Polymorphic ventricular tachycardia is a tachycardia originating in the ventricles, where the QRS complexes have variable morphology, amplitude, and direction, with frequencies ranging between 200 and 250 bpm; it may be self-limited or degenerate into ventricular fibrillation. Torsades de Pointes (TdP) is a type of polymorphic ventricular tachycardia characterized by complexes with an electrical axis that rotates around the isoelectric line and that is associated with long QT interval. We present the case of a patient with a pacemaker who presents episodes of polymorphic ventricular tachycardia, with a typical morphology of TdP, without documentation of previous or current prolonged QT, generated by ventricular stimulation on the T wave, accidentally due to displacement of the atrial electrode to the Right Ventricle (RV).

Assessment of QT Interval Abnormalities on Electrocardiogram in Children With Breath-Holding Spells

Objective: To assess QT interval abnormalities among children with breath-holding spells. Methods: This case control study included 204 children (104 cases of breath-holding spells and 100 healthy children) younger than 3 years. Breath-holding spells were evaluated for age of onset, type (pallid/cyanotic), triggering factors, frequency and presence of family history. Twelve- lead surface electrocardiogram (ECG) was analyzed for QT interval (QT), corrected QT interval (QTc), QT dispersion (QTD) and QTc dispersion (QTcD) in milliseconds. Results: The mean (SD) QT, QTc, QTD and QTcD interval in milliseconds were 320 (0.05), 420 (0.07), 61.15 (16.20), 102.3 (17.24), respectively for breath-holding spells as compared to control group [300 (0.02), 370 (0.03), 38.6(14.28), 78.6 (14.28), respectively] (P<0.001). Similarly, pallid breathholding spells had prolonged mean (SD) QT, QTc, QTD and QTcD interval in milliseconds [380 (0.04), 520 (0.08), 78.88 (10.78), 123.33 (10.28), respectively] as compared to cyanotic spells [310 (0.04), 400 (0.04), 57.44 (14.64), 97.90 (15.03), respectively] (P<0.001). The mean QTc interval was 590 (0.03) and 400 (0.04) milliseconds in prolonged and non-prolonged QTc group, respectively (P<0.001). Conclusion: Abnormal QT, QTc, QTD and QTcD were observed among children with breath-holding spells. ECG should be strongly considered, especially in pallid, frequent spells occurring at younger age and having positive family history, to identify long QT syndrome.

Taquicardia ventricular polimorfa en un paciente con fibrilación auricular de respuesta ventricular rápida. Reporte de Caso

Las taquicardiomiopatías por su fisiopatología de pérdida del acoplamiento miocárdico, proporcionan el sustrato adecuado para la disfunción ventricular que dan paso a arritmias ventriculares letales. Se reporta el caso de una paciente femenina de 75 años, sin antecedentes personales patológicos conocidos, que acude con historia de disnea de medianos esfuerzos que rápidamente progresa a disnea de pequeños esfuerzos asociado a palpitaciones. Posteriormente desarrolla taquicardia ventricular polimorfa no sostenida durante su estancia hospitalaria por lo que fue necesario realizar en dos ocasiones maniobras de reanimación con cardioversión eléctrica y el restablecimiento del ritmo sinusal con fármacos para mejorar la función del ventrículo izquierdo. (provisto por Infomedic International)

  Tachycardiomyopathies due to their pathophysiology of loss of myocardial coupling, provide the adequate substrate for ventricular dysfunction that leads to lethal ventricular arrhythmias. The following is the case of a 75-year-old female patient, with no known history, who presented with symptoms of advanced heart failure and atrial fibrillation, who later developed non-sustained polimorphic ventricular tachycardia during her hospital stay for which it was necessary to perform resuscitation maneuvers with electrical cardioversion on two separate occasions and the restoration of sinus rhythm with drugs to improve left ventricular function. (provided by Infomedic International)

A Rare Case Report of “Torsades De Pointes” Induced by Fluconazole-Levetiracetam Combined Therapy

Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the QT interval on the surface electrocardiogram and the morphologically distinctive polymorphic ventricular tachycardia that results is known as «torsade de pointe». «Torsade de pointe» (TDP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface electrocardiogram by QT interval prolongation. It typically occurs in self-limiting bursts, causing dizziness and syncope, but may occasionally progress to ventricular fibrillation and sudden death. This rare case report showed the potential higher risk of the occurrences of «Tdp» when levetiracetam (KEPPRA) was used in combination therapy with fluconazole, which is already a known medication with the risk of causing polymorphic ventricular arrhythmia.

Syndrome de QT long découvert en postpartum: à propos d'un cas à Fianarantsoa, Madagascar / Long QT syndrome discovered in postpartum: about a case in Fianarantsoa, Madagascar

Le syndrome de QT long congénital est une canalopathie arythmogène rare mais grave pouvant être responsable d'une mort subite prématurée chez l'enfant et les sujets jeunes. La période du postpartum est particulièrement à risque de survenue d'évènement cardiaque chez la femme. Nous rapportons le cas d'une femme de 29 ans porteuse d'un syndrome de QT long congénitale probable déclenché avec trouble du rythme cardiaque déclenché par le postpartum dont le risque de mort subite à court terme a été imminent en absence de traitement

Severe primary hypothyroidism presenting as polymorphic ventricular tachycardia / Hipotiroidismo primario grave que se presenta como taquicardia ventricular polimórfica

Abstract Introduction: Hypothyroidism may have various cardiovascular manifestations due to morphological, functional and electrical alterations in the heart. The usual electrocardiographic findings being sinus bradycardia, low voltage complexes, and slowed intraventricular conduction. Hypothyroidism manifesting as polymorphic ventricular tachycardia has only been reported in a few case reports. Clinical case. A 60-year-old lady presented to us in the emergency department in an unresponsive and unconscious state and electrocardiogram showed a polymorphic ventricular tachycardia. After initial resuscitation with direct current cardioversion and supportive care, she found to have severe hypothyroidism and responded well to thyroid replacement therapy. Conclusion. Polymorphic ventricular tachycardia is a life threatening emergency that can have various etiologies. Polymorphic ventricular tachycardia secondary to primary hypothyroidism is a rare presentation but it is treatable and reversible with thyroid replacement therapy. In patients presenting with QT interval prolongation and ventricular tachycardia, hypothyroidism should be one of the differential diagnosis.

Resumen Introducción: El hipotiroidismo puede presentar diferentes manifestaciones cardiovasculares dadas por alteraciones morfológicas, funcionales y eléctricas en el corazón, siendo los hallazgos electrocardiográficos usuales son la bradicardia sinusal, los complejos de bajo voltaje y la conducción intraventricular lenta. El hipotiroidismo manifestado como taquicardia ventricular polimórfica solo se ha descrito en unos pocos reportes de caso. Caso clínico: Se trata de una mujer de 60 años que acudió que acurdió al servicio de urgencias en un estado inconsciente y sin respuesta a estímulos, y el electrocardiograma reveló taquicardia ventricular polimórfica. Luego de la reanimación inicial con cardioversión con corriente directa y tratamiento sintomático se le encontró un hipotiroidismo grave, el cual se trató con terapia de reemplazo con hormona tiroidea. y se obtuvo una buena respuesta Conclusión. La taquicardia ventricular polimórfica es una emergencia vital que puede tener varias etiologías. La taquicardia ventricular polimórfica secundaria a un hipotiroidismo primario es una presentación poco común, pero es tratable y reversible con la terapia de reemplazo con hormona tiroidea. En los pacientes que presentan una prolongación del intervalo QT y taquicardia ventricular, es pertinente incluir el hipotiroidismo en el diagnóstico diferencial.

Determinação do risco potencial de interações medicamentosas prolongadoras do intervalo QT em idosos internados em unidade de terapia intensiva

Introdução: Pacientes hospitalizados em unidade de terapia intensiva, em especial idosos, são particularmente expostos a interações medicamentosas prolongadoras do intervalo QT. Objetivo: Determinar a incidência de interações medicamentosas prolongadoras do intervalo QT potenciais (IMQT) e seus preditores clínicos e terapêuticos em idosos hospitalizados em unidade de terapia intensiva. Metodologia: Coorte retrospectiva conduzida em unidade de terapia intensiva adulto. Foram incluídos prontuários de pacientes com idade igual ou superior a 60 anos com tempo de internação mínimo de 24 h e que utilizaram dois ou mais medicamentos. O Credi-bleMeds foi utilizado para classificação dos medicamentos com risco de prolongar o intervalo QT; em seguida, o Micromedex foi acessado para identificar e classificar as interações medicamentosas. Preditores clínicos e terapêuticos das interações foram examinados a partir de um modelo de regressão logística múltiplo. Resultados: A incidência de IMQT potenciais foi de 43,9 %. Os medicamentos mais frequentemente combinados nas IMQT potenciais foram ondansetrona (25 %), quetiapina (22,5 %), amiodarona (18,6 %) e haloperidol (17,5 %). As IMQT potenciais mais frequentes foram haloperidol + ondansetrona (25,4 %) seguidas pela dupla ondansetrona + quetiapina (13,1 %). Os preditores de IMQT potenciais foram uso de polifar-mácia (p=0,002), antipsicóticos (p<0,001), antidepressivos (p< 0,001) e antiarrítmicos (p=0,002). Conclusão: A gestão das IMQT requer abordagem pautada em fatores de risco individuais e também, obrigatoriamente, em condutas genéricas relativas a exames bioquímicos, instalação de monitores cardíacos, eletrocardiogramas periódicos e uso de sistemas de alerta para IMQT.

SUMMARY Introduction: Patients hospitalized in the intensive care unit, especially the elderly, are particularly exposed to drug interactions that prolong the QT interval. AIM: To determine the incidence of potential QT-prolonging drug interactions (IMQT) and their clinical and therapeutic predictors in elderly patients hospitalized in an intensive care unit. Methodology: Retrospective cohort conducted in an adult intensive care unit. Medical records of patients aged 60 years or older with a minimum hospital stay of 24 hours and who used two or more medications were included. CredibleMeds was used to classify drugs at risk of prolonging the QT interval; then, Micromedex was accessed to identify and classify drug interactions. Clinical and therapeutic predictors of interactions were examined using a multiple logistic regression model. Results: The incidence of potential IMQT was 43.9 %. The drugs most frequently combined in potential MTMI were ondansetron (25 %), quetiapine (22.5 %), amiodarone (18.6 %) and haloperidol (17.5 %). The most frequent potential MTMI were haloperidol + ondansetron (25.4 %) followed by the dual ondansetron + quetiapine (13.1 %). Potential IMQT predictors were use of polypharmacy (p=0.002), antipsychotics (p<0.001), antidepressants (p<0.001) and antiarrhythmics (p=0.002). Conclusion: The management of IMQT requires an approach based on individual risk factors and also, necessarily, on generic conducts related to biochemical tests, installation of cardiac monitors, periodic electrocardiograms and use of warning systems for IMQT.

Introducción: Los pacientes hospitalizados en la unidad de cuidados intensivos, especialmente los ancianos, están particularmente expuestos a interacciones medicamentosas que prolongan el intervalo QT. Objetivo: Determinar la incidencia de posibles interacciones medicamentosas prolongadoras del intervalo QT (IMQT) y sus predictores clínicos y terapéuticos en pacientes ancianos hospitalizados en una unidad de cuidados intensivos. Metodología: Cohorte retrospectiva realizada en una unidad de cuidados intensivos para adultos. Se incluyeron historias clínicas de pacientes de 60 años o más con una estancia hospitalaria mínima de 24 horas y que utilizaban dos o más medicamentos. Se utilizó CredibleMeds para clasificar los fármacos con riesgo de prolongar el intervalo QT; luego, se accedió a Micromedex para identificar y clasificar las interacciones medicamentosas. Los predictores clínicos y terapéuticos de interacciones se examinaron mediante un modelo de regresión logística múltiple. Resultados: La incidencia de IMQT potencial fue del 43,9 %. Los fármacos combinados con mayor frecuencia en posibles MTMI fueron ondansetrón (25 %), quetiapina (22,5 %), amiodarona (18,6 %) y haloperidol (17,5 %). Los MTMI potenciales más frecuentes fueron haloperidol + ondansetrón (25,4 %) seguido de ondansetrón dual + quetiapina (13,1 %). Los posibles predictores del IMQT fueron el uso de polifarmacia (p=0,002), antipsicóticos (p<0,001), antidepresivos (p<0,001) y antiarrítmicos (p=0,002). Conclusión: El manejo del IMQT requiere un abordaje basado en factores de riesgo individuales y también, obligatoriamente, en conductas genéricas relacionadas con pruebas bioquímicas, instalación de monitores cardíacos, electrocardiogramas periódicos y uso de sistemas de alerta para IMQT.

Prevalencia de medicamentos que prolongan el intervalo QT en salas de cardiología de un hospital de alta complejidad / Drug induced prolongation of Q-T interval in cardiology wards

Resumen: Antecedentes: La prevalencia del síndrome del QT largo (SQTL) producido por medicamentos es una de las reacciones adversas que en el último tiempo ha aumentado en prevalencia y mortalidad. No solamente ocurre con el uso de medicamentos para el tratamiento de cardiopatías, sino también en medicamentos con otra acción terapéutica. Objetivo: Evaluar la prevalencia del síndrome del SQTL inducido por medicamentos en salas de cardiología de un hospital de alta complejidad. Métodos: Estudio prospectivo, de tipo descriptivo y de corte transversal en 36 pacientes cardiópatas, que consistió en evaluar la frecuencia del uso de medicamentos que son capaces de producir un SQTL y la prevalencia de este efecto adverso. Los datos clínicos se recolectaron de la ficha clínica y de entrevistas con los pacientes. Se efectuó un seguimiento para detectar la aparición de prolongación del intervalo QT. Los resultados obtenidos fueron presentados por medio de estadística descriptiva (programa estadístico Statgraphics Centurion, versión XVI). No hubo estadística inferencial dada la ausencia de un grupo control. Resultados: 41,7%, de los 36 pacientes presentaron SQTL que en 86,7% de ellos fue asociado a un medicamento. Los medicamentos más frecuentemente asociados a este efecto adverso fueron Amiodarona (38,5%) y Ondansetrón (23,1%), y el factor de riesgo mayormente involucrado fue el sexo femenino (61,5%). Conclusión: Existió una alta prevalencia del uso de medicamentos que producen un SQTL, destacándose que existen medicamentos utilizados para otras patologías que también pueden producirlo.

Abstract: Background: The prevalence of the Long QT interval syndrome (LQTS) associated to drugs has increased en the last decades along with an increased mortality due to this condition. It occurs not only with drugs used to treat cardiac disease but also to other drugs. Aim: To evaluate the prevalence of drug induced LQTS in cardiology wards of a high complexity hospital. Method: This is a prospective, descriptive and cross sectional study in 36 patients with heart disease. The use of drugs known to affect the QT interval along with the frequency of LGTS were evaluated. Clincal data was obtained from clinical records and personal interviews. Patients were followed for the appearance of LQTS. Descriptive were used to present the results. No inferential statistics were used as no control group was involved (Statgraphics Centurion, version XVI). Results: 41.7% of the 36 patients developed LQTS and the association with drugs was present in 86.7% of them. The drugs most commonly identified were amiodarone (38.5%) and ondansetron (23.1%) of patients. Female geneder was the most common associated condition (61.5%). Conclusion: There was a frequent use of drugs known to produce LQTS, but other drugs may also be associated int this group of patients with heart disease admitted to intensive or intermediate care facilities.

The QT Interval: What the Pulmonologist Needs to Know

The QT interval is an electrocardiographical measurement that denotes the time interval between the commencement and completion of the cardiac ventricular contraction process. Alterations in its value indicate abnormal cardiac rhythm and herald the risk of torsades de pointes; a fatal ventricular arrhythmia. Causes leading to a prolonged QT interval encompass a heterogeneous gamut including genetic conditions, electrolyte imbalances, hormonal imbalances, and drugs. A wide range of drugs can lead to a prolonged QT interval and these include certain crucial drugs which are routinely prescribed by a pulmonologist for infectious as well as non-infectious pulmonary indications. This becomes particularly relevant in this decade which has witnessed an excrescence in drug-resistant tuberculosis cases. Certain vital drugs employed in its management prolong QT interval significantly. In these situations, the clinician faces the predicament of cautiously prescribing these drugs to eradicate the disease microbiologically whilst balancing the risk of sudden cardiac death due to torsades de pointes. We summarise the basics of QT interval which every pulmonologist presently needs to know.

Diagnostic Lacunae and Implications of an Automated Implantable Cardioverter Defibrillator Implantation in a Child with Type 3 Long QT (LQT3) Syndrome

A diagnosis of congenital long QT interval syndrome based on history and electrocardiogram was made in a child in the absence of readily available genetic testing. A genotype 3 (LQT3) was suspected after exclusion of other variants as the child was non?responsive to beta?blocker and sodium channel blocker medication. As the child continues to show episodic bradycardia, polymorphic ventricular ectopy, and T?wave alternans, a single?chamber automated implantable cardioverter?defibrillator implantation was done successfully. This report highlights how the diagnosis of LQT3 was arrived at as well as the anesthetic challenges in the management of patients with LQTS.

Arritmias ventriculares en el síndrome de takotsubo: cuestión de sexo / Sex-related risk of arrhythmia in takotsubo syndrome

Resumen El síndrome de takotsubo, también conocido como miocardiopatía de estrés, representa un difícil reto diagnóstico, pues en muchos casos su presentación es superponible al infarto de miocardio por ruptura de placa; el diagnóstico definitivo se basa en la ausencia de lesiones culpables en la coronariografía. La fisiopatología de la enfermedad no está por completo establecida, y tiene un pronóstico generalmente benigno. Sin embargo, existe un porcentaje no despreciable de pacientes que sufren complicaciones graves, entre las que destacan las arritmias malignas tipo taquicardia ventricular polimórfica por prolongación del intervalo QT. A pesar de que el síndrome de takotsubo afecta principalmente a las mujeres, quienes por otra parte también suelen tener intervalos QT más prolongados en condiciones basales, la muerte súbita de origen arrítmico aparece con mayor frecuencia en los hombres que sufren esta enfermedad. Se presentan dos casos de ensanchamiento extremo del intervalo QT corregido en pacientes con takotsubo que tuvieron desenlaces diferentes. El propósito de este trabajo es destacar y revisar las diferencias electrocardiográficas y pronósticas relacionadas con el sexo de los sujetos que desarrollan esta controvertida enfermedad.

Abstract Takotsubo syndrome, also known as stress cardiomyopathy, is a difficult diagnostic challenge as, in many cases, its presentation can overlap with that of myocardial infarction due to plaque rupture. The definitive diagnosis is based on the lack of culprit lesions on coronariography. The pathophysiology of the disease has not been completely ascertained, and it has a generally benign prognosis. However, a not inconsiderable percentage of patients experience serious complications, notably malignant arrhythmias like polymorphic ventricular tachycardia due to a prolonged QT interval. Despite takotsubo syndrome affecting mainly women who, furthermore, generally have longer basal QT intervals, sudden death due to arrhythmias is more common in men with this disease. Two cases are presented of extremely prolonged corrected QT intervals in patients with takotsubo, with different outcomes. The purpose of this paper is to highlight and review the electrocardiographic and prognostic differences related to the gender of the individuals who develop this controversial disease.

Effects of insulin on the QT interval and induced arrhythmias of human cardiomycytes / 西安交通大学学报(医学版)

【Objective】 To explore the effects of insulin on the QT interval and induced arrhythmias of cardiomyocytes derived from human induced pluripotent stem cells （hiPSC-CMs）. 【Methods】 Immunofluorescence staining and flow cytometry were used to analyze the purity of hiPSC-CMs. Microelectrode array （MEA） was utilized to detect the electrophysiological changes including heart rate （HR）， field potential duration （FPD， which is similar to QT interval in ECG）， FPDc （FPD corrected by HR）， conduction velocity （CV）， and spike amplitude before and after insulin treatment. The effects of E4031 on QT interval prolongation and induced arrhythmias of hiPSC-CMs were evaluated before and after treatment with insulin. 【Results】 hiPSC-CMs highly expressed myocardial specific marker cTnT. The purity of hiPSC-CMs was 97.1%. After 5-day insulin treatment of hiPSC-CMs， HR increased by （11.9±3.3）%， FPD shortened by （22.7±2.8）%， FPDc shortened by （15.6±1.6）%， and spike amplitude increased by （39.1±7.9）% when compared with untreated group， but CV remained unchanged. 10 nmol/L of E4031 could prolong the FPDc of hiPSC-CMs by （37.8±9.0）%， and 30 nmol/L of E4031 could induce arrhythmias. After insulin treatment， 10 nmol/L of E4031 prolonged the FPDc of hiPSC-CMs by （21.8±3.1）% （compared with the untreated group， insulin decreased FPDc prolongation by E4031， 37.8%±9.0% vs. 21.8%±3.1%， P<0.05）， while 30 nmol/L of E4031 did not induce arrhythmias. 【Conclusion】 Insulin can shorten the QT interval of hiPSC-CMs and significantly reduce the QT interval prolongation and the risk of arrhythmias induced by drugs.

Evaluation of cardiac safety of hydroxyrutaecarpine, hERG channel inhibitor / 药学学报

Drug-induced long QT syndrome (LQTS) has become an important clinical research topic, and the occurrence of acquired long QT syndrome (acLQTS) is mainly caused by drug inhibition of the human ether-α-go-go related gene (hERG) channel. The hERG gene encodes the α subunit of the fast-activating delayed rectifying potassium ion channel (Ikr), which plays an important role in the process of action potential phase 3 repolarization and is also the target of most antiarrhythmic drugs. The purpose of this study was to investigate the effect of hydroxyrutaecarpine (HRU) on the hERG channel and to evaluate its cardiotoxicity. The whole cell patch clamp technique was used to detect the effects of HRU on the current and kinetics of the hERG channel, and to confirm the binding site on the hERG channel. PCR was used to determine the effect of HRU on hERG mRNA expression. Western blotting was used to detect the effects of HRU on the expression of hERG protein and transcription factor Sp1. Immunofluorescence was used to confirm the effects of HRU on localization and expression of hERG protein and transcription factor Sp1. Studies have shown that transient HRU can inhibit hERG current and shorten the inactivation time constant. Its binding sites to the hERG channel are F656 and Y652. After incubation for 24 h, HRU can reduce the expression of hERG protein, inhibit the hERG current, reduce the level of hERG mRNA, and reduce the expression of transcription factor Sp1 in the nucleus and hERG protein in the cytoplasm. Immunofluorescence experiments also showed the same results suggesting that the inhibition of Sp1 expression by HRU is the cause of the decreased expression of hERG mRNA. In conclusion, the acute inhibition of HRU accelerates the channel inactivation process and reduces the inactivation time constant by binding to the F656 and Y652 sites in the hERG channel, thus reducing the hERG current. In addition, HRU also inhibits the expression of hERG protein, mainly by inhibiting the expression of transcription factor Sp1, the transcription function of hERG channel protein is down-regulated, so that the hERG protein is reduced.

Mutation spectrum and clinical features of congenital long QT syndrome in 20 children: a single center study / 中华实用儿科临床杂志

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.