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.

Smartphone electrocardiogram for QT interval monitoring in Coronavirus Disease 2019 (COVID-19) patients treated with Hydroxychloroquine

@#Introduction: The global pandemic of Corona Virus Disease 2019 (COVID-19) has led to the re-purposing of medications, such as hydroxychloroquine and lopinavir-ritonavir in the treatment of the earlier phase of COVID-19 before the recognized benefit of steroids and antiviral. We aim to explore the corrected QT (QTc) interval and ‘torsadogenic’ potential of hydroxychloroquine and lopinavir-ritonavir utilising a combination of smartphone electrocardiogram and 12-lead electrocardiogram monitoring. Materials and Methods: Between 16-April-2020 to 30-April2020, patients with suspected or confirmed for COVID-19 indicated for in-patient treatment with hydroxychloroquine with or without lopinavir-ritonavir to the Sarawak General Hospital were monitored with KardiaMobile smartphone electrocardiogram (AliveCor®, Mountain View, CA) or standard 12-lead electrocardiogram. The baseline and serial QTc intervals were monitored till the last dose of medications or until the normalization of the QTc interval. Results: Thirty patients were treated with hydroxychloroquine, and 20 (66.7%) patients received a combination of hydroxychloroquine and lopinavir-ritonavir therapy. The maximum QTc interval was significantly prolonged compared to baseline (434.6±28.2msec vs. 458.6±47.1msec, p=0.001). The maximum QTc interval (456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not significantly different between patients on hydroxychloroquine or a combination of hydroxychloroquine and lopinavir-ritonavir. Five (16.7%) patients had QTc of 500msec or more. Four (13.3%) patients required discontinuation of hydroxychloroquine and 3 (10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de pointes was observed. Conclusions: QTc monitoring using smartphone electrocardiogram was feasible in COVID-19 patients treated with hydroxychloroquine with or without lopinavir-ritonavir. The usage of hydroxychloroquine and lopinavir-ritonavir resulted in QTc prolongation, but no torsade de pointes or arrhythmogenic death was observed.

Research Advances on Non-Clinical Evaluation in Vitro of Drug-Induced Arrhythmias / 中国药学杂志

Drug-induced arrhythmia is one of the main causes of failure in drug development, and it is also a major cause of drug withdrawal, therefore, accurate prediction of drug-induced arrhythmia in the non-clinical research stage is the best way to reduce cost. Literature was retrieved by formally searching PubMed, Metstr, CNKI and Baidu Scholar, 1 479 published articles were found through search method, 63 full-text articles were included. After reviewed the relevant literatures, the advantages and disadvantages of the different experimental cells and the related evaluation methods are assessed, in order to provide reference for toxicity evaluation.

Glucantime y prolongación del intervalo QTc: una combinación fatal / Glucantime and QTc interval prolongation: A fatal combination

Resumen La leishmaniosis cutánea es una enfermedad causada por un parásito pro tozoo intracelular; el glucantime es una opción terapéutica, aunque está asociado con alteraciones cardiovasculares, siendo la más frecuente la prolongación del intervalo QTc que se presenta entre el 17,8 % y 19 % de los pacientes. Si este efecto no es detectado a tiempo puede causar una arritmia fatal por torsade de pointes. Se presenta el caso de una paciente de 77 años quien se encontraba en tratamiento con glucantime intramus cular como tratamiento de leishmaniosis cutánea e ingresó por un cuadro clínico de hipocalemia severa refractaria y episodios de torsade de pointes; posteriormente, presentó fibrilación ventricular que no respondió a des fibrilación y reanimación. Las alteraciones en la repolarización cardiaca producidas por este medicamento se consideran secundarias a la acu mulación de compuestos pentavalentes y trivalentes en el miocardio. No existe tratamiento específico para esta situación, pero siempre se debe realizar manejo de soporte, evitar fármacos que prolonguen el intervalo QT, normalizar los niveles de potasio y de magnesio, elevar la frecuencia cardiaca con isoproterenol e implantar marcapaso transvenoso para lograr sobre-estimulación y reducción de los periodos refractarios.

Abstract Cutaneous leishmaniasis is a disease caused by an intracellular protozoan parasite; Glucantime is a therapeutic option, although it is associated with cardiovascular alterations, the most frequent being the prolongation of the QTc interval, that occurs between 17.8% and 19% of patients. If this effect is not early recognized, it can cause a fatal arrhythmia due to torsade de pointes. The case of a 77-year-old patient who was receiving intramuscu lar glucantime as treatment for cutaneous leishmaniasis is presented, the patient was admitted with severe refractory hypokalemia and episodes of torsade de pointes; subsequently, presented ventricular fibrillation that did not respond to defibrillation and resuscitation. The alterations in cardiac repolarization produced by this medicine are considered secondary to the accumulation of pentavalent and trivalent compounds in the myocardium. There is no specific treatment for this situation, but supportive manage ment should always be performed, avoid drugs that prolong the QT inter val, normalize potassium and magnesium levels, raise the heart rate with isoproterenol and implant transvenous pacemaker to achieve over-stimulation and reduction of refractory periods.

Introduction to in silico model for proarrhythmic risk assessment under the CiPA initiative

In 2005, the International Council for Harmonization (ICH) established cardiotoxicity assessment guidelines to identify the risk of Torsade de Pointes (TdP). It is focused on the blockade of the human ether-à-go-go-related gene (hERG) channel known to cause QT/QTc prolongation and the QT/QTc prolongation shown on the electrocardiogram. However, these biomarkers are not the direct risks of TdP with low specificity as the action potential is influenced by multiple channels along with the hERG channel. Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative emerged to address limitations of the current model. The objective of CiPA is to develop a standardized in silico model of a human ventricular cell to quantitively evaluate the cardiac response for the cardiac toxicity risk and to come up with a metric for the TdP risk assessment. In silico working group under CiPA developed a standardized and reliable in silico model and a metric that can quantitatively evaluate cellular cardiac electrophysiologic activity. The implementation mainly consists of hERG fitting, Hill fitting, and action potential simulation. In this review, we explained how the in silico model of CiPA works, and briefly summarized current overall CiPA studies. We hope this review helps clinical pharmacologists to understand the underlying estimation process of CiPA in silico modeling.

Analysis of Selective Serotonin Reuptake Inhibitors Associated with QT Prolongation and Torsade de Pointes Adverse Events Based on Data Mining Methods / 中国药学杂志

OBJECTIVE: To excavate and evaluate the risk signals of QT prolongation and torsade de pointes(TdP) induced by selective serotonin reuptake inhibitors(SSRIs), provide references for clinical use. METHODS: Data from FDA adverse event reporting system (FAERS, from January 2004 through June 2018) were analyzed for each SSRIs, including fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine. When QT prolongation and TdP cases were identified using preferred terms (PT) and standardised MedDRA queries (SMQ), three different data mining algorithms were used to detect signalsreporting odds ratio (ROR), medicines and healthcare products regulatory agency (MHRA), and bayesian confidence popagation neural network (BCPNN), if all the three algorithms were positive, suggesting the generation of signals. RESULTS: A total of 3 912 reports of QT prolongation and TdP associated with SSRIs were retrieved through the SMQ. Among which, more females than males(2 349 vs. 1 150), mainly aged 18-44 and 45-64 years, and 90.64% were serious adverse events. The signals were found for fluoxetine, sertraline, citalopram, escitalopram, paroxetine and fluvoxamine at the SMQ level, the RORs (95%CI) were 5.25(4.79-5.76), 2.08(1.79-2.27), 2.86(6.32-7.44), 3.41(3.03-3.84), 2.09(1.84-2.37) and 10.44(8.17-13.33) respectively; the PRRs (X2) were 5.20(1 494.43), 2.01(140.41), 6.77(2 911.71), 3.93(462.34), 2.09(136.58) and 10.21(538.26) respectively; the Ics (IC-2SD) were 2.15(2.12), 1.54(1.52), 2.67(2.65), 2.34(2.31) 1.14(1.12) and 3.16(3.10) respectively. Analysis of the PT included in the SMQ for TdP/QT prolongation, except paroxetine was only detected electrocardiogram QT prolonged signal, all the other SSRIs were detected electrocardiogram QT prolonged and TdP signals. CONCLUSION: QT prolongation may be a SSRIs class effect, but TdP just for fluoxetine, sertraline, citalopram, escitalopram and fluvoxamine. Clinical staff should pay more attention to the differences in adverse drug reaction related to SSRIs, and take pertinence measure to prevent.

Tormenta eléctrica y torsade de pointes asociados a tratamiento con antimoniales en un paciente con leishmaniasis cutánea / Electrical storm and torsade de pointes associated with antimonial treatment in a patient with cutaneous leishmaniasis

Resumen La toxicidad por antimoniales puede comprometer múltiples sistemas y llega a ser potencialmente fatal. Se presenta el caso de un joven militar quien durante el tratamiento de su segundo episodio de leishmaniasis cutánea presentó toxicidad pancreática y cardiaca, desarrollando un síndrome de QT largo adquirido y tormenta eléctrica con episodios frecuentes de taquicardia ventricular que incluían torsade de pointes. Se realizó tratamiento en unidad de cuidados intensivos, donde requirió múltiples descargas de desfibrilador y la administración de sulfato de magnesio hasta la resolución del cuadro clínico.

Abstract The toxicity due to antimonial can compromise multiple systems, and is potentially fatal. The case is presented of a young soldier, who had pancreatic and cardiac toxicity during the treatment of his second episode of cutaneous leishmaniasis. This developed into an acquired long QT syndrome and an electrical storm with frequent episodes of ventricular that included torsade de pointes. Treatment was given in the Intensive Care Unit, where he required multiple defibrillator discharges and the administering of magnesium sulphate until the clinical symptoms were resolved.

Pain medication and long QT syndrome

Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation. Other substances, not used in the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics are also associated with long QT syndrome. When the possible benefits of therapy outweigh the associated risks, slow dose titration and electrocardiography monitoring are recommended.

Literature Review of Torsade de Pointes Induced by Ibutilide / 中国药师

Objective:To analyze the general patterns and characteristics of torsade de pointes(Tdp) associated with ibutilide and provide feasible suggestions and preventive measurements combined with the experience of pharmaceutical monitoring. Methods: The cases of TdP associated with ibutilide were retrieved from the literatures reported at home and abroad during January 1990 and April 2017,and the clinical data including gender,age,original diseases, dosage of drugs, injection time, TdP occurrence time, potassi-um,QTc and ECG monitoring before and after the medication, complications, treatment drugs and methods and conversion outcome were statistically analyzed. Results: A total of 9 cases were enrolled in the analysis. After the treatment with ibutilide withdrawal, electroversion and potassium and magnesium supplement, all the patients converted to sinus rhythm.Conclusion: Ibutilide must be prescribed very carefully in senile female patients complicated with extended QTc,low potassium,organic heart disease and heart fail-ure. With dosing interval,injection time or injection speed not compatible with the specification,the occurrence of TdP is significantly different,suggesting that clinical pharmacists strengthen the monitoring of injection time,speed,dosing interval and blood concentra-tion of ibutilide according to the instruction strictly.

Pharmaceutical Care Performed by Clinical Pharmacists for One Patient with Torsade de Pointes / 中国药师

Objective: To study the entry points of pharmaceutical care performed by clinical pharmacists for patients in ICU.Methods: Clinical pharmacists participated in the medication treatment process of one case of patient with torsade de pointes by providing individualized pharmaceutical service, including antiarrhythmic drug selection, anti-infection therapy adjustment and electrolyte disorder rectification.Results: The therapeutic effect and medication safety of the patient were both improved by giving clinical pharmaceutical care.The vital signs of the patient were stable, and then the patient transferred from ICU and continued to be treated with rehabilitation therapy.Conclusion: Clinical pharmacists can play an active role in the rescue of ICU patients by the pharmaceutical thinking and provide efficient pharmaceutical care with high quality.

Progress of reasonable application and control in long QT syndrome associated with drugs / 中国药学杂志

This article has made an review including definition of drug-related long QT interval, clinical features, mechanisms and influencing factors, prevention and treatment of drug-related QT long syndrome, and its clinical research progresses. It is proposed that clinical pharmacists need to focus more attention on QT prolongation drugs. It can prevent acute arrhythmic events, and promote rationality and safety of drug.

QTc prolongation with concurrent use of azithromycin and diltiazem in an old female patient: a case report.

Azithromycin is widely prescribed for the treatment of respiratory tract infections. Incidence of corrected QT interval (QTc) prolongation and cardiac arrest has not been reported after concomitant administration of azithromycin and diltiazem. Here we present a 69-year-old female patient who developed profound QTc prolongation and cardiac arrest after three days of concomitant administration of azithromycin and diltiazem. The patient was successfully resuscitated, intravenous magnesium was given and azithromycin therapy was discontinued. The QTc interval dropped to 412 ms 24 hours after azithromycin discontinuation. One week later, the patient was discharged home after full recovery. This case illustrates a possible drug interaction between azithromycin and P-glycoprotein inhibitor drugs and/or drugs having an effect on cardiac repolarization.

A Case of Long QT Syndrome Type 3 Aggravated by Beta-Blockers and Alleviated by Mexiletine: The Role of Epinephrine Provocation Test

Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be beta-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during beta-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation.

Torsade de Pointes Induced by Long-Term Oral Amiodarone Therapy / 영남의대학술지

Although amiodarone is generally regarded as safe with a low incidence of associated arrhythmias, torsade de pointes (TdP) has been observed usually in the presence of predisposing factors. We report a case of amiodarone-induced TdP after long-term administration of a low dose of oral amiodarone in the absence of predisposing factors.

Postanesthetic torsade de pointes in a patient with unrecognized long QT syndrome: A case report / 대한마취과학회지

Torsade de pointes (TdP) is a devastating form of polymorphic ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. TdP usually terminates spontaneously but frequently recurs and may degenerate to ventricular fibrillation. The present report describes a case of TdP in a patient being transferred to the postanesthetic care unit following an emergency laparoscopic appendectomy. The patient had undergone open heart surgery 1 week before. Retrospective electrocardiogram analysis revealed the patient had QTc and Tpeak-Tend interval prolongation that had gone unrecognized. We believe TdP may have been induced by accentuation of sympathetic nervous system during emergence from general anesthesia.

Complete Atrioventricular Block-Induced Torsade de Pointes, Manifested by Epilepsy

Complete atrioventricular (AV) block is frequently regarded as a cause of informed syncopal attacks, even though the escape rhythm is maintained. Torsade de pointes (TdP) may be a significant complication of AV block associated with QT prolongation. Here, we report the case of a 42-year-old female who was referred to our hospital due to recurrent seizure-like attacks while taking anti-convulsant drugs at a psychiatric hospital. TdP with a long QT interval (corrected QT = 0.591 seconds) was observed on an electrocardiogram (ECG) taken in the emergency department. The patient's drug history revealed olanzapine as the suspicious agent. Even after the medication was stopped, however, the QT interval remained within an abnormal range and multiple episodes of TdP and related seizure-like symptoms were found via ECG monitoring. A permanent pacemaker was thus implanted, and the ventricular rate was set at over 80 beats/min. There was no recurrence of tachyarrhythmia or other symptoms.

QT Prolongation and Life Threatening Ventricular Tachycardia in a Patient Injected With Intravenous Meperidine (Demerol(R))

QT prolongation is a serious adverse drug effect, which is associated with an increased risk of Torsade de pointes and sudden death. Many drugs, including both cardiac and non-cardiac drugs, have been reported to cause prolongation of QT interval. Although meperidine has not been considered proarrhythmic, we present a unique case of a 16-year-old boy without an underlying cardiac disease, who developed polymorphic ventricular tachycardia, ventricular fibrillation and QT prolongation after an intravenous meperidine injection. He had no mutation in long QT syndrome genes (KCNQ1, KCNH2, and SCN5A), but single nucleotide polymorphisms were reported, including H558R in SCNA5A and K897T in KCNH2.

Long QT Syndrome and Torsade de Pointes Associated with Takotsubo Cardiomyopathy

Prolongation of QTc interval associated with Takotsubo cardiomyopathy (TC) has previously been reported in published case series. We report an unusual case of a patient who presented with TC associated with long-QT syndrome and developed cardiac arrest secondary to torsade de pointes. Since QT prolongation and bradycardia persisted after the resolution of TC, the patient received permanent pacemaker. Since then additional event did not occur. QT prolongation and bradycardia could be persistent even after recovery of TC, and permanent pacemaker insertion may be a treatment option of long QT syndrome related with TC.

Erythromycin induced torsade de pointes in a methadone maintenance patient: case report

Objective: This case report highlights the risk of Torsade de Pointes (TdP), a life threatening cardiac arrhythmia in a heroin dependent patient receiving methadone substitution therapy who was prescribed erythromycin for upper respiratory tract infection. Method: We report a case of a 35-year-old Malay man on methadone maintenance treatment who developed TdP possibly due to drug interaction between methadone and erythromycin. Results: The patient reported feeling unwell, chest pain and feeling dizzy after consuming 2 doses of erythromycin. ECG monitoring showed prolonged rate-corrected QT interval leading to TdP. The patient was admitted to the ward where the cardiac arrhythmia ceased following methadone discontinuation. This cardiac arrhythmia was most likely due to drug interaction between methadone and erythromycin (an enzyme inhibitor) which led to an increase in methadone concentration and potentiated the adverse effects. Conclusion: As methadone is a beneficial treatment for heroin dependent patients, the risk of cardiac arrhythmia is of great concern. To avoid complications of drug interaction, patients on methadone therapy should be advised to seek medical assessment before taking other drugs. As TdP is life threatening, it is thus important that physicians and psychiatrists involved in the treatment of heroin dependent patients on methadone substitution therapy be made aware of this risk.

Acute Pulmonary Edema after Cardioversion for Torsade de Pointes:A Case Report / 대한구급학회지

Cardioversion used for the treatment of various cardiac arrhythmias is a safe and effective procedure with infrequent complication. The restoration of sinus rhythm is followed by a improvement in hemodynamics, but acute pulmonary edema has been reported as a rare complication following successful electrical reversion of various tachyarrhythmia to normal sinus rhythm. This report describes a 42-year-old woman with a history of schizophrenia who experienced pulmonary edema after cardioversion for torsade de pointes. She had taken chlorpromazine and haloperidol for schizophrenia. The antipsychotic drugs were suspected to induce QT interval prolongation and resultant torsade de pointes. Two hours after cardioversion, pulmonary edema developed on chest X-ray and chest computed tomography. She responded to conservative treatment including oxygen therapy and the pulmonary edema improved on the second hospital day. The mechanism of pulmonary edema after cardioversion is still uncertain and remains controversial.