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)

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

Anomalies électrocardiographiques chez les patients hospitalisés pour COVID-19 à Fianarantsoa, Madagascar

Les anomalies électrocardiographiques sont l'expression d'une atteinte cardiovasculaire lors de la COVID-19. Les troubles du rythme et de la conduction cardiaque peuvent mettre en jeu le pronostic vital à court terme au cours de la COVID -19. Notre objectif principal est de décrire les anomalies électrocardiographiques et leurs fréquences chez les patients atteints de la COVID -19. L'objectif secondaire est de déterminer l'association entre ces anomalies électrocardiographiques et la gravité de la maladie. Méthodes : Il s'agit d'une étude rétrospective à visée descriptive des patients hospitalisés pour COVID-19 dans les centres de traitement COVID -19 de Fianarantsoa sur une période de 14 mois. Résultats : Nous avons retenu 101 patients. Le sex-ratio était de 1,06. La moyenne d'âge était de 59,81ans +/- 11,9. Tous les patients retenus avaient un électrocardiogramme à 12 dérivations et un test positif à la COVID-19. L'électrocardiogramme (ECG) était anormal chez 87 (86,1%) patients. Dans les formes graves et modérées de la maladie nous avons enregistré à l'ECG: 51 (50,5%) tachycardies sinusales, 13 (12,8%) blocs de branche incomplets droits, 13 (12,8%) profil S1Q3T3, 24 (23,7%) ondes Q pathologiques, 19 (18,8%) anomalies du segment ST. Dans les formes graves de la maladie nous avons enregistré à l'ECG: 2 (3,8%) bloc auriculoventriculaire complet (BAV complet), 7 (13,4%) blocs de branche gauche complet (BBG), 5 (9,6%) blocs de branche droit complet (BBD). La tachycardie sinusale avait une association significative avec la gravité de la maladie (p=0,002). Conclusion : Des anomalies électrocardiographiques ont été observées dans notre étude. La tachycardie sinusale était associée à la gravité de la maladie. Une surveillance rythmique, des explorations cardiaques plus pertinentes sont nécessaires pour une meilleure prise charge de la COVID-19

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 long-term efficacy of left cardiac sympathetic denervation in long QT syndrome / 中华心血管病杂志

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.

Taquicardia tipo torcida de puntas secundaria a prolongación del intervalo QT por uso de Amitriptilina a propósito de un caso / Torsades de pointes due to prologed QT interval by amitriptilin use

El intervalo QT representa la actividad eléctrica ventricular, tanto la despolarización como la repolarización. Definimos como intervalo QT prolongado a una medida del QT corregido > 450 ms en varones y > 470 ms en mujeres. Se diferencian 2 grandes grupos dentro del síndrome del QT prolongado: el congénito, asociado con mutaciones en determinados genes, y la variante adquirida. El síndrome de QT prolongado es un conjunto de entidades infrecuentes que se manifiestan en el ECG por la prolongación del intervalo QT y la predisposición a la taquicardia ventricular polimórfica. Una de las principales etiologías del síndrome de QT congénito adquirido es el uso de fármacos prolongadores del intervalo QT. En la actualidad la lista de fármacos que pueden prolongarlo a dosis terapéuticas es amplia y está en continuo crecimiento. La prolongación del intervalo QT puede predisponer a la aparición de taquicardia ventricular polimórfica grave denominada torcida de puntas (TdP), cuya aparición no es muy frecuente, pero es causa de muerte súbita. En el presente reporte presentamos un caso de desarrollo de torcida de puntas debido a uso de amitriptilina

QTc, Tp-e Interval and Tp-e/QTc Ratio in Patients with Hypocalcemia-case Control Study

Abstract Background: To the best of our knowledge, there are studies related to QT and QTc interval in patients with hypocalcemia, but there are no studies evaluating T wave peak and end interval (Tp-e interval), Tp-e/QT and Tp-e/QTc ratios used to evaluate cardiac arrhythmia risk and ventricular repolarization changes rates. Objectives: Therefore, we aimed to investigate whether there is a change in Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in patients with hypocalcemia. Methods: Retrospectively, 29 patients with hypocalcemia in the emergency department were included in the study. Twenty-nine patients with similar age and sex distribution were included in the study as the control group. All patients underwent 12-lead electrocardiography (ECG). In addition to routine measurements, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured on ECG. The study data were grouped as patients with and without hypocalcemia. Results: The mean age of the patients was 66.24 ± 4.95 years. QTc interval, Tp-e interval and Tp-e/QTc values were found to be significantly higher in patients with hypocalcemia (p <0.001 for each). QTc interval, Tp-e interval and Tp-e/QTc ratio showed a significant negative correlation with calcium levels. Conclusion: Tp-e interval and Tp-e/QTc ratios are significantly increased in patients with hypocalcemia compared to those without hypocalcemia and this can be used more effectively in the follow-up of cardiac fatal arrhythmias.

Analyses of triggers for recurrent cardiac events in 38 patients with symptomatic long QT syndrome / 中华心血管病杂志

Objective: To evaluate the main triggers of recurrent cardiac events in patients with symptomatic congenital long QT syndrome (cLQTS). Methods: In this retrospective case analysis study, clinical characteristics were reviewed from 38 patients with recurrent cardiac events after first visit out of 66 symptomatic cLQTS patients. General clinical data such as gender, age, clinical presentation, family history and treatment were collected, auxiliary examination results such as electrocardiogram and gene detection were analyzed. LQTS-related cardiac events were defined as arrhythmogenic syncope, implantable cardioverter defibrillator (ICD) shock, inappropriate ICD shock, aborted cardiac arrest, sudden cardiac death or ventricular tachycardia. Results: A total of 38 patients with recurrent symptoms were enrolled in this study, including 30 females (79%) and 14 children (37%). The average age of onset was (15.6±14.6) years, and the recurrence time was (3.6±3.5) years. Subtype analysis showed that there were 11 cases (29%) of LQT1 (including 2 cases of jervel-Lange Nielson syndrome), 19 cases (50%) of LQT2, 5 cases (13%) of LQT3 and 3 cases (8%) of other rare subtypes (1 LQT5, 1 LQT7 and 1 LQT11) in this patient cohort. LQT1 patients experienced recurrent cardiac event due to drug withdrawal (6 (55%)), specific triggers (exercise and emotional excitement) (4 (36%)) and medication adjustment (1 (9%)). For LQT2 patients, main triggers for cardiac events were drug withdrawal (16 (84%)), specific triggers (shock, sound stimulation, waking up (6 (32%)). One patient (5%) had recurrent syncope after pregnancy. One patient (20%) had inappropriate ICD shock. For LQT3 patients, 4 (80%) patients developed syncope during resting state, and 1 (20%) developed ventricular tachycardia during exercise test. One LQT5 patients experienced syncope and ICD shock under specific triggers (emotional excitement). One LQT11 patient had repeated ICD shocks under specific inducement (fatigue). One LQT7 patient experienced inappropriate ICD shock. Left cardiac sympathetic denervation (LCSD) significantly alleviated the symptoms in 2 children with Jervell-Lange Nielson syndrome (JLNS) post ineffective β-blocker medication. Nadolol succeeded in eliminating cardiac events in one patient with LQT2 post ineffective metoprolol medication. Mexiletine significantly improved symptoms in 2 patients with LQT2 post ineffective β-blocker medication. Conclusions: Medication withdrawal is an important trigger of the recurrence of cardiac events among patients with symptomatic congenital long QT syndrome.

A new ECG sign for sudden death: Transient prolonged QT interval following premature contraction / 中南大学学报(医学版)

Early recognition and treatment for early warning electrocardiogram (ECG) of sudden death are very important to prevent and treat malignant arrhythmia and sudden death. Previous studies have found that R-on-T and T wave alternation, and QT interval prolongation are closely related to malignant arrhythmia or sudden death, which are included in the critical value of ECG.By analyzing the ECG characteristics of 4 patients with sudden death, we found that although the causes of the patients were different, there were transient prolongation of QT interval after premature contraction in 12 lead ECG, followed by malignant arrhythmia or sudden death. Thus, we thought that the transient prolongation of QT interval after premature contraction had a high value for warning malignant arrhythmia or sudden death. This phenomenon should be paid enough attention to reduce the risk of sudden death.

Evaluación y validación diagnóstica de las variables iQT, razón iQTRR, razón iRTRR para el diagnóstico DEQTc prolongado / Validation of iQT, iQTRR, iRT/RR ratio for estimation of QTc

ANTECEDENTES: El intervalo QT representa la despolarización y repolarización ventricular y su prolongación está asociada a un mayor riesgo de arritmias graves y muerte súbita. Depende de la frecuencia cardíaca y su rápida valoración es difícil de obtener en la práctica clínica. Una forma que facilita este proceso es medir sólo el intervalo QT pero este no siempre se relaciona con un intervalo QTc prolongado. Debido a esto, se postula que una variable compuesta debería tener mejor rendimiento diagnóstico para este objetivo. OBJETIVO: Describir la correlación de 3 variables electrocardiográficas; intervalo QT (iQT), razón del intervalo QT intervalo RR (%iQTRR) y razón del intervalo RT intervalo RR (%iRTRR), en relación a la variable QT corregido (iQTc). Se efectuó una evaluación diagnóstica y validación de las variables mencionadas para establecer el diagnóstico de intervalo QT largo y las propiedades diagnósticas de las mismas para el diagnóstico de iQTc prolongado según la fórmula Bazett. METODOS Y RESULTADOS: Se efectuó un estudio transversal descriptivo-relacional, usando una muestra no probabilística formada por 220 electrocardiogramas registrados en la base de datos del centro cardiovascular. Las mediciones provenían de ECGs registrados en reposo con medición con cáliper de los intervalos QT y RR en derivadas D2 y/o V5, expresadas en milisegundos. Se excluyó la presencia de isquemia, preexcitación y repolarización precoz. Se obtuvo como resultado que la variable razón iQTRR tiene mejor correlación, concordancia, sensibilidad y valor predictivo negativo para el diagnóstico del iQTc prolongado, versus las variables iQT y razón iRTRR, principalmente en mujeres. CONCLUSIONES: La variable razón iQTRR tiene una mejor correlación, concordancia, sensibilidad y valor predictivo negativo (VPN) para el diagnóstico del iQTc prolongado, comparado con las variables iQT y razón iRTRR, principalmente, en mujeres. Utilizando ambas variables este efecto se potencia y permite concluir que si una mujer tiene un iQT observado <470 ms, y una razón QTRR< 47,5%, esto se corresponde con un intervalo QTc normal, con un VPN de 100% .

BACKGROUND: The QT interval (QT) includes depolarization and repolarization phases of cardiac cycle. Its prolongation is associated to an increa sed risk of serious arrhythmia and sudden death. QT depends on heart rate and it is usually corrected using the Bazett formula (QTc). Prolonged QT is not usually well related to QTc. We postulate that a composite formula muy have a greater value for predicting serious arrhythmia. AIM: To correlate the predictive value of a different approach to estimate a corrected QT interval: the ratio of RT to RR intervals (QT/RR, expressed as a percentage METHODS and RESULTS: A non probabilistic sample of 220 ECGs were obtained from our data base. ECGs were recorded at rest and measurements were performed in leads Ds and/or V5 using zetcalipers, the values being expressed in ms. The presence of ischemia, pre excitation and early repolarization were excluded. The QT/RR ratio showed better correlation, concordance, sensitivity, and negative predicted value with the usual QTc interval compared to QT alone or de RT/RR ratio, especially so in women.

Severe hypokalemia secondary to abuse of ß-adrenergic agonists in a pediatric patient: Case report / Hipocalemia grave secundária a abuso de agonistas ß-adrenérgicos em paciente pediátrico: relato de caso

ABSTRACT This study reports a case of a 13-year-old male with a 3-year history of severe and intermittent hypokalemia episodes of unknown origin, requiring admission to the intensive care unit (ICU) for long QT syndrome (LQTS), finally diagnosed of redistributive hypokalemia secondary to the abuse of β-adrenergic agonists in the context of a probable factitious disorder.

RESUMO O presente estudo relata o caso de um jovem de 13 anos de idade com histórico, há três anos, de episódios de hipocalemia grave intermitente de origem desconhecida, internado em unidade de terapia intensiva (UTI) por síndrome do QT longo (SQTL). O paciente foi diagnosticado com hipocalemia por redistribuição secundária ao abuso de agonistas β-adrenérgicos, em contexto de provável transtorno factício.

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.

Interações Medicamentosas Prolongadoras do Intervalo QT em Unidade de Terapia Intensiva: Coorte de idosos / QT Interval Prolonging Drug - Drug Interactions in an Intensive Care Unit: Elderly cohort

Em Unidades de Terapia Intensiva (UTI), a ocorrência de interações medicamentosas representa um dos motivos precipitantes do prolongamento do intervalo QT, o qual pode contribuir para a Síndrome do Intervalo QT Prolongado Adquirida (ALQTS), que pode resultar em desfechos clínicos potencialmente catastróficos como síncope, parada cardíaca e morte súbita. Deste modo, o objetivo deste estudo foi determinar a incidência de interações medicamentosas prolongadoras de intervalo QT (IMP QT) e as variáveis clínicas e terapêuticas preditoras de IMP QT, e identificar associação entre a ocorrência de IMP QT e óbito. Analisaram-se prescrições médicas de pacientes idosos internados em UTI do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As IMP QT foram identificadas segundo DRUG-REAX® da base de dados Micromedex. Na análise dos dados utilizaram-se os testes Pearson's Chi-squared test, Wilcoxon-Mann-Whitney test e Welch Two Sample t-test e regressão logística, com significância de p ≤0,05. A incidência de IMP QT foi de 43,9%. Foram identificadas 86 IMP QT cuja maioria (93,0%) foi de gravidade "Maior". Os preditores para IMP QT foram potássio sérico ≤3.5 mEq/L (p=0,044), uso de antipsicóticos (p<0.001), de antidepressivos (p=0,003), de antiarrítmicos (p=0,006), ocorrência de IMP geral de gravidade "Maior" (p=0,002) e IMP geral de gravidade "Contraindicada" (p=0,004). A frequência de óbitos entre pacientes expostos a IMP QT foi 38,5% e cujos preditores foram a ocorrência de choque séptico (p<0,001), o uso de diurético de alça (p=0.048), o uso de antibióticos (p=0.049), a ocorrência de IMP QT "Contraindicada" (p=0.006). No contexto da UTI, os estudos farmacoepidemioilógicos podem trazer informações acerca do risco e do impacto das IMP, contribuindo assim na elaboração de práticas de cuidado que visem o uso seguro de medicamentos em pacientes idosos gravemente enfermos.

In Intensive Care Units (ICU), the occurrence of drug-drug interactions (DDI) represents one of the precipitating reasons for the prolongation of the QT interval, which can contribute to the Acquired Long QT Interval Syndrome (ALQTS), which can result in potentially catastrophic clinical outcomes such as syncope, cardiac arrest and sudden death. Thus, the aim of this study was to determine the incidence of QT interval-prolonging drug-drug interactions (QT DDI) and the clinical and therapeutic variables that predict QT DDI, and to identify an association between the occurrence of QT DDI and death. Medical prescriptions of elderly patients admitted to the ICU of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo were analyzed. QT DDI were identified according to DRUG-REAX® from the Micromedex database. Pearson's Chi-squared test, Wilcoxon-Mann-Whitney test and Welch Two Sample t-test and logistic regression were used in the data analysis, with significance of p 0.05. The incidence of QT DDI was 43.9%. 86 QT DDI were identified, the majority (93.0%) of which was Major in severity. Predictors for QT DDI were serum potassium 3.5 mEq / L (p = 0.044), use of antipsychotics (p <0.001), antidepressants (p = 0.003), antiarrhythmics (p = 0.006), occurrence of general severity IMP Major (p = 0.002) and general IMP of severity Contraindicated (p = 0.004). The frequency of deaths among patients exposed to QT DDI was 38.5% and whose predictors were the occurrence of septic shock (p <0.001), the use of loop diuretics (p = 0.048), the use of antibiotics (p = 0.049) ), the occurrence of Contraindicated QT DDI (p = 0.006). In the context of the ICU, pharmacoepidemioilogical studies can bring information about the risk and impact of PPIs, thus contributing to the elaboration of care practices aimed at the safe use of medicines in seriously ill elderly patients.

Cardiomiopatia periparto associada à síndrome do QT longo e síncope por taquicardia ventricular polimórfica: relato de caso / Peripartum cardiomyopathy associated with long QT syndrome and polymorphic ventricular tachycardia syncope: a case report

A cardiomiopatia periparto é uma causa rara de insuficiência cardíaca no período entre o último mês de gestação e os cinco meses após o parto. A síndrome do QT longo caracteriza-se pelo atraso da repolarização ventricular e pode se manifestar com síncope e morte súbita devido a um tipo de taquicardia ventricular polimórfica conhecida como torsades de pointes. Descrição do caso: J.S., 26 anos, sexo feminino, natural e procedente de São Paulo. Paciente puérpera - 40º dia (G3P3A0), procurou o pronto-socorro com queixa de síncope durante amamentação e dispneia em moderados esforços. Durante a avaliação no PS, evoluiu para desconforto torácico e agitação psicomotora, sendo notada taquicardia ventricular não sustentada no monitor cardíaco ( torsades de pointes), que foi controlada com cardioversão elétrica e sulfato de magnésio intravenoso. O eletrocardiograma mostrou ritmo sinusal, alteração difusa da repolarização ventricular e intervalo QTc de 580 ms. O ecocardiograma mostrou disfunção sistólica moderada, com fração de ejeção do ventrículo esquerdo de 43% à custa de hipocinesia difusa. Após avaliação da equipe de arritmologia chegou-se ao diagnóstico de cardiomiopatia periparto associado à síndrome do QT longo. Foi iniciado tratamento otimizado para insuficiência cardíaca e implantado cardiodesfibrilador por causa de episódios recorrentes de arritmia durante a internação. Discussão: A cardiomiopatia periparto é uma doença rara, porém, tem taxa de mortalidade elevada, entre 18% e 56%. A paciente descrita satisfez os quatro critérios para o diagnóstico: sintomas de insuficiência cardíaca nos primeiros 5 meses depois do parto, ausência de cardiomiopatia prévia, etiologia desconhecida e disfunção sistólica com FEVE < 45%. A síndrome do QT longo é uma doença genética de apresentações variáveis. Os fatores que desencadeiam as taquiarritmias são situações de instabilidade elétrica por hiperatividade do sistema simpático e também situações raras, como a cardiomiopatia periparto. Em casos de arritmias ventriculares graves, o tratamento é o implante de cardiodesfibrilador. Conclusão: A associação da cardiomiopatia periparto com a síndrome do QT longo é rara. A gravidade associada a essas condições torna importante o diagnóstico precoce e tratamento imediato pelo potencial risco de morte associado a ambas as condições clínicas

Peripartum cardiomyopathy is a rare cause of heart failure during the period between the last month of pregnancy and five months after delivery. Long QT syndrome is characterized by a delay in ventricular repolarization and may manifest with syncope and sudden death due to a type of polymorphic ventricular tachycardia known as torsades de pointes. Case description: J.S., 26-years-old, female, born and residing in São Paulo, Puerperal - 40th day (G3C3A0), went to the emergency room complaining of syncope during breastfeeding and dyspnea on moderate exertion. During evaluation in the ER, the patient developed thoracic discomfort and psychomotor agitation, with non-sustained ventricular tachycardia on the cardiac monitor (torsades de pointes), which was controlled with electrical cardioversion and intravenous magnesium sulfate. The electrocardiogram showed sinus rhythm, diffuse alteration of ventricular repolarization and QTc interval of 580 ms. The echocardiogram showed moderate systolic dysfunction, with a left ventricular ejection fraction of 43% influenced by diffuse hypokinesia. After evaluation by the arrhythmology team, the diagnosis of peripartum cardiomyopathy associated with long QT syndrome was made. Optimized treatment for heart failure was initiated and a cardioverter-defibrillator was implanted due to recurrent episodes of arrhythmia during hospitalization. Discussion: Peripartum cardiomyopathy is a rare disease, but it has a high mortality rate, between 18% and 56%. The patient described met the 4 diagnostic criteria: symptoms of heart failure in the first 5 months after delivery, absence of prior cardiomyopathy, unknown etiology, and systolic dysfunction with LVEF<45%. Long QT syndrome is a genetic disease of varying presentations. The factors that trigger the tachyarrhythmias are situations of electrical instability due to sympathetic system hyperactivity and rare situations, such as peripartum cardiomyopathy. In cases of severe ventricular arrhythmias, the treatment is a cardioverter-defibrillator implant. Conclusion: The association of peripartum cardiomyopathy with long QT syndrome is rare. The severity associated with these conditions points out early diagnosis and immediate treatment important because of the potential risk of death associated with both clinical conditions

Repolarización ventricular en la terapia oncológica / Ventricular repolarization in cancer therapy

RESUMEN Se discuten los procesos de despolarización y repolarización ventriculares, con su falta de uniformidad y su heterogeneidad, tanto en pacientes con corazón sano como en aquellos enfermos, cuestión de rangos. Se analizan las mediciones que expresan las características de la repolarización ventricular: el intervalo QT y otras mediciones incluso más fidedignas como el intervalo TPICO-TFINAL, su dispersión y otras. Se precisa la existencia del signo y del síndrome de QT largo, así como los tres procesos básicos de la arritmogenia: la heterogeneidad, la alternancia y la dispersión, con las diferencias de los potenciales de acción en las tres zonas del miocardio ventricular. Se precisan los factores de riesgo del QT largo (común con esta terapia), de las arritmias ventriculares (en especial la torsión de puntas, extremadamente rara en estos casos) y se discute la necesidad de valorar datos clínicos, eléctricos, comorbilidades, conflictos agregados y las medidas a tomar en estos pacientes.

ABSTRACT Ventricular depolarization and repolarization processes are discussed, including their differences and heterogeneity both in patients with a healthy/sick heart, a matter of ranges. Measurements expressing the characteristics of ventricular repolarization are analyzed: the QT interval and other even more reliable measurements such as the TPEAK-TEND interval, its dispersion and others. We emphasize on the existence of the long QT syndrome (and sign) and the three basic processes of arrhythmogenesis: heterogeneity, alternation and dispersion, with differences in action potentials in the three zones of the ventricular myocardium. The risk factors of long QT (common in this therapy) and ventricular arrhythmias (especially torsades de pointes, extremely rare in these cases) are highlighted. The need to assess clinical and electrical features, comorbidities, aggregate conflicts, and management of these patients is also discussed.