RESUMEN
BACKGROUND: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. RESULTS: We included 14 RCTs comprising 16â196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%). CONCLUSION: Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.
Asunto(s)
Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Síndrome de QT Prolongado , Inhibidores de Proteínas Quinasas , Femenino , Humanos , Aminopiridinas/efectos adversos , Aminopiridinas/uso terapéutico , Aminopiridinas/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Síndrome de QT Prolongado/inducido químicamente , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Purinas/efectos adversos , Purinas/uso terapéutico , Purinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Roscovitina/efectos adversosRESUMEN
OBJECTIVE: QT interval prolongation can increase patients' hospital stay and mortality rate. This study aims to determine the incidence of drug-induced QT interval prolongation and establish which QT interval measurement method is the most appropriate for electrocardiographic monitoring. METHOD: A retrospective observational study was conducted of patients admitted to the Clínica Bíblica Hospital during 2018. The electronic medical records of patients hospitalized for longer than 48 hours and whose drug regimen included at least one drug potentially able to prolong the QT interval were reviewed. Manually-measured QT intervals were corrected using Fridericia's and Rautaharju's formulae, while automatically- measured QT intervals were corrected with Bazett's formula. Risk was assessed using the RISQ-PATH scale. RESULTS: Of the 141 patients analyzed, 23 had arrhythmia as per their clinical history and 14 suffered a complication during their stay in hospital. A total of 113 (80%) had a high RISQ-PATH score and only 64 were subjected to an electrocardiogram on admission. Patients received a mean of three potentially QT interval prolonging drugs. Most of the QT intervals measured automatically were shorter than those obtained manually. Of all corrections, the longest QTc interval values were obtained with Bazett's formula, and the shortest with Rautaharju's formula. None of the patients developed TdP or complex ventricular tachycardia. CONCLUSIONS: Every effort should be made to implement strategies conducive to more effective monitoring of the QT interval to prevent QT nterval prolongation related complications in hospitalized patients.
OBJETIVO: La prolongación del intervalo QT puede aumentar la estancia hospitalaria y la tasa de mortalidad de los pacientes. Esta investigación determina la incidencia de prolongación del intervalo QT debido al uso de medicamentos y evalúa el método más apropiado para realizar el monitoreo electrocardiográfico.Método: Se realizó un estudio observacional retrospectivo en pacientes hospitalizados en el Hospital Clínica Bíblica durante el año 2018. Se revisaron los expedientes de los pacientes con hospitalización superior a 48 horas cuya historia clínica incluyera al menos tratamiento con un medicamento que prolongara el intervalo QT y que las medidas manuales del intervalo QT fueran corregidas con la fórmula Fridericia y Rautaharju, y las medidas automáticas con la fórmula Bazett. La valoración del riesgo se realizó con la escala RISQ-PATH. RESULTADOS: De los 141 pacientes analizados, 23 tenían una arritmia previa en su historia clínica y 14 de ellos sufrieron complicaciones durante la hospitalización. Un total de 113 (80%) pacientes tenían un valor alto RISQPATH y sólo a 64 se les realizó un electrocardiograma al ingreso. En promedio, los pacientes recibieron tres medicamentos que aumentaban el intervalo QT. La mayoría de los QT obtenidos automáticamente fueron más cortos que aquellos obtenidos en forma manual. De todas las correcciones, los valores del intervalo QT más largos se obtuvieron con la fórmula de Bazett, y los más cortos con la fórmula Rautaharju. No ocurrieron eventos como taquicardia ventricular compleja o torsade de pointes durante el estudio. CONCLUSIONES: Es necesario implementar estrategias que permitan una mejor monitorización del intervalo QT con el fin de prevenir las complicaciones derivadas en los pacientes hospitalizados.
Asunto(s)
Síndrome de QT Prolongado , Proteínas de Unión al ADN/farmacología , Electrocardiografía/métodos , Frecuencia Cardíaca , Humanos , Tiempo de Internación , Síndrome de QT Prolongado/inducido químicamenteRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/epidemiología , Electrocardiografía , Amiodarona/efectos adversos , Estudios Prospectivos , Amiodarona/administración & dosificaciónRESUMEN
Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Síndrome de QT Prolongado/inducido químicamente , Torsades de Pointes/inducido químicamente , Humanos , Preparaciones Farmacéuticas , Factores de RiesgoRESUMEN
PURPOSE: Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early pandemic period. It is well-known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID-19 patients treated with these drugs. METHODS: We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500 ms, peak QTc change ≥60 ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta-analyses were conducted using a random-effects model. RESULTS: Forty-seven studies (three case series, 35 cohorts, and nine randomized controlled trials [RCTs]) involving 13 087 patients were included. The pooled prevalence of peak QTc ≥500 ms was 9% (95% confidence interval [95%CI], 3%-18%) and 8% (95%CI, 3%-14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56-4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16-9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation. CONCLUSIONS: COVID-19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low, probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.
Asunto(s)
Azitromicina/efectos adversos , Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/epidemiología , Azitromicina/administración & dosificación , COVID-19/diagnóstico , COVID-19/epidemiología , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Humanos , Hidroxicloroquina/administración & dosificación , Síndrome de QT Prolongado/diagnóstico , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Estudios Observacionales como Asunto/métodos , Ritonavir/administración & dosificación , Ritonavir/efectos adversosRESUMEN
BACKGROUND: Abiraterone is a medication frequently used for metastatic castrate-resistant prostate cancer. We report a case of non-sustained episodes of TdP associated with severe hypokalemia due to androgen-deprivation therapy. Few case presentations describe this association; the novelty lies in the potentially lethal cardiovascular events among cancer patients receiving hormonal therapy. CASE PRESENTATION: A 70-year-old male presented with recurrent syncope without prodrome. ECG revealed frequent ventricular ectopy, non-sustained episodes of TdP, and severe hypomagnesemia and hypokalemia. During potassium and magnesium infusion for repletion, the patient underwent temporary transvenous atrial pacing. As part of the work-up, coronary angiography revealed a mild coronary artery disease, and transthoracic echocardiogram showed a moderately depressed ejection fraction. After electrolyte disturbances were corrected, the QT interval normalized, and transvenous pacing was no longer necessary. Abiraterone was discontinued during the admission, and the patient returned to baseline. CONCLUSIONS: Cancer treatment is complex and requires a multidisciplinary approach. We presented a case of non-sustained TdP associated with androgen-deprivation therapy in an elderly patient with mild coronary artery disease and moderately reduced ejection fraction. Close follow-up and increased awareness are required in patients with hormonal treatment, especially in the setting of other cardiovascular risk factors.
Asunto(s)
Acetato de Abiraterona/efectos adversos , Antineoplásicos/efectos adversos , Frecuencia Cardíaca/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Inhibidores de la Síntesis de Esteroides/efectos adversos , Síncope/inducido químicamente , Torsades de Pointes/inducido químicamente , Anciano , Estimulación Cardíaca Artificial , Fluidoterapia , Humanos , Síndrome de QT Prolongado/diagnóstico por imagen , Síndrome de QT Prolongado/fisiopatología , Síndrome de QT Prolongado/terapia , Masculino , Síncope/diagnóstico , Síncope/fisiopatología , Síncope/terapia , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatología , Torsades de Pointes/terapia , Resultado del TratamientoRESUMEN
Long QT syndrome type 3 (LQT-3) is a disease related to abnormal cardiac sodium channel function (Nav 1.5), usually due to augmented late sodium current (INaL ), and may lead to ventricular fibrillation. Amiodarone is approved for ventricular fibrillation. Thus, we investigated whether pacing frequency impacts the ability of amiodarone to reverse the arrhythmic phenotype observed in LQT-3. Anemone neurotoxin 2 (ATX-II, here named only ATX) was used to enhance INaL in mice left ventricular myocytes (LVM). A video detector system monitored sarcomere shortening. At 1 Hz, amiodarone attenuated sarcomere shortening only at 10 µmol/L; at 3 and 5 Hz, 0.1 and 1 µmol/L amiodarone also reduced sarcomere shortening. However, no effect of amiodarone was observed on time to 50% of sarcomere contraction and relaxation. In LVM exposed to ATX (10 nmol/L), an arrhythmic phenotype was observed, and it was more severe when cells were paced at 1 Hz. Amiodarone failed to reverse the ATX induced phenotype at different pacing frequencies. Thus, our results suggest that amiodarone's ability to reverse arrhythmias induced by augmentation of INaL is limited. These findings suggest further experimentation will be required to clarify whether a clinical effect can be ascribed to an effect of amiodarone on other ion channels in LQT-3.
Asunto(s)
Amiodarona/farmacología , Trastorno del Sistema de Conducción Cardíaco/tratamiento farmacológico , Síndrome de QT Prolongado/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Amiodarona/uso terapéutico , Animales , Trastorno del Sistema de Conducción Cardíaco/inducido químicamente , Trastorno del Sistema de Conducción Cardíaco/fisiopatología , Células Cultivadas , Venenos de Cnidarios/farmacología , Modelos Animales de Enfermedad , Humanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/fisiopatología , Masculino , Ratones , Miocitos Cardíacos/fisiología , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Cultivo Primario de Células , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéuticoRESUMEN
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.
Asunto(s)
Humanos , Masculino , Adolescente , Síndrome de QT Prolongado/inducido químicamente , Agonistas Adrenérgicos beta/efectos adversos , Trastornos Fingidos/diagnóstico , Hipopotasemia/inducido químicamente , Potasio/sangre , Potasio/uso terapéutico , Recurrencia , Síndrome de QT Prolongado/psicología , Agonistas Adrenérgicos beta/sangre , Albuterol/sangre , Sobredosis de Droga/complicaciones , Hipopotasemia/psicología , Hipopotasemia/sangreRESUMEN
COVID-19 infection has shown rapid growth worldwide, and different therapies have been proposed for treatment, in particular, the combination of immune response modulating drugs such as chloroquine and hydroxychloroquine (antimalarials) alone or in combination with azithromycin. Although the clinical evidence supporting their use is scarce, the off label use of these drugs has spread very quickly in face of the progression of the epidemic and the high mortality rate in susceptible populations. However, these medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.
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Antimaláricos/efectos adversos , Infecciones por Coronavirus/tratamiento farmacológico , Electrocardiografía , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/diagnóstico por imagen , Neumonía Viral/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Adulto , Anciano , Antimaláricos/administración & dosificación , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/epidemiología , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , COVID-19 , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Pandemias/estadística & datos numéricos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Pronóstico , Medición de Riesgo , Tratamiento Farmacológico de COVID-19RESUMEN
Long QT syndrome is characterized by prolongation of the corrected QT interval and is associated with fatal arrhythmias. R on T phenomenon is the coincidence of a premature ventricular complex with a T wave and may result to syncope and sudden cardiac death. Here we present a case of a 59-year-old woman with no previous history of medication, receiving moxifloxacin for community-acquired pneumonia. She was admitted complaining for thoracic pain and shortness of breath. Electrocardiogram showed both R on T phenomenon and QT prolongation. After discontinuation of the antibiotic symptoms and electrocardiography features were resolved. Physicians should always be vigilant about this rare and potentially fatal adverse drug reaction especially in high risk patients. General practitioners in particular being the first point of access in care have to carefully assess and detect high risk patients before the administration of moxifloxacin.
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Antibacterianos/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Moxifloxacino/efectos adversos , Antibacterianos/administración & dosificación , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Electrocardiografía , Femenino , Humanos , Síndrome de QT Prolongado/diagnóstico , Persona de Mediana Edad , Moxifloxacino/administración & dosificación , Neumonía Bacteriana/tratamiento farmacológicoRESUMEN
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 ß-adrenergic agonists in the context of a probable factitious disorder.
Asunto(s)
Agonistas Adrenérgicos beta/efectos adversos , Trastornos Fingidos/diagnóstico , Hipopotasemia/inducido químicamente , Síndrome de QT Prolongado/inducido químicamente , Adolescente , Agonistas Adrenérgicos beta/sangre , Albuterol/sangre , Sobredosis de Droga/complicaciones , Humanos , Hipopotasemia/sangre , Hipopotasemia/psicología , Síndrome de QT Prolongado/psicología , Masculino , Potasio/sangre , Potasio/uso terapéutico , RecurrenciaRESUMEN
INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.
Asunto(s)
Antimaláricos/efectos adversos , Artemisininas/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Malaria Falciparum/tratamiento farmacológico , Quinolinas/efectos adversos , Adulto , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Quimioterapia Combinada , Electrocardiografía , Femenino , Humanos , Síndrome de QT Prolongado/diagnóstico , Masculino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Estudios RetrospectivosRESUMEN
Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Quinolinas/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Malaria Falciparum/tratamiento farmacológico , Artemisininas/efectos adversos , Antimaláricos/efectos adversos , Quinolinas/uso terapéutico , Síndrome de QT Prolongado/diagnóstico , Estudios Retrospectivos , Artemisininas/uso terapéutico , Quimioterapia Combinada , Electrocardiografía , Persona de Mediana Edad , Antimaláricos/uso terapéuticoRESUMEN
BACKGROUND: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. METHOD: Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. RESULTS: In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. CONCLUSION: Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease.
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Antidepresivos/efectos adversos , Corazón/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Trastornos Mentales/tratamiento farmacológico , Torsades de Pointes/inducido químicamente , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Electrocardiografía , Humanos , Síndrome de QT Prolongado/diagnóstico , Factores de Riesgo , Torsades de Pointes/diagnósticoRESUMEN
BACKGROUND: Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-ß. OBJECTIVES: The aim of this study was to investigate whether Ab-ß, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2). METHODS/RESULTS: The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5µM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-ß) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-ß, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-ß perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-ß, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-ß-induced arrhythmias. Ab-ß, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2. CONCLUSION: The results indicate that Ab-ß were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-ß-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-ß-induced arrhythmias.
Asunto(s)
Arritmias Cardíacas/sangre , Arritmias Cardíacas/fisiopatología , Autoanticuerpos/sangre , Cardiomiopatía Chagásica/sangre , Síndrome de QT Prolongado/fisiopatología , Receptores Adrenérgicos beta 1/sangre , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Antiarrítmicos/toxicidad , Arritmias Cardíacas/etiología , Electrocardiografía/efectos de los fármacos , Electrocardiografía/métodos , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Síndrome de QT Prolongado/inducido químicamente , Estudios Longitudinales , Masculino , Conejos , Estudios RetrospectivosRESUMEN
A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine). OBJECTIVE: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine. RESEARCH DESIGN AND METHODS: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We measured meperidine and normeperidine by gas chromatography. Values are expressed as mean ± SD (range). RESULTS: 58 patients were studied (43.1% males). All patients received meperidine at a dose of 304 ± 133 (120 - 480) mg/day. Meperidine and normeperidine concentrations were 369 ± 60 (265 - 519) and 49 ± 17 (15 - 78) ng/mL, respectively. Intratreatment control found QTcB 370 ± 30 (305 - 433), QTcFri 353 ± 35 (281 - 429), QTcFra 360 ± 30 (299 - 429), QTcH 359 ± 27 (304 - 427), ΔQTcB +9 ± 42 (-90 to +136), ΔQTcFri +4 ± 45 (-86 to +137), ΔQTcFra +5 ± 40 (-77 to +129), and ΔQTcH +7 ± 40 (-76 to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and ΔQTc (R > 0.69) but the correlation was even better for normeperidine concentration, QTc (R > 0.52) and ΔQTc (R > 0.81). Depending on the QTc correction formula used, 13 - 15 patients (22.41 - 25.86%) presented ΔQTc values > 30 ms, and 7 - 8 patients (12.07- 13.79%) showed ΔQTc values > 60 ms. Renal failure was associated with risk for ΔQTc > 30 ms of 3.74 (IC95% 1.73 - 8.10) and for ΔQTc > 60 ms of 4.27 (IC 95% 1.26 - 14.48). No patient developed arrhythmias during the study. CONCLUSIONS: Meperidine treatment causes ECG changes (QTc-interval prolongation) in high correlation with normeperidine plasma concentration. Renal failure increases the risk.â©.
Asunto(s)
Analgésicos Opioides/efectos adversos , Sistema de Conducción Cardíaco/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Meperidina/efectos adversos , Potenciales de Acción/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/sangre , Analgésicos Opioides/farmacocinética , Argentina/epidemiología , Biotransformación , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/epidemiología , Síndrome de QT Prolongado/fisiopatología , Estudios Longitudinales , Masculino , Meperidina/análogos & derivados , Meperidina/sangre , Meperidina/farmacocinética , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Insuficiencia Renal/epidemiología , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death. METHOD: Bibliographic databases as MEDLINE and EMBASE, reports and drug alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT, arrhythmias, intensive care unit and Torsade de Pointes. Such research involved materials produced up to December 2017. RESULTS: Because of their mechanism of action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are associated to the prolongation of the QTc interval. For this reason, they require constant monitoring when administered. Other noncardiovascular drugs that are widely used in the Intensive Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics, typical and atypical antipsychotics agents such as haloperidol, thioridazine, and sertindole are also frequently associated with the prolongation of the QTc interval. As a consequence, critical patients should be closely followed and evaluated. CONCLUSION: ICU patients are particularly prone to experience a QTc interval prolongation mainly for two reasons. In the first place, they are exposed to certain drugs that can prolong the repolarization phase, either by their mechanism of action or through the interaction with other drugs. In the second place, the risk factors for TdP are prevalent clinical conditions among critically ill patients. As a consequence, the attending physician is expected to perform preventive monitoring and ECG checks to control the QTc interval.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Unidades de Cuidados Intensivos , Síndrome de QT Prolongado/inducido químicamente , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Enfermedad Crítica , Muerte Súbita Cardíaca/etiología , Humanos , Síndrome de QT Prolongado/epidemiología , Factores de Riesgo , Torsades de Pointes/inducido químicamente , Torsades de Pointes/epidemiologíaRESUMEN
AIMS: Medication is one of the main causes of long QT syndrome (LQTS) and torsades de pointes (TdP), and the older adult population is at particularly high risk. The aim of the present study was to describe the prescription patterns of drugs with a risk of TdP in the Colombian older adult population. METHODS: Patients older than 65 years who received medication with a risk of TdP during three consecutive months were selected. The medication was obtained and classified according to the QT Drug List from Crediblemeds.org. The data were analysed using SPSS-22. RESULTS: A total of 55 932 patients were chronically receiving QT-prolonging drugs; 61.9% (n = 34 ,632) were women and the mean age of the sample was 75.6 years. Drugs with a conditional risk were consumed by 95.2% of patients, 5.3% received drugs with a known risk and 2.9% received drugs with a possible risk. Two or more QT-prolonging drugs were consumed by 10.3% of the patients (n = 5786). Most of the sample (96.8%, n = 54 170) had at least one additional risk factor for LQTS, with a mean of 3.1 ± 0.9 risk factors. Patients receiving QT-prolonging drugs for psychiatric and neurological disease were at a higher risk of major polypharmacy [odds ratio (OR) 3.0; 95% confidence interval (CI) 2.80, 3.22) and of receiving high doses of QT-prolonging drugs (OR 3.8; 95% CI 3.52, 4.05). CONCLUSIONS: The widespread use of medication that causes TdP and the high prevalence of additional risks in the older adult population raise the need for accurate prediction of risk and constant patient monitoring. Patients taking psychiatric drugs are at a higher risk of TdP.