Electrocardiographic effect of artemisinin-piperaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine treatment in falciparum malaria patients

Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.

Association of QRS Complex Fragmentation with QT Interval Prolongation in Patients with Ischemic Heart Disease.

BACKGROUND: The fragmented QRS complex (FQRS) was found to be associated to malignant ventricular arrhythmias and sudden death in patients with hypertrophic cardiomyopathy and other entities. There is scant data available correlating the presence of FQRS with QT interval prolongation in patients with ischemic heart disease (IHD). METHODS: A descriptive, retrospective, cross-sectional study was performed in 123 patients with IHD to analyze and correlate the presence of FQRS with QT interval prolongation in the conventional 12-leads electrocardiogram in patients with documented chronic IHD. RESULTS: There were 62% male patients. The mean age was 63.8±12.6 years. Thirty six (44%) patients had fragmented QRS (64% men and 36% women). The duration of QT and QTc, the mean values were 413±59ms, and 463±67ms, respectively. Of the 36 patients with FQRS, 23 patients have prolongation of the QTc interval, and 13 patients did not present it. Of the 45 patients without FQRS, 21 of them have prolongation of the QTc interval, and 24 patients did not have it. These data resulted in a sensitivity of 52% with a moderate SnNout, a specificity of 65% with moderate SpPin, a positive predictive accuracy of 64%, a negative predictive accuracy of 53%. These data resulted in a prevalence of 54%. CONCLUSION: the presence of FQRS in the ECG has a moderate sensitivity and specificity, as well as, moderate negative and positive predictive value of the existence of QT interval prolongation in patients with ischemic heart disease.

Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death.

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures increase P-gp expression in the brain, which is associated with membrane depolarization in the hippocampus, and in the heart, which is associated with fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and severe arrhythmias, and both are related with SUDEP. Here, we investigate whether SE induces the expression of hypoxia-inducible transcription factor (HIF)-1α and P-gp in cardiomyocytes, which is associated with altered heart rhythm, and if these changes are related with the spontaneous death rate. SE was induced in Wistar rats once a week for 3 weeks, by lithium-pilocarpine-paradigm. Electrocardiograms, HIF-1α, and P-gp expression in cardiomyocytes, were evaluated in basal conditions and 72 h after SE. All spontaneous deaths occurred 48 h after each SE was registered. We observed that repeated SE induced HIF-1α and P-gp expression in cardiomyocytes, electrocardiographic (ECG) changes, and a high rate of spontaneous death. Our results suggest that the highly accumulated burden of convulsive stress results in a hypoxic heart insult, where P-gp expression may play a depolarizing role in cardiomyocyte membranes and in the development of the ECG changes, such as QT interval prolongation, that could be related with SUDEP. We postulate that this mechanism could explain, in part, the higher SUDEP risk in patients with RE or SE.

[Electrocardiographic abnormalities in anorexia nervosa: a critical review of the literature]. / Alteraciones electrocardiográficas en anorexia nervosa: revisión crítica de la literatura.

BACKGROUND: Anorexia nervosa is an eating disorder in which cardiac arrhythmias and sudden death are frequent causes of mortality, which makes electrocardiographic monitoring indispensable in these patients. There are many suggestive findings but results are contradictory, making a critical review of the scientific literature is necessary. METHODS: The most relevant studies on electrocardiographic (EKG) changes in patients with AN, found in PubMed from 1974 to February 2014, were reviewed using the MeSH terms: eating disorders, nervosa anorexia, sinus bradycardia, QT prolongation, QT dispersion, electrocardiography, EKG, and electrocardiogram. FINDINGS AND DISCUSSION: The two most common EKG findings reported in the literature are sinus bradycardia and changes in depolarization, as shown by prolongation and increased dispersion of the QT interval. Electrolyte disturbances seem to be the cause of these disturbances in some patients, but other reasons are also discussed in detail, such as QRS right axis deviation, disturbances of heart rate variability, low R wave voltage in V6, amplitude decrease of the QRS and T wave, and QRS prolongation. The majority of authors report that these changes are reversible after treatment of AN. CONCLUSIONS: These findings support the need for initial and follow-up EKGs in patients with AN and for early diagnosis and treatment of cardiovascular disturbances that are associated with morbidity and mortality. They also support the need for the rational use of psychopharmacology, and that does not increase the risk of arrhythmias and sudden death in these patients.

Alteraciones electrocardiográficas en anorexia nervosa: revisión crítica de la literatura / Electrocardiographic abnormalities in anorexia nervosa: a critical review of the literature

Introducción: La anorexia nervosa (AN) es un trastorno de la conducta alimentaria y, entre sus causas de mortalidad, las arritmias cardiacas y la muerte súbita son frecuentes, por lo que es indispensable la monitorización electrocardiográfica. Se han descrito muchos hallazgos con resultados contradictorios, por lo que es necesaria una revisión crítica de la literatura científica. Metodología: Revisión de los estudios relevantes sobre cambios electrocardiográficos en AN, consultados en PubMed desde 1974 hasta febrero de 2014, utilizando los términos MeSH: Eating disorders, nervosa anorexia, sinusal bradycardia, QT prolongation, QT dispersion, electrocardiography, EKG, electrocardiogram. Resultados y discusión: Las dos alteraciones más comunes reportadas incluyen la bradicardia sinusal y los cambios en la repolarización evidenciados en prolongación del QT e incremento de su dispersión. Los trastornos electrolíticos parecen ser la causa de estas alteraciones en algunos pacientes, pero otras razones se discuten en detalle, como la desviación del eje del QRS a la derecha, la alteración en variabilidad de la frecuencia cardiaca, R en derivación V6 de bajo voltaje, disminución de la amplitud del QRS y onda T y alargamiento del QRS. La mayoría de los autores hablan de reversibilidad de los cambios después del tratamiento. Conclusiones: Estos resultados siguen apoyando la necesidad de valorar a los pacientes con AN con electrocardiogramas inicial y de seguimiento, para el diagnóstico temprano y tratamiento de alteraciones cardiovasculares relacionadas con alta morbimortalidad. También apoyan la necesidad del uso racional de psicofármacos para no aumentar el riesgo de arritmias cardiacas y muerte súbita.

Background: Anorexia nervosa is an eating disorder in which cardiac arrhythmias and sudden death are frequent causes of mortality, which makes electrocardiographic monitoring indispensable in these patients. There are many suggestive findings but results are contradictory, making a critical review of the scientific literature is necessary. Methods: The most relevant studies on electrocardiographic (EKG) changes in patients with AN, found in PubMed from 1974 to February 2014, were reviewed using the MeSH terms: eating disorders, nervosa anorexia, sinus bradycardia, QT prolongation, QT dispersion, electrocardio graphy, EKG, and electrocardiogram. Findings and discussion: The two most common EKG findings reported in the literature are sinus bradycardia and changes in depolarization, as shown by prolongation and increased dispersion of the QT interval. Electrolyte disturbances seem to be the cause of these disturbances in some patients, but other reasons are also discussed in detail, such as QRS right axis deviation, disturbances of heart rate variability, low R wave voltage in V6, amplitude decrease of the QRS and T wave, and QRS prolongation. The majority of authors report that these changes are reversible after treatment of AN. Conclusions: These findings support the need for initial and follow-up EKGs in patients with AN and for early diagnosis and treatment of cardiovascular disturbances that are associated with morbidity and mortality. They also support the need for the rational use of psychop harmacology, and that does not increase the risk of arrhythmias and sudden death in these patients.

QT interval prolongation associated with azithromycin/methadone combination / Prolongación del intervalo QT asociada con combinación de azitromicina/metadona

This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

Este reporte documenta la ocurrencia de la prolongación del intervalo QT en un hombre de 57 años, en la terapia de reemplazo con metadona, tratado con azitromicina por pulmonía adquirida en la comunidad. Este caso destaca una interacción de medicamentos desconocida hasta ahora. En vista del uso cada vez mayor de la azitromicina, resulta absolutamente necesario usarla con precaución en pacientes que ya están bajo tratamiento con medicamentos de los cuales se sabe que causan prolongación del intervalo QT o que causan torsades de pointes.