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.

Study of cardiac manifestations in patients with chronic liver disease

Background: Chronic liver disease is a common cause of mortality and morbidity worldwide. This has pathological effects on various systems in the body including cardiovascular system which usually is unnoticed. In majority of cases of chronic liver disease, cardiovascular complications develop as a subclinical condition which manifests only during stressful situations. Hence early detection of cirrhotic cardiomyopathy by echocardiography and 2D-ECHO studies in all patients of chronic liver disease helps in reducing the morbidity and mortality.Methods: 100 cases of chronic liver disease were included in the study. Data was collected through a prepared proforma. All patients were subjected to cardiac evaluation by ECG and Echocardiography. Serum pro-BNP levels were done for selected patients. Severity of the liver disease was assessed by using Child-Pugh score. Cardiac abnormalities were noted and correlated with the severity of the liver disease.Results: Out of 100 patients studied, 83% were males. 80% of the patients had history of alcoholism. 59% of the patients had abnormal ECG finding. 40% of them had QT prolongation and was related to the severity of liver disease. 60% of the total patients studied had positive pro-BNP values in patients with significant cardiac dysfunction. 46% of the patients had normal echocardiographic finding; most common abnormal finding was diastolic dysfunction (43%) and positively correlated with severity of liver disease.Conclusions: In chronic liver disease patient’s QT prolongation is the most common ECG abnormality. Most common Echocardiographic finding was diastolic dysfunction which had strong correlation with the severity of the liver disease.

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.

QT-interval prolongation due to medication found in the preoperative evaluation

QT prolongation is an electrocardiographic change that can lead to lethal arrhythmia. Acquired QT prolongation is known to be caused by drugs and electrolyte abnormalities. We report three cases in which the prolonged QT interval was improved at the time of operation by briefly discontinuing the drugs suspected to have caused the QT prolongation observed on preoperative electrocardiography. The QTc of cases 1, 2, and 3 improved from 518 to 429 ms, 463 to 441 ms, and 473 to 443 ms on discontinuing the use of a gastrointestinal prokinetic agent, a proton pump inhibitor, and a molecular targeted drug, respectively. These cases were considered to have drug-induced QT prolongation. We reaffirmed that even drugs administered for conditions unrelated to cardiac diseases can have adverse side effect of QT prolongation. In conclusion, our cases indicate that dental surgeons should be aware of the dangerous and even potentially lethal side effects of QT prolongation. For safe oral and maxillofacial surgery, cooperation with medical departments in various fields is important.

Pharmaceutical Care for Sotalol-induced QT Prolongation in Aged Patient with Heart Failure / 中国药房

OBJECTIVE:To explore the role of clinical pharmacists participating in the prevention and treatment of sotalol-in-duced QT prolongation in aged patient with heart failure. METHODS:Clinical pharmacists participated in the treatment for a aged patient with heart failure,and assisted physicians to identify and assess the risk of sotalol-induced QT prolongation. According to the clinical symptoms and laboratory indexes,it was suggested to continue to use sotalol for antiarrhythmic,adjust the hepatoprotec-tive drug,given pharmaceutical care of ECG,electrolyte level monitoring,drug education and so on. RESULTS:Physicians adopt-ed the suggestions of clinical pharmacists to relive the illness without malignant arrhythmia and discharged after 11 d. CONCLU-SIONS:The patient with heart failure should be dominated by improving cardiac function and maintaining hemodynamic stability;combined with related guidelines and documentation,clinical pharmacists can assist physicians to identify the drug that induced QT prolongation,asses the risk of torsades de pointes ventricular tachycardia and other bad consequences,develop and optimize the regimen and strengthen pharmaceutical care to ensure the safe and effective treatment.

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.

Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

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.

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.

A Data Warehouse Based Retrospective Post-marketing Surveillance Method: A Feasibility Test with Fluoxetine / 대한의료정보학회지

OBJECTIVE: Post-marketing surveillance (PMS) is an adverse events monitoring practice of pharmaceutical drugs on the market. Traditional PMS methods are labor intensive and expensive to perform, because they are largely based on manual work including phone-calling, mailing, or direct visits to relevant subjects. The objective of this study was to develop and validate a PMS methodology based on the clinical data warehouse (CDW). METHODS: We constructed a archival DB using a hospital information system and a refined CDW from three different hospitals. Fluoxetine hydrochloride, an antidepressant, was selected as the target monitoring drug. Corrected QT prolongation on ECG was selected as the target adverse outcome. The Wilcoxon signed rank test was performed to analyze the difference in the corrected QT interval before and after the target drug administration. RESULTS: A refined CDW was successfully constructed from three different hospitals. Table specifications and an entity-relation diagram were developed and are presented. A total of 13 subjects were selected for monitoring. There was no statistically significant difference in the QT interval before and after target drug administration (p=0.727). CONCLUSION: The PMS method based on CDW was successfully performed on the target drug. This IT-based alternative surveillance method might be beneficial in the PMS environment of the future.

A case of Sheehan's syndrome presented by recurrent ventricular tachycardia / 대한내과학회지

Electrocardiographic abnormalities commonly associated with hypopituitarism are low QRS voltage, ST-segment depression, inverted T waves and a prolonged QT interval. Although the mechanism remains unclear, glucocorticoid therapy, an intracelluar-extracellular electrolyte imbalance of myocytes, and histopathological changes in the myocardium are thought to play a role in this disorder. We discribe a 64 year old woman with recurrent ventricular tachycardia associated with QT prolongation in Sheehan's syndrome. Ventricualr tachycardia was treated by lidocain and direct current cardioversion. Sheehan's syndrome was confirmed by past history, anterior pituirary stimulation test and brain MRI showed empty sella. After hormone replacement treatment, inverted T waves and prolonged QT interval was normalized and ventricular tachycardia did not recur.

Electrocardiographic Changes after Hormone Replacement Treatment in Patients with Sheehan's Syndrome / 대한내분비학회지

BACKGROUND: Electrocardiographic abnormalities were studied to find if they were reversible during adequate hormonal treatment and to investigate regional inhomogenicity of ventricular repolarization in patients with Sheehan's syndrome. METHODS: Eleven women with Sheehan syndrome, who treated with prednisolone and levothyroxine, were the subjects of this study. Before and after hormonal replacement, the plasma thyroxine, cortisol and resting standard EKG were checked RESULTS: The most frequent electrocardiographic finding was inversion or flattening of the T waves, which occurred in 10 patients, with QT prolongation (7 patients), ST depression (2 patients) being the other findings. After prednisolone and levothyroxine replacement, the T wave abnormalities were normalized in 8 patients (80%) and the ST depression all patients. The QT (437 27 msec vs. 379 29 msec, p<0.05) and QTc intervals (478 80 msec vs 403 73 msec, p<0.005) were shortened by hormone replacement. CONCLUSION: High incidences of electrocardiographic abnormalities, including T wave inversion or flattening, QT prolongation and ST depression, were noted in patients with Sheehan's syndrome. The majority of these abnormalities recovered due to hormone replacement. The QT and QTc interval values were significantly shortened after treatment. Therefore, the regional inhomogenicity of ventricular repolarization may recover with hormone replacement