Prolonged Rate-corrected QT Interval Research Articles

Major Drug-Drug Interaction Exposure Among Medicaid-Insured Children in the Outpatient Setting.

Drug-drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for ≥1 day) and the adverse physiologic effects of each DDI were identified using DrugBank's interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). Of 781 019 children with ≥2 medication exposures, 21.4% experienced ≥1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). One in 5 Medicaid-insured children with ≥2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting.

Importance of exercise stress testing in evaluation of unexplained cardiac arrest survivor.

In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required. We describe 3survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission. All 3patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest-related heart rate-corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up. When they were subjected to exercise stress testing during follow-up, adelayed diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was made. As aresult, these patients were initially managed inappropriately, and their family members were initially not screened for CPVT. In sudden cardiac arrest survivors without an immediately identifiable cause, omission of exercise stress testing or erroneous interpretation of the results can lead to adelayed or missed diagnosis of CPVT, which may have considerable implications for survivors and their family.

Sex differences in long QT syndrome.

Long QT Syndrome (LQTS) is a rare, inherited channelopathy characterized by cardiac repolarization dysfunction, leading to a prolonged rate-corrected QT interval in patients who are at risk for malignant ventricular tachyarrhythmias, syncope, and even sudden cardiac death. A complex genetic origin, variable expressivity as well as incomplete penetrance make the diagnosis a clinical challenge. In the last 10 years, there has been a continuous improvement in diagnostic and personalized treatment options. Therefore, several factors such as sex, age diagnosis, QTc interval, and genetic background may contribute to risk stratification of patients, but it still currently remains as a main challenge in LQTS. It is widely accepted that sex is a risk factor itself for some arrhythmias. Female sex has been suggested as a risk factor in the development of malignant arrhythmias associated with LQTS. The existing differences between the sexes are only manifested after puberty, being the hormones the main inducers of arrhythmias. Despite the increased risk in females, no more than 10% of the available publications on LQTS include sex-related data concerning the risk of malignant arrhythmias in females. Therein, the relevance of our review data update concerning women and LQTS.

Heart rate-corrected QT interval prolongation is associated with decreased heart rate variability in patients with type 2 diabetes.

We investigated the association between the heart rate-corrected QT interval (QTc interval) measured by standard electrocardiography and heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). From March 1, 2009, to December 12, 2009, 411 patients with T2DM who underwent resting 12-lead electrocardiography and cardiovascular autonomic function testing concurrently without the exclusion criteria were consecutively recruited in this cross-sectional study. Time- and frequency-domain HRV variables were assessed for 5 minutes by beat-to-beat HRV recording. The QT interval was corrected for the heart rate using Bazett's formula. QTc interval measurements of >440 ms were considered abnormally prolonged. The mean age and diabetes duration were 56.3 ± 10.6 years and 9.6 ± 7.3 years, respectively. A total of 90 patients had QTc interval prolongation (21.9%). The participants with a prolonged QTc interval were older (59.4 ± 10.1 years vs 55.5 ± 10.6 years, P = .002), were more likely to be a woman (72.2% vs 51.7%, P = .001), had a higher prevalence of hypertension (46.7% vs 33.4%, P = .022), had a higher hemoglobin A1c level (8.8% ± 2.2% vs 8.2% ± 1.8%, P = .045), and had decreased values for the variables measuring HRV, except for the low frequency (LF)/high frequency (HF) ratio (total power [TP], 147.7 [74.1-335.9] ms vs 328.7 [185.7-721.7] ms, P = .002). After adjusting for multiple confounders, QTc interval prolongation was associated with the lowest quartile of the HRV parameters of TP (odds ratio [OR] = 3.99; 95% confidence interval [CI]: 2.29-6.96), HF (OR = 3.20; 95% CI: 1.84-5.58), LF (OR = 3.68; 95% CI: 2.10-6.43), standard deviation of the normal-to-normal interval (OR = 3.31; 95% CI: 1.89-5.77), and root-mean-square of the successive differences (OR = 1.98; 95% CI: 1.13-3.47) in patients with T2DM. Decreased values for the variables measuring HRV, except for the LF/HF ratio, might be associated with QTc interval prolongation in patients with T2DM.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

BackgroundHeart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.MethodsWe investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro.ResultsIn patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr).ConclusionFor the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans

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Cardiac injury in organophosphate poisoning after acute ingestion.

Sparse data and conflicting evidence exist on the prevalence and prognosis of organophosphate (OP)-related cardiac toxicity. We aimed to characterize the cardiac abnormalities of OP after an acute cholinergic crisis in adults without previous cardiovascular conditions. We did a prospective observational study in a tertiary-care hospital of north India (Postgraduate Institute of Medical Education and Research, Chandigarh) in 74 patients aged ≥ 13years admitted with acute OP poisoning after self-ingestion. A systemic evaluation, including clinical characteristics, electrocardiography, and echocardiography, was performed to estimate the prevalence and prognosis of cardiac injury. A rate-corrected QT interval was calculated using Bazett's method, and >440 milliseconds was used to define prolongation. Chlorpyrifos was the most commonly ingested OP (n=29). The patients had a similar occurrence of hypotension (n=10) and hypertension (n=9) at admission, and electrocardiography demonstrated sinus tachycardia in 38 (51.3%) and sinus bradycardia in one case. During the hospital stay, 3 out of 74 patients had a prolonged rate-corrected QT interval (457, 468, and 461 milliseconds), and one patient developed supraventricular tachycardia. Eight (10.8%) patients developed the intermediate syndrome, and six (8.1%) died. None of the hemodynamic or electrocardiographic abnormalities was associated with in-hospital mortality or intermediate syndrome development on univariant analysis. Baseline echocardiography at hospital discharge was performed in 27 patients (admitted during 2018) and normal in all except mild tricuspid regurgitation in one. At a 6-month follow-up, 23 cases were available for cardiovascular screening (including echocardiography) and had a normal evaluation. Cardiac toxicity is uncommon after acute OP self-ingestion and lacks prognostic significance.

Investigating the Impact of Gadolinium-Based Contrast Agents on the Corrected QT Interval.

IntroductionThe manufacturing labels for all currently marketed gadolinium-based MRI contrast agents describe adverse cardiac events reported during post-market use. The goal of this study was to determine prolongation of the rate-corrected QT interval occurs in the immediate setting after gadolinium-based MRI contrast agent injection.MethodsThis study enrolled adults scheduled to have a gadolinium-based MRI contrast agent injection as part of a diagnostic MRI. A single-lead electrocardiogram was recorded using the AliveCor Kardia® ECG (Mountain View, CA) device before and after injection. The rate-corrected QT interval was subsequently measured by two independent investigators. The QT interval was corrected for rate using the two most common formulas, originally cited by Bazett and Fridericia. These rate-corrected QT intervals from before and after gadolinium-based MRI contrast agent injection were compared using the Wilcoxon signed-rank test paired analysis.ResultsA total of 24 consenting adults had electrocardiogram that were free of motion artifact. The mean age of the final patient cohort was 59.4 years. There was an equal split of 12 men and 12 women. The mean pre-injection, rate-corrected QT interval, corrected using Bazett’s formula, was 395 msec. The mean post-injection, rate-corrected QT interval, corrected using Bazett’s formula, was 396 msec. The corrections using Fridericia's formula were 384 and 381 msec, respectively. There was no statistically significant change in Bazett-corrected QT interval (QTc-B) when pre-injection and post-injection values were directly compared.DiscussionThe results of the present investigation support the conclusion that gadolinium-based MRI contrast agents do not commonly affect rate-corrected QT interval in routine clinical use. While the frequency of rate-corrected QT interval prolongation might be overstated, the severity of adverse events is definitively not. A role for concomitant rate-corrected QT interval-prolonging drugs or unidentified rare factors such as genetic predisposition cannot be ruled out. The limitations of this study include its relatively small size and the implementation of a single-lead electrocardiogram to measure rate-corrected QT interval.ConclusionThe present investigation revealed that significant rate-corrected QT interval prolongation, while previously reported in as many as 55% of patients after gadolinium-based MRI contrast agent injection, is not a common occurrence in the routine clinical setting.

IL-6 (Interleukin 6) Blockade and Heart Rate Corrected QT Interval Prolongation in COVID-19.

IL-6 (Interleukin 6) Blockade and Heart Rate Corrected QT Interval Prolongation in COVID-19.

Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A.

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

Prolongation of rate-corrected QT interval during phenol-croton oil peels

Prolongation of rate-corrected QT interval during phenol-croton oil peels

Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring.

Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of heart rate-corrected QT interval prolongation and atrial fibrillation in patients with type 2 diabetes. Currently, no data exist regarding the relationship between NAFLD and ventricular arrhythmias in this patient population. We retrospectively analyzed the data of 330 outpatients with type 2 diabetes without preexisting atrial fibrillation, end-stage renal disease, or known liver diseases who had undergone 24-h Holter monitoring for clinical reasons between 2013 and 2015. Ventricular arrhythmias were defined as the presence of nonsustained ventricular tachycardia (VT), >30 premature ventricular complexes (PVCs) per hour, or both. NAFLD was diagnosed by ultrasonography. Compared with patients without NAFLD, those with NAFLD (n = 238, 72%) had a significantly higher prevalence of >30 PVCs/h (19.3% vs. 6.5%, P < 0.005), nonsustained VT (14.7% vs. 4.3%, P < 0.005), or both (27.3% vs. 9.8%, P < 0.001). NAFLD was associated with a 3.5-fold increased risk of ventricular arrhythmias (unadjusted odds ratio [OR] 3.47 [95% CI 1.65-7.30], P < 0.001). This association remained significant even after adjusting for age, sex, BMI, smoking, hypertension, ischemic heart disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, serum γ-glutamyltransferase levels, medication use, and left ventricular ejection fraction (adjusted OR 3.01 [95% CI 1.26-7.17], P = 0.013). This is the first observational study to show that NAFLD is independently associated with an increased risk of prevalent ventricular arrhythmias in patients with type 2 diabetes.

Heart rate-corrected QT interval prolongation as a prognostic marker for 3-year survival in people with Type 2 diabetes undergoing above-ankle amputation.

To evaluate whether heart rate-corrected QT interval is a plausible prognostic factor for survival after major amputation in people with Type 2 diabetes. All people with Type 2 diabetes aged<80years who underwent a major amputation at two hospitals with multidisciplinary diabetic foot teams were evaluated and grouped according to whether their heart rate-corrected QT interval was ≤ or >440ms. A total of 70 patients with a median age of 72years were included in the study. During the 3years of follow-up, 38 patients (54%) died. Heart rate-corrected QT interval prolongation was present in 51.4% of the patients and was strongly associated with 3-year mortality (73 vs 36%; P<0.001). In a Cox proportional hazard model, heart rate-corrected QT interval prolongation was the strongest independent risk factor for 3-year mortality [hazard ratio 2.20 (95% CI 1.11-4.38)]. Treatment with metformin seemed to have a protective effect [hazard ratio 0.22 (95% CI 0.05-0.94)]. The findings of the present study indicate that heart rate-corrected QT interval prolongation is associated with increased mortality in people with Type 2 diabetes undergoing above-ankle amputation.

Bedaquiline: a novel antitubercular agent for the treatment of multidrug-resistant tuberculosis.

Bedaquiline is a diarylquinoline antitubercular drug with a novel mechanism of action against Mycobacterium tuberculosis. Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. Bedaquiline is indicated for the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with at least three other antitubercular drugs when no other effective regimen is available. The recommended bedaquiline dosage is 400 mg orally once/day for 2 weeks followed by 200 mg orally 3 times/week for 22 weeks. Bedaquiline should be administered with food, which increases the bioavailability 2-fold. Bedaquiline is metabolized by cytochrome P450 isoenzyme 3A4 and is impacted by both inducers and inhibitors of this isoenzyme. Concentration-dependent bactericidal activity was observed in laboratory and murine studies. Accelerated approval was granted in the United States and European Union based on the results of two phase IIb clinical studies that used sputum culture clearance as a surrogate end point for clinical efficacy. These studies showed greater sputum culture clearance up to week 24 for the bedaquiline group compared with placebo. Common adverse events in clinical trials included nausea, arthralgia, and headache. Serious adverse events included elevated serum transaminase levels and rate-corrected QT-interval prolongation. Unexplained higher mortality was seen in patients receiving bedaquiline versus those receiving placebo. Bedaquiline is a novel agent with a unique mechanism of action and has the potential to meet a great need in patients with MDR TB who have no other treatment options. Due to safety concerns and limited clinical information, phase III trials are needed to fully determine its place in therapy.

In vivo Electrophysiological Characterization of TASK-1 Deficient Mice

Background/Aims: TASK-1 is a potassium channel predominantly expressed in heart and brain. We have previously shown that anesthetized TASK-1^-/-mice have prolonged QT intervals in surface electrocardiograms (ECGs). In addition, heart rate variability quantified by time and frequency domain parameters was significantly altered in TASK-1^-/-mice with a sympathetic preponderance. Aims of the present study were the analysis of QT intervals by telemetric ECGs, to determine potential influences of anesthesia and β-adrenergic stimulation on repolarization in surface ECGs, to investigate in vivo electrophysiological parameters by intracardiac electrical stimulation and to quantify heart rate turbulence after ischemia/reperfusion or ventricular pacing in TASK-1^+/+ and TASK-1^-/-mice. Methods: Rate corrected QT intervals (QTc) were recorded in conscious mice by telemetry and in surface ECGs following administration of various anesthetics (tribromoethanol (Avertin®), pentobarbital and isoflurane). TASK-1^+/+ and TASK-1^-/mice were characterized by programmed electrical stimulation using an intracardiac octapolar catheter. The baroreceptor reflex was analyzed by heart rate turbulence (turbulence onset and slope) after ischemia/reperfusion and by stimulated premature ventricular contractions. Results: Telemetric and surface ECGs in mice sedated with Avertin®and pentobarbital, showed a significantly lengthened rate corrected QT interval in TASK-1^-/-mice (telemetry: TASK-1^+/+ 43±3ms vs. TASK-1^-/-49±5ms, n=6, p<0.05; Avertin®: TASK-1^+/+ 36±8ms vs. TASK-1^-/-48±4ms, n=13/16, p<0.0001). The prolongation of the QT interval was most pronounced at lower heart rates. Isoflurane, known for its stimulatory effects on the TASK channel family, attenuated the rate corrected QT interval prolongation in TASK-1^-/-mice. Intracardiac electrical stimulation revealed normal values for electrical conduction and refractoriness. No significant arrhythmias after atrial and ventricular burst stimulation were induced before and after adrenergic challenge in both genotypes. Turbulence onset after premature ventricular contraction was significantly altered in TASK-1^-/-mice. Conclusion: TASK-1^-/-mice exhibit a phenotype of QT prolongation, which distinct relation to heart rate. TASK-1 deficiency does neither alter key electrophysiological parameters nor increases atrial/ventricular vulnerability after electrical stimulation. The heart rate response after premature ventricular contractions is significantly abolished indicating a diminished baroreceptor reflex in TASK-1^-/-mice.

Abstract 16964: SCN5A Splice Variant Potentiates Dysfunction of a Novel LQT3 Mutation Associated with Life-threatening Arrhythmia in a 19 Week Fetus

BACKGROUND: Inherited arrhythmia susceptibility such as the congenital long-QT syndrome (LQTS) can contribute to infant mortality, but the biological basis for LQTS presenting in utero is poorly understood. The purpose of this study was to elucidate the molecular genetic and pathophysiologic basis for LQTS and torsade de pointes in a fetus presenting at 19-weeks gestation, the earliest known presentation of this disease. METHODS: Molecular genetic studies of an affected fetus demonstrated a de novo SCN5A mutation. To elucidate the functional consequences of the mutation, in vitro electrophysiological studies were conducted on wild type (WT) and mutant human cardiac sodium channels in the canonical channel and in an alternatively spliced form expressed in fetal heart. RESULTS: A fetus presented at 19-6/7 weeks with episodes of ventricular ectopy that progressed to incessant ventricular tachycardia and hydrops fetalis. Family history did not suggest inherited arrhythmia susceptibility, but fetal magnetocardiography demonstrated torsade de pointes and a prolonged rate-corrected QT interval (604 ms). Genetic analysis following pregnancy termination disclosed a novel, de novo heterozygous SCN5A mutation (L409P) and homozygosity for the common SCN5A variant H558R. In vitro studies demonstrated that the mutation in combination with R558 causes significant depolarized shifts in voltage-dependence of steady-state inactivation and activation, accelerated recovery from inactivation and a 7-fold increase in persistent current (1.4% of peak current vs 0.2% for WT). However, when the mutation was expressed in the background of a fetal-expressed SCN5A transcript, channel dysfunction was potentiated with a marked increase in persistent current (11% of peak current) and greater shifts in voltage-dependence. Also, R558 alone in the fetal splice variant evoked a large increased persistent current (3.7% of peak current), hence both alleles were dysfunctional. CONCLUSION: Fetal LQTS may present as early as 19 weeks gestation. The functional effects of certain SCN5A mutations and variants may be magnified by alternative splicing events during fetal development helping to explain the unusual clinical severity of LQT3 in this setting.

Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia

Congenital long-QT syndrome (LQTS) may present during fetal development and can be life-threatening. The molecular mechanism for the unusual early onset of LQTS during fetal development is unknown. We sought to elucidate the molecular basis for severe fetal LQTS presenting at 19 weeks' gestation, the earliest known presentation of this disease. Fetal magnetocardiography was used to demonstrated torsades de pointes and a prolonged rate-corrected QT interval. In vitro electrophysiological studies were performed to determine functional consequences of a novel SCN5A mutation found in the fetus. The fetus presented with episodes of ventricular ectopy progressing to incessant ventricular tachycardia and hydrops fetalis. Genetic analysis disclosed a novel, de novo heterozygous mutation (L409P) and a homozygous common variant (R558 in SCN5A). In vitro electrophysiological studies demonstrated that the mutation in combination with R558 caused significant depolarized shifts in the voltage dependence of inactivation and activation, faster recovery from inactivation, and a 7-fold higher level of persistent current. When the mutation was engineered in a fetal-expressed SCN5A splice isoform, channel dysfunction was markedly potentiated. Also, R558 alone in the fetal splice isoform evoked a large persistent current, and hence both alleles were dysfunctional. We report the earliest confirmed diagnosis of symptomatic LQTS and present evidence that mutant cardiac sodium channel dysfunction is potentiated by a developmentally regulated alternative splicing event in SCN5A. Our findings provide a plausible mechanism for the unusual severity and early onset of cardiac arrhythmia in fetal LQTS.

Antipsychotic Drug Administration Does Not Correlate with Prolonged Rate-Corrected QT Interval in Children and Adolescents: Results from a Nested Case–Control Study

The rate-corrected QT interval (QTc) prolongation is a risk factor for sudden cardiac death and may be induced by antipsychotic drugs. To determine the clinical characteristics associated with QTc prolongation (440 msec or greater) in children and adolescents hospitalized for treatment of psychiatric disorders. We determined the frequency of baseline prolongation of QTc in 811 psychiatric pediatric inpatients (15.5 ± 2.4 years of age). QTc duration was 440 msec or greater (range 441-481 msec) in 16 patients (1.97%). In a 1:5 nested case-control design, the 16 patients with prolonged QTc were age- and gender-matched with 80 patients with QTc of <421 msec. Patients with normal and prolonged QTc had similar utilization of antipsychotics (43.8% vs. 40.8%) and daily chlorpromazine equivalents (165 ± 110 vs. 168 ± 218 mg). Hypokalemia (p = 0.009) and obesity (p = 0.032) were more common among patients with prolonged QTc. The correlation between obesity and QTc prolongation was confirmed in logistic regression analysis. In a large cohort of youth hospitalized for treatment of psychiatric disorders, a prolonged QTc on admission was rare and correlated with the presence of obesity, but not with current use of antipsychotic drugs.

Itraconazole Induced Torsade De Pointes in a Patient Receiving Methadone Substitution Therapy

Issues. Methadone, a pharmacological agent used to treat heroin dependence is relatively safe, but may cause cardiac arrhythmias in the concurrent presence of other risk factors. Approach and Key Findings. This case report highlights the risk of Torsade de Pointes, a life-threatening cardiac arrhythmia, in a heroin-dependent patient receiving methadone substitution therapy who was prescribed itraconazole for vaginal thrush. The patient presented to the accident and emergency department for chest discomfort and an episode of syncope following two doses of itraconazole (200 mg). Electrocardiogram monitoring at the accident and emergency department showed prolonged rate-corrected QT interval leading to Torsade de Pointes. The patient was admitted for cardiac monitoring, and electrocardiogram returned to normal upon discontinuation of methadone. Implication. This cardiac arrhythmia was most likely as a result of a drug interaction between methadone and itraconazole because the patient presented with no other risk factors. Conclusion. Given the benefits of methadone as a substitution treatment for heroin-dependent individuals, the association between methadone and cardiac arrhythmias is of great concern. Physicians treating heroin-dependent patients on methadone substitution therapy should therefore be cautious of the potential risk of drug interactions that may lead to fatal cardiac arrhythmias.

Itraconazole‐induced Torsade de Pointes in a patient receiving methadone substitution therapy

Methadone, a pharmacological agent used to treat heroin dependence is relatively safe, but may cause cardiac arrhythmias in the concurrent presence of other risk factors. APPROACH AND KEY FINDINGS: This case report highlights the risk of torsade de pointes, a life-threatening cardiac arrhythmia, in a heroin-dependent patient receiving methadone substitution therapy who was prescribed itraconazole for vaginal thrush. The patient presented to the accident and emergency department for chest discomfort and an episode of syncope following two doses of itraconazole (200 mg). Electrocardiogram monitoring at the accident and emergency department showed prolonged rate-corrected QT interval leading to torsade de pointes. The patient was admitted for cardiac monitoring, and electrocardiogram returned to normal upon discontinuation of methadone. This cardiac arrhythmia was most likely as a result of a drug interaction between methadone and itraconazole because the patient presented with no other risk factors. Given the benefits of methadone as a substitution treatment for heroin-dependent individuals, the association between methadone and cardiac arrhythmias is of great concern. Physicians treating heroin-dependent patients on methadone substitution therapy should therefore be cautious of the potential risk of drug interactions that may lead to fatal cardiac arrhythmias.