International Cohort of Neonatal Timothy Syndrome.

INTRODUCTION: Timothy syndrome (TS) is an extremely rare, multisystem disorder classically associated with long QT, syndactyly, ventricular arrhythmias, and hypoglycaemia. A neonatal diagnosis allows maximal medical and device therapy to be implemented to avoid malignant arrhythmias and sudden cardiac death. METHODS: This was a retrospective case series study of type I TS (TS1) patients using data from the Timothy Syndrome Foundation's international registry, encompassing patients with a genetic diagnosis (CACNA1C variant G406R in exon 8A) recruited over a 28-year period. RESULTS: Forty-four cases of TS1 were included (26 male; 60%). Mean gestational age (GA) was 35.6 weeks (range 28 weeks - term), with 43% of patients born less than 37 weeks GA. In TS1 patients presenting with foetal bradycardia, mean GA was significantly lower (34.2 weeks, p < 0.05). Foetal bradycardia secondary to atrioventricular block was present in 20 patients (45%), resulting in premature delivery in 14 patients (32%). Fifteen patients (34%) were diagnosed with TS1 as neonates. Long QT at birth helped secure a diagnosis in 25 patients (57%). Syndactyly was seen in most patients (n = 40, 91%). Twenty patients died, with an average age of death of 2.3 years (range 1 month-6 years). Of the 7 patients who died before the first year of life (16%), the average age of death was 2.5 months. CONCLUSION: TS is associated with high early mortality. TS should be considered in paediatric patients presenting with long QT and syndactyly. Recognition of TS in the neonatal period allows for early intervention to prevent life-threatening arrhythmias.

Torsade de pointes secondary to long QT syndrome after intragastric balloon placement. A rare but severe complication.

The obesity pandemic is becoming one of the most prevalent diseases nowadays. There is a wide spectrum of treatment, ranging from hygienic-dietary measures to bariatric surgery. Endoscopic intragastric balloon placement is becoming increasingly more frequent, due to its technical simplicity, safety and short-term success(1). Although complications are rare some can be severe, so pre-endoscopic evaluation must be carried out carefully. A 43-year-old woman with a history of grade I obesity (BMI 32.7) had an Orbera® intragastric balloon implanted successfully. After the procedure she presented frequent nausea and vomiting, partially controlled with antiemetics. She attended the Emergency Department(ED) with a persistent emetic syndrome - oral intolerance and short-term loss of consciousness(syncope), for which she was admitted. Lab tests showed metabolic alkalosis with severe hypokalemia(K+ 1.8mmol/L), so fluid therapy was initiated for hydroelectrolytic replacement. During the patient's stay in the ED, two episodes of polymorphic ventricular tachychardia "Torsades de Pointes" (PVT-TDP) occurred, leading to cardiac arrest and requiring electrical cardioversion to restore sinus rhythm, in addition to a temporary pacemaker placement. Telemetry showed a corrected QT interval of >500ms, compatible with Long QT Syndrome(LQTS). Once the patient was hemodynamically stabilized a gastroscopy was performed. The intragastric balloon located in the fundus was removed using an extraction kit, puncturing and aspirating 500ml of saline solution, and extracting the collapsed balloon without any complications. The patient achieved an adequate oral intake afterwards, and no recurrence of emetic episodes were noticed. Previous ECGs revealed a prolonged QT interval and a genetic study confirmed a congenital type 1 LQTS. Treatment was initiated with beta-blockers and a bicameral automatic defibrillator was implanted in order to prevent recurrences. Intragastric balloon placement is generally a safe procedure, serious complications present in 0.70% of cases(2). It is essential to have a proper pre-endoscopic evaluation, including patient's medical history and comorbidities. Episodes of PVT-TDP may present precipitated by certain medications (eg. metoclopramide) or hydroelectrolytic imbalances (eg, hypokalemia)(3). A standardized evaluation of ECG before intragastric balloon placement may be useful to prevent these rare but serious complications.

Genetic variant annotation scores in congenital long QT syndrome.

BACKGROUND: Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact. METHODS: We evaluated 2025 patients with unique mutations for LQT1-LQT3. A patient-specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen-2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life-threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C-index. RESULTS: A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen-2. However, none of the genetic scores correlated with the risk of CE (Harrell's C-index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen-2 = 0.52) or LTE (Harrell's C-index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen-2 = 0.52). In contrast, high-risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001). CONCLUSION: In congenital LQTS patients, well-established algorithms (CADD, SIFT, REVEL, and PolyPhen-2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations.

Phenotypes of Overdiagnosed Long QT Syndrome.

BACKGROUND: Long QT syndrome (LQTS) predisposes individuals to arrhythmic syncope or seizure, sudden cardiac arrest, or sudden cardiac death (SCD). Increased physician and public awareness of LQTS-associated warning signs and an increase in electrocardiographic screening programs may contribute to overdiagnosis of LQTS. OBJECTIVES: This study sought to identify the diagnostic miscues underlying the continued overdiagnosis of LQTS. METHODS: Electronic medical records were reviewed for patients who arrived with an outside diagnosis of LQTS but were dismissed as having normal findings subsequently. Data were abstracted for details on referral, clinical history, and both cardiologic and genetic test results. RESULTS: Overall, 290 of 1,841 (16%) patients with original diagnosis of LQTS (174 [60%] female; mean age at first Mayo Clinic evaluation, 22 ± 14 years; mean QTc interval, 427 ± 25 milliseconds) were dismissed as having normal findings. The main cause of LQTS misdiagnosis or overdiagnosis was a prolonged QTc interval secondary to vasovagal syncope (n = 87; 30%), followed by a seemingly positive genetic test result for a variant in 1 of the main LQTS genes (n = 68; 23%) that was ultimately deemed not to be of clinical significance. Furthermore, patients received misdiagnoses because of a positive family history of SCD that was deemed unrelated to LQTS (n = 46; 16%), isolated/transient QT prolongation (n = 44; 15%), or misinterpretation of the QTc interval as a result of inclusion of the U-wave (n = 40, 14%). CONCLUSIONS: Knowing the 5 main determinants of discordance between a previously rendered diagnosis of LQTS and full diagnostic reversal or removal (vasovagal syncope, "pseudo"-positive genetic test result in LQTS-causative genes, family history of SCD, transient QT prolongation, and misinterpretation of the QTc interval) increases awareness and provides critical guidance to reduce this burden of overdiagnosed LQTS.

A QTc risk score in patients with obstructive sleep apnea.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) are at risk for QTc prolongation, a known risk factor for increased mortality. The pro-QTc score can help identify individuals at increased risk for mortality associated with increased QTc however, it has not been evaluated in patients with OSA. The goal of this study was to evaluate the pro-QTc score in patients with OSA. METHODS: Medical records of patients undergoing a sleep study at our sleep center from February 2012 to August 2020 were analyzed. Presence or absence of OSA was determined by polysomnography. The pro-QTc score was calculated with 1 point assigned for each of the following: female sex, QT-prolonging diagnoses and conditions, QT-prolonging electrolyte abnormalities, and medications with known risk for QT-prolongation. Mortality was determined from the electronic medical record of an integrated healthcare system. RESULTS: There were 2246 patients (age 58 ± 15 years, 54% male, 82 dead) with OSA and 421 patients (age 54 ± 18 years, 43% male, 18 dead) without OSA. Of those with OSA, 1628 (72.5%) had at least one risk factor for QTc prolongation. A higher pro-QTc score was associated with greater mortality in patients with OSA (HR 1.48 per pro-QTc score, p < 0.001, 95% CI 1.3-1.7) but not in patients without OSA (HR 1.25 per pro-QTc score, p = 0.30, 95% CI 0.82-1.9), after adjusting for age, body mass index (BMI), and smoking status. CONCLUSION: In patients with OSA, a higher pro-QTc score was associated with greater mortality.

Right ventricular epicardial arrhythmogenic substrate in long-QT syndrome patients at risk of sudden death.

AIMS: The long-QT syndrome (LQTS) represents a leading cause of sudden cardiac death (SCD). The aim of this study was to assess the presence of an underlying electroanatomical arrhythmogenic substrate in high-risk LQTS patients. METHODS AND RESULTS: The present study enrolled 11 consecutive LQTS patients who had experienced frequent implantable cardioverter-defibrillator (ICD discharges triggered by ventricular fibrillation (VF). We acquired electroanatomical biventricular maps of both endo and epicardial regions for all patients and analyzed electrograms sampled from several myocardial regions. Abnormal electrical activities were targeted and eliminated by the means of radiofrequency catheter ablation. VF episodes caused a median of four ICD discharges in eleven patients (6 male, 54.5%; mean age 44.0 ± 7.8 years, range 22-53) prior to our mapping and ablation procedures. The average QTc interval was 500.0 ± 30.2 ms. Endo-epicardial biventricular maps displayed abnormally fragmented, low-voltage (0.9 ± 0.2 mV) and prolonged electrograms (89.9 ± 24.1 ms) exclusively localized in the right ventricular epicardium. We found electrical abnormalities extending over a mean epicardial area of 15.7 ± 3.1 cm2. Catheter ablation of the abnormal epicardial area completely suppressed malignant arrhythmias over a mean 12 months of follow-up (median VF episodes before vs. after ablation, 4 vs. 0; P = 0.003). After the procedure, the QTc interval measured in a 12-lead ECG analysis shortened to a mean of 461.8 ± 23.6 ms (P = 0.004). CONCLUSION: This study reveals that, among high-risk LQTS patients, regions localized in the epicardium of the right ventricle harbour structural electrophysiological abnormalities. Elimination of these abnormal electrical activities successfully prevented malignant ventricular arrhythmia recurrences.

The QT interval prolongation potential of anticancer and supportive drugs: a comprehensive overview.

Patients with cancer are prone to prolongation of the corrected QT interval (QTc) due to the use of anticancer drugs with QTc-prolonging potential in combination with electrolyte imbalances caused by, for example, gastrointestinal side-effects. However, most anticancer drugs were approved with little information on their QTc-prolonging potential and the added risk of torsade de pointes. The absence of this information on the drug label poses a considerable challenge to clinicians regarding the measures that need to be taken to safely start anticancer treatment. In this Review, we provide a comprehensive overview of the evidence for the QTc-prolonging properties of 205 anticancer drugs and 14 antiemetic drugs available from drug labels, assessment reports, and published studies. We classify the drugs as low-risk, moderate-risk, or high-risk for QTc prolongation. We also discuss the clinical relevance of these findings and include practical recommendations to guide clinicians to select the drugs with the least QTc-prolonging properties and to adequately monitor susceptible patients.

ß-blocker adherence among patients with congenital long QT syndrome: a nationwide study.

AIM: ß-blockers are the first line of treatment in patients with congenital long QT syndrome (cLQTS) (class I or II recommendation) in order to prevent malignant arrhythmias. Hence, we examined long-term ß-blocker adherence and associated risk factors among patients with cLQTS. METHODS AND RESULTS: Danish patients with cLQTS claiming a prescription for any ß-blocker after their cLQTS diagnosis were identified using data from nationwide registries and specialized inherited cardiac disease clinics (1995-2017). Patients were followed for up to 5 years. Treatment breaks >60 days were assessed (i.e. proxy for reduced adherence). Multivariable Cox regression was used to identify risk factors associated with breaks of >60 days in ß-blocker treatment. Overall, 500 out of 633 (79%) patients with cLQTS claimed at least one prescription for any ß-blocker after cLQTS diagnosis. During follow-up, 38.4% had a treatment break. Risk factors significantly associated with treatment breaks were implantable cardioverter defibrillator (ICD) [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.08-2.53], ß-blocker side effects (HR = 2.69, 95% CI: 1.75-4.13), and psychiatric disease (HR = 1.63, 95% CI: 1.04-2.57). In contrast, patients presenting with ventricular tachycardia/syncope as cLQTS disease manifestation were less likely to have a treatment break compared with asymptomatic patients (HR = 0.55, 95% CI: 0.33-0.92). CONCLUSION: Reduced ß-blocker adherence was common with more than a third of patients having a treatment break >60 days after cLQTS diagnosis. Patients with psychiatric disease, self-reported ß-blocker side effects, and an ICD were more likely to display reduced adherence, whereas a severe cLQTS disease manifestation was associated with optimal ß-blocker adherence.

Propensity score-matching analysis comparing safety outcomes of appetite-stimulating medications in oncology patients.

PURPOSE: Anorexia and weight loss are common complications in the elderly, advanced cancer population. Appetite stimulants are commonly used therapies for oncology patients with weight loss, yet their safety comparison remains unknown. METHODS: This was a two-center, retrospective, study conducted in New York City at Mount Sinai Beth Israel and New York University Langone from January 2016 to July 2019 in adult patients with histologic evidence of malignancy who were taking either megestrol acetate or mirtazapine as an appetite-stimulating medication. Endpoints included safety concerns of mortality, QTc prolongation, venous thromboembolism, fall, somnolence, xerostomia, and hallucinations. Effectiveness of weight gain or maintenance of weight was not assessed. A propensity score-matching analysis was performed using a logistic regression analysis to assess the two comparable groups. RESULTS: The study included 350 patients (69.56 ± 13.31 years) with the most common malignancies being gastrointestinal, breast, and hematologic with metastasis present in over half the patients. Adverse events were commonly seen in the oncology population. After a propensity score-matched analysis, all safety outcomes associated with mirtazapine compared to megestrol acetate were similar; all-cause mortality (7%, n = 7 vs. 12%, n = 12, p = 0.23), QTc prolongation (31%, n = 31 vs. 31%, n = 31, p = 1.00), thromboembolism (11%, n = 11 vs. 11%, n = 11, p = 1.00), somnolence (29%, n = 30 vs. 22%, n = 23, p = 0.34), xerostomia (27%, n = 28 vs. 18%, n = 19, p = 0.24), and hallucinations (17%, n = 18 vs. 8%, n = 8, p = 0.06), respectfully. CONCLUSION: There were no safety differences seen when evaluating both agents.

QT interval measurement in ventricular pacing: Implications for assessment of drug effects and pro-arrhythmia risk.

QT interval prolongation is a known risk factor for development of malignant ventricular arrhythmias. Measurement of the QT interval is difficult in the setting of ventricular pacing (VP), which can prolong depolarization and increase the QT interval, overestimating repolarization time. VP and cardiac resynchronization therapies have become commonplace in modern cardiac care and may contribute to repolarization heterogeneity and subsequent increased risk for ventricular arrhythmias including Torsades de Pointes. It is imperative for the clinician caring for acutely ill cardiac patients to understand the relationship between QT interval prolongation, both drug-induced and pacing-induced, and repolarization changes with subsequent ventricular arrhythmia risk. In this review, we discuss the components of QT interval assessment for arrhythmogenic risk including arrhythmogenic QT prolongation, methods for adjusting the QT interval to identify repolarization changes, methods to adjust for heart rate, and propose a framework for medication management to assess for drug-induced long QT syndrome in patients with VP.

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

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

Aborted Cardiac Arrest in LQT2 Related to Novel KCNH2 (hERG) Variant Identified in One Lithuanian Family.

Congenital long QT syndrome (LQTS) is a hereditary ion channelopathy associated with ventricular arrhythmia and sudden cardiac death starting from young age due to prolonged cardiac repolarization, which is represented by QT interval changes in electrocardiogram (ECG). Mutations in human ether-à-go-go related gene (KCNH2 (7q36.1), formerly named hERG) are responsible for Long QT syndrome type 2 (LQT2). LQT2 is the second most common type of LQTS. A resuscitated 31-year-old male with the diagnosis of LQT2 and his family are described. Sequencing analysis of their genomic DNA was performed. Amino acid alteration p.(Ser631Pro) in KCNH2 gene was found. This variant had not been previously described in literature, and it was found in three nuclear family members with different clinical course of the disease. Better understanding of genetic alterations and genotype-phenotype correlations aids in risk stratification and more effective management of these patients, especially when employing a trigger-specific approach to risk-assessment and individually tailored therapy.

Comparison of the Limb-lead Electrocardiogram to the 12-Lead Electrocardiogram for Identifying Conditions Associated with Sudden Cardiac Death in Youth Athletes.

The optimal screening strategy to prevent sudden cardiac death (SCD) in athletes remains unknown. Pre-participation screening with electrocardiogram (ECG) remains controversial. The utility and accuracy of limb-lead (LL) ECG alone in identifying cardiac abnormalities associated with SCD has not been studied. This study was a comparative secondary data analysis, comparing the interpretation accuracy of 4 physicians evaluating publicly available ECGs of the most common cardiac conditions associated with SCD in athletes. Each physician interpreted a total of 100 ECGs: 50 normal ECGs (25 LL and 25 standard 12L) and 50 abnormal ECGs (25 LL and 25 standard 12L). The agreement between LL ECGs and 12L ECGs was assessed by Cohen's kappa coefficient and the accuracy of identifying an abnormal ECG was compared across LL and 12L ECGs using a chi-squared test. Inter-rater reliability was assessed by estimating the Fleiss's kappa coefficient. The sensitivity of LL ECG and 12L ECG was identical at 86%. The specificity of LL ECG was 75% (95% CI = 65% to 83%) and 12L ECG was 82% (95% CI = 73% to 89%). Substantial agreement was seen between LL ECG and 12L ECG interpretation across all readers (k = 0.63; 95% CI = 0.49 to 0.77). Interpretation accuracy was 81% (95% CI = 74% to 86%) and 84% (95% CI 78% to 89%) using LL ECG and 12L ECG, respectively (p = 0.43). In conclusion, the accuracy, sensitivity, and specificity were high and comparable for both LL ECG and 12L ECG in identifying cardiovascular conditions associated with SCD. Agreement between LL ECG and 12L ECG was substantial.

QT interval prolongation and the risk of malignant ventricular dysrhythmia and/or cardiac arrest: Systematic search and narrative review of risk related to the magnitude of QT interval length.

Prolongation of the QTc interval is associated with an increased risk of malignant ventricular dysrhythmias, such as ventricular tachycardia (VT), and sudden cardiac death. The quantifiable risk rates of adverse dysrhythmic outcome in relation to specific QTc interval length are not known. We conducted a literature review on the topic of QT interval prolongation in adult patients and the associated risk of malignant dysrhythmic event. We specifically formulated our literature search and subsequent literature review to address the following question: Can the clinician identify specific QTc intervals at which a specific quantifiable risk of malignant dysrhythmic event (malignant ventricular dysrhythmia and/or cardiac arrest) occurs in an undifferentiated adult patient population? In the literature search, we identified 701 studies; upon review using specific, pre-determined inclusion criteria, we identified 16 articles for inclusion in the review. From this literature, we were unable to answer the question in a quantifiable manner and only noted that the risk of malignant dysrhythmic event increases with progressively longer QTc interval. The current literature on this topic is inadequate to answer this important question due to heterogenous study methodology, patient populations, endpoints, and periods of observation. Additional prospective research is required on this topic, aimed at addressing the important issue of specific, quantifiable risk and its relation to degree of prolongation of the QTc interval.

Correlation Between QTc Prolongation and Obstructive Sleep Apnea in Patients with Type 2 Diabetes Mellitus.

BACKGROUND Obstructive sleep apnea (OSA) plays an important role in the progression of cardiovascular disease (CVD), and is a common symptom in patients with type 2 diabetes mellitus (T2DM). Prolongation of corrected QT interval (QTc) reflects ventricular arrhythmias and CVD. The aim of this study was to explore the relationship between OSA and QTc in T2DM patients and to evaluate the potential application of QTc in clinical practice. MATERIAL AND METHODS A total of 358 T2DM patients were involved in this study. OSA was diagnosed with apnea-hypopnea index ≥5 by full-night polysomnography and QTc was measured by a 12-lead electrocardiogram (ECG). Patients were grouped into 2 groups based on median QTc, and clinical data were studied. Logistic regression analysis was used to investigate the association between OSA and QTc with adjusted age, sex, body mass index (BMI), hypertension, total bilirubin (TBL), and smoking history. RESULTS Among 358 T2DM patients, 59.2% had OSA. Compared to those in the QTc <418 ms group, older patients, females, patients with higher BMI, and OSA patients in the QTc ≥418 ms group were more likely to have OSA (p<0.05). Correlation analysis suggested that OSA was associated with longer QTc (OR: 2.355, 95% CI: 1.529-3.626, p<0.001). For T2DM patients with QTc ≥418 ms, older patients (OR: 1.042, 95% CI: 1.042-1.064, p<0.001), females (OR: 2.36, 95% CI: 1.371-4.063, p<0.01), and patients with higher BMI (OR: 1.113, 95% CI: 1.037-1.195, p<0.01) were significantly more likely to have OSA. CONCLUSIONS In this cross-sectional study, we found that the presence and severity of OSA was associated with QTc prolongation in 358 patients with T2DM, and age, female sex, and BMI appear to be independent risk factors for OSA and CVD.

A rare coincidence: the long QT syndrome and cardio-facio-cutaneous syndrome.

Cardio-facio-cutaneous syndrome is a genetic anomaly characterised by craniofacial dysmorphia, developmental retardation, skin lesions, mental retardation/learning disability, and cardiac malformations. Cardio-facio-cutaneous syndrome rarely causes arrhythmias and has not been previously associated with long QT in the literature. With this report, it was aimed to draw attention to a different presentation of the long QT syndrome.

The effects of ondansetron versus dexamethasone on electrocardiographic markers of ventricular repolarization in children undergoing cochlear implant.

INTRODUCTION: Congenital hearing loss is associated with cardiac rhythm disturbances namely long Q-T syndrome. This study was designed to investigate the effect of anti-emetic doses of ondansetron and dexamethasone on ECG recordings in children undergoing cochlear implant surgery. METHODS: Sixty-three pediatric patients scheduled for elective cochlear implantation were enrolled in the study. Two patients were excluded as their baseline ECG showed long QT syndrome. Anesthesia was induced with fentanyl, propofol and atracurium and maintained with propofol. Dexamethasone 0.1 mg.kg-1or ondansetron 0.2 mg.kg-1was randomly administered for the participants approximately 30 min before the end of surgery. ECG recording was performed 15 min after induction of anesthesia and 15 min after dexamethasone/ondansetron administration. RR interval, QRS duration, QT interval, and Tp-e interval were measured by a blinded cardiologist. RESULTS: Ondansetron resulted in no significant changes in RR, JTc and QTc intervals; while prolongedTp-e interval. Multivariable logistic regression analysis showed that use of ondansetron was an independent predictor of QTc prolongation after adjustment for age, gender and baseline QTc (OR = 17.94, CI 95% 1.97-168.70, p = 0.011). The incidence of postoperative retching/vomiting in ondansetron group was significantly lower than dexamethasone group. (3.2% vs. 26.7%, p = 0.011). CONCLUSION: The risk of arrhythmias with the use of ondansetron in otherwise healthy candidates of cochlear implant is very low. However, the drug may induce significant changes in ECG parameters. The clinical significance of these changes in patients with cardiac conduction abnormalities should be investigated in further studies.

QTc Interval-Prolonging Medications Among Patients With Lung Cancer: Implications for Clinical Trial Eligibility and Clinical Care.

BACKGROUND: Concomitant medication use, including agents that prolong the corrected QT (QTc) interval, can result in the exclusion of patients with cancer from clinical trials. To estimate the potential effects on accrual, we determined the prevalence of QTc-prolonging medication prescriptions in a national patient cohort. PATIENTS AND METHODS: We identified adult patients in the Veterans Affairs system with a diagnosis of lung cancer from 2003 to 2016. The use of QTc interval-prolonging medications and risk category were obtained from CredibleMeds. We calculated the prevalence of prescriptions for QTc-prolonging medications with a known or possible risk of torsade de pointes in the 3 months up to and including the date of cancer diagnosis. The rates across patient groups were compared using χ2 test. RESULTS: A total of 280,068 patients were included in the present study. The mean age was 70 years, 98% were male, and 72% were white. Overall, 28.4% had been prescribed a QTc-prolonging medication, and 7.3% had been prescribed ≥2 in the 3 months before the cancer diagnosis. The most commonly prescribed QTc-prolonging medications were antimicrobial agents (14.0%), psychiatric agents (10.2%), antiemetic agents (2.6%), and cardiac medications (1.7%). Excluding the antimicrobial agents, 18.4% of the patients had been prescribed a QTc-prolonging medication. CONCLUSIONS: A substantial proportion of individuals with lung cancer will be prescribed QTc-prolonging medications. These prescriptions can limit patients' eligibility for clinical trials and complicate the administration of standard cancer therapies. Further research into the actual clinical risks and optimal management of QTc-prolonging medications in cancer populations is warranted.

QTc Prolongation and Risk of Torsades de Pointes in Hospitalized Pediatric Oncology Patients.

OBJECTIVE: To evaluate the prevalence of torsades de pointes and to identify risk factors associated with QTc prolongation of ≥500 milliseconds in hospitalized pediatric oncology patients. A QTc prolongation of ≥500 milliseconds is associated with higher mortality in hospitalized adults but has not been demonstrated in pediatrics. STUDY DESIGN: A single-center, retrospective review of all hospitalized oncology patients ≤21 years of age was performed from 2014 to 2016. Patients with long/short QT syndrome or a QRS interval of ≥120 ms were excluded. Rapid response events were reviewed to determine the prevalence of torsades. In patients with ECGs for review, data were compared between patients with a QTc of <500 and ≥500 ms via logistic regression. RESULTS: There were 1934 hospitalized patients included. Rapid response events occurred in 90 patients (4.7%) with 2 torsades events (0.1%). There were 1412 electrocardiograms performed in 287 unique patients (10.6 ± 6.3 years of age; 43% female). The mean QTc was 448 ± 31 ms; 25 patients (8.7%) had ≥1 ECG with a QTc of ≥500 ms. The prevalence of torsades was greater in patients with a QTc of ≥500 ms (8% vs 0%; P<.01). In multivariate analysis, factors associated with a QTc of ≥500 ms included female sex, (OR 2.95) and ≥2 QT-prolonging medications (OR, 2.95). CONCLUSIONS: The prevalence of torsades in hospitalized pediatric oncology patients was low (0.1%), although the risk was significantly greater in patients with a QTc of ≥500 ms. Routine monitoring of electrocardiograms and electrolytes is essential in patients with risk factors predisposing to QTc prolongation.