Two Cases of Symptomatic Familial Hypocalciuric Hypercalcemia: Treatment Response to Calcimimetic Therapy.

Familial hypocalciuric hypercalcemia (FHH) is marked by mild to moderate hypercalcemia, normal-elevated serum PTH levels, and relative hypocalciuria. Cinacalcet, a calcimimetic therapy, has been reported to reduce symptom burden and serum calcium levels in FHH. We report 2 adult males with chronic hypercalcemia, with initial concerns for primary hyperparathyroidism. Urine calcium screening and genetic testing confirmed FHH in both patients. Shortened QTc normalized while on cinacalcet in the first patient and reductions in serum calcium and PTH levels without symptomatic hypercalcemia were noted in the second patient. Calcimimetic therapy can potentially be offered to FHH patients, particularly those with hypercalcemia symptoms, serum calcium levels >1 mg/dL (0.25 mmol/L) above normal or at risk of cardiac arrhythmias. Cinacalcet treatment was overall well tolerated and significantly reduced serum calcium and PTH levels in 2 adult FHH patients over time. Calcimimetic therapy has shown promise in managing persistent hypercalcemia and potential adverse events in FHH patients. Potential barriers include indefinite treatment, cost, and possible adverse effects.

Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment.

BACKGROUND: Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD. METHODS: This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included. RESULTS: The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9-25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3-38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study. CONCLUSION: CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers.

Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (ΔQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (ΔΔQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (Cmax) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.

Congenital Long QT Syndrome in Children and Adolescents: A General Overview.

Congenital long QT syndrome (LQTS) represents a disorder of myocardial repolarization characterized by a prolongation of QTc interval on ECG, which can degenerate into fast polymorphic ventricular arrhythmias. The typical symptoms of LQTS are syncope and palpitations, mainly triggered by adrenergic stimuli, but it can also manifest with cardiac arrest. At least 17 genotypes have been associated with LQTS, with a specific genotype-phenotype relationship described for the three most common subtypes (LQTS1, -2, and -3). ß-Blockers are the first-line therapy for LQTS, even if the choice of the appropriate patients needing to be treated may be challenging. In specific cases, interventional measures, such as an implantable cardioverter-defibrillator (ICD) or left cardiac sympathetic denervation (LCSD), are useful. The aim of this review is to highlight the current state-of-the-art knowledge on LQTS, providing an updated picture of possible diagnostic algorithms and therapeutic management.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

OBJECTIVE: Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. DESIGN: Retrospective study, July 1, 2017-May 31, 2022. SETTING: Tertiary children's hospital. PATIENTS: Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). CONCLUSIONS: The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Delayed Serotonin Syndrome and Non-cardiogenic Pulmonary Edema Following Bupropion Overdose in a Seven-Year-Old Female: A Case Report and Review of Literature.

Bupropion is an atypical antidepressant prescribed for depression and attention-deficit/hyperactivity disorder and to aid in smoking cessation. Bupropion overdose management is largely aimed toward common sequelae, including seizures, tachycardia, and QTc prolongation. In this case report, we identify a rare event of pediatric bupropion overdose with aforementioned common sequela and atypical features, including a delayed presentation of serotonin syndrome and non-cardiogenic pulmonary edema. This case follows a seven-year-old Caucasian female with autism spectrum disorder (ASD) who presented in status epilepticus following an accidental bupropion overdose and required multiple anti-seizure medications, endotracheal intubation, and admission to the pediatric intensive care unit (PICU). The patient's condition improved, and she was extubated 25 hours after admission and transitioned to high-flow nasal cannula therapy. On day 3 of admission, she became febrile and developed dyspnea with decreased breath sounds and intercostal retractions, tachycardia, a rigid abdomen and extremities with sporadic tremors, pulmonary edema, and a prolonged QTc interval. Targeted therapies were initiated, and following treatment, our patient showed remarkable improvement in the subsequent 24 hours and was discharged home five days after the initial presentation. This case identifies a delayed presentation of uncommon and serious complications of bupropion overdose, including pulmonary edema and serotonin syndrome, in a pediatric patient. Prompt investigation and identification of bupropion toxicity can help practitioners mitigate further complications during admission and reduce morbidity and mortality.

Pharmacist Reported Protocols for QTc Monitoring of Psychiatric Medications.

Background Psychiatric medications, such as antipsychotics and antidepressants, are associated with QTc interval prolongation. There is currently no consensus best practice on how to mitigate this risk. This study aimed to collect and analyze information about methods used for QTc monitoring in patients taking psychiatric medications to better understand current practice. Methods An anonymous electronic survey was distributed on September 22, 2022, using a national psychiatric pharmacist organization email list. The survey closed on December 15, 2022. Descriptive statistics were used to analyze the multiple-choice questions. Qualitative analysis applying grounded theory for thematic analysis was performed for free response questions. Results A total of 48 initiated the survey. Of the respondents, 11.4% (5/44) reported that their institution had a formal protocol for monitoring QTc intervals in patients receiving psychiatric medications, while 32.4% (12/37) reported that their institution had an informal process. Out of those with a protocol or process, approximately half reported that it was drug-specific. Among the respondents, 88.6% (31/35) reported that there was a psychiatric clinical pharmacy specialist at their institution and 34.3% (12/35) reported that pharmacists could order an electrocardiogram (ECG). Major themes that emerged from the qualitative analysis included pharmacist-driven QTc monitoring, referring the patient to another provider for monitoring, and encountering significant barriers to monitoring. Conclusion A variety of methods are currently being employed to monitor QTc prolongation risk in patients taking psychiatric medications. Pharmacist authorization to order ECGs may be an opportunity to advance practice and improve care for this population. Further research is needed to more clearly understand best practices for QTc prolongation risk mitigation in patients receiving psychiatric medications.

Use of portable single-lead electrocardiogram device as an alternative for QTc monitoring in critically ill patients.

PURPOSE: Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead, mobile alternative to conventional 12-lead electrocardiogram (12-L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use. METHODS: We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12-L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t-test, agreement using Bland-Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12-L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc). RESULTS: We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12-L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801-0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (-13.99 ms), QT-prolonging drugs (13.84 ms), antiarrhythmic drugs (-12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (-11.26 ms). CONCLUSION: Our study validates the clinical viability of KM1L, a single-lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.

Polymorphic Ventricular Tachycardia in Acute Cervical Spinal Cord Injury: A Rare Occurrence in the Setting of Normal QTc.

Cardiovascular manifestations like bradycardia, hypotension, fluctuation of blood pressure, and supraventricular arrhythmia are common in acute spinal cervical injury above the C6 level and are the major cause of mortality and morbidity in them. Ventricular tachycardia (VT) and fibrillation have only been reported in a few cases, but polymorphic VT (PMVT) has not been reported. We report a very rare case of acute cervical spinal cord injury patient who developed PMVT in the setting of normal QT interval degenerating to ventricular fibrillation, causing cardiac arrest before surgery.

Evaluation of the Efficacy and Safety of Quetiapine in the Treatment of Delirium in Adult ICU Patients: A Retrospective Comparative Study.

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes.

QTc intervals at rest and during exercise assessed by group correction formulas in survivors of childhood acute lymphoblastic leukemia.

INTRODUCTION: Early signs of subclinical cardiac damage must be identified before they turn into clinical manifestations. Tailoring a formula is relevant for precise QTc evaluation in childhood acute lymphoblastic leukemia (ALL) survivors considering they are at risk of long-term cardiac problems. Therefore, we aim to develop group heart rate correction formulas for QT intervals in childhood ALL survivors at rest and during exercise, and to assess the applicability of these methods across a variety of risk groups exposed to diverse chemotherapy dosages. METHODS: Two hundred and fifty childhood ALL survivors in the PETALE study were classified into 3 groups depending on their prognostic risk group. ECG measurements (QT and RR intervals) were made at rest and during a cardiopulmonary exercise test. QT correction for heart rate was applied using 5 different formulas, which included 2 previously published formulas and 3 group-specific formulas for each sex. RESULTS: The QT/RR relation showed 2 different curves between rest and during exercise, which was worse for females. Group-specific QTc formulas allowed adequate heart rate-corrected QT interval, independently of the cumulative dose of doxorubicin received during treatment. Group-specific formulas showed significantly shorter QTc intervals than QTc from Bazett's formula. QTc (Bazett's formula) values surpassed the established clinical norm in 22 males (11%) and 22 females (11%), with a majority occurring during exercise, affecting 15 males (7.5%) and 10 females (5%). CONCLUSION: This study shows the applicability of personalized group correction of QT/RR data in childhood ALL survivors. Our comprehensive assessments (spanning rest, exercise, and recovery) is an effective approach for risk stratification of cardiac complications in childhood ALL survivors.

Evaluation of the Renal and Cardiovascular Effects of Long-Term Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Cardiovascular diseases constitute a significant cause of morbidity and mortality in individuals with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to assess the long-term effects of tolvaptan on the kidneys and heart in rapidly progressing ADPKD. METHODS: Among 354 patients diagnosed with ADPKD, 58 meeting the eligibility criteria for tolvaptan were included in the study. The study comprised two groups with similar demographic and clinical characteristics: 29 patients receiving tolvaptan treatment and 29 in the control group. Several included genetic analysis, magnetic resonance imaging, and echocardiography. Clinical and cardiac changes were recorded in both groups after a 3-year follow-up. RESULTS: Tolvaptan treatment demonstrated a significant reduction in the rate of eGFR decline compared to the control group. Furthermore, it was observed that tolvaptan could prevent the development of cardiac arrhythmias by inhibiting an increase in QTc interval and heart rate. CONCLUSION: These findings suggest that, in addition to slowing kidney progression in ADPKD management, tolvaptan may potentially benefit in preventing cardiac complications.

ANOCA patients with and without coronary vasomotor dysfunction present with limited electrocardiographic remodeling.

Background: Coronary vasomotor dysfunction (CVDys) comprises coronary vasospasm (CVS) and/or coronary microvascular dysfunction (CMD) and is highly prevalent in patients with angina and non-obstructive coronary artery disease (ANOCA). Invasive coronary function testing (CFT) to diagnose CVDys is becoming more common, enabling pathophysiologic research of CVDys. This study aims to explore the electrophysiological characteristics of ANOCA patients with CVDys. Methods: We collected pre-procedural 12-lead electrocardiograms of ANOCA patients with CVS (n = 35), CMD (n = 24), CVS/CMD (n = 26) and patients without CVDys (CFT-, n = 23) who participated in the NL-CFT registry and underwent CFT. Heart axis and conduction times were compared between patients with CVS, CMD or CVS/CMD and patients without CVDys. Results: Heart axis, heart rate, PQ interval and QRS duration were comparable between the groups. A small prolongation of the QT-interval corrected with Bazett (QTcB) and Fridericia (QTcF) was observed in patients with CVDys compared to patients without CVDys (CVS vs CFT-: QTcB = 422 ± 18 vs 414 ± 18 ms (p = 0.14), QTcF = 410 ± 14 vs 406 ± 12 ms (p = 0.21); CMD vs CFT-: QTcB = 426 ± 17 vs 414 ± 18 ms (p = 0.03), QTcF = 413 ± 11 vs 406 ± 12 ms (p = 0.04); CVS/CMD vs CFT-: QTcB = 424 ± 17 vs 414 ± 18 ms (p = 0.05), QTcF = 414 ± 14 vs 406 ± 12 ms (p = 0.04)). Conclusions: Pre-procedural 12-lead electrocardiograms were comparable between patients with and without CVDys undergoing CFT except for a slightly longer QTc interval in patients with CVDys compared to patients without CVDys, suggesting limited cardiac remodeling in patients with CVDys.

Prevalence of Medication Associated with QTc Prolongation Used Among Critically Ill Patients.

Background: Acquired prolonged corrected QT (QTc) interval can lead to life-threatening Torsade de Pointes (TdP) arrhythmia. Multiple risk factors including medications, comorbidities, and electrolyte imbalances contribute significantly to acquired manifestations of the QTc prolongation. Critically ill patients are particularly more vulnerable to TdP due to complex medical conditions, aging, and polypharmacy. Objective: This study aimed to assess the prevalence of TdP-associated medication prescribing, identify risk factors for QTc prolongation and TdP, and determine primary predictors of high TdP medication usage in critically ill patients in Jordan. Methods: We conducted a retrospective cross-sectional analysis of electronic medical records for patients from King Abdullah University Hospital who were admitted to Intensive Care Unit (ICU) between (July 2012-July 2022). We collected data on patients' demographics, clinical characteristics, comorbidities, laboratory results, and prescribed medications. Medications were categorized into three TdP risk levels according to CredibleMeds® assessment tool. Data were analyzed using descriptive statistics and a binary logistic regression model. Results: Of the 13,300 patients (58.2% male, median age 62 years). Prescribing prevalence for medications with known TdP risk was 19%, possible risk (24.7%), conditional risk (21.6%), and confirmed conditional risk (8.3%). Common comorbidities included hypertension (40.9%), diabetes (33.3%), and cancer (15.4%). Drugs with known TdP risk included citalopram, amiodarone, clarithromycin, and ciprofloxacin. A binary regression model revealed that as age increased, the odds of TdP associated medication prescribing decreased (OR = 0.989, p < 0.001), while patients on more than five medications had higher odds (OR = 4.281, p < 0.001). Conclusion: The study identified a notable prevalence of prescribing for medications with QTc prolongation/TdP risk in critically ill patients. Healthcare providers in the ICU should exercise caution to minimize the inadvertent prescription of TdP associated medications especially among older patients and those with polypharmacy.

Pilot Study on QTc Interval in Dogs Treated with Domperidone.

Domperidone is used as an immunomodulatory drug for Leishmania infantum infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported in humans. This pilot study evaluated the corrected QT (QTc) interval in dogs treated with domperidone for preventive or therapeutic management of leishmaniosis. The electrocardiogram and blood concentration of creatinine, urea nitrogen, sodium, potassium, and chloride were evaluated seven days before the start and on the last day of therapy in 17 dogs receiving domperidone for four weeks. In two dogs, the QTc interval was measured before and 2 h, 3 h, and 12 h after administration of the drug on the first day of treatment. After treatment, QTc measures and chloride concentrations increased significantly, although the QTc value slightly exceeded the upper reference limit only in one dog, and chloride concentrations were always normal. Creatinine concentrations significantly decreased after therapy. In the two dogs monitored at different times on the first day of treatment, QTc values were always normal. Domperidone caused a slight prolongation of QTc interval, and further studies should be made for a risk assessment in dogs with cardiac diseases, electrolytic imbalance, and in those receiving drugs increasing QT interval or competing with domperidone metabolism.

Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study.

Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory period of ventricular and atrial myocytes by blocking the K+ current. Nifekalant is used to prevent ventricular tachycardia/ventricular fibrillation. QT interval prolongation is the main measurable drug effect. However, due to the complicated dosing plan in clinic, the relationship among dosage, time, drug concentration and efficacy is not fully understood. In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood samples were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27 L and 45.6 L, respectively. A nonlinear dose-response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101 ms and 342 ng/mL, respectively.

Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

Plastic additive components of PM2.5 increase corrected QT interval: Screening for exposure markers based on airborne exposome.

The impact of industrial chemical components of ambient fine particles (e.g. PM2.5) on cardiovascular health has been poorly explored. Our study reports for the first time the associations between human exposure to complex plastic additive (PA) components of PM2.5 and prolongation of heart rate-corrected QT (QTC) interval by employing a screening-to-validation strategy based on a cohort of 373 participants (136 in the screening set and 237 in the validation set) recruited from 7 communities across China. The high-throughput airborne exposome framework revealed ubiquitous occurrences of 95 of 224 target PAs in PM2.5, totaling from 66.3 to 555 ng m-3 across the study locations. Joint effects were identified for 9 of the 13 groups of PAs with positive associations with QTC interval. Independent effect analysis also identified and validated tris(2-chloroisopropyl) phosphate, di-n-butyl/diisobutyl adipate, and 3,5-di-tert-butyl-4-hydroxybenzaldehyde as the key exposure markers for QTC interval prolongation and changes of selected cardiovascular biomarkers. Our findings highlight the important contributions of airborne industrial chemicals to the risks of cardiovascular diseases and underline the critical need for further research on the underlying mechanisms, toxic modes of action, and human exposure risks.

Estudio de cohortes para evaluar la prevalencia de QT prolongado y arritmias en pacientes críticos durante la primera fase de la pandemia por COVID-19 / Cohort study to assess the prevalence of prolonged QT and arrhythmias in critically ill patients during the early phase of the COVID-19 pandemic

Antecedentes y objetivo: Los pacientes con infección por SARS-CoV-2 pueden presentar afectación cardiovascular, incluyendo miocarditis, arritmias y prolongación del intervalo QT. Nuestro objetivo fue evaluar el impacto de la COVID-19 y su tratamiento en la repolarización ventricular y el desarrollo de arritmias en pacientes críticos. Material y métodos: Estudio de cohortes retrospectivo de pacientes críticos con infección confirmada por SARS-CoV-2 durante un periodo de 3meses. Se registraron los datos clínicos relevantes y el tratamiento específico administrado para la COVID-19. Se consideró QTc prolongado cuando medía ≥460ms en mujeres y ≥450ms en hombres. Se registró la incidencia y el tipo de arritmias durante el mismo periodo. Resultados: Se evaluaron 77 pacientes con una edad media de 62±13años: 20 mujeres y 57 hombres. El 60% de los pacientes eran hipertensos, el 52% presentaban un IMC>30 y el 70% desarrollaron fracaso renal agudo durante el ingreso. El 56% de los pacientes presentaron prolongación del QTc. El 44% presentaron algún tipo de arritmia durante su estancia en la UCI, siendo en el 21% arritmias auriculares. La mortalidad global fue del 53%, sin diferencias entre los pacientes con o sin QTc prolongado. Conclusiones: En nuestra serie, una elevada proporción de pacientes críticos con COVID-19 han presentado QTc prolongado y arritmias. Los factores implicados se han relacionado con la elevación de biomarcadores cardiacos, la propia afectación miocárdica del virus y la medicación concomitante recibida en la UCI.(AU)

Introduction and objective: Patients with SARS-CoV-2 infection may present cardiovascular involvement including myocarditis, arrhythmias and QT interval prolongation. Our objective was to evaluate the impact of COVID-19 and its treatment on ventricular repolarization and development of arrhythmias in critically ill patients. Material and methods: Retrospective cohort study of critically ill COVID-19 patients during a 3-month period in whom at least one ECG was available. Relevant clinical data and specific treatment administered for COVID-19 were recorded. Prolonged QTc was considered prolonged when it measured ≥460ms in women and ≥450ms in men. The incidence and type of arrhythmias during the same period were recorded. Results: A total of 77 patients with a mean age of 62±13years, 20 women and 57 men, were evaluated. Sixty percent of the patients were hypertensive, 52% had a BMI>30, and 70% developed acute renal failure during admission. Some 56% of the patients presented QTc prolongation. Forty-four percent presented some type of arrhythmia during their stay in the ICU, 21% of which were atrial arrhythmias. Overall mortality was 53%, with no differences between patients with or without prolonged QTc. Conclusions: In our series, a high proportion of critical patients with COVID-19 presented prolonged QTc and arrhythmias. The factors involved have been related to the elevation of cardiac biomarkers, the myocardial involvement of the virus and concomitant medication received in the ICU.(AU)

A Case of Bradycardia-Induced Torsades De Pointes in a Patient Presenting to the Emergency Room With Cardiac Arrest.

Torsades de pointes (TdP) is a less common type of ventricular tachycardia (VT) characterized by polymorphic VT of changing amplitude and characteristic twists around the isoelectric baseline. It is almost always associated with QT interval prolongation. Unless immediately intervened, it can lead to ventricular fibrillation followed by cardiac arrest. We report a case of a patient with bradycardia-induced TdP who presented to the emergency room with cardiac arrest.