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Aim: There is no consensus on the best prophylaxis for supraventricular tachycardia (SVT) in infancy. We studied the efficacy and safety of sotalol. Method: This retrospective study comprised infants diagnosed with SVT before 1 year of age and treated with sotalol during 2002–2018 in Stockholm, Sweden. The patients' characteristics, comorbidities, sotalol dosages, QT intervals and outcomes were extracted from their medical records. Results: We studied 85 infants (65% boys) with a median age of eight (range 0–288) days at the time of diagnosis, including 78 with re‐entry tachycardia. Sotalol was completely or partially successful in the 67/75 patients who completed the treatment, as well as in four of the seven patients with other tachycardia mechanisms. The 48 infants with postnatal debut had significantly higher success rates than the 27 with foetal debut (96% vs. 78%, p = 0.04). Prolongation of corrected QT (QTc) intervals of ≥450 ms occurred in 16% of the total cohort and two patients with QTc intervals of ≥500 ms had their treatment changed. There were no cases of proarrhythmia after sotalol treatment. Conclusion: Sotalol provided effective and safe prophylaxis for SVT during infancy. QTc prolongation rarely caused treatment discontinuation and there were no cases of proarrhythmia. [ABSTRACT FROM AUTHOR]

Background: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. Methods: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. Results: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (− 7.5 ± 8.7 bpm vs. − 8.5 ± 13.9 bpm vs. − 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). Conclusion: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias. [ABSTRACT FROM AUTHOR]

This work outlines the development of a voltammetric method for a sensitive, rapid, and environmentally friendly determination of the antihypertensive sotalol (SOT) in several sample types employing the anodically pretreated boron‐doped diamond electrode. Cyclic voltammograms of SOT presented a well‐defined irreversible oxidation peak at 1.21 V (Ag/AgCl (3.0 mol L−1 KCl)) in Britton–Robinson buffer solution (pH 3.0). Figures of merits recommended by the validation guidelines were evaluated for the validation of the present method. Employing differential pulse voltammetry linearity of SOT was obtained in the concentration range of 0.39–4.22 μmol L−1 in 0.1 mol L−1 H2SO4 solution, with a limit of detection of 0.031 μmol L−1. The selectivity of the method was assessed against interferers and show relative standard deviation (RSD) values lower than 6 %. Recovery tests yielded percentages ranging from 93 % to 96 % in urine sample and from 100 % to 107 % in tap water sample. The proposed method was successfully applied in pharmaceutical, environmental, and biological samples offering a suitable green analytical chemistry profile. [ABSTRACT FROM AUTHOR]

This article discusses the use of anti-arrhythmic drugs before, during, and after transvenous electrical cardioversion (TVEC) in horses with atrial fibrillation (AF). TVEC is a treatment option for AF, but it can be associated with immediate or early recurrence of AF. To prevent recurrence, anti-arrhythmic drugs such as sotalol and amiodarone are often used. However, these drugs can have potential risks and side effects, including cardiac dysfunction and hypotension. The article emphasizes the importance of weighing the benefits and risks of using anti-arrhythmic drugs in horses with AF and highlights the need for good communication between veterinarians, anesthesiologists, and horse owners. Future research is also discussed, including the investigation of new drugs and ablation therapy for AF in horses. [Extracted from the article]

β-adrenergic receptor (β-AR) signaling in cardiac myocytes is central to cardiac function, but spatiotemporal activation within myocytes is unresolved. In rabbit ventricular myocytes, β-AR agonists or high extracellular [Ca] were applied locally at one end, to measure β-AR signal propagation as Ca-transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca uptake. High local [Ca]o, increased CaT amplitude under the pipette faster than did ISO, but was also more spatially restricted. Local isoproterenol (ISO) or norepinephrine (NE) increased CaT amplitude and SR Ca uptake, that spread along the myocyte to the unexposed end. Thus, local [Ca]i decline kinetics reflect spatio-temporal progression of β-AR end-effects in myocytes. To test whether intracellular β-ARs contribute to this response, we used β-AR-blockers that are membrane permeant (propranolol) or not (sotalol). Propranolol completely blocked NE-dependent CaT effects. However, blocking surface β-ARs only (sotalol) suppressed only ∼50% of the NE-induced increase in CaT peak and rate of [Ca]i decline, but these changes spread more gradually than NE alone. We also tested whether A-kinase anchoring protein 7γ (AKAP7γ; that interacts with phospholamban) is mobile, such that it might contribute to intracellular spatial propagation of β-AR signaling. We found AKAP7γ to be highly mobile using fluorescence recovery after photobleach of GFP tagged AKAP7γ, and that PKA activation accelerated AKAP7γ-GFP wash-out upon myocyte saponin-permeabilization, suggesting increased AKAP7γ mobility. We conclude that local β-AR activation can activate SR Ca uptake at remote myocyte sites, and that intracellular β-AR and AKAP7γ mobility may play a role in this spread of activation.

Drug isomers may differ in their proarrhythmia risk. An interesting example is the drug sotalol, an antiarrhythmic drug comprising d- and l- enantiomers that both block the hERG cardiac potassium channel and confer differing degrees of proarrhythmic risk. We developed a multi-scale in silico pipeline focusing on hERG channel - drug interactions and used it to probe and predict the mechanisms of pro-arrhythmia risks of the two enantiomers of sotalol. Molecular dynamics (MD) simulations predicted comparable hERG channel binding affinities for d- and l-sotalol, which were validated with electrophysiology experiments. MD derived thermodynamic and kinetic parameters were used to build multi-scale functional computational models of cardiac electrophysiology at the cell and tissue scales. Functional models were used to predict inactivated state binding affinities to recapitulate electrocardiogram (ECG) QT interval prolongation observed in clinical data. Our study demonstrates how modeling and simulation can be applied to predict drug effects from the atom to the rhythm for dl-sotalol and also increased proarrhythmia proclivity of d- vs. l-sotalol when accounting for stereospecific beta-adrenergic receptor blocking.

Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome. The purpose of this study was to compare the incidences of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control vs matched control patients treated with cardioselective beta-blockers. This population-based cohort study included AF patients from the Swedish National Patient Registry (2006–2017) who underwent rhythm control after a second cardioversion. Incidence rates (IRs) and adjusted hazard ratios (aHRs) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score matched cohort of d,l-sotalol vs beta-blocker treatment. Among patient treated with d,l-sotalol (n = 4987) and beta-blocker (n = 27,078) (mean follow-up 458 days), all-cause mortality was lower in patients treated with d,l-sotalol: IR 1.21; 95% confidence interval 0.95–1.52 vs 2.42 (2.26–2.60) deaths per 100 patient-years; aHR 0.66 (0.52–0.83). The difference in mortality persisted in the propensity score matched comparison (n = 4953 in each group): aHR 0.63 (0.48–0.86). No differences were observed in the composite outcome: IR in propensity cohorts 2.13 (1.78–2.52) vs 2.07 (1.73–2.53) events per 100 years; aHR 1.01 (0.78–1.29). There was no excess mortality with d,l-sotalol compared with cardioselective beta-blockers in patients undergoing rhythm control treatment for AF after a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Fetal atrial flutter (AF), accounting for 30% of all fetal tachyarrhythmias, predominantly (over 80%) manifests as a 2:1 atrioventricular conduction. Swift referral and timely intervention become imperative in instances of severe persistent arrhythmia. Case Presentation: We discuss the case of a 32-year-old multiparous Chinese woman, at 30+2 weeks of gestation, wherein an ultrasonographic examination revealed persistent fetal AF (atrial rate ranging from 219 to 445 beats/min and ventricular rate from 219 to 228 beats/min, with a 2:1 or 1:1 down transmission) and minor ascites. Despite the maternal ingestion of digoxin and sotalol, the fetal heart rhythm remained uncorrected. Following this, at 32+3 weeks of gestation, an intramuscular injection of cedilanid, guided by ultrasound, was administered to the fetus. Postoperatively, the fetal ventricular rate demonstrated a decline after 6 days, and the ascites resolved. Subsequently, at 33+3 weeks, a cesarean section was necessitated due to maternal intolerance to the medication, resulting in the delivery of the infant. Remarkably, the infant's cardiac rhythm spontaneously converted to sinus rhythm within 5 min of birth. A follow-up conducted 1 year postpartum revealed no recurrence of AF. Conclusions: This case illustrates that in the event of transplacental drug treatment failure, intrauterine therapeutic intervention should be considered. Moreover, it highlights the encouraging prognosis associated with fetal AF, as the cardiac rhythm spontaneously reverted to sinus rhythm postbirth in this instance. [ABSTRACT FROM AUTHOR]

Summary: Atrial fibrillation (AF) is a pathological arrhythmia affecting performance horses and is termed paroxysmal (pAF) when self‐terminating to sinus rhythm. Little is known about pAF as its sporadic nature makes it difficult to diagnose. Therefore, continuous electrocardiographic monitoring devices, such as implantable loop recorders (ILR), are necessary to detect the time of onset and episode duration. This case report presents the detection of pAF in a 9‐year‐old Warmblood horse after successful transvenous electrical cardioversion (TVEC). An ILR continuously monitored the heart rhythm over 28 months and detected 12 episodes of pAF of which two episodes were associated with reduced performance, while others occurred asymptomatically at rest. The estimated episode duration ranged from 6 min to 46.5 h. The antiarrhythmic drug sotalol (2 mg/kg bwt BID PO) was given prior to TVEC and then for 4 weeks. As episodes continued to occur, sotalol was prescribed for another 4 weeks, 6 months after TVEC. Continuous monitoring after TVEC allows for detection of AF recurrence and identification of AF burden, approximate time of onset and possible identification of trigger events. Early diagnosis and antiarrhythmic treatment may prevent a progression to persistent AF. [ABSTRACT FROM AUTHOR]

Introduction: Various agents may be utilized to manage supraventricular tachycardia (SVT) in neonates and infants. Recently, sotalol has piqued interest given its reported success in managing neonates and infants with SVTs, especially with the intravenous formulation. While the manufacturer recommends using an age‐related nomogram in neonates and young infants to guide doses, clinical reports describe various dosing based on weight (mg/kg) or on body surface area (BSA) in mg/m2. Given the reported variation in clinical practice with regard to dosing in neonates, there is a gap in the literature and translation into clinical practice regarding applicability of the nomogram into clinical practice. The purpose of this study was to describe sotalol doses based on body weight and BSA in neonates for SVT. Methods: This is a single center retrospective study evaluating effective sotalol dosing from January 2011 and June 2021 (inclusive). Neonates who received intravenous (IV) or oral (PO) sotalol for SVT were eligible for inclusion. The primary outcome was to describe sotalol doses based on body weight and BSA. Secondary outcomes include comparison of doses to the manufacturer nomogram, description of dose titrations, reported adverse outcomes, and change in therapy. Two‐sided Wilcoxon signed‐rank tests were used to determine statistically significant differences. Results: Thirty‐one eligible patients were included in this study. The median (range) age and weight were 16.5 (1−28) days and 3.2 (1.8−4.9) kg, respectively. The median initial dose was 7.3 (1.9−10.8) mg/kg or 114.3 (30.9−166.7) mg/m2/day. Fourteen (45.2%) of patients required a dose increase for SVT control. The median dose required for rhythm control was 8.5 (2−14.8) mg/kg/day or 120.7 (30.9−225) mg/m2/day. Of note, the median recommended dose per manufacturer nomogram for our patients would have been 51.3 (16.2−73.8) mg/m2/day, which is significantly lower than both the initial dose (p <.001) and final doses (p <.001) utilized in our study. A total of 7 (22.9%) patients were uncontrolled on sotalol monotherapy using our dosing regimen. Two patients (6.5%) had reports of hypotension and one patient (3.3%) had a report of bradycardia requiring discontinuation of therapy. The average change in baseline QTC following sotalol initiation was 6.8%. Twenty‐seven (87.1%), 3 (9.7%), 1 (3.3%) experienced prolongation, no change, or a decrease in QTc, respectively. Conclusions: This study demonstrates that a sotalol strategy significantly higher than the manufacture dose recommendations are required for rhythm control in neonates with SVT. There were few adverse events reported with this dosing. Further prospective studies would be advantageous to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: There are limited comparative data on safety and efficacy within commonly used Vaughan‐Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with atrial fibrillation (AF). Hypothesis: We hypothesized that dronedarone and sotalol, two commonly prescribed VW class III AADs with class II properties, have different safety and efficacy effects in patients with nonpermanent AF. Methods: A systematic literature review was conducted searching MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021 (NCT05279833). Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Bayesian random‐effects network meta‐analysis (NMA) was used to quantify comparative safety and efficacy. Where feasible, we performed sensitivity analyses by including only randomized controlled trials (RCTs). Results: Of 3581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 nonrandomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all‐cause death versus sotalol (hazard ratio [HR] = 0.38 [95% credible interval, CrI: 0.19, 0.74]). The association was numerically similar in the sensitivity analysis (HR = 0.46 [95% CrI: 0.21, 1.02]). AF recurrence and cardiovascular death results were not significantly different between dronedarone and sotalol in all‐studies and sensitivity analyses. Conclusion: The NMA findings indicate that, across all clinical trials and observational studies included, dronedarone compared with sotalol was associated with a lower risk of all‐cause death, but with no difference in AF recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Understanding symptom patterns in atrial fibrillation (AF) can help in disease management. We report on the application of natural language processing (NLP) to electronic medical records (EMRs) to capture symptom reports in patients with newly diagnosed (incident) AF. Methods and Results: This observational retrospective study included adult patients with an index diagnosis of incident AF during January 1, 2016 through June 30, 2018, in the Optum datasets. The baseline and follow‐up periods were 1 year before/after the index date, respectively. The primary objective was identification of the following predefined symptom reports: dyspnea or shortness of breath; syncope, presyncope, lightheadedness, or dizziness; chest pain; fatigue; and palpitations. In an exploratory analysis, the incidence rates of symptom reports and cardiovascular hospitalization were assessed in propensity‐matched patient cohorts with incident AF receiving first‐line dronedarone or sotalol. Among 30 447 patients with an index AF diagnosis, the NLP algorithm identified at least 1 predefined symptom in 9734 (31.9%) patients. The incidence rate of symptom reports was highest at 0–3 months post‐diagnosis and lower at >3–6 and >6–12 months (pre‐defined timepoints). Across all time periods, the most common symptoms were dyspnea or shortness of breath, followed by syncope, presyncope, lightheadedness, or dizziness. Similar temporal patterns of symptom reports were observed among patients with prescriptions for dronedarone or sotalol as first‐line treatment. Conclusion: This study illustrates that NLP can be applied to EMR data to characterize symptom reports in patients with incident AF, and the potential for these methods to inform comparative effectiveness. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable progressive myocardial disorder that predisposes patients to ventricular arrhythmias and sudden cardiac death. Antiarrhythmic medications have an important role in reducing the frequency of ventricular arrhythmias and the morbidity associated with recurrent implantable cardioverter-defibrillator (ICD) shocks. Although several studies have examined the use of antiarrhythmic drugs in ARVC, these have been mostly retrospective in nature and inconsistent in their methodology, patient population and endpoints. Thus, current prescribing practices are largely based on expert opinion and extrapolation from other diseases. Herein, we discuss the major studies of the use of antiarrhythmics in ARVC, present the current approach employed at the Johns Hopkins Hospital and identify areas where further research is needed. Most notably, there is a great need for high-quality studies with consistent methodology and randomized controlled trial data into the use of antiarrhythmic drugs in ARVC. This would improve management of the condition and ensure antiarrhythmic prescribing is based on robust evidence. [ABSTRACT FROM AUTHOR]

Fetal arrhythmia develops in 0.1–5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed. [ABSTRACT FROM AUTHOR]

Abstract Background Transvenous electrical cardioversion (TVEC) is 1 of the main treatment options for atrial fibrillation (AF) in horses. Large‐scale studies on factors affecting success and prognosis have primarily been performed in Standardbred populations. Hypothesis/Objectives To determine factors affecting cardioversion success, cardioversion difficulty and recurrence in a predominant Warmblood study sample. Animals TVEC records of 199 horses. Methods Retrospective study of TVEC procedures of horses admitted for AF without severe echocardiographic abnormalities. Horse and procedural factors for success and cumulative amount of energy (≤ 600 J vs > 600 J) were determined using multivariable logistic regression. A survival analysis was performed to determine risk factors for recurrence. Results Two hundred and thirty‐one TVEC procedures were included, with a 94.4% success rate and 31.9% recurrence rate (51/160). Mitral regurgitation (OR 0.151, 95% CI 0.032‐0.715, P = .02) and AF cycle length (OR 1.05, 95% CI 1.01‐1.09, P = .02) were independent determinants for success. Catheter type (OR 0.154, 95% CI 0.074‐0.322, P

BackgroundSotalol is a commonly used antiarrhythmic drug that may alter ventricular function.ObjectiveTo determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias.AnimalsThirty-five client-owned dogs with ventricular arrhythmias.MethodsDogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5-minute ECG performed at baseline and 2-4 hours post-sotalol (2-2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within-day variability controls). Left ventricular (LV) internal dimension at end-systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function.ResultsAll indices except TAPSE had mild decreases in systolic function post-sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly (P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5-minutes, and arrhythmia grade also were decreased post-sotalol (all P ≤ .01) compared with baseline when assessed by a 5-minutes ECG. No dog experienced an adverse event post-sotalol, including dogs with systolic dysfunction or atrial enlargement.Conclusions and clinical importanceA single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction.

The (bio)availability of pharmaceuticals at solid/water interfaces is governed by their sorption, which determines their concentrations in groundwaters and surface waters in contact with biota, and can be affected by the presence of other contaminants such as metallic trace elements likely to compete for adsorption sites and form complexes with pharmaceuticals. We studied the adsorption of the pharmaceuticals propranolol and sotalol—two β‐blockers—on one soil and one sediment using batch experiments to assess their (bio)availability. The influence of contact time, pH, and concentration was studied. As in the real environment these contaminants are not alone but in mixtures, and they were studied alone, simultaneously added, and in the presence of Cu2+, which is known to form coordination complexes with propranolol and sotalol, but their presence in mixtures did not alter their adsorption properties. Sotalol was more mobile in water and thus more bioavailable for organisms than propranolol. The mobility in surface waters of both β‐blockers and thus their bioavailabity for organisms is more important than their risk of transfer to groundwater during rainwater infiltration and to surface water due to runoff. Environ Toxicol Chem 2022;41:2700–2707. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Stereoselective dependence of active pharmaceutical ingredients for their pharmacokinetics inspired the researchers to develop new analytical methods for enantiomeric separation to enhance drug therapeutics. Enantiomeric separation of three β-blockers, namely, (RS)-pindolol, (RS)-alprenolol, and (RS)-sotalol has been achieved by direct thin-layer chromatographic approaches involving l-glutamic acid (l-Glu) as chiral selector. Three different approaches adopted were as follows: (i) chiral thin-layer plates were prepared by adding l-Glu in the silica gel slurry, (ii) mobile phase and stationary phases were achiral where chiral auxiliary was pre-mixed with active pharmaceutical ingredients solution in the specific ratio (1:3), and (iii) l-Glu was mixed in the mobile phase and plain plates without l-Glu were used. Several combinations of solvents were thriving in three different approaches for the enantioresolution of three pharmaceuticals. After optimizing successful resolution, spots of corresponding isomers were located using iodine as a detecting agent. The detection limits for each enantiomer were reported to be between 1.3 and 1.7 μg spot−1. [ABSTRACT FROM AUTHOR]

Analysis of untreated municipal wastewater is recognized as an innovative approach to assess population exposure to or consumption of various substances. Currently, there are no published wastewater-based studies investigating the relationships between catchment social, demographic, and economic characteristics with chemicals using advanced non-targeted techniques. In this study, fifteen wastewater samples covering 27% of the Australian population were collected during a population Census. The samples were analysed with a workflow employing liquid chromatography high-resolution mass spectrometry and chemometric tools for non-target analysis. Socioeconomic characteristics of catchment areas were generated using Geospatial Information Systems software. Potential correlations were explored between pseudo-mass loads of the identified compounds and socioeconomic and demographic descriptors of the wastewater catchments derived from Census data. Markers of public health (e.g., cardiac arrhythmia, cardiovascular disease, anxiety disorder and type 2 diabetes) were identified in the wastewater samples by the proposed workflow. They were positively correlated with descriptors of disadvantage in education, occupation, marital status and income, and negatively correlated with descriptors of advantage in education and occupation. In addition, markers of polypropylene glycol (PPG) and polyethylene glycol (PEG) related compounds were positively correlated with housing and occupation disadvantage. High positive correlations were found between separated and divorced people and specific drugs used to treat cardiac arrhythmia, cardiovascular disease, and depression. Our robust non-targeted methodology in combination with Census data can identify relationships between biomarkers of public health, human behaviour and lifestyle and socio-demographics of whole populations. Furthermore, it can identify specific areas and socioeconomic groups that may need more assistance than others for public health issues. This approach complements important public health information and enables large-scale national coverage with a relatively small number of samples.

The extent of sotalol‐induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the extent of drug‐induced QTc prolongation remains unclear. This was studied around peak plasma concentration in a large cohort of 376 healthy male and 614 healthy female subjects who received 80 mg of sotalol orally. Baseline QTc was 379 ± 16 ms in men and 393 ± 15 ms in women (P <.0001). The change in QTc from baseline was highly variable among both sexes and was greater in women than in men (26.5 ± 13.2 vs.13.0 ± 10.8 ms; P <.0001). The slope of the regression line between QTc on sotalol and baseline QTc did not significantly differ from unity in men and in women, indicating that the extent of QTc prolongation with sotalol was not influenced by baseline QTc. Assessing QTc after administration of an IKr blocker may be more important than measuring a baseline QTc. [ABSTRACT FROM AUTHOR]