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• Solubility of cardiovascular sotalol hydrochloride were determined in buffers, 1-octanol and n-hexane. • Agreement between the calculated pH-solubility profile of the drug and the experimental water solubility was obtained. • The temperature dependences of the distribution coefficients of drug in model systems were measured. • Thermodynamic functions of drug dissolution and transfer in solvents used were calculated. The shake-flask method was used to determine the solubility of sotalol hydrochloride (STL), a cardiovascular drug, in solvents modeling a variety of body media within the temperature range (293.15–313.15) K. In the descending order of the drug solubility the solvents can be arranged as follows: buffer pH 2.0, buffer pH 7.4, 1-octanol, n-hexane. The experimental values of solubility of the drug in aqueous solvents agree well with the calculated values of the pH-solubility profile. The study shows that the maximum solubility of the salt is observed within the pH range from 2.9 to pH max equal to 6.1. Temperature dependencies of the STL distribution coefficients were obtained in 1-octanol/buffer pH 7.4 and n-hexane/buffer pH 7.4 systems. Since the values of the partition coefficients of hydrophilic STL are low, it was concluded that the diffusion through the lipid biolayer of cell membranes was unfavorable and that the paracellular transport of the drug molecules might prevail. The thermodynamic functions of dissolution and transfer were calculated and discussed taking into account the physicochemical properties of STL and the solvents used. [ABSTRACT FROM AUTHOR]

Sudden cardiac death and the heaviest arrhythmic events are connected to ventricular arrhythmias (VA). The issue of optimization of drug therapy for VA remains relevant. Given the possible multidirectional effects of antiarrhythmic drugs on the functional state, in order to determine the effectiveness of pharmacotherapy in patients with VA it is advisable to use a stepwise integrated approach. Aim. Compare the effects of bisoprolol, nebivolol and sotalol on the functional state of patients with VA. Materials and methods. 120 patients with VA of grade IIV based on the В. Lown grading system, III groups based on J. Bigger grading system against the background of essential hypertension or its combination with coronary heart disease took part in the research, they were randomized into three groups for treatment with bisoprolol, nebivolol and sotalol. As part of combination therapy, patients were administered lisinopril, and if indicated, acetylsalicylic acid, atorvastatin. Initially and after 24 weeks of therapy the following was done: quantitative assessment of regulatory-adaptive status by cardio-respiratory synchronism test, treadmill test, six-minute walk test, subjective assessment of quality of life, all-day monitoring of blood pressure and electrocardiogram. Results. With comparable hypotensive and antiarrhythmic effects, therapy with nebivolol had a positive effect on the regulatory-adaptive status, had a better effect on exercise tolerance in comparison with bisoprolol and sotalol, more improved the quality of life, in comparison with bisoprolol and sotalol. Conclusion. In patients with VA against the background of essential hypertension or its combination with coronary heart disease as part of combination therapy the use of nebivolol may be preferable to bisoprolol or sotalol due to a more pronounced positive effect on the functional state.

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.

Introduction: There exists variability in the administration of in‐patient sotalol therapy for symptomatic atrial fibrillation (AF). The impact of this variability on patient in‐hospital and 30‐day posthospitalization costs and outcomes is not known. Also, the cost impact of intravenous sotalol, which can accelerate drug loading to therapeutic levels, is unknown. Methods: One hundred and thirty‐three AF patients admitted for oral sotalol initiation at an Intermountain Healthcare Hospital from January 2017 to December 2018 were included. Patient and dosing characteristics were described descriptively and the impact of dosing schedule was correlated with daily hospital costs/clinical outcomes during the index hospitalization and for 30 days. The Centers for Medicare and Medicaid Services reimbursement for 3‐day sotalol initiation is $9263.51. Projections of cost savings were made considering a 1‐day load using intravenous sotalol that costs $2500.00 to administer. Results: The average age was 70.3 ± 12.3 years and 60.2% were male with comorbidities of hypertension (83%), diabetes (36%), and coronary artery disease (53%). The mean ejection fraction was 59.9 ± 7.8% and the median corrected QT interval was 453.7 ± 37.6 ms before sotalol dosing. No ventricular arrhythmias developed, but bradycardia (<60 bpm) was observed in 37.6% of patients. The average length of stay was 3.9 ± 4.6 (median: 2.2) days. Postdischarge outcomes and rehospitalization rates stratified by length of stay were similar. The cost per day was estimated at $2931.55 (1. $2931.55, 2. $5863.10, 3. $8794.65, 4. $11 726.20). Conclusions: In‐patient oral sotalol dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. In consideration of estimated costs, there is the potential for $871.55 cost savings compared to a 2‐day oral load and $3803.10 compared to a 3‐day oral load. [ABSTRACT FROM AUTHOR]

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 <.001), previous AF episode (OR 3.10, 95% CI 1.20‐8.01, P =.02), tricuspid regurgitation (OR 2.54, 95% CI 1.25‐5.13, P =.01), and body weight (OR 1.009, 95% CI 1.003‐1.015, P =.004) were significantly correlated with cumulative amount of energy delivered. Significant risk factors for recurrence after a first AF episode were sex (stallion; HR 3.05, 95% CI 1.34‐6.95, P =.008), mitral regurgitation (HR 1.91, 95% CI 1.08‐3.38, P =.03), and AF duration (HR 1.001, 95% CI 1.0001‐1.0026, P =.04). Conclusions and Clinical Importance: Both horse and procedural factors should be considered when assessing treatment options and prognosis in horses with AF. [ABSTRACT FROM AUTHOR]

Background: Junctional ectopic tachycardia (JET) is a common arrhythmia after congenital heart disease surgery. There is variability in the choice of antiarrhythmic therapy, with amiodarone used commonly. Intravenous (IV) sotalol is a newly available agent that may be useful for JET.Objective: The purpose of this study was to evaluate the safety and efficacy of IV sotalol for postoperative JET and compare outcomes with IV amiodarone.Methods: This is a retrospective single-center study of all patients who received IV sotalol or IV amiodarone for postoperative JET at Texas Children's Hospital from December 15, 2015, to December 15, 2020. Data included antiarrhythmic efficacy, hemodynamics, and adverse effects. Successful JET control was defined as a decrease in JET rate to <170 beats/min (or decrease by >20%), or conversion to sinus rhythm, with persistent control over 24 hours without requiring alternative antiarrhythmics or mechanical support.Results: A total of 32 patients (median age 71 days; interquartile range 17-221 days) received IV amiodarone (n = 20 [62%]) or IV sotalol (n = 12 [38%]) for postoperative JET. Amiodarone was successful in treating JET in 75% of cases; sotalol was successful in 83%. The JET rate decreased faster over the first 90 minutes after a sotalol bolus (25 beats/min per hour) than after an amiodarone bolus (8 beats/min per hour) (P < .01); no heart rate difference was seen after 24 hours. Amiodarone infusion was discontinued early because of hypotension/bradycardia in 2 patients; this was not required in any patients receiving sotalol.Conclusion: For children with postoperative JET, both IV sotalol and amiodarone are safe and efficacious. IV sotalol may lead to a faster improvement in heart rate. [ABSTRACT FROM AUTHOR]

The aim of the work. To develop a method for spectrophotometric determination of sotalol with diazonium salts. Establish optimal conditions for the quantitative determination of sotalol in drugs. Validate the developed methodology. Materials and methods. Reagents and solvents used in the study were: diazole red 2J (obtained from NVF “Sinbias”), tablets “Sotalol Sandoz” 40 mg (Salyutas Pharma GmbH, series JZ1188), “Sotalol Sandoz” 80 mg (Salyutas Pharma GmbH, series KA0464) and “Sotalol Sandoz” 160 mg (Salyutas Pharma GmbH, series JY3504), methanol (LAB-SCAN, Ireland, batch No. 5120/13), sodium carbonate (Sinbias) and purified water were also used. Analytical equipment: spectrophotometer “SPECORD-200” (Analytic Jena AG, Germany), scales laboratory electronic RADWAG XA 210.4Y, bath ultrasonic Sonorex Digitec DT100H, laboratory glassware of class A. All studies were conducted in the experimental pharmaceutical research department of the scientific medical laboratory center (SMLC) of the Zaporizhzhia State Medical University. Results and discussion. The technique of spectrophotometric determination of the quantitative content of sotalol based on its reaction with red diazole in water-methanol medium has been developed. The stoichiometric ratios of the reactive components as 1:1 were obtained by the methods of continuous changes and the saturation method. Validation of the developed on such indicators as linearity, precision, correctness and robustness is carried out. Based on these data, the developed method is correct and could be used in the quality control departments of chemical and pharmaceutical companies. Conclusions. A method of quantitative spectrophotometric determination of sotalol in the tablet dosage form “Sotalol Sandoz” 40 mg, “Sotalol Sandoz” 80 mg and “Sotalol Sandoz” 160 mg of industrial production was developed, validation characteristics were investigated: linearity, precision, correctness, range of application and robustness. [ABSTRACT FROM AUTHOR]

The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially adrenaline (AD). AD improves contextual fear memory, acting specifically on peripheral β2-adrenoceptors. Propranolol (peripheral and central β-adrenoceptor antagonist) treatment was shown to prevent post-traumatic stress disorder (PTSD) development and reduce its symptoms. However, propranolol has several side effects. Thus, we aimed to evaluate if sotalol (a peripheral β-adrenoceptor antagonist) treatment interferes with retrieval, expression, and/or reconsolidation of traumatic memories in a validated mice model that mimics the signs/symptoms of PTSD, thus intending to decrease them. Female mice were induced with PTSD following an established protocol. Sotalol (2.0 mg/kg) or vehicle were administered on days 2, 7, and 14. The percentage of freezing was calculated, and behavioral tests were carried out. Catecholamines in plasma were quantified by HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of NR4A family genes in hippocampus. Following the submission of the animals to the same aversive context on days 2, 7, and 14, sotalol-treated mice exhibited significant less freezing behavior. In the elevated plus-maze test, the time spent and number of entries in the open arms, and total arm entries were increased in sotalol-treated mice. Also, the light-dark transition test revealed higher time spent, number of transitions to the light, and total number of transitions in sotalol-treated mice. Moreover, plasma AD was significantly decreased in sotalol-treated mice. On day 14, sotalol-treated mice exhibited a decrease in mRNA expression of Nr4a1 in the hippocampus. In conclusion, in PTSD mice model, sotalol appears to decrease traumatic memories and anxiety-like behavior, probably due to a decrease in peripheral adrenergic activity, which influences traumatic memories. The effects of sotalol upon re-exposure to the traumatic context may be consistent with interference in the retrieval, expression, and/or reconsolidation processes of contextual traumatic memory, resulting in a long-term reduction of PTSD symptoms and signs. The decreased Nr4a1 mRNA expression in the hippocampal formation may be crucial for these mice to develop diminished traumatic contextual memories after sotalol therapy in PTSD. [ABSTRACT FROM AUTHOR]

Aim.Compare the effects of bisoprolol, nebivolol and sotalol on the functional state of patients with ventricular arrhythmias (VA). Material and methods.120 patients with VA against the background of essential hypertension or its combination with coronary heart disease took part in the research, they were randomized into three groups for treatment with bisoprolol, nebivolol and sotalol. As part of combination therapy, patients were administered lisinopril, and if indicated, acetylsalicylic acid, atorvastatin. Initially and after 24 weeks of therapy the following was done: echocardiography, treadmill test, six-minute walk test, subjective assessment of quality of life, all-day monitoring of blood pressure and electrocardiogram. Results.With comparable hypotensive and antiarrhythmic effects, therapy with nebivolol increased exercise tolerance to a greater extent, in comparison with bisoprolol and sotalol. Nebivolol and sotalol improved the quality of life, in comparison with bisoprolol. Conclusion.In patients with VA against the background of essential hypertension or its combination with coronary heart disease as part of combination therapy the use of nebivolol may be preferable to bisoprolol or sotalol due to a more pronounced positive effect on the functional state.

The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially adrenaline (AD). AD improves contextual fear memory, acting specifically on peripheral β2-adrenoceptors. Propranolol (peripheral and central β-adrenoceptor antagonist) treatment was shown to prevent post-traumatic stress disorder (PTSD) development and reduce its symptoms. However, propranolol has several side effects. Thus, we aimed to evaluate if sotalol (a peripheral β-adrenoceptor antagonist) treatment interferes with retrieval, expression, and/or reconsolidation of traumatic memories in a validated mice model that mimics the signs/symptoms of PTSD, thus intending to decrease them. Female mice were induced with PTSD following an established protocol. Sotalol (2.0 mg/kg) or vehicle were administered on days 2, 7, and 14. The percentage of freezing was calculated, and behavioral tests were carried out. Catecholamines in plasma were quantified by HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of NR4A family genes in hippocampus. Following the submission of the animals to the same aversive context on days 2, 7, and 14, sotalol-treated mice exhibited significant less freezing behavior. In the elevated plus-maze test, the time spent and number of entries in the open arms, and total arm entries were increased in sotalol-treated mice. Also, the light-dark transition test revealed higher time spent, number of transitions to the light, and total number of transitions in sotalol-treated mice. Moreover, plasma AD was significantly decreased in sotalol-treated mice. On day 14, sotalol-treated mice exhibited a decrease in mRNA expression of Nr4a1 in the hippocampus. In conclusion, in PTSD mice model, sotalol appears to decrease traumatic memories and anxiety-like behavior, probably due to a decrease in peripheral adrenergic activity, which influences traumatic memories. The effects of sotalol upon re-exposure to the traumatic context may be consistent with interference in the retrieval, expression, and/or reconsolidation processes of contextual traumatic memory, resulting in a long-term reduction of PTSD symptoms and signs. The decreased Nr4a1 mRNA expression in the hippocampal formation may be crucial for these mice to develop diminished traumatic contextual memories after sotalol therapy in PTSD.

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.

Background. Pharmacological therapy of atrial fibrillation (AF) in subclinical dysfunction of the thyroid – is the most important problem of modern clinical medicine. The purpose of the study is to conduct a complex assessment of electrophysiological indicators of the heart and lipid profile in patients with subclinical thyrotoxicosis and paroxysmal AF during antiarrhythmic and thyrostatic therapy. Pharmacological therapy of atrial fibrillation (AF) in subclinical dysfunction of the thyroid is the most important problem of modern clinical medicine. Materials and methods. 126 patients with frequent paroxysms of AF with subclinical thyrotoxicosis were examined. All patients underwent ECG control, EP study, assessment of thyroid hormones level and lipid profile. Therapy included treatment with bisoprolol, sotalol, thiamazole and their combinations. Results. Electrophysiological predictors of AF in subclinical thyrotoxicosis were identified. It was found that euthyroid status does not reduce a number of spontaneous paroxysms of AF. High antiarrhythmic efficacy of combined use of bisoprolol with thiamazole and sotalol with thiamazole has been proven.

Abstract Background The risk of ventricular arrhythmias in patients on QT prolonging drugs is indicated to be increased early after cardioversion (CV) of atrial fibrillation (AF) to sinus rhythm (SR). Sotalol, used to prevent AF relapse, prolongs cardiac repolarization and corrected QT interval (QTc). A pronounced QTc prolongation is an established marker of pro‐arrhythmias. Our objective was to use novel technique to quantify and evaluate the diurnal variation of the QTc interval after elective CV to SR in patients on sotalol or metoprolol. Methods Fifty patients underwent twelve‐lead Holter recording for 24 hr after elective CV for persistent AF. All patients had the highest tolerable stable dose of sotalol (n = 27) or metoprolol (n = 23). Measurements of QT and RR intervals were performed on all valid beats. Results A clear diurnal variation of both HR and QTc was seen in both groups, more pronounced in patients on sotalol, where a high percentage of heartbeats with QTc >500 ms was observed, especially at night. Six patients (22%) on sotalol but none on metoprolol had >20% of all heart beats within the 24‐hour recording with QTc >500 ms. Conclusion Twenty‐four‐hour Holter recordings with QT‐measurement immediately after CV demonstrated that one in five patients on sotalol had >20% of all heart beats with prolonged QTc >500 ms, especially during night‐time. The QTc diurnal variation was retained in patients on β‐blockade or a potent class III anti‐arrhythmic drug with β‐blocking properties.

Introduction: Sotalol and flecainide are used as second line agents in children for the treatment of supraventricular arrhythmias (SA) refractory to anti‐beta adrenergic antiarrhythmics or digoxin. Efficacy and adverse events in this cohort have not been well described. Here, we report our institutional experience of second line treatment initiation for SA in children. Methods and Results: Utilizing an institutional database, 247 patients initiated on sotalol and 81 patients initiated on flecainide were identified. Congenital heart disease (CHD) was present in 40% of patients. Arrhythmia‐free discharge on single or dual agent therapy (in combination with other antiarrhythmics) was 87% for sotalol and 91% for flecainide. Neither age, sex, dosing, presence of CHD nor arrhythmia subtype were associated with alterations in in‐hospital efficacy. Compared to baseline, QTc intervals in sotalol patients (436 [416–452 ms] vs. 415 [400–431 ms], p <.01) and QRS intervals in flecainide patients (75 [68–88 ms] vs. 62 [56–71 ms], p <.01) were prolonged. Dose reduction or discontinuation due to QRS prolongation occurred in 9% of patients on flecainide. QTc prolongation resulting in dose reduction/discontinuation of sotalol was encountered in 9 patients (4%) and death with documented torsade de pointes in 2 patients (1%), with 9 of 11 patients having underlying CHD. Conclusion: In children requiring second line agents for treatment of SA, both sotalol and flecainide appear to be highly efficacious. Although predominantly safe in otherwise healthy patients, electrocardiogram changes can occur and children with underlying cardiac disease may have an increased risk of adverse events and rhythm‐related side effects during initiation. [ABSTRACT FROM AUTHOR]

Background: The risk of ventricular arrhythmias in patients on QT prolonging drugs is indicated to be increased early after cardioversion (CV) of atrial fibrillation (AF) to sinus rhythm (SR). Sotalol, used to prevent AF relapse, prolongs cardiac repolarization and corrected QT interval (QTc). A pronounced QTc prolongation is an established marker of pro-arrhythmias. Our objective was to use novel technique to quantify and evaluate the diurnal variation of the QTc interval after elective CV to SR in patients on sotalol or metoprolol.Methods: Fifty patients underwent twelve-lead Holter recording for 24 hr after elective CV for persistent AF. All patients had the highest tolerable stable dose of sotalol (n = 27) or metoprolol (n = 23). Measurements of QT and RR intervals were performed on all valid beats.Results: A clear diurnal variation of both HR and QTc was seen in both groups, more pronounced in patients on sotalol, where a high percentage of heartbeats with QTc >500 ms was observed, especially at night. Six patients (22%) on sotalol but none on metoprolol had >20% of all heart beats within the 24-hour recording with QTc >500 ms.Conclusion: Twenty-four-hour Holter recordings with QT-measurement immediately after CV demonstrated that one in five patients on sotalol had >20% of all heart beats with prolonged QTc >500 ms, especially during night-time. The QTc diurnal variation was retained in patients on β-blockade or a potent class III anti-arrhythmic drug with β-blocking properties. [ABSTRACT FROM AUTHOR]

A 10-year-old male American Shorthair cat was presented after a witnessed syncopal event. A Holter monitor demonstrated a long QT interval and revealed a rhythm characteristic of torsades de pointes (TdP) coincident with a bout of syncope. On subsequent Holter monitor recordings, sotalol did not prolong the QT interval further and did not reduce the severity of the underlying ventricular tachyarrhythmias, but no TdP was identified. When another syncopal event occurred, sotalol was discontinued, and oral amiodarone and magnesium were started. This resulted in improvement in the ventricular tachyarrhythmia. No syncopal events occurred in the ensuing 3 months, but the cat died of an unrelated disease shortly after. This is the first report of naturally occurring torsades de pointes in a domestic cat. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed "in silico mutagenesis" by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical formulation of the M54T MiRP1 latent mutation and simulated a provocative test. In this setting, application of dofetilide dramatically amplified the predicted QT interval duration in the M54T hMiRP1 mutation compared to wild-type.

Background: Inpatient monitoring is recommended for sotalol initiation., Objective: The purpose of this study was to assess the safety of outpatient sotalol commencement., Methods: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated., Results: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation ( P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy., Conclusion: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol., Competing Interests: Dr Emami reports that the 10.13039/501100001786University of Adelaide has received on his behalf consulting fees from 10.13039/100004374Medtronic and 10.13039/100007497Biosense Webster. Dr Sanders reports having served on the advisory board of Medtronic, Abbott Medical, Boston Scientific, PaceMate, and CathRx. Dr Sanders reports that the 10.13039/501100001786University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston Scientific, and 10.13039/100000046Abbott Medical. Dr Sanders reports that the 10.13039/501100001786University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, 10.13039/100008497Boston Scientific, and MicroPort. All other authors have no disclosures., (Crown Copyright © 2024 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD include promoting a healthy lifestyle, following United States Preventive Service Task Force recommendations related to cardiovascular disease, and controlling comorbid conditions. For a patient experiencing SCA, early cardiopulmonary resuscitation and defibrillation should be performed. Implantable cardioverter defibrillators are more effective at secondary prevention compared with drug therapy but medications such as amiodarone, beta-blockers, and sotalol may be helpful adjuncts to reduce the risk of SCD or improve a patient's symptoms (eg, palpitations and inappropriate defibrillator shocks)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this work, a commercially available, chirally pure pharmaceutical containing carboxylic group, namely, levofloxacin was utilized as chiral selector for the enantioresolution of sotalol. The TLC plates were prepared by mixing levofloxacin in silica gel slurry. The racemic mixture of sotalol was applied on TLC plates using MeCN–MeOH–H2O (5.2:2.0:0.8, V/V; pH = 5.0) as the mobile phase at 22 (± 2) °C. The separation conditions were optimized in terms of concentration of chiral selector, pH, and temperature to get successful separation. The resolution value was observed to be 2.6. The enantiomers so separated were isolated from TLC plates and characterized using various techniques. The method found to be linear with calibration equation [y = 0.79x + 0.054] and a regression coefficient (r2) value of 0.996. The limits of detection and quantification for the enantiomers were 2.3 μg/spot and 6.7 μg/spot, respectively. The recovery of the enantiomers isolated from TLC plates was in the range of 76–85%. [ABSTRACT FROM AUTHOR]

Fetal supraventricular tachycardia (SVT) and atrial flutter (AF) can be associated with significant morbidity and mortality. Digoxin is often used as first-line therapy but can be ineffective and is poorly transferred to the fetus in the presence of fetal hydrops. As an alternative to digoxin monotherapy, we have been using sotalol at presentation in fetuses with SVT or AF with, or at risk of, developing hydrops to attempt to achieve more rapid control of the arrhythmia. The present study was a retrospective review of the clinical, echocardiographic, and electrocardiographic data from all pregnancies with fetal tachycardia diagnosed and managed at a single center from 2004 to 2008. Of 29 affected pregnancies, 21 (16 SVT and 5 AF) were treated with sotalol at presentation, with or without concurrent administration of digoxin. Of the 21, 11 (6 SVT and 5 AF) had resolution of the tachycardia within 5 days (median 1). Six others showed some response (less frequent tachycardia, rate slowing, resolution of hydrops) without complete conversion. In 1 fetus with a slow response, the mother chose pregnancy termination. The 5 survivors with a slow response were all difficult to treat postnatally, including 1 requiring radiofrequency ablation as a neonate. One fetus developed blocked atrial extrasystoles after 1 dose of sotalol and was prematurely delivered for fetal bradycardia. Three grossly hydropic fetuses with SVT showed no response and died within 1 to 3 days of treatment. In conclusion, transplacental sotalol, alone or combined with digoxin, is effective for the treatment of fetal SVT and AF, with an 85% complete or partial response rate in our series.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease in children, and can lead to sudden cardiac death (SCD). Propafenone is classIC antiarrhythmic medication, and its side effects include cardiovascular compromise in the form of hypotension, bradycardia, ventricular dysrhythmias, QRS widening, and heart block. Propafenone has been reported causing QRS widening, but rarely in children. In this article, we presented a boy diagnosed with ARVC who meets diagnosis criteria based on typical symptoms, electrocardiograph (ECG), echocardiography (Echo), cardiac magnetic resonance imaging (CMRI), sudden death of first family member, and genetic mutation in desmosomal DSG2 gene. Antiarrhythmic drugs have been used for treating patients with ARVC, by eliminating or decreasing the occurring frequency of arrhythmias. As his ECG showed frequent premature ventricular contractions (PVC), he was prescribed with oral propafenone. One day after the drug treatment, he presented dizziness accompanied with significant QRS widening in ECG. His dizziness was improved when Propafenone dose was reduced, and resolved after sotalol replacement, with ECG recovered to nearly normal state of QRS. Propafenone may lead to QRS widening and increase the risk of ventricular tachycardia, and it may not reduce ARVC associated mortality. This report may serve as a precaution for clinicians when providing cares for ARVC patients.

A presente investigação teve por objetivo avaliar os efeitos do Sotalol sobre o eletrocardiograma de alta resolução (ECGAR), em uma população com arritmia ventricular idiopática. Foi estudado um grupo de 12 pacientes submetidos a um ensaio clínico do tipo duplo-cego cruzado e randomizado, para avaliaçao da eficácia da droga. Foram obtidos ECGAR em condiçoes de controle (C), uso de placebo (P) e de droga (O), confrontando os resultados entre as três situações e a eficácia medicamentosa. No vetor-magnitude foram analisados os seguintes parâmetros: voltagem média dos 40 ms terminais do complexo QRS filtrado (VM - normal > 20 µV), duração dos sinais de baixa amplitude < 40 µV no final da ativação (SBA - normal < 38 ms) e duração total do complexo QRS filtrado (OQRS - normal < 114.0 ms). Em função da resposta terapêutica, os pacientes foram divididos em responsivos (G1) e não-responsivos (G2). Não foram observadas diferenças estatisticamente significativas entre C e P. No Grupo I, composto por 5 pacientes (42% de eficácia), não foram observadas diferenças significativas nas 3 variáveis avaliadas entre as condições de P e O. No Grupo 11, composto por 7 pacientes, ocorreram modificaçoes nos SBA, cujos valores no P estavam em 24.80 ± 7.60 ms e passando com a O para 29.10 ± 14.76 ms (p < 0,01). Em 5 dos 7 pacientes deste grupo (71%), prolongaram-se no pós-droga os SBA, numa média de 11.20 ± 4.80 ms, com significância estatística em relaçao ao placebo (p < 0.04). Frente aos resultados observados com os SBA, foram obtidos sensibilidade de 71 %, especificidade de 86%, valor preditivo positivo de 83% e negativo de 75% para definir a populaçao responsiva à droga. Concluiu-se que na população estudada, o Sotalol, quando efetivo, não produziu modificações significativas nos parâmetros do ECGAR. Um incremento médio dos SBA de 11.2 ± 4.8 ms, por influência da droga, associou-se a uma ausência de resposta terapêutica.

In this investigation a visible spectrophotometric method for the determination of sotalol based on the absorbance of colored product of the reaction between sotalol hydrochloride and bromcresol purple in acetone medium at 399 nm measurement was developed. The optimal conditions for the quantitative determination of sotalol hydrochloride in the content of pharmaceutical drugs were established. The stoichiometric relationship coefficients between sotalol hydrochloride and bromcresol purple were determined. The validation of the worked out procedure on such validated characteristics as linearity, precision, accuracy and robustness was carried out. The aim. To develop a highly sensitive, easy to use, cost-effective and valid method for quantitative determination of sotalol hydrochloride in dosage forms. The analysis method. Visible spectrophotometry. The analytical parameters such as molar absorptivity, Beer’s law limits and Sandell’s sensitivity values were calculated. The developed methods give the result with repeatability sufficient for dependable determination the investigated substance in pharmaceutical formulations. Accuracy established by analyte addition technique. Determined factors that influence on the absorbance value: reagent quantity and timing stability. Sample solutions stable during 30 min. Addition to sample solution ± 10% bromcresol purple solution is not change the absorbance value. Established that reaction between sotalol hydrochloride and bromcresol purple proceeds in acetone medium at room temperature. Molar absorption coefficient is 2,62∙10^3.

Aim. To compare the efficacy of combinational therapy with added bisoprolol or sotalol, in patients with ventricular rhythm disorders (VRD) via the assessment of regulatory-adaptive status (RAS).Material and methods. Sixty VRD patients with II-III Bigger type or I-IV Lown, and with essential systemic hypertension II-III stages and/or coronary heart disease, were randomized to two groups. Group 1 received bisoprolol 6,4±1,8 mg daily, group 2 — sotalol 166,7±49,4 mg daily. As combinational therapy, all patients were taking lisinopril (12,5±4,1 mg daily and 14,0±4,6 mg daily, respectively). At baseline and in 6 months of combinational therapy, the following measures were done: quantitative assessment of RAS (by the test with cardiorespiratory synchronism), echocardiography, threadmill-test, 6-minute walking test, Holter blood pressure and electrocardiography monitoring, life quality assessment.Results. Sotalol less prominently decreases RAS than bisoprolol. Both equally improved structural and functional condition of the heart, increased exercise tolerance, showed comparable hypotensive and antiarrhythmic effects. Sotalol, comparing to bisoprolol, improved life quality more significantly.Conclusion. In VRD patients with essential systemic hypertension and/or coronary heart diease, combinational therapy with sotalol, comparing to bisoprolol, might be more preferrable due to less negative influence on RAS.

Atrial Tachycardia is one of the most refractory arrhythmias in children. To manage this arrhythmia, several strategies have been introduced with varying degrees of success. We had a case of a neonatal patient with long RP tachycardia who had different antiarrhythmic drugs to control tachycardia. Eventually, recurrent episodes of tachycardia were stopped by a combination of the Flecainide and Sotalol. [ABSTRACT FROM AUTHOR]

Background: Patients initiated on sotalol and dofetilide require inpatient monitoring and dose adjustments due to risks of corrected QT (QTc) prolongation and Torsades de pointes (TdP). Patients may receive higher initial doses than recommended due to close monitoring by specialized practitioners. The objective of this study was to describe prescribing practices of sotalol and dofetilide and to compare safety outcomes between standard and nonstandard dosing strategies.Methods: This was a single-center retrospective analysis of adult inpatients who underwent sotalol or dofetilide initiation between June 1, 2015, and August 1, 2018. The end points of this study included the percentage of patients who received standard and nonstandard dosing, incidence of QTc prolongation (≥500 milliseconds or ≥15% from baseline), incidence of TdP, and dose reduction or medication discontinuation.Results: A total of 379 patients (195 sotalol and 184 dofetilide) were included in this analysis. There were 110 (56.4%) patients in the sotalol group and 111 (58.4%) patients in the dofetilide group that received nonstandard initial dosing. Nonstandard dosing was associated with a greater incidence of QTc prolongation compared to standard dosing (57.5% vs 43.0%, P = .005). Only one patient in the nonstandard dosing group experienced TdP. Patients initiated on nonstandard dosing required dose reduction or therapy discontinuation (37.6% vs 23.4%, P = .003) more frequently.Conclusion: Higher than recommended initial doses of sotalol or dofetilide were associated with higher incidence of QTc prolongation and more frequent therapy modification. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the incidence, type, and management of supraventricular tachyarrhythmias (SVT) during the first year of life in a retrospective, population‐based, single‐center study during a 10‐year period. Methods: The analyzed patient cohort is based on data from the only specialized center managing all cases of neonatal and infant SVTs between 2009 and 2018 in the Slovak Republic (5.5 million population). A total of 116 consecutive patients <366 days old were included in the study. Results: Calculated SVT incidence ratio was 1:4500 in the first year of life. AV reentry tachycardia was the leading arrhythmia (49%). SVT in this specific population was frequently a transient problem with spontaneous resolution in 87% of patients during a median 3‐year follow up. Congenital heart disease was common (16%). Intrauterine treatment by drugs administered to mother was safe and effective in preventing unnecessary cesarean deliveries. In arrhythmia termination, amiodarone and propafenone were equally safe and effective, with possible more favorable pharmacodynamics of the former. For prophylactic treatment, sotalol and propafenone were equally safe and effective and became the preferred basis of long‐term drug therapy in our center. However, this therapy requires intensive monitoring during its initiation. Conclusion: The prognosis of SVT in the first year of life is good: with optimized pharmacological treatment, the need for early catheter ablation and mortality rate are low (<1%) and there is a high rate of spontaneous arrhythmia resolution. Heart failure is a possible predictor of arrhythmia persistence with need for ablation in later life. [ABSTRACT FROM AUTHOR]

Background: Sotalol is an important antiarrhythmic drug in the pediatric population. Given the risk of proarrhythmia, sotalol is initiated in inpatient settings, with adult studies as recent as 2015 supporting this practice.Objective: The purpose of this study was to determine the frequency of adverse events (AEs) during sotalol initiation for the management of atrial, supraventricular, or ventricular arrhythmias in pediatric patients.Methods: A retrospective cohort analysis of pediatric patients 21 years or younger initiated on oral sotalol for supraventricular tachycardia or ventricular tachycardia (VT) at Boston Children's Hospital from January 1, 2007, through July 1, 2016, was performed. The primary end point was an AE defined as significant bradycardia, new or increased ventricular arrhythmias, conduction block, or corrected QT interval (QTc) prolongation, resulting in dose reduction or cessation.Results: There were 190 patients who met inclusion criteria, with 110 patients (58%) 6 months or younger. A total of 115 patients (60%) had congenital heart disease. Arrhythmias for which sotalol was initiated included atrioventricular reciprocating tachycardia/atrioventricular nodal reciprocating tachycardia (n = 105 [55%]), atrial flutter (n = 31 [16%]), ectopic atrial tachycardia (n = 26 [14%]), VT (n = 21 [11%]), and atrial fibrillation (n = 7 [4%]). The median pre-sotalol QTc was 438 ms (interquartile range 348-530 ms). Five patients (3%) (aged 0.1-18 years) had AEs including bradycardia <40 beats/min (n = 2) and <100 beats/min (n = 1) and QTc prolongation (n = 2). All 5 patients with AEs had repaired congenital heart disease.Conclusion: The incidence of AEs in pediatric patients initiating sotalol for atrial tachycardia, supraventricular tachycardia, or VT is low (3%), with no deaths or malignant rhythms reported in this series. [ABSTRACT FROM AUTHOR]

Sustained fetal supraventricular tachycardia (SVT) complicated by hydrops fetalis carries a significant risk of morbidity and mortality. While there is no clear consensus on first- and second-line therapy options for the management of fetal SVT with or without hydrops fetalis, there exists significant nonrandomized experience with a number of antiarrhythmic agents that has founded the basis for management. Furthermore, recently published meta-analyses and ongoing multicenter prospective studies have aimed to bridge the gap in the literature. We report two cases of sustained fetal SVT with severe secondary hydrops fetalis managed successfully with flecainide-sotalol combination therapy in one case and sotalol-digoxin combination therapy in the second and review the literature for the management of fetal SVT. [ABSTRACT FROM AUTHOR]