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Heart Rhythm Nov 2023Use 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...
BACKGROUND
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.
OBJECTIVE
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
Topics: Humans; Sotalol; Atrial Fibrillation; Anti-Arrhythmia Agents; Cohort Studies; Adrenergic beta-Antagonists
PubMed: 37598987
DOI: 10.1016/j.hrthm.2023.08.019 -
Journal of Veterinary Cardiology : the... Jun 2024Studies on the use of amiodarone or sotalol are limited in dogs. Therefore, this study aimed to provide data on the efficacy and safety of these drugs in dogs with...
INTRODUCTION/OBJECTIVE
Studies on the use of amiodarone or sotalol are limited in dogs. Therefore, this study aimed to provide data on the efficacy and safety of these drugs in dogs with ventricular tachyarrhythmia (VT) and/or supraventricular tachyarrhythmia (SvT).
ANIMALS, MATERIALS, AND METHODS
Dogs with VT and/or SvT treated with amiodarone or sotalol as a first-line therapy were retrospectively evaluated. Signalment, clinical, diagnostic, therapeutic, and outcome data were retrieved. For VT, efficacy was demonstrated through a decrease of the Lown-Wolf grade to less than five or a reduction of at least 85% in the number of ventricular premature complexes observed on Holter monitoring. For SvT, efficacy was represented by cardioversion or a reduction in the mean heart rate on Holter monitoring ≤140 beats/min. Treatment-related side effects (TRSEs) were classified as clinically relevant and irrelevant. Statistical analysis was performed to compare data before and after antiarrhythmic prescription.
RESULTS
Sixty-four dogs were included. Amiodarone and sotalol were efficacious in treating both VT (85.7% and 90.0% of cases, respectively) and SvT (75% and 71.4% of cases, respectively). No significant differences were found when comparing their efficacy rates in dogs with VT and SvT (P=0.531 and 0.483, respectively). Clinically relevant TRSEs were rare with both amiodarone and sotalol (8.3% and 5% of cases, respectively), while clinically irrelevant TRSEs occurred more frequently with amiodarone (29.2%) than with sotalol (10%).
DISCUSSION
In dogs with tachyarrhythmias, amiodarone and sotalol are generally efficacious and safe, as clinically relevant TRSEs seem rare.
CONCLUSIONS
This study provides novel data on the effects of amiodarone and sotalol in dogs with tachyarrhythmias.
Topics: Animals; Dogs; Sotalol; Amiodarone; Anti-Arrhythmia Agents; Dog Diseases; Retrospective Studies; Male; Female; Treatment Outcome; Tachycardia, Ventricular; Tachycardia, Supraventricular
PubMed: 38608438
DOI: 10.1016/j.jvc.2024.03.002 -
Journal of Veterinary Cardiology : the... Feb 2024The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats.
INTRODUCTION/OBJECTIVES
The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats.
ANIMALS
Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max).
RESULTS
Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (C) and time to C were 0.94 μg/mL (0.45-1.17 μg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91-2.48 μg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose.
CONCLUSIONS
Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.
Topics: Cats; Animals; Sotalol; Cross-Over Studies; Infusions, Intravenous; Chromatography, High Pressure Liquid; Biological Availability; Administration, Oral; Half-Life
PubMed: 38118234
DOI: 10.1016/j.jvc.2023.11.015 -
Journal of Cardiovascular... Mar 2024Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia that are encountered in the clinical practice. Recent data suggests that high PVC... (Review)
Review
INTRODUCTION
Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia that are encountered in the clinical practice. Recent data suggests that high PVC burden may lead to the development of PVC-induced cardiomyopathy (PVC-CM) even in patients without structural heart disease. Treatment for effective suppression of PVCs, can reverse PVC-CM. Both antiarrhythmic drugs (AADs) and catheter ablation (CA) are recognized treatment modalities for any cardiac arrhythmias. However, with increasing preference of CA, the role of AADs needs further defining regarding their efficacy, safety, indications and patient selection to treat PVC-CM.
METHODS
To ascertain the role of AADs to treat PVC-CM; whether they are indicated to treat PVC-CM, and if so, when, we interrogated PubMed and other search engines for English language publications with key words premature ventricular complexes (PVCs), cardiomyopathy, anti-arrhythmic drugs, catheter ablation, and pharmacological agents. All publications were carefully reviewed and scrutinized by the authors for their inclusion in the review paper. For illustration of cases, ethical standard was observed as per the 1975 Declaration of Helsinki, and the patient was treated as per the prevailing standard of care. Informed consent was obtained from the patient for conducting the ablation procedure.
RESULTS
Our literature search specifically the pharmacological treatment of PVC-CM with AADs revealed significant paradigm shift in treatment approach for PVCs and PVC-induced cardiomyopathy. No major large, randomized control trials of AADs versus CA for PVC-CM were found. We found that beta-blockers and calcium channel blockers are particularly effective in the treatment of PVCs originating from right ventricular outflow tract. For Class Ic AADs - flecainide and propafenone, small clinical studies showed Class Ic AADs to be effective in PVC suppression, but their usage was not recommended in patients with significant coronary artery disease. Mexiletine was found to have modest effect on PVC suppression. Studies showed sotalol to significantly reduce PVCs frequency in patients receiving both low and high doses. Studies also showed amiodarone to have higher successful PVC suppression, but not recommended as a first-line treatment for patients with idiopathic PVCs in the absence of symptoms and left ventricular dysfunction. For dronedarone, no major clinical data were available.
CONCLUSIONS
Based on the available data in the literature, we conclude that AADs play important role in the treatment of PVC-induced cardiomyopathy. However, appropriate patient selection criteria are vitally important, and in general terms AADs are indicated or polymorphic PVCs, epicardial PVCs; and when CA procedure is contraindicated, or not feasible or failed.
Topics: Humans; Anti-Arrhythmia Agents; Ventricular Premature Complexes; Stroke Volume; Ventricular Dysfunction, Left; Cardiomyopathies; Catheter Ablation
PubMed: 37676022
DOI: 10.1111/jce.16055 -
Europace : European Pacing,... Feb 2024Although guidelines for the management of atrial fibrillation (AF) are regularly published, many controversial issues remain, limiting their implementation. We aim to...
Current management of atrial fibrillation in routine practice according to the last ESC guidelines: an EHRA physician survey-how are we dealing with controversial approaches?
AIMS
Although guidelines for the management of atrial fibrillation (AF) are regularly published, many controversial issues remain, limiting their implementation. We aim to describe current clinical practice among European Heart Rhythm Association (EHRA) community according to last guidelines.
METHODS AND RESULTS
A 30 multiple-choice questionnaire covering the most controversial topics related to AF management was distributed through the EHRA Research Network, National Societies, and social media between January and February 2023. One hundred and eighty-one physicians responded the survey, 61% from university hospitals. Atrial fibrillation screening in high-risk patients is regularly performed by 57%. Only 42% has access to at least one programme aiming at diagnosing/managing comorbidities and lifestyle modifications, with marked heterogeneity between countries. Direct oral anticoagulants are the preferred antithrombotic (97%). Rhythm control is the preferred strategy in most AF phenotypes: symptomatic vs. asymptomatic paroxysmal AF (97% vs. 77%), low vs. high risk for recurrence persistent AF (90% vs. 72%), and permanent AF (20%). I-C drugs and amiodarone are preferred while dronedarone and sotalol barely used. Ablation is the first-line therapy for symptomatic paroxysmal AF (69%) and persistent AF with markers of atrial disease (57%) and is performed independently of symptoms by 15%. In persistent AF, 68% performs only pulmonary vein isolation and 32% also additional lesions.
CONCLUSION
There is marked heterogeneity in AF management and limited accordance to last guidelines in the EHRA community. Most of the discrepancies are related to the main controversial issues, such as those related to AF screening, management of comorbidities, pharmacological treatment, and ablation strategy.
Topics: Humans; Atrial Fibrillation; Comorbidity; Surveys and Questionnaires; Sotalol; Anticoagulants; Treatment Outcome
PubMed: 38227804
DOI: 10.1093/europace/euae012 -
Association of sotalol versus atenolol therapy with survival in dogs with severe subaortic stenosis.Journal of Veterinary Cardiology : the... Aug 2023Dogs with severe subaortic stenosis (SAS) are at risk of dying suddenly from fatal arrhythmias. Survival is not improved when treated with pure beta-adrenergic receptor...
INTRODUCTION/OBJECTIVES
Dogs with severe subaortic stenosis (SAS) are at risk of dying suddenly from fatal arrhythmias. Survival is not improved when treated with pure beta-adrenergic receptor (β)-blockers; however, the effect of other antiarrhythmic drugs on survival is unknown. Sotalol is both a β-blocker and a class III antiarrhythmic drug; the combination of these differing mechanisms may provide benefit to dogs with severe SAS. The primary objective of this study was to compare survival in dogs with severe SAS that were treated with either sotalol or atenolol. The secondary objective was to evaluate the effect of pressure gradient (PG), age, breed, and aortic regurgitation on survival.
ANIMALS
Forty-three client-owned dogs.
MATERIALS AND METHODS
Retrospective cohort study. Medical records of dogs diagnosed with severe SAS (PG ≥ 80 mmHg) between 2003 and 2020 were reviewed.
RESULTS
No statistical difference was identified in survival time between dogs treated with sotalol (n=14) and those treated with atenolol (n=29) when evaluating all-cause mortality (p=0.172) or cardiac-related mortality (p=0.157). Of the dogs that died suddenly, survival time was significantly shorter in dogs treated with sotalol compared to those treated with atenolol (p=0.046). Multivariable analysis showed that PG (p=0.002) and treatment with sotalol (p=0.050) negatively influenced survival in the dogs that died suddenly.
CONCLUSIONS
Sotalol did not have a significant effect on survival overall but may increase the risk of sudden death in dogs with severe SAS compared to atenolol.
Topics: Dogs; Animals; Sotalol; Atenolol; Constriction, Pathologic; Retrospective Studies; Anti-Arrhythmia Agents; Adrenergic beta-Antagonists; Aortic Stenosis, Subvalvular; Dog Diseases
PubMed: 37307692
DOI: 10.1016/j.jvc.2023.05.003 -
Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.Journal of Interventional Cardiac... May 2024The 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...
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.
PubMed: 38761294
DOI: 10.1007/s10840-024-01829-4 -
The American Journal of Cardiology Oct 2023This chapter discusses the American College of Cardiology/American Heart Association/ Heart Rhythm Society (AHA/ACC/HRS) and European Society of Cardiology (ESC)...
This chapter discusses the American College of Cardiology/American Heart Association/ Heart Rhythm Society (AHA/ACC/HRS) and European Society of Cardiology (ESC) guidelines for atrial fibrillation (AF) management with particular focus on antiarrhythmic drug (AAD) selection and the identification of individuals for whom AAD treatment is appropriate. Discussion includes AAD indications, when to start an AAD, choosing among AADs, how to minimize proarrhythmic risk, how to determine efficacy, and the use of adjuvant interventions. The indications for all AADs are based on safety; the current AHA/ACC/HRS and ESC guidelines state that the choice of AAD is based on the presence or absence of structural heart disease (SHD), coronary artery disease, or heart failure (HF), with further recommendations in the ESC guidelines based on HF type (e.g., HF with reduced ejection fraction [HFrEF] versus HF with preserved ejection fraction [HFpEF]). The chapter closes with a discussion of the lack of consistent use of guideline-directed care, with a review of supportive data from the recently reported AIM-AF survey-a multinational survey on AF management that involved both cardiologists and electrophysiologists. In AIM-AF, inappropriate drug selection in terms of suitable candidate selection and drug choice occurred with all types of drugs and in most patient groups. Most notable was the overuse of amiodarone in patients without SHD, and the widespread use of sotalol, including its use in patients with HFrEF. Chapter 5 is summarized as follows.
Topics: Humans; Anti-Arrhythmia Agents; Atrial Fibrillation; Heart Failure; Sotalol; Stroke Volume; United States
PubMed: 37777295
DOI: 10.1016/j.amjcard.2023.08.029 -
Circulation Apr 2024Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily...
BACKGROUND
Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (I) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We aimed to investigate the dynamics of hERG channels in response to sotalol and to identify regulators of the susceptibility to developing diLQT.
METHODS
We measured electrophysiological activity and cellular distribution of hERG channels after hERG blocker treatment in iPS-CMs derived from patients with highest sensitivity (HS) or lowest sensitivity (LS) to sotalol administration in vivo (ie, on the basis of the measure of the maximal change in QT interval 3 hours after administration). Specific small interfering RNAs and CAVIN1-T2A-GFP adenovirus were used to manipulate expression.
RESULTS
Whereas HS and LS iPS-CMs showed similar electrophysiological characteristics at baseline, the late repolarization phase was prolonged and I significantly decreased after exposure of HS iPS-CMs to low sotalol concentrations. I reduction was caused by a rapid translocation of hERG channel from the membrane to the cytoskeleton-associated fractions upon sotalol application. , essential for caveolae biogenesis, was 2× more highly expressed in HS iPS-CMs, and its knockdown by small interfering RNA reduced their sensitivity to sotalol. overexpression in LS iPS-CMs using adenovirus showed reciprocal effects. We found that treatment with sotalol promoted translocation of the hERG channel from the plasma membrane to the cytoskeleton fractions in a process dependent on CAVIN1 (caveolae associated protein 1) expression. silencing reduced the number of caveolae at the membrane and abrogated the translocation of hERG channel in sotalol-treated HS iPS-CMs. CAVIN1 also controlled cardiomyocyte responses to other hERG blockers, such as E4031, vandetanib, and clarithromycin.
CONCLUSIONS
Our study identifies unbridled turnover of the potassium channel hERG as a mechanism supporting the interindividual susceptibility underlying diLQT development and demonstrates how this phenomenon is finely tuned by CAVIN1.
PubMed: 38682330
DOI: 10.1161/CIRCULATIONAHA.123.063917 -
Biomedicine & Pharmacotherapy =... May 2024Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III... (Review)
Review
Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (I). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through I blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.
Topics: Amiodarone; Humans; Anti-Arrhythmia Agents; Animals; Action Potentials; Ion Channels; Myocardium; Electrophysiological Phenomena; Long QT Syndrome
PubMed: 38565056
DOI: 10.1016/j.biopha.2024.116513