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JACC. Clinical Electrophysiology Jan 2022Increasing maternal mortality and incidence of arrhythmias in pregnancy have been noted over the past 2 decades in the United States. Pregnancy is associated with a... (Review)
Review
Increasing maternal mortality and incidence of arrhythmias in pregnancy have been noted over the past 2 decades in the United States. Pregnancy is associated with a greater risk of arrhythmias, and patients with a history of arrhythmias are at significant risk of arrhythmia recurrence during pregnancy. The incidence of atrial fibrillation in pregnancy is rising. This review discusses the management of tachyarrhythmias and bradyarrhythmias in pregnancy, including management of cardiac arrest. Management of fetal arrhythmias are also reviewed. For patients without structural heart disease, β-blocker therapy, especially propranolol and metoprolol, and antiarrhythmic drugs, such as flecainide and sotalol, can be safely used to treat tachyarrhythmias. As a last resort, catheter ablation with minimal fluoroscopy can be performed. Device implantation can be safely performed with minimal fluoroscopy and under echocardiographic or ultrasound guidance in patients with clear indications for devices during pregnancy. Because of rising maternal mortality in the United States, which is partly driven by increasing maternal age and comorbidities, a multidisciplinary and/or integrative approach to arrhythmia management from the prepartum to the postpartum period is needed.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Female; Flecainide; Humans; Pregnancy; Sotalol; Tachycardia
PubMed: 35057977
DOI: 10.1016/j.jacep.2021.10.004 -
Basic & Clinical Pharmacology &... Aug 2019Beta-blocker overdose is potentially harmful due to the strong blood pressure-lowering and heart rate-lowering effects. However, conflicting data exist as to their...
Beta-blocker overdose is potentially harmful due to the strong blood pressure-lowering and heart rate-lowering effects. However, conflicting data exist as to their differential toxicity, single-substance exposures and the effect of co-exposure with additional antihypertensive medication. For this, a 10-year retrospective, explorative analysis of the Mainz Poison Center/Germany database with regard to circumstances of beta-blocker exposure, doses, symptoms and treatment was carried out. Analyses were restricted to adult patients with single-substance exposures and co-exposures with one additional antihypertensive substance. Written follow-up information was obtained in half the cases. A total of 2967 cases were analysed, of which 697 were single-substance exposures. Metoprolol was most frequently reported followed by bisoprolol, atenolol, propranolol and sotalol. Metoprolol showed a linear dose-symptom relationship, whereas propranolol and sotalol seemed to have a threshold dose beyond which symptoms aggravated. Symptoms did not differ substantially, except for more seizures being reported with propranolol, and more CNS depression/vomiting with sotalol. Activated charcoal was used in 38%, gastric lavage in 11%, temporary pacemaker in 3%, glucagon in 1%, intubation for respiratory insufficiency and cardiopulmonary resuscitation in 1% and 0.5%. All patients recovered. In 174 co-exposure cases, the distribution of poisoning severity and rate of worsening of symptoms was comparable with single-substance exposures except one patient deceased after bisoprolol and verapamil co-exposure. In adults with beta-blocker overdose, no significant differences in poisoning severity among beta-blockers were detected, and no fatalities were observed with single-substance exposures. Co-exposures with other antihypertensives, sedatives or alcohol should be carefully attended to as fatalities might occur.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Charcoal; Dose-Response Relationship, Drug; Drug Overdose; Female; Gastric Lavage; Germany; Humans; Male; Middle Aged; Poison Control Centers; Retrospective Studies; Severity of Illness Index; Treatment Outcome
PubMed: 30916882
DOI: 10.1111/bcpt.13231 -
The Cochrane Database of Systematic... Sep 2019Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation often recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been...
BACKGROUND
Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation often recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been widely used to prevent recurrence. This is an update of a review previously published in 2006, 2012 and 2015.
OBJECTIVES
To determine the effects of long-term treatment with antiarrhythmic drugs on death, stroke, drug adverse effects and recurrence of atrial fibrillation in people who had recovered sinus rhythm after having atrial fibrillation.
SEARCH METHODS
We updated the searches of CENTRAL, MEDLINE and Embase in January 2019, and ClinicalTrials.gov and WHO ICTRP in February 2019. We checked the reference lists of retrieved articles, recent reviews and meta-analyses.
SELECTION CRITERIA
Two authors independently selected randomised controlled trials (RCTs) comparing any antiarrhythmic drug with a control (no treatment, placebo, drugs for rate control) or with another antiarrhythmic drug in adults who had atrial fibrillation and in whom sinus rhythm was restored, spontaneously or by any intervention. We excluded postoperative atrial fibrillation.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed quality and extracted data. We pooled studies, if appropriate, using Mantel-Haenszel risk ratios (RR), with 95% confidence intervals (CI). All results were calculated at one year of follow-up or the nearest time point.
MAIN RESULTS
This update included one new study (100 participants) and excluded one previously included study because of double publication. Finally, we included 59 RCTs comprising 20,981 participants studying quinidine, disopyramide, propafenone, flecainide, metoprolol, amiodarone, dofetilide, dronedarone and sotalol. Overall, mean follow-up was 10.2 months.All-cause mortalityHigh-certainty evidence from five RCTs indicated that treatment with sotalol was associated with a higher all-cause mortality rate compared with placebo or no treatment (RR 2.23, 95% CI 1.03 to 4.81; participants = 1882). The number need to treat for an additional harmful outcome (NNTH) for sotalol was 102 participants treated for one year to have one additional death. Low-certainty evidence from six RCTs suggested that risk of mortality may be higher in people taking quinidine (RR 2.01, 95% CI 0.84 to 4.77; participants = 1646). Moderate-certainty evidence showed increased RR for mortality but with very wide CIs for metoprolol (RR 2.02, 95% CI 0.37 to 11.05, 2 RCTs, participants = 562) and amiodarone (RR 1.66, 95% CI 0.55 to 4.99, 2 RCTs, participants = 444), compared with placebo.We found little or no difference in mortality with dofetilide (RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence) or dronedarone (RR 0.86, 95% CI 0.68 to 1.09; high-certainty evidence) compared to placebo/no treatment. There were few data on mortality for disopyramide, flecainide and propafenone, making impossible a reliable estimation for those drugs.Withdrawals due to adverse eventsAll analysed drugs increased withdrawals due to adverse effects compared to placebo or no treatment (quinidine: RR 1.56, 95% CI 0.87 to 2.78; disopyramide: RR 3.68, 95% CI 0.95 to 14.24; propafenone: RR 1.62, 95% CI 1.07 to 2.46; flecainide: RR 15.41, 95% CI 0.91 to 260.19; metoprolol: RR 3.47, 95% CI 1.48 to 8.15; amiodarone: RR 6.70, 95% CI 1.91 to 23.45; dofetilide: RR 1.77, 95% CI 0.75 to 4.18; dronedarone: RR 1.58, 95% CI 1.34 to 1.85; sotalol: RR 1.95, 95% CI 1.23 to 3.11). Certainty of the evidence for this outcome was low for disopyramide, amiodarone, dofetilide and flecainide; moderate to high for the remaining drugs.ProarrhythmiaVirtually all studied antiarrhythmics showed increased proarrhythmic effects (counting both tachyarrhythmias and bradyarrhythmias attributable to treatment) (quinidine: RR 2.05, 95% CI 0.95 to 4.41; disopyramide: no data; flecainide: RR 4.80, 95% CI 1.30 to 17.77; metoprolol: RR 18.14, 95% CI 2.42 to 135.66; amiodarone: RR 2.22, 95% CI 0.71 to 6.96; dofetilide: RR 5.50, 95% CI 1.33 to 22.76; dronedarone: RR 1.95, 95% CI 0.77 to 4.98; sotalol: RR 3.55, 95% CI 2.16 to 5.83); with the exception of propafenone (RR 1.32, 95% CI 0.39 to 4.47) for which the certainty of evidence was very low and we were uncertain about the effect. Certainty of the evidence for this outcome for the other drugs was moderate to high.StrokeEleven studies reported stroke outcomes with quinidine, disopyramide, flecainide, amiodarone, dronedarone and sotalol. High-certainty evidence from two RCTs suggested that dronedarone may be associated with reduced risk of stroke (RR 0.66, 95% CI 0.47 to 0.95; participants = 5872). This result is attributed to one study dominating the meta-analysis and has yet to be reproduced in other studies. There was no apparent effect on stroke rates with the other antiarrhythmics.Recurrence of atrial fibrillationModerate- to high-certainty evidence, with the exception of disopyramide which was low-certainty evidence, showed that all analysed drugs, including metoprolol, reduced recurrence of atrial fibrillation (quinidine: RR 0.83, 95% CI 0.78 to 0.88; disopyramide: RR 0.77, 95% CI 0.59 to 1.01; propafenone: RR 0.67, 95% CI 0.61 to 0.74; flecainide: RR 0.65, 95% CI 0.55 to 0.77; metoprolol: RR 0.83 95% CI 0.68 to 1.02; amiodarone: RR 0.52, 95% CI 0.46 to 0.58; dofetilide: RR 0.72, 95% CI 0.61 to 0.85; dronedarone: RR 0.85, 95% CI 0.80 to 0.91; sotalol: RR 0.83, 95% CI 0.80 to 0.87). Despite this reduction, atrial fibrillation still recurred in 43% to 67% of people treated with antiarrhythmics.
AUTHORS' CONCLUSIONS
There is high-certainty evidence of increased mortality associated with sotalol treatment, and low-certainty evidence suggesting increased mortality with quinidine, when used for maintaining sinus rhythm in people with atrial fibrillation. We found few data on mortality in people taking disopyramide, flecainide and propafenone, so it was not possible to make a reliable estimation of the mortality risk for these drugs. However, we did find moderate-certainty evidence of marked increases in proarrhythmia and adverse effects with flecainide.Overall, there is evidence showing that antiarrhythmic drugs increase adverse events, increase proarrhythmic events and some antiarrhythmics may increase mortality. Conversely, although they reduce recurrences of atrial fibrillation, there is no evidence of any benefit on other clinical outcomes, compared with placebo or no treatment.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 31483500
DOI: 10.1002/14651858.CD005049.pub5 -
Journal of the American Heart... May 2022Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease,...
Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.
Topics: Arrhythmias, Cardiac; Child; Heart Defects, Congenital; Humans; Infant; Registries; Sotalol; Tachycardia, Supraventricular
PubMed: 35491986
DOI: 10.1161/JAHA.121.024375 -
Communications Medicine Jul 2023Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic...
BACKGROUND
Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.
METHODS
This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan-Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.
RESULTS
Here we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994-4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.
CONCLUSIONS
DOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.
PubMed: 37468544
DOI: 10.1038/s43856-023-00315-8 -
Economics and outcomes of sotalol in-patient dosing approaches in patients with atrial fibrillation.Journal of Cardiovascular... Mar 2022There exists variability in the administration of in-patient sotalol therapy for symptomatic atrial fibrillation (AF). The impact of this variability on patient...
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.
Topics: Aftercare; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Male; Medicare; Middle Aged; Patient Discharge; Sotalol; United States
PubMed: 34953091
DOI: 10.1111/jce.15342 -
Environmental Toxicology and Chemistry Nov 2022The (bio)availability of pharmaceuticals at solid/water interfaces is governed by their sorption, which determines their concentrations in groundwaters and surface...
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 Cu , 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.
Topics: Soil; Adsorption; Copper; Trace Elements; Propranolol; Sotalol; Coordination Complexes; Adrenergic beta-Antagonists; Water Pollutants, Chemical; Water; Pharmaceutical Preparations
PubMed: 35899978
DOI: 10.1002/etc.5448