-
Journal of the American Heart... May 2022
PubMed: 35243871
DOI: 10.1161/JAHA.120.020803 -
Frontiers in Pharmacology 2021The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially...
Sotalol Treatment may Interfere With Retrieval, Expression, and/or Reconsolidation Processes Thus Disrupting Traumatic Memories in a Post-Traumatic Stress Disorder Mice Model.
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 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 mRNA expression in the hippocampal formation may be crucial for these mice to develop diminished traumatic contextual memories after sotalol therapy in PTSD.
PubMed: 35173611
DOI: 10.3389/fphar.2021.809271 -
Journal of Clinical Medicine Feb 2022Sustained fetal tachycardias are rare but represent a high risk of mortality and morbidity. Consensus has yet to be found regarding their optimal management. The aim of... (Review)
Review
Sustained fetal tachycardias are rare but represent a high risk of mortality and morbidity. Consensus has yet to be found regarding their optimal management. The aim of this narrative review is to summarize the data available in the current literature regarding the efficacy and safety of medications used in the management of intrauterine tachyarrhythmias and to provide possible treatment protocols. In this review, we would like to emphasize the importance of a thorough evaluation of both the fetus and the mother, prior to transplacental antiarrhythmic drug initiation. Factors such as the hemodynamic status of the fetus, possible mechanisms of fetal arrhythmia, and concomitant maternal conditions are of primordial importance. As a possible treatment protocol, we would like to recommend the following: due to the risk of sustained supraventricular tachycardia (SVT), fetuses with frequent premature atrial beats should be evaluated more frequently by echocardiography. A careful hemodynamic evaluation of a fetus with tachycardia is primordial in forestalling the appearance of hydrops. In the case of atrial flutter (AFL), sotalol therapy could represent a first choice, whereas when dealing with SVT patients, flecainide should be considered, especially for hydropic patients. These data require consolidation through larger scale, non-randomized studies and should be handled with caution.
PubMed: 35160256
DOI: 10.3390/jcm11030804 -
Frontiers in Neuroscience 2021Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8-17% of patients with epilepsy. Although the mechanisms of SUDEP are unknown, one proposed...
Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8-17% of patients with epilepsy. Although the mechanisms of SUDEP are unknown, one proposed mechanism is abnormal control of the heart by the autonomic nervous system (ANS). Our objective was to determine whether the broad changes in ictal heart rate experienced by mouse models of SUDEP are (1) due to the ANS and (2) contribute to seizure-induced death. Seizures were induced by electrical stimulation of the hippocampus of a mouse carrying the human encephalopathy mutation p.Asn1768Asp (N1768D; "D/+ mice"). Using standard autonomic pharmacology, the relative roles of the parasympathetic and sympathetic nervous systems on heart rate changes associated with seizures were determined. All induced seizures had pronounced ictal bradycardia and postictal tachycardia. Seizure susceptibility or severity were unchanged by the pharmacological agents. Administration of Atropine, a muscarinic antagonist, eliminated ictal bradycardia, while carbachol, a muscarinic agonist, had no effect on ictal bradycardia, but reduced postictal tachycardia. Sotalol, an adrenergic β-receptor antagonist, had no effect on ictal bradycardia, but did suppress postictal tachycardia. Isoproterenol, a β-receptor agonist, had no effect on either ictal bradycardia or postictal tachycardia. Administration of the α1-receptor antagonist prazosin increases the incidence of seizure-induced death in D/+ mice. Although postictal heart rate was lower for these fatal seizures in the presence of prazosin, rates were not as low as that recorded for carbachol treated mice, which all survived. Both ictal bradycardia and postictal tachycardia are manifestations of the ANS. Bradycardia is mediated by a maximal activation of the parasympathetic arm of the ANS, and tachycardia is mediated by parasympathetic inactivation and sympathetic activation. While the changes in heart rate during seizures are profound, suppression of postictal heart rate did not increase seizure mortality.
PubMed: 35126041
DOI: 10.3389/fnins.2021.795145 -
Journal of the American Heart... Feb 2022Background Atrial tachyarrhythmias are common after atrial fibrillation ablation, so adjunctive antiarrhythmic drug therapy is often used. Data on the effectiveness and...
Background Atrial tachyarrhythmias are common after atrial fibrillation ablation, so adjunctive antiarrhythmic drug therapy is often used. Data on the effectiveness and safety of dronedarone and sotalol after AF ablation are limited. Here, we compared health outcomes of ablated patients treated with dronedarone versus sotalol. Methods and Results A comparative analysis of propensity score-matched retrospective cohorts was performed using IBM MarketScan Research Databases. Patients treated with dronedarone after atrial fibrillation ablation were matched 1:1 to patients treated with sotalol between January 1, 2013 and March 31, 2018. Outcomes of interest included cardiovascular hospitalization, proarrhythmia, repeat ablation, and cardioversion. This study was exempt from institutional review board review. Among 30 696 patients who underwent atrial fibrillation ablation, 2086 were treated with dronedarone and 3665 with sotalol after ablation. Propensity-score matching resulted in 1815 patients receiving dronedarone matched 1:1 to patients receiving sotalol. Risk of cardiovascular hospitalization was lower with dronedarone versus sotalol at 3 months (adjusted hazard ratio [aHR], 0.77 [95% CI, 0.61-0.97]), 6 months (aHR, 0.76 [95% CI, 0.63-0.93]), and 12 months after ablation (aHR, 0.70 [95% CI, 0.66-0.93]). Risk of repeat ablation and cardioversion generally did not differ between the 2 groups. A lower risk of proarrhythmia was associated with dronedarone versus sotalol at 3 months (aHR, 0.76 [95% CI, 0.64-0.90]), 6 months (aHR, 0.80 [95% CI, 0.70-0.93]), and 12 months (aHR, 0.83 [95% CI, 0.73-0.94]) after ablation. Conclusions These data suggest that dronedarone may be a more effective and safer alternative after ablation than sotalol.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Dronedarone; Humans; Retrospective Studies; Sotalol
PubMed: 35060388
DOI: 10.1161/JAHA.120.020506 -
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 -
The Journal of Veterinary Medical... Mar 2022Although Toxoplasma gondii represents an oft-cited cause of myocarditis in veterinary medicine, the existing literature on the pre-mortem demonstration of T....
Although Toxoplasma gondii represents an oft-cited cause of myocarditis in veterinary medicine, the existing literature on the pre-mortem demonstration of T. gondii-associated myocardial injury (MI) in dogs is scant. In this case series, we provide detailed clinical, laboratory, echocardiographic and electrocardiographic description of three T. gondii-positive dogs diagnosed with MI. In all cases, etiological diagnosis was based on the antibody screening test (all dogs had IgM titres ≥1:64) and MI was demonstrated by a concomitant increase of the serum concentration of cardiac troponin I (0.25-9.6 ng/ml, upper hospital limit <0.15 ng/ml). In all dogs, MI was aggravated by complex arrhythmias (ventricular in two dogs, and either ventricular and supraventricular in the remaining dog). In one case, left ventricular systolic dysfunction was also present. All dogs underwent an extensive diagnostic work-up aimed at excluding additional comorbidities, either cardiac and extra-cardiac, possibly able to contribute to MI, arrhythmias and systolic dysfunction. All dogs received appropriate antiprotozoal (i.e., clindamycin) and antiarrhythmic (i.e., amiodarone, sotalol) therapy. This was systematically followed by a simultaneous decline in T. gondii serology titres, normalisation of troponin level and left ventricular systolic function, and the resolution of clinical and electrocardiographic abnormalities. In light of this result, therapies were interrupted and subsequent controls ruled out any disease relapse. In these cases, the clinical and instrumental findings obtained at admission and rechecks strongly supported the clinical suspicion of toxoplasmic myocarditis.
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dog Diseases; Dogs; Echocardiography; Electrocardiography; Toxoplasma
PubMed: 34955461
DOI: 10.1292/jvms.21-0571 -
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 -
British Journal of Clinical Pharmacology Jul 2022The extent of sotalol-induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the...
The extent of sotalol-induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the extent of drug-induced QTc prolongation remains unclear. This was studied around peak plasma concentration in a large cohort of 376 healthy male and 614 healthy female subjects who received 80 mg of sotalol orally. Baseline QTc was 379 ± 16 ms in men and 393 ± 15 ms in women (P < .0001). The change in QTc from baseline was highly variable among both sexes and was greater in women than in men (26.5 ± 13.2 vs.13.0 ± 10.8 ms; P < .0001). The slope of the regression line between QTc on sotalol and baseline QTc did not significantly differ from unity in men and in women, indicating that the extent of QTc prolongation with sotalol was not influenced by baseline QTc. Assessing QTc after administration of an I blocker may be more important than measuring a baseline QTc.
Topics: Anti-Arrhythmia Agents; Cohort Studies; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Sotalol
PubMed: 34921433
DOI: 10.1111/bcp.15188 -
International Journal of Environmental... Dec 2021The clinical course of COVID in the pediatric population is considered to be much milder when compared to adults; however, the occurrence of severe and fatal forms of...
The clinical course of COVID in the pediatric population is considered to be much milder when compared to adults; however, the occurrence of severe and fatal forms of the disease in children is non-negligible, especially in patients with comorbidities such as prematurity or cardiac disease. We report a case of a newborn with sotalol-controlled fetal ventricular tachycardia, who was postnatally diagnosed with COVID infection. The myocardial injury was sustained on the basis of pericardial effusion, left ventricular dysfunction, rapid progression to coronary artery dilation, and an arrhythmic storm. We believe that, in our case, there is a significant overlap between fetal ventricular tachycardia, associated with impaired left ventricular function, and COVID infection, diagnosed after birth; both factors contribute to the myocardial dysfunction with a fulminant clinical evolution. To our knowledge, this is the first case describing neonatal myocardial dysfunction associated with SARS-CoV infection complicating the clinical course of rare fetal tachyarrhythmia.
Topics: COVID-19; Child; Humans; Infant, Newborn; Myocarditis; Pericardial Effusion; SARS-CoV-2; Tachycardia, Ventricular
PubMed: 34886523
DOI: 10.3390/ijerph182312796