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Bulletin of Experimental Biology and... Jul 2024We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence...
We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 μg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.
PubMed: 38954299
DOI: 10.1007/s10517-024-06131-x -
Journal of the American Heart... Oct 2023
PubMed: 37815124
DOI: 10.1161/JAHA.120.027739 -
The Australian Journal of Rural Health May 2024Direct current cardioversion (DCCV) remains one of the recommended management strategies for symptomatic atrial fibrillation (AF). Antiarrhythmic drugs (AAD) are...
INTRODUCTION
Direct current cardioversion (DCCV) remains one of the recommended management strategies for symptomatic atrial fibrillation (AF). Antiarrhythmic drugs (AAD) are prescribed post procedure to maintain sinus rhythm (SR). Limited literature exists on the AAD prescribing practices and their efficacy, post-DCCV in rural Australia.
OBJECTIVE
The primary aim was to determine the preferred AAD post-DCCV and the factors affecting AAD prescribing practices. The secondary aim was to assess the efficacy of the AAD in maintaining SR.
DESIGN
A retrospective observational audit of patients with non-valvular AF who underwent successful elective DCCV for symptomatic AF, during 2015-2020 at a regional hospital in New South Wales (NSW) (Dubbo Base Hospital). Patients were followed up for a duration of 12 months post-DCCV.
RESULTS
233 patients underwent successful DCCV during the study duration. Amiodarone was the preferred AAD of choice post-DCCV followed by sotalol and flecainide, respectively (36.5% vs. 27.8% vs. 1.3%). 35.2% patients were not prescribed AAD. Amiodarone and sotalol had similar but modest efficacies and neither were superior to no AAD, in maintaining SR 12 months post-DCCV (AF recurrence rate 61.5% vs. 68.2% vs. 71.6% respectively, p = 0.37). Antecedent cerebrovascular accident (CVA), pulmonary disease, smoking, prior treatment with digoxin, diuretics and left ventricular (LV) dysfunction were factors that influenced AAD prescribing practices.
CONCLUSION
The study demonstrates equal efficacies of amiodarone, sotalol and no AAD in maintaining SR 12 months post-DCCV. Prescribing practices post-DCCV at Dubbo Base Hospital differ from observed national trends and guidelines. AAD prescription requires a multifaceted approach with a key consideration to prioritise safety over efficacy, being mindful of challenges in delivering optimal healthcare in a rural setting.
PubMed: 38766693
DOI: 10.1111/ajr.13138 -
Netherlands Heart Journal : Monthly... Apr 2024Postoperative atrial fibrillation (POAF) is a common phenomenon following cardiac surgery. In this study, we assessed current preventive strategies used by Dutch...
INTRODUCTION
Postoperative atrial fibrillation (POAF) is a common phenomenon following cardiac surgery. In this study, we assessed current preventive strategies used by Dutch cardiothoracic centres, identified common views on this matter and related these to international guidelines.
METHODS
We developed an online questionnaire and sent it to all cardiothoracic surgery centres in the Netherlands. The questionnaire concerned the management of POAF and the use of pharmaceutical therapies (beta-blockers and calcium antagonists) and non-pharmaceutical methods (posterior left pericardiotomy, pericardial flushing and epicardial botulinum toxin type A injections). Usage of electrical cardioversions, anticoagulants and left atrial appendage closure were also enquired.
RESULTS
Of the 15 centres, 14 (93%) responded to the survey and 13 reported a POAF incidence, ranging from 20 to 30%. Of these 14 centres, 6 prescribed preoperative AF prophylaxis to their patients, of which non-sotalol beta-blockers were prescribed most commonly (57%). Postoperative medication was administered by all centres and included non-sotalol beta-blockers (38%), sotalol (24%), digoxin (14%), calcium antagonists (13%) and amiodarone (10%). Only 2 centres used posterior left pericardiotomy or pericardial flushing as surgical manoeuvres to prevent POAF. Moreover, respondents expressed the need for guidance on anticoagulant use.
CONCLUSION
Despite the use of various preventive strategies, the reported incidence of POAF was similar in Dutch cardiothoracic centres. This study highlights limited use of prophylactic amiodarone and colchicine, despite recommendations by numerous guidelines, and restricted implementation of surgical strategies to prevent POAF.
PubMed: 38358408
DOI: 10.1007/s12471-023-01849-1 -
Pharmacology Research & Perspectives Dec 2023Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in...
Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased β1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.
Topics: Humans; Aged; Aged, 80 and over; Metoprolol; Adrenergic beta-Antagonists; Carvedilol
PubMed: 37885367
DOI: 10.1002/prp2.1126 -
Cureus Sep 2023Catheter ablation has become an important treatment strategy for the management of atrial fibrillation (AF) in symptomatic patients. Pulmonary vein isolation (PVI) is...
Catheter ablation has become an important treatment strategy for the management of atrial fibrillation (AF) in symptomatic patients. Pulmonary vein isolation (PVI) is increasingly used to restore rhythm in patients with AF and flutter. The serious procedural complication rate has significantly reduced over time and most patients undergo PVI without any adverse events. We present the case of a 70-year-old man with symptomatic AF who underwent elective PVI that was complicated by large pericardial effusion from left atrial appendage (LAA) perforation resulting in cardiac tamponade requiring emergency pericardiocentesis followed by sternotomy to suture the LAA. The perforated LAA was sutured and the LAA was closed surgically through sternotomy by using AtriClip and a large amount of blood was evacuated achieving good cardiac output and hemodynamic stability. A surgical PVI was performed twice restoring normal sinus rhythm. The patient was discharged home, however, he returned to the hospital a few days later with atrial flutter with a rapid ventricular response. He underwent direct current cardioversion (DCCV) and remained in sinus rhythm during the rest of his admission. His bisoprolol was switched to Sotalol to maintain normal sinus rhythm and he was discharged home with outpatient follow-up.
PubMed: 37829980
DOI: 10.7759/cureus.44989 -
Molecules (Basel, Switzerland) Jan 2024In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography...
In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography (HPLC) protocol. Further characterization of these substances was then performed via liquid chromatography-mass spectroscopy (LC-MS/MS) and nuclear magnetic resonance (NMR) approaches. For these analyses, commercial STHCl samples were used for quantitative HPLC studies and the degradation of STHCl under acidic (1M HCl), alkaline (1M NaOH), oxidative (30% HO), photolytic (4500 Lx), and thermal stress conditions (100 °C) was assessed. This approach revealed this drug to be resistant to acidic, alkaline, and high-temperature conditions, whereas it was susceptible to light and oxidation as confirmed through long-term experiments. The putative mechanisms governing RS formation were also explored, revealing that RS3 was derived from the manufacturing process, whereas RS2 was generated via oxidation and RS1 was generated in response to light exposure. The cytotoxicity of these RS compounds was then assessed using MTT assays and acute toxicity test. Overall, this study provides details regarding the characterization, isolation, quantification, and toxicological evaluation of STHCl and associated RS compounds together with details regarding the precise, specific, and reliable novel HPLC technique, thus providing the requisite information necessary to ensure STHCl purity and safety.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Sotalol; Tandem Mass Spectrometry; Hydrogen Peroxide; Liquid Chromatography-Mass Spectrometry; Drug Stability; Hydrolysis; Oxidation-Reduction; Photolysis
PubMed: 38338332
DOI: 10.3390/molecules29030588 -
Cureus Aug 2023Fetal tachyarrhythmia and aortic stenosis (AS) both disrupt fetal hemodynamics, leading to congestive heart failure, hydrops, and intrauterine demise. Traditional...
Fetal tachyarrhythmia and aortic stenosis (AS) both disrupt fetal hemodynamics, leading to congestive heart failure, hydrops, and intrauterine demise. Traditional transplacental treatments for fetal supraventricular tachycardia (SVT) include digoxin, flecainide, and sotalol. However, the treatment of fetal SVT in the setting of AS has not been described, particularly in cases of refractory SVT. We present a case of a 27-year-old nulliparous female carrying a fetus with fetal AS diagnosed at 25 weeks of gestational age (GA). The patient was not a candidate for in utero valvuloplasty. During ultrasound monitoring at 32 and 6/7 weeks of gestation, fetal SVT with a heart rate of 230-260 beats per minute (bpm) was diagnosed. Maternal digoxin was initiated, and sotalol was subsequently added. Due to persistent fetal SVT and a worsening cardiac function, the patient was treated with direct adenosine administration via cordocentesis successfully terminating the fetal arrhythmia. Despite continued transplacental treatment with digoxin and sotalol throughout the course of pregnancy, the fetal SVT recurred at 35 and 5/7 weeks of gestation prompting delivery. Our case illustrates the use of direct intrauterine adenosine as a novel treatment for refractory fetal SVT in the setting of congenital aortic stenosis and concern about progression to fetal hydrops and fetal demise.
PubMed: 37667701
DOI: 10.7759/cureus.42931 -
Ecotoxicology and Environmental Safety Jul 2024Microplastics and organic micropollutants are two emerging contaminants that interact with each other in environmental and engineered systems. Sorption of organic...
Microplastics and organic micropollutants are two emerging contaminants that interact with each other in environmental and engineered systems. Sorption of organic micropollutants, such as pharmaceuticals, pesticides and industrial compounds, to microplastics can modify their bioavailability and biodegradation. The present study investigated the capacity of ultra-high density polyethylene particles (125 µm in diameter), before and after aging, to sorb 21 organic micropollutants at different environmentally relevant concentration. Furthermore, the biodegradation of these organic micropollutants by a biofilm microbial community growing on the microplastic surface was compared with the biodegradation by a microbial community originating from activated sludge. Among all tested organic micropollutants, propranolol (70%), trimethoprim (25%) and sotalol (15%) were sorbed in the presence of polyethylene particles. Growth of a biofilm on the polyethylene particles had a beneficial effect on the sorption of bromoxynil, caffeine and chloridazon and on the biodegradation of irbesartan, atenolol and benzotriazole. On the other hand, the biofilm limited the sorption of trimethoprim, propranolol, sotalol and benzotriazole and the biodegradation of 2,4-D. These results showed that ultra-high density polyethylene particles can affect both in a positive and negative way for the abiotic and biotic removal of organic micropollutants in wastewater. This project highlights the need for further investigation regarding the interaction between microplastics and organic micropollutants in the aquatic environment.
Topics: Biofilms; Biodegradation, Environmental; Water Pollutants, Chemical; Polyethylene; Microplastics; Adsorption; Propranolol; Trimethoprim; Atenolol; Triazoles; Sewage
PubMed: 38810284
DOI: 10.1016/j.ecoenv.2024.116510 -
PharmacoEconomics Aug 2023Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality...
BACKGROUND
Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality via rate or rhythm control. This study aimed to review the literature on the cost effectiveness of treatment strategies to manage AF among adults living in low-, middle- and high-income countries.
METHODS
We searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit and Google Scholar for relevant studies between September 2022 and November 2022. The search strategy involved medical subject headings or related text words. Data management and selection was performed using EndNote library. The titles and abstracts were screened followed by eligibility assessment of full texts. Selection, assessment of the risk of bias within the studies, and data extraction were conducted by two independent reviewers. The cost-effectiveness results were synthesised narratively. The analysis was performed using Microsoft Excel 365. The incremental cost effectiveness ratio for each study was adjusted to 2021 USD values.
RESULTS
Fifty studies were included in the analysis after selection and risk of bias assessment. In high-income countries, apixaban was predominantly cost effective for stroke prevention in patients at low and moderate risk of stroke, while left atrial appendage closure (LAAC) was cost effective in patients at high risk of stroke. Propranolol was the cost-effective choice for rate control, while catheter ablation and the convergent procedure were cost-effective strategies in patients with paroxysmal and persistent AF, respectively. Among the anti-arrhythmic drugs, sotalol was the cost-effective strategy for rhythm control. In middle-income countries, apixaban was the cost-effective choice for stroke prevention in patients at low and moderate risk of stroke while high-dose edoxaban was cost effective in patients at high risk of stroke. Radiofrequency catheter ablation was the cost-effective option in rhythm control. No data were available for low-income countries.
CONCLUSION
This systematic review has shown that there are several cost-effective strategies to manage AF in different resource settings. However, the decision to use any strategy should be guided by objective clinical and economic evidence supported by sound clinical judgement.
REGISTRATION
CRD42022360590.
Topics: Adult; Humans; Atrial Fibrillation; Cost-Effectiveness Analysis; Developed Countries; Cost-Benefit Analysis; Stroke
PubMed: 37204698
DOI: 10.1007/s40273-023-01276-5