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Veterinary Research Forum : An... 2023Acute pulmonary edema in puppies generally occurs due to congenital left-right shunts such as patent ductus arteriosus or large ventricular septal defects. Herein, we...
Acute pulmonary edema in puppies generally occurs due to congenital left-right shunts such as patent ductus arteriosus or large ventricular septal defects. Herein, we presented two cases of puppies with no apparent congenital cardiovascular disease. Case 1: A 12-day-old male Labrador Retriever, weighing 1.15 kg, was unable to suckle sufficiently from its dam and exhibited laboured breathing. Pulmonary edema was identified in all lung lobes by radiography, furthermore, echocardiography revealed significant enlargement of the left side of the heart. Pulmonary edema secondary to volume overload was suspected and furosemide was administered. The respiratory status was improved on the following day. Pimobendan was administered orally in addition to furosemide and both were withdrawn 6 weeks later when the heart size was normalized. Case 2: A 15-day-old female Standard Poodle, weighing 0.68 kg, was less active than other littermates and exhibited laboured breathing. Radiography revealed pulmonary edema in the right posterior lobe, dilatation of the caudal vena cava and ascites. Echocardiography revealed significant enlargement of the left atrium and ventricle perhaps owing to decreased left ventricular contractility. Furosemide and pimobendan were administered. One week later, appetite was improved and supraventricular tachycardia of 375 bpm was observed. Therefore, tachycardia-induced dilated cardiomyopathy was suspected which returned to sinus rhythm with diltiazem treatment, however, it was recurred. Upon sotalol monotherapy, a normal heart size was observed seven months later. In conclusion, we encountered two new-born puppies with transient pulmonary edema that were temporarily treated with pimobendan and furosemide.
PubMed: 37181856
DOI: 10.30466/vrf.2022.546719.3349 -
JACC. Clinical Electrophysiology Apr 2023
Topics: Humans; Anti-Arrhythmia Agents; Sotalol; Amiodarone; Torsades de Pointes
PubMed: 37100535
DOI: 10.1016/j.jacep.2022.12.027 -
The Korean Journal of Physiology &... May 2023Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem...
Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) selective inhibition of I and I currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration balanced inhibition of I and I currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration dominant inhibition of I currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.
PubMed: 37078300
DOI: 10.4196/kjpp.2023.27.3.267 -
Clinical Cardiology Jun 2023There are limited comparative data on safety and efficacy within commonly used Vaughan-Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
There are limited comparative data on safety and efficacy within commonly used Vaughan-Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with atrial fibrillation (AF).
HYPOTHESIS
We hypothesized that dronedarone and sotalol, two commonly prescribed VW class III AADs with class II properties, have different safety and efficacy effects in patients with nonpermanent AF.
METHODS
A systematic literature review was conducted searching MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021 (NCT05279833). Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Bayesian random-effects network meta-analysis (NMA) was used to quantify comparative safety and efficacy. Where feasible, we performed sensitivity analyses by including only randomized controlled trials (RCTs).
RESULTS
Of 3581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 nonrandomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all-cause death versus sotalol (hazard ratio [HR] = 0.38 [95% credible interval, CrI: 0.19, 0.74]). The association was numerically similar in the sensitivity analysis (HR = 0.46 [95% CrI: 0.21, 1.02]). AF recurrence and cardiovascular death results were not significantly different between dronedarone and sotalol in all-studies and sensitivity analyses.
CONCLUSION
The NMA findings indicate that, across all clinical trials and observational studies included, dronedarone compared with sotalol was associated with a lower risk of all-cause death, but with no difference in AF recurrence.
Topics: Adult; Humans; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Network Meta-Analysis; Sotalol
PubMed: 37025083
DOI: 10.1002/clc.24011 -
JACC. Clinical Electrophysiology Apr 2023Inpatient initiation of sotalol is recommended owing to its proarrhythmic effects.
BACKGROUND
Inpatient initiation of sotalol is recommended owing to its proarrhythmic effects.
OBJECTIVES
The DASH-AF (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation) trial evaluates the safety and feasibility of intravenous (IV) sotalol, achieving a steady state with maximum QTc prolongation within 6 hours instead of the traditional 5-dose inpatient oral (PO) titration.
METHODS
DASH-AF is a prospective, nonrandomized, multicenter, open-label trial consisting of patients who underwent IV sotalol loading dose to initiate rapid oral therapy for atrial arrhythmias. IV dose was calculated based on the target oral dose as indicated by baseline QTc and renal function. Patients' QTc (in sinus) was measured via electrocardiography at 15-minute intervals and after IV loading completion. Patients were discharged 4 hours after first oral dose. All patients were monitored via mobile cardiac outpatient telemetry for 72 hours. The control group was composed of patients admitted for the traditional 5 PO doses. Safety outcomes were assessed in both groups.
RESULTS
A total of 120 patients from 3 centers were enrolled from 2021 to 2022 in the IV loading group (compared with type of AF- and renal function-matched patients in the conventional PO loading cohort). This study demonstrated no significant change in ΔQTc in both groups, with a significantly lower number of patients requiring dose adjustment in the IV arm compared with the PO arm (4.1% vs 16.6%; P = 0.003). This led to potential cost savings of up to $3,500.68 per admission.
CONCLUSIONS
The DASH-AF trial shows that rapid IV sotalol loading in atrial fibrillation/flutter patients for rhythm control is feasible and safe compared with conventional oral loading with significant cost reduction. (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation [DASH-AF]; NCT04473807).
Topics: Humans; Adult; Sotalol; Atrial Fibrillation; Anti-Arrhythmia Agents; Prospective Studies; Feasibility Studies
PubMed: 37014289
DOI: 10.1016/j.jacep.2022.11.026 -
Europace : European Pacing,... May 2023Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the...
AIMS
Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study.
METHODS AND RESULTS
National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes.
CONCLUSION
The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.
Topics: Humans; Anti-Arrhythmia Agents; Atrial Fibrillation; Propafenone; Administration, Oral; Brain Ischemia; Anticoagulants; Stroke; Amiodarone; Dronedarone; Ischemic Stroke
PubMed: 37000581
DOI: 10.1093/europace/euad083 -
Journal of Comparative Effectiveness... Apr 2023The budgetary consequences of increasing dronedarone utilization for treatment of atrial fibrillation were evaluated from a US payer perspective. A budget impact model...
The budgetary consequences of increasing dronedarone utilization for treatment of atrial fibrillation were evaluated from a US payer perspective. A budget impact model over a 5-year time horizon was developed, including drug-related costs and risks for long-term clinical outcomes (LTCOs). Treatments included antiarrhythmic drugs (AADs; dronedarone, amiodarone, sotalol, propafenone, dofetilide, flecainide), rate control medications, and ablation. Direct comparisons and temporal and non-temporal combination scenarios investigating treatment order were analyzed as costs per patient per month (PPPM). By projected year 5, costs PPPM for dronedarone versus other AADs decreased by $37.69 due to fewer LTCOs, treatment with dronedarone versus ablation or rate control medications + ablation resulted in cost savings ($359.94 and $370.54, respectively), and AADs placed before ablation decreased PPPM costs by $242 compared with ablation before AADs. Increased dronedarone utilization demonstrated incremental cost reductions over time.
Topics: Humans; Dronedarone; Anti-Arrhythmia Agents; Amiodarone; Atrial Fibrillation; Sotalol
PubMed: 36916711
DOI: 10.57264/cer-2022-0196 -
Environmental Pollution (Barking, Essex... May 2023Riverine fish in densely populated areas is constantly exposed to wastewater-borne contaminants from effluent discharges. These can enter the organism through the skin,... (Review)
Review
Riverine fish in densely populated areas is constantly exposed to wastewater-borne contaminants from effluent discharges. These can enter the organism through the skin, gills or by ingestion. Whereas most studies assessing the contaminant burden in exposed fish have focused either on muscle or a limited set of tissues. Here we set out to generate a more comprehensive overview of the distribution of pollutants across tissues by analyzing a panel of matrices including liver, kidney, skin, brain, muscle, heart, plasma and bile. To achieve a broad analyte coverage with a minimal bias towards a specific contaminant class, sample extracts from four fish species were analyzed by High-Performance Liquid Chromatography (HPLC) - high-resolution mass spectrometry (HRMS) for the presence of 600 wastewater-borne pharmaceutically active compounds (PhACs) with known environmental relevance in river water through a suspect-screening analysis. A total of 30 compounds were detected by suspect screening in at least one of the analyzed tissues with a clear prevalence of antidepressants. Of these, 15 were detected at confidence level 2.a (Schymanski scale), and 15 were detected at confidence level 1 following confirmation with authentic standards, which furthermore enabled their quantification. The detected PhACs confirmed with level 1 of confidence included acridone, acetaminophen, caffeine, clarithromycin, codeine, diazepam, diltiazem, fluoxetine, ketoprofen, loratadine, metoprolol, sertraline, sotalol, trimethoprim, and venlafaxine. Among these substances, sertraline stood out as it displayed the highest detection frequency. The values of tissue partition coefficients for sertraline in the liver, kidney, brain and muscle were correlated with its physicochemical properties. Based on inter-matrix comparison of detection frequencies, liver, kidney, skin and heart should be included in the biomonitoring studies of PhACs in riverine fish.
Topics: Animals; Wastewater; Sertraline; Water Pollutants, Chemical; Fishes; Body Fluids; Pharmaceutical Preparations; Environmental Monitoring
PubMed: 36858105
DOI: 10.1016/j.envpol.2023.121374 -
Protocol Development and Initial Experience With Intravenous Sotalol Loading for Atrial Arrhythmias.Critical Pathways in Cardiology Mar 2023Oral sotalol is a class III antiarrhythmic commonly used for the maintenance of sinus rhythm in patients with atrial fibrillation (AF). Recently, the Food and Drug...
BACKGROUND
Oral sotalol is a class III antiarrhythmic commonly used for the maintenance of sinus rhythm in patients with atrial fibrillation (AF). Recently, the Food and Drug Administration (FDA) approved the use of IV sotalol loading, based primarily on modeling data for the infusion. We aimed to describe a protocol and experience with IV sotalol loading for elective treatment of adult patients with AF and atrial flutter (AFL).
METHODS
We present our institutional protocol and retrospective review of initial patients treated with IV sotalol for AF/AFL at the University of Utah Hospital between September 2020 and April 2021.
RESULTS
Eleven patients received IV sotalol for initial loading or dose escalation. All patients were male, aged 56-88 years (median 69). Mean QT interval (QTc) intervals increased from baseline (mean 384 ms) immediately after infusion of IV sotalol (mean change 42ms), but no patient required discontinuation of the medication. Six patients were discharged after 1 night; 4 patients were discharged after 2 nights; and 1 patient was discharged after 4 nights. Nine patients underwent electrical cardioversion prior to discharge (2 prior to load; 7 post-load on the day of discharge). There were no adverse events during the infusion or within 6 months of discharge. Persistence of therapy was 73% (8 of 11) at mean 9.9 weeks to follow up, with no discontinuations for adverse effects.
CONCLUSIONS
We employed a streamlined protocol that was successfully implemented to facilitate the use of IV sotalol loading for atrial arrhythmias. Our initial experience suggests feasibility, safety, and tolerability while reducing hospitalization duration. Additional data are needed to augment this experience as IV sotalol use is broadened across different patient populations.
Topics: Adult; Humans; Male; Female; Sotalol; Atrial Fibrillation; Anti-Arrhythmia Agents; Atrial Flutter; Electric Countershock
PubMed: 36812336
DOI: 10.1097/HPC.0000000000000308 -
International Journal of Molecular... Jan 2023Fetal 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...
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 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 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.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chromatography, High Pressure Liquid; Digoxin; Drug Monitoring; Hydrops Fetalis; Pregnant Women; Sotalol; Tachycardia; Tachycardia, Supraventricular; Tandem Mass Spectrometry
PubMed: 36768172
DOI: 10.3390/ijms24031848