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HeartRhythm Case Reports Nov 2021
PubMed: 34820269
DOI: 10.1016/j.hrcr.2021.07.010 -
Europace : European Pacing,... Jul 2022To evaluate the effectiveness and safety of dronedarone compared with other commonly used antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrences. (Observational Study)
Observational Study
AIMS
To evaluate the effectiveness and safety of dronedarone compared with other commonly used antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrences.
METHODS AND RESULTS
An international observational cohort study in Germany, Spain, Italy, and the USA enrolling patients with AF receiving AAD therapy. Patients with New York Heart Association (NYHA) Class IV heart failure were excluded. Participants were followed for up to 18 months, regardless of discontinuation or subsequent AAD switches. Atrial fibrillation recurrence was captured by hospitalization, emergency room visit, or electrocardiogram-based documentation of AF. Confounding bias was controlled for in the analysis of AF recurrence using multivariate models of 19 variables for adjustment. A total of 1009 participants [mean age 67.2 (10.8) years, male to female ratio 1.3] were recruited from 170 centres, 693 (69%) of which were from across Europe and the remaining 316 (31%) from the USA. At the time of enrolment, participants were taking dronedarone (51%) or other AADs (49%) [flecainide or propafenone (42%), sotalol (11%), and amiodarone (47%)]. No significant differences in the risk of first confirmed AF recurrence with dronedarone vs. other AADs [crude hazard ratio (HR) 1.10 (95% confidence interval 0.85-1.42); adjusted HR 1.16 (0.87-1.55)] were found, irrespective of whether univariate or multivariate models were used. Reported safety events were in accordance with the known safety profile of dronedarone.
CONCLUSION
In this population of patients from either Europe or the USA receiving dronedarone or another AAD, the effectiveness of dronedarone was comparable to that observed for other AADs in preventing first AF recurrence.
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cohort Studies; Dronedarone; Female; Humans; Male
PubMed: 34792111
DOI: 10.1093/europace/euab262 -
International Journal of Molecular... Oct 2021Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in humans. It has previously been demonstrated that amiodarone and its metabolite...
Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in humans. It has previously been demonstrated that amiodarone and its metabolite (desethylamiodarone, DEA) can inhibit mitochondrial function, particularly complexes I (CI) and II (CII) of the electron transport system in various animal tissues and cell types. The present study, performed in human peripheral blood cells, and one liver-derived human cell line, is primarily aimed at assessing the concentration-dependent effects of these drugs on mitochondrial function (respiration and cellular ATP levels). Furthermore, we explore the efficacy of a novel cell-permeable succinate prodrug in alleviating the drug-induced acute mitochondrial dysfunction. Amiodarone and DEA elicit a concentration-dependent impairment of mitochondrial respiration in both intact and permeabilized platelets via the inhibition of both CI- and CII-supported respiration. The inhibitory effect seen in human platelets is also confirmed in mononuclear cells (PBMCs) and HepG2 cells. Additionally, amiodarone elicits a severe concentration-dependent ATP depletion in PBMCs, which cannot be explained solely by mitochondrial inhibition. The succinate prodrug NV118 alleviates the respiratory deficit in platelets and HepG2 cells acutely exposed to amiodarone. In conclusion, amiodarone severely inhibits metabolism in primary human mitochondria, which can be counteracted by increasing mitochondrial function using intracellular delivery of succinate.
Topics: Adenosine Triphosphate; Amiodarone; Anti-Arrhythmia Agents; Blood Platelets; Cell Respiration; Hep G2 Cells; Humans; Mitochondria; Prodrugs; Protective Agents; Succinic Acid
PubMed: 34769217
DOI: 10.3390/ijms222111786 -
Frontiers in Physiology 2021Amphibians may be more vulnerable to climate-driven habitat modification because of their complex life cycle dependence on land and water. Considering the current rate...
Amphibians may be more vulnerable to climate-driven habitat modification because of their complex life cycle dependence on land and water. Considering the current rate of global warming, it is critical to identify the vulnerability of a species by assessing its potential to acclimate to warming temperatures. In many species, thermal acclimation provides a reversible physiological adjustment in response to temperature changes, conferring resilience in a changing climate. Here, we investigate the effects of temperature acclimation on the physiological performance of tadpoles of a stream-breeding savanna tree frog () in relation to the thermal conditions naturally experienced in their microhabitat (range: 18.8-24.6°C). We quantified performance measures such as routine and maximum metabolic rate at different test (15, 20, 25, 30, and 34°C) and acclimation temperatures (18 and 25°C). We also measured heart rate before and after autonomic blockade with atropine and sotalol at the respective acclimation temperatures. Further, we determined the critical thermal maximum and warming tolerance (critical thermal maximum minus maximum microhabitat temperature), which were not affected by acclimation. Mass-specific routine and mass-specific maximum metabolic rate, as well as heart rate, increased with increasing test temperatures; however, acclimation elevated mass-specific routine metabolic rate while not affecting mass-specific maximum metabolic rate. Heart rate before and after the pharmacological blockade was also unaffected by acclimation. Aerobic scope in animals acclimated to 25°C was substantially reduced, suggesting that physiological performance at the highest temperatures experienced in their natural habitat is compromised. In conclusion, the data suggest that the tadpoles of , living in a thermally stable environment, have a limited capacity to physiologically adjust to the highest temperatures found in their micro-habitat, making the species more vulnerable to future climate change.
PubMed: 34690802
DOI: 10.3389/fphys.2021.726440 -
Frontiers in Physiology 2021We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for evaluating multiple AADs in patients with atrial...
We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for evaluating multiple AADs in patients with atrial fibrillation (AF). We explored the anti-AF mechanisms of AADs and spatial change in the AF wave-dynamics by a realistic computational model. We used realistic computational modeling of 25 AF patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal AF) reflecting the anatomy, histology, and electrophysiology of the left atrium (LA) to characterize the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone). We evaluated the spatial change in the AF wave-dynamics by measuring the mean dominant frequency (DF) and its coefficient of variation [dominant frequency-coefficient of variation (DF-COV)] in 10 segments of the LA. The mean DF and DF-COV were compared according to the pulmonary vein (PV) vs. extra-PV, maximal slope of the restitution curves (Smax), and defragmentation of AF. The mean DF decreased after the administration of AADs in the dose dependent manner ( < 0.001). Under AADs, the DF was significantly lower ( < 0.001) and COV-DF higher ( = 0.003) in the PV than extra-PV region. The mean DF was significantly lower at a high Smax (≥1.4) than a lower Smax condition under AADs. During the episodes of AF defragmentation, the mean DF was lower ( < 0.001), but the COV-DF was higher ( < 0.001) than that in those without defragmentation. The DF reduction with AADs is predominant in the PVs and during a high Smax condition and causes AF termination or defragmentation during a lower DF and spatially unstable (higher DF-COV) condition.
PubMed: 34630153
DOI: 10.3389/fphys.2021.733543 -
American Journal of Cardiovascular... Nov 2021Antiarrhythmic drugs are often used in the management of patients with atrial fibrillation (AF). Sotalol is conventionally initiated in the inpatient setting for...
BACKGROUND
Antiarrhythmic drugs are often used in the management of patients with atrial fibrillation (AF). Sotalol is conventionally initiated in the inpatient setting for monitoring efficacy and adverse effects, including QTc interval prolongation and torsades de pointes (TdP) proarrhythmia.
OBJECTIVE
We aimed to evaluate the efficacy and safety of outpatient initiation of sotalol for the treatment of AF in a select group of patients with cardiac implantable electronic devices (CIEDs): permanent pacemakers (PPMs), implantable cardioverter defibrillators (ICDs), and implantable loop recorders (ILRs) capable of continuous rhythm monitoring remotely.
METHODS
We conducted our clinical study in a real-world practice setting with longitudinal follow-up of the study cohort. We included adult patients with symptomatic paroxysmal and persistent AF eligible for sotalol for rhythm control strategy and who had CIEDs in our study. Patients with a known contraindication to sotalol were excluded. After making a shared management decision with patients, sotalol was initiated as an outpatient, with regular clinical encounters with patients to assess the efficacy and safety of treatment, and monitoring cardiac rhythm and QTc intervals with CIEDs utilizing their remote monitoring platforms.
RESULTS
The study cohort comprised 105 patients; 38 (36%) females, mean age ± standard deviation (SD) 73.9 ± 10.36 years, and with a CHADS-VASc score of 3.26 ± 1.37 and left ventricular ejection fraction of 60.16 ± 9.10%. Twenty-six (24.8%) patients were implanted with PPMs, 10 (9.5%) with dual-chamber ICDs, and 69 (65.7%) with ILRs. Over a follow-up period of 23 ± 15 months, sotalol was continued at a steady median dose of 80 mg twice daily, 105 ± 42 mg (mean ± SD) in 77 (73%) patients who maintained sinus rhythm, and discontinued in 28 (27%) patients because of inefficacy or development of adverse effects. No adverse effects relating to QTc prolongation and TdP or mortality were observed during the study period.
CONCLUSIONS
Effective and safe outpatient initiation and maintenance of sotalol therapy is possible in select patients who have CIEDs for continuous remote monitoring and surveillance capabilities.
Topics: Atrial Fibrillation; Defibrillators, Implantable; Humans; Monitoring, Physiologic; Outpatients; Sotalol
PubMed: 34291437
DOI: 10.1007/s40256-021-00493-7 -
Marked and prolonged serotonin toxicity in a tramadol-poisoned patient with a pharmacokinetic study.Clinical Toxicology (Philadelphia, Pa.) Mar 2022Tramadol poisoning rarely causes serotonin toxicity, which mechanisms remain poorly understood. We investigated alterations in tramadol pharmacokinetics in a...
BACKGROUND
Tramadol poisoning rarely causes serotonin toxicity, which mechanisms remain poorly understood. We investigated alterations in tramadol pharmacokinetics in a tramadol-poisoned patient who presented with marked and prolonged serotonin toxicity.
CASE REPORT
A 21-year-old male self-ingested 750 mg-tramadol, 200 mg-sotalol, 400 mg-propranolol and 6 mg-lorazepam. He was a kidney transplant patient treated with mycophenolate, tacrolimus, prednisone, and paroxetine. He developed transitory cardiovascular failure and prolonged serotonin toxicity requiring sedation, muscle paralysis, and cyproheptadine, with a favorable outcome.
METHODS
We measured plasma concentrations of tramadol, M1, M2, and M5 using liquid-chromatography-tandem mass spectrometry, calculated elimination half-lives and metabolic ratios of the compounds, and genotyped cytochromes involved in tramadol metabolism.
RESULTS
Elimination half-lives of tramadol (6.1 h) and M1 (7.1 h) were normal while those of M2 (26.5 h) and M5 (16.7 h) prolonged. M1 metabolic ratio (0.12) was 2-fold reduced, M2 metabolic ratio (197) 1000-fold increased and M5 metabolic ratio (0.12) normal. This metabolic profile in a patient with normal CYP2D6-metabolizer status based on genotyping supports CYP2D6 inhibition by paroxetine and propranolol, two strong mechanism-based inhibitors. Only M2 present in sufficient concentrations up to 48 h could explain the prolonged serotonin toxicity.
CONCLUSION
Marked and prolonged serotonin toxicity was attributed to increased M2 production due to paroxetine- and propranolol-related CYP2D6 inhibition of tramadol metabolism.
Topics: Adult; Cytochrome P-450 CYP2D6; Humans; Male; Serotonin; Tramadol; Young Adult
PubMed: 34287102
DOI: 10.1080/15563650.2021.1955912 -
Cureus Jun 2021Atrial fibrillation is the most common sustained cardiac arrhythmia. While there have been reports of atrial fibrillation caused by the compression of pulmonary veins,...
Refractory Atrial Fibrillation With Rapid Ventricular Rate in a Patient With Small Cell Carcinoma of the Lung Encasing the Right Pulmonary Artery: A Case Report and Insight Into Therapeutic Options.
Atrial fibrillation is the most common sustained cardiac arrhythmia. While there have been reports of atrial fibrillation caused by the compression of pulmonary veins, we have not found reports of atrial fibrillation caused by the compression of the pulmonary artery. This report highlights the possible pathophysiology and management of atrial fibrillation in a patient with small cell lung cancer. The patient was admitted for hyponatremia secondary to syndrome of inappropriate antidiuretic hormone (SIADH) but subsequently developed tachycardia which progressed to atrial flutter and atrial fibrillation. Antiarrhythmics were ineffective until the patient received his first palliative chemotherapy for his small cell lung cancer. Subsequently, rate control was achieved with sotalol, with eventual conversion back to sinus rhythm. Management of atrial fibrillation is complex and sometimes depends on the underlying etiology. Early chemotherapy, in addition to antiarrhythmic drugs, may be beneficial in the management of patients with small cell lung cancer and atrial fibrillation. The CHA2DS2-VASc score does not take active malignancy into account and anti-coagulation should be evaluated on a case-by-case basis in this patient population.
PubMed: 34277299
DOI: 10.7759/cureus.16027 -
HeartRhythm Case Reports Jun 2021
PubMed: 34194993
DOI: 10.1016/j.hrcr.2021.03.020 -
PloS One 2021To evaluate if specific AADs prescribed in the blanking period (BP) after catheter ablation of atrial fibrillation (AF) may be associated with reduced risk of early... (Observational Study)
Observational Study
Association between specific antiarrhythmic drug prescription in the post-procedural blanking period and recurrent atrial arrhythmias after catheter ablation for atrial fibrillation.
PURPOSE
To evaluate if specific AADs prescribed in the blanking period (BP) after catheter ablation of atrial fibrillation (AF) may be associated with reduced risk of early recurrence (ER) and/or late recurrence (LR) of atrial arrhythmias.
METHODS
A total of 478 patients undergoing first-time ablation at a single institution were included. Outcomes were: ER, LR, discontinuation of AAD less than 90 days post-ablation, and second ablation. ER was defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) > 30 seconds within BP. LR was defined as AF/AFL/AT > 30 seconds after BP.
RESULTS
Of 478 patients, 14.9% were prescribed no AAD, 26.4% propafenone/flecainide, 34.5% sotalol/dofetilide, 10.7% dronedarone, and 13.6% amiodarone. Patients prescribed amiodarone were more likely to have persistent AF, hypertension, diabetes, and other comorbidities. In unadjusted analyses, there were no differences between groups in relation to ER (log rank P = 0.171), discontinuation of AAD before ninety days post-ablation (log rank P = 0.235), or freedom from second ablation (log rank P = 0.147). After multivariable adjustment, patients prescribed amiodarone or dronedarone were more likely to experience LR than those prescribed no AAD [Adjusted Hazard Ratio (AHR) 1.83, 95% CI 1.10-3.04, p = 0.02; AHR 1.79, 95% CI 1.05-3.05, p = 0.03, respectively].
CONCLUSION
Following first-time catheter ablation, there were no differences between specific AAD prescription and risk of ER, while those prescribed amiodarone or dronedarone in the BP were more likely to experience LR than those prescribed no AAD, which may represent an association due to confounding by indication.
Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Drug Prescriptions; Female; Humans; Male; Middle Aged; Recurrence; Registries
PubMed: 34166392
DOI: 10.1371/journal.pone.0253266