Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer.

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.

Ivabradine for congenital ectopic tachycardia in newborn.

INTRODUCTION: Congenital junctional ectopic tachycardia is a rare arrhythmia that occurs in patients without previous cardiac surgery. In this report, we wanted to present a 6-hour-old newborn with congenital junctional ectopic tachycardia resistant to conventional anti-arrhythmic medications, who was successfully treated with ivabradine and amiadarone combination. CASE: A six-hour-old newborn girl was hospitalised in neonatal ICU because transient tachypnoea of the newborn. She was tachycardic, and supraventricular tachycardia was noticed. There was no answer to the adenosine esmolol treatment; even synchronised direct cardioversion intravenous amiodarone was started. Junctional ectopic tachycardia was diagnosed. We have added propranolol to the treatment and followed patient for 2 days. On the fourth day, junctional ectopic tachycardia rhythm still persisted; therefore, ivabradine treatment was added to the treatment. On the following day, the heart rhythm was slowed to 110/min, and propranolol was stopped; intravenous amiodarone treatment was changed to the oral form. The rhythm turned into sinus; two days after starting ivabradine and oral amiodarone. CONCLUSION: Tachyarrhythmia originating in the atrioventricular node and atrioventricular junction including the bundle of His complex are junctional ectopic tachycardia. Congenital junctional ectopic tachycardia is rare, and it is mostly resistant to the conventional treatment.Ivabradine is a new anti-arrhythmic agent, used extensively to decrease sinus rate in the treatment of cardiac failure. Ivabradine may be an option for the resistant congenital ectopic tachycardia.

Prevention of postoperative atrial fibrillation in cardiac surgery: a quality improvement project.

PURPOSE: Postoperative atrial fibrillation (POAF) has an incidence of 20-60% in cardiac surgery. The Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anaesthesiology Practice Advisory have recommended postoperative beta blockers and amiodarone for the prevention of POAF. By employing quality improvement (QI) strategies, we sought to increase the use of these agents and to reduce the incidence of POAF among our patients undergoing cardiac surgery. METHODS: This single-centre QI initiative followed the traditional Plan, Do, Study, Act (PDSA) cycle scientific methodology. A POAF risk score was developed to categorize all patients undergoing cardiac surgery as either normal or elevated risk. Risk stratification was incorporated into a preprinted prescribing guide, which recommended postoperative beta blockade for all patients and a postoperative amiodarone protocol for patients with elevated risk starting on postoperative day one (POD1). A longitudinal audit of all patients undergoing cardiac surgery was conducted over 11 months to track the use of prophylactic medications and the incidence of POAF. RESULTS: Five hundred and sixty patients undergoing surgery were included in the QI initiative from 1 December 2020 to 1 November 2021. The baseline rate of POAF across all surgical subtypes was 39% (198/560). The use of prophylactic amiodarone in high-risk patients increased from 13% (1/8) at the start of the project to 41% (48/116) at the end of the audit period. The percentage of patients receiving a beta blocker on POD1 did fluctuate, but remained essentially unchanged throughout the audit (34.8% in December 2020 vs 46.7% in October 2021). After 11 months, the overall incidence of POAF was 29% (24.9% relative reduction). Notable reductions in the incidence of POAF were observed in more complex surgical subtypes by the end of the audit, including multiple valve replacement (89% vs 56%), aortic repair (50% vs 33%), and mitral valve surgery (45% vs 33%). CONCLUSIONS: This single-centre QI intervention increased the use of prophylactic amiodarone by 28% for patients at elevated risk of POAF, with no change in the early postoperative initiation of beta blockers (46.7% of patients by POD1). There was a notable reduction in the incidence of POAF in patients at elevated risk undergoing surgery.

RéSUMé: OBJECTIF: Il y a une incidence de 20 à 60 % de fibrillation auriculaire postopératoire (FAPO) en chirurgie cardiaque. Dans un avis de pratique, la Society of Cardiovascular Anesthesiologists et l'European Association of Cardiothoracic Anaesthesiology ont recommandé l'utilisation de bêtabloquants et d'amiodarone en postopératoire pour la prévention du FAPO. En employant des stratégies d'amélioration de la qualité (AQ), nous avons cherché à augmenter l'utilisation de ces agents et à réduire l'incidence de FAPO chez nos patient·es bénéficiant d'une chirurgie cardiaque. MéTHODE: Cette initiative d'AQ monocentrique a suivi la méthodologie scientifique traditionnelle du cycle Plan, Do, Study, Act (PDSA), soit Planifier, Réaliser, Étudier, Agir. Un score de risque de FAPO a été mis au point pour catégoriser toute la patientèle bénéficiant d'une chirurgie cardiaque comme présentant un risque normal ou élevé. La stratification du risque a été intégrée dans un guide de prescription préimprimé, qui recommandait des bêtabloquants en période postopératoire pour tou·tes les patient·es et un protocole postopératoire d'amiodarone pour celles et ceux présentant un risque élevé et débutant à partir du premier jour postopératoire (JPO1). Une vérification longitudinale de toute la patientèle bénéficiant d'une chirurgie cardiaque a été menée sur une période de 11 mois afin de suivre l'utilisation de médicaments prophylactiques et l'incidence de FAPO. RéSULTATS: Cinq cent soixante personnes opérées ont été incluses dans l'initiative d'AQ entre le 1er décembre 2020 et le 1er novembre 2021. Le taux initial de FAPO pour tous les sous-types chirurgicaux était de 39 % (198/560). L'utilisation d'amiodarone prophylactique chez les patient·es à risque élevé est passée de 13 % (1/8) au début du projet à 41 % (48/116) à la fin de la période de vérification. Le pourcentage de patient·es recevant un bêtabloquant au JPO1 a fluctué, mais est resté fondamentalement inchangé tout au long de la période de vérification (34,8 % en décembre 2020 vs 46,7 % en octobre 2021). Après 11 mois, l'incidence globale de FAPO était de 29 % (réduction relative de 24,9 %). Des réductions notables de l'incidence de FAPO ont été observées dans des sous-types chirurgicaux plus complexes à la fin de la vérification, y compris le remplacement de plusieurs valves (89 % vs 56 %), la réparation aortique (50 % vs 33 %) et la chirurgie valvulaire mitrale (45 % vs 33 %). CONCLUSION: Cette intervention monocentrique d'amélioration de la qualité a augmenté l'utilisation de l'amiodarone prophylactique de 28 % chez les patient·es présentant un risque élevé de FAPO, sans changement dans l'amorce postopératoire précoce des bêtabloquants (46,7 % des patient·es au JPO1). Il y a eu une réduction notable de l'incidence de FAPO chez les patient·es à risque élevé bénéficiant d'une intervention chirurgicale.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Postoperative Atrial Fibrillation After Surgical Aortic Valve Replacement: Amiodarone and Warfarin Use.

INTRODUCTION: The association between amiodarone treatment for postoperative atrial fibrillation (POAF) after surgical aortic valve replacement (SAVR) and both the return to normal sinus rhythm (NSR) and anticoagulation use at discharge has not been extensively studied. METHODS: We retrospectively identified all patients who underwent biological SAVR with or without concomitant coronary artery bypass grafting (CABG) at a Veterans Affairs Medical Center (2005-2015). We reviewed new-onset POAF, amiodarone use, return to NSR, and anticoagulation use with warfarin. Discharge rhythm and warfarin administration were compared among patients with POAF who were treated with amiodarone and patients who did not receive amiodarone. RESULTS: Of the 395 patients (186 AVR/coronary artery bypass grafting; 209 AVR) studied, POAF developed in 191 patients (48.0%); 80.1% (153/191) of these patients received amiodarone. Among patients treated with amiodarone, 70.6% (108/153) were in SR at the time of discharge versus 65.8% (25/38) of POAF patients who were not treated with amiodarone (P = 0.57). Among amiodarone-treated patients, 30.7% (47/153) were discharged with warfarin; among patients not treated with amiodarone, 31.6% (12/38) were discharged with warfarin (P = 0.92). Among amiodarone-treated patients discharged in NSR, 89.9% (97/108 patients) were not discharged with warfarin; among patients not treated with amiodarone who were discharged in NSR, 92% (23/25) were not discharged with warfarin (P = 0.74). CONCLUSIONS: POAF after SAVR appears common. Although amiodarone is often used for POAF patients, its use does not appear to be associated with surgeons' decision to anticoagulate patients. Surgeons' preferences for using rhythm control and antithrombotic therapy for POAF after SAVR warrant further exploration.

Effectiveness of pharmacological cardioversion of new-onset atrial fibrillation during thoracic surgery operations: a single-centre experience.

OBJECTIVE: Prophylactic pharmacological conversion agents could reduce the incidence of postoperative atrial fibrillation (AF) in patients undergoing thoracic operations. The current study examined whether the use of pharmacological conversion agents could help to restore sinus rhythm in patients with AF newly developed during thoracic operations. METHODS: Medical records of 18,605 patients from January 1, 2015 to December 31, 2019, at the Shanghai Chest Hospital were reviewed. Patients with non-sinus rhythm prior to the surgery (n = 128) were excluded from data analysis. The final analysis included 18,477 patients (n = 16,292 undergoing lung operations; n = 2,185 undergoing esophageal operations). RESULTS: Intraoperative AF (defined as AF lasting for at least 5 min) occurred in 646 out of a total of 18,477 subjects (3.49%). Within the 646 subjects, 258 received pharmacological conversion agents during the surgery. sinus rhythm was restored in 20.15% (52/248) of patients treated with pharmacological cardioversion and in 20.87% (81/399) patients not receiving pharmacological intervention. In a subgroup analysis of the 258 patients receiving pharmacological conversion agents, recovery of sinus rhythm was highest in beta-blocker group (35.59%, 21/59 vs. 15.78%, 15/95 in amiodarone group, p = 0.008, 5.55%, and 1/18 in amiodarone plus beta-blockers group, p = 0.016). The incidence of hypotension was higher in pharmacological conversion (27.5% vs. 9.3% in patients not receiving pharmacological intervention, p < 0.001). In subjects not recovering to sinus rhythm during the surgery (n = 513), electrical cardioversion in post-anesthesia care unit (PACU) restored sinus rhythm in > 98% of the cases (155/158 vs. 63/355 in subjects not receiving cardioversion; p < 0.001). CONCLUSIONS: Our experience shows that pharmacological conversion, in general, failed to show better treatment effectiveness on intraoperative new-onset AF within period of surgery except for beta-blockers. Patients with AF persisting beyond the surgery could be effectively managed with electrical cardioversion.

Amiodarone-drove XBP1s aggravates endoplasmic reticulum stress and apoptosis in Hashimoto's thyroiditis through regulating LINC00842/miR-214/FASL axis.

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease, that eventually lead to hypothyroidism. XBP1s is an endoplasmic reticulum stress related protein and participates in the pathogenesis of several diseases. Nevertheless, the potential role of XBP1s in amiodarone (AMIO)-treated HT patients remains unknown. In this study, AMIO aggravated the endoplasmic reticulum stress responses in HT patients and thyroid epithelial follicular cells. Moreover, MTT assay and flow cytometry analysis revealed that knockdown of XBP1s suppressed AMIO-induced thyroid epithelial follicular cells apoptosis. Mechanically, the Chromatin Immunoprecipitation (ChIP) and luciferase activity assay proved that XBP1s enhanced LINC00842 expression in HT patients and thyroid epithelial follicular cells via binding to LINC00842 promoter. LINC00842 functioned as a miR-214 sponge in HT patients and thyroid epithelial follicular cells. Besides, LINC00842 up-regulated Fas ligand (FASL) expression via inhibition of miR-214. In rescue experiments, overexpression of FASL reversed shXBP1s-induced suppression of cell apoptosis in AMIO-treated thyroid epithelial follicular cells. These findings concluded that AMIO-drove XBP1s aggravated endoplasmic reticulum stress and apoptosis in HT via modulating LINC00842/miR-214/FASL axis, providing a new sight for the therapeutic strategy of AMIO-induced HT.

Efficacy of Intraoperative Low Dose Intravenous Amiodarone in Pharmacologic Cardioversion in Patients with Preoperative Atrial Fibrillation Presenting for Mitral Valve Replacement Surgery Randomized Control Trial.

BACKGROUND: Atrial fibrillation (AF) is the most common form of dysrhythmia observed in the clinical field, causing multiple morbidities, such as thromboembolic complications. Hence, the maintenance of sinus rhythm is superior to rate control. This study tests the efficacy of single- and low-dose amiodarone on the persistence of AF after surgery before transfer to the intensive care unit. METHODS: A double-blinded, randomized controlled trial assessed 113 patients who underwent mitral valve surgery with preoperative chronic AF. Patients were divided into two groups: the control group (N = 55) who received 50 mL of 5% dextrose over 10 min after general anesthesia induction, and the amiodarone group (N = 58) who received 1 mg/kg of amiodarone diluted in 50 mL of 5% dextrose over 10 min shortly after anesthesia induction. RESULTS: The amiodarone group had a statistically significant successful conversion of preoperative AF to normal sinus rhythm in 40 patients (72.73%). The control group demonstrated spontaneous conversion from AF to a normal sinus rhythm in seven patients (12.73%). The sinus rhythm was maintained in 60% of patients (36), as four patients reverted to AF during the hospital stay despite the initial normal sinus rhythm after the operation. In contrast, 53 (96.36%) patients in the control group were discharged from the hospital with a controlled rate of AF. In addition, low-dose amiodarone caused a statistically significant reduction in heart rates at 10, 30, and 60 min after declamping, extended throughout the first 24 h with mean heart rates of 97.233±7.311, 99.509±8.482, and 97.940±7.715 bpm, respectively. In comparison, the control group had heart rates of 115.382±7.547, 115.055±13.919, and 113.618±8.765 bpm at these times. The mean postoperative heart rate at the end of the first 24 h was 97.793±7.189 bpm in the amiodarone group and 113.036±9.737 bpm in the control group. No mortality or need for mechanical support was recorded in either group. CONCLUSIONS: Single and low-dose intraoperative intravenous amiodarone during mitral valve surgery may be practical to aid in pharmacological cardioversion of patients with preoperative chronic AF presenting for mitral valve surgery.

Amiodarona: fortalezas y debilidades / Amiodarone strengths and weaknesses

Prescritos en la práctica clínica por su eficacia. En su inicio se utilizó para tratar la angina de pecho. hoy día es usado para el tratamiento de cualquier forma de taquicardia. Objetivo: Reconocer la prescripción de la Amiodarona y sus efectos adversos. Métodos: Se realizó una revisión descriptiva en las bases de datos de Lilacs donde se encontraron 18 artículos y en PubMed/Medline (Mesh) 206 artículos, de los cuales se le aplicaron los criterios de inclusión a 51 artículos. Conclusiones: La amiodarona es uno de los antiarrítmicos más utilizados para el tratamiento de las arritmias, su variedad de efectos adversos y toxicidad es conocida, por tanto, los pacientes en tratamiento ameritan un minucioso monitoreo(AU)

Introduction: Amiodarone is one of the most prescribed antiarrhythmic drugs in clinical practice due to its efficacy. Initially it was used to treat angina pectoris, however, today it is used to treat any form of tachycardia. Objective: To identify the prescription of amiodarone and its adverse effects. Methods: A descriptive review was carried out in Lilacs databases where 18 articles were found and in PubMed/Medline (Mesh) 206 articles were retrieved. The inclusion criteria were applied to 51 articles. Conclusions: Amiodarone is one of the most widely used antiarrhythmic drugs for the treatment of arrhythmias, its variety of adverse effects and toxicity is known, therefore, patients undergoing treatment justify careful monitoring(AU)

Amiodarone with or without N-Acetylcysteine for the Prevention of Atrial Fibrillation after Thoracic Surgery: A Double-blind, Randomized Trial.

BACKGROUND: Postoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation. METHODS: In this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year. RESULTS: Among 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups. CONCLUSIONS: Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery.

Cardioprotective effects of amiodarone in a rat model of epilepsy-induced cardiac dysfunction.

Cardiac dysfunction is one of the leading causes of death in epilepsy. The anti-arrhythmic drug, amiodarone, is under investigation for its therapeutic effects in epilepsy. We aimed to evaluate the possible effects of amiodarone on cardiac injury during status epilepticus, as it can cause prolongation of the QT interval. Five rat groups were enrolled in the study; three control groups (1) Control, (2) Control-lithium and (3) Control-Amio, treated with 150 mg/kg/intraperitoneal amiodarone, (4) Epilepsy model, induced by sequential lithium/pilocarpine administration, and (5) the epilepsy-Amio group. The model group expressed a typical clinical picture of epileptiform activity confirmed by the augmented electroencephalogram alpha and beta spikes. The anticonvulsive effect of amiodarone was prominent, it diminished (p < 0.001) the severity of seizures and hence, deaths and reduced serum noradrenaline levels. In the model group, the electrocardiogram findings revealed tachycardia, prolongation of the corrected QT (QTc) interval, depressed ST segments and increased myocardial oxidative stress. The in-vitro myocardial performance (contraction force and - (df/dt)max ) was also reduced. Amiodarone decreased (p < 0.001) the heart rate, improved ST segment depression, and myocardial contractility with no significant change in the duration of the QTc interval. Amiodarone preserved the cardiac histological structure and reduced the myocardial injury markers represented by serum Troponin-I, oxidative stress and IL-1. Amiodarone pretreatment prevented the anticipated cardiac injury induced during epilepsy. Amiodarone possessed an anticonvulsive potential, protected the cardiac muscle and preserved its histological architecture. Therefore, amiodarone could be recommended as a protective therapy against cardiac dysfunction during epileptic seizures with favourable effect on seizure activity.

Sotalol versus amiodarone for postoperative junctional tachycardia after congenital heart surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) is a common arrhythmia after congenital heart disease surgery. There is variability in the choice of antiarrhythmic therapy, with amiodarone used commonly. Intravenous (IV) sotalol is a newly available agent that may be useful for JET. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of IV sotalol for postoperative JET and compare outcomes with IV amiodarone. METHODS: This is a retrospective single-center study of all patients who received IV sotalol or IV amiodarone for postoperative JET at Texas Children's Hospital from December 15, 2015, to December 15, 2020. Data included antiarrhythmic efficacy, hemodynamics, and adverse effects. Successful JET control was defined as a decrease in JET rate to <170 beats/min (or decrease by >20%), or conversion to sinus rhythm, with persistent control over 24 hours without requiring alternative antiarrhythmics or mechanical support. RESULTS: A total of 32 patients (median age 71 days; interquartile range 17-221 days) received IV amiodarone (n = 20 [62%]) or IV sotalol (n = 12 [38%]) for postoperative JET. Amiodarone was successful in treating JET in 75% of cases; sotalol was successful in 83%. The JET rate decreased faster over the first 90 minutes after a sotalol bolus (25 beats/min per hour) than after an amiodarone bolus (8 beats/min per hour) (P < .01); no heart rate difference was seen after 24 hours. Amiodarone infusion was discontinued early because of hypotension/bradycardia in 2 patients; this was not required in any patients receiving sotalol. CONCLUSION: For children with postoperative JET, both IV sotalol and amiodarone are safe and efficacious. IV sotalol may lead to a faster improvement in heart rate.

Effect of the therapy of amiodarone combined with atorvastatin on cardiac function of patients with acute myocardial infarction after percutaneous coronary intervention (PCI).

This study aimed to investigate the effect of the therapy of amiodarone combined with atorvastatin on cardiac function of patients with acute myocardial infarction after percutaneous coronary intervention (PCI). A total of 90 patients with acute myocardial infarction who underwent PCI in the tertiary care hospital from January 2019 to January 2020 were selected as the subjects and randomly assigned into the control group and the study group, with 45 cases in each group. All the subjects had undergone PCI. The control group received amiodarone while those the study group received atorvastatin additionally. Comparison was done on the clinical efficacy, cardiac function, myocardial injury indicator and inflammatory factor between the two groups. The overall response rate (ORR) in the study group was significantly higher than that in the control group (P<0.05); patients in the study group had markedly better cardiac function compared with those in the control group (P<0.001); patients in the study group had considerably lower creatine kinase (CK) index, creatine kinase-MB (CK-MB) index, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) as opposed to those in the control group (P<0.001). It was observed that the therapy of amiodarone combined with atorvastatin could effectively improve the clinical indicators and cardiac function of patients with acute myocardial infarction after PCI. It is effective and worthy of wide promotion and application.

Perioperative Amiodarone to Prevent Atrial fibrillation after Septal Myectomy in obstrUctive hypeRtroPHic cardiomyopathy.

AIMS: Amiodarone reduces the incidence of atrial fibrillation (AF) following coronary artery bypass surgery; however, the benefit of perioperative amiodarone in patients undergoing septal myectomy (SM) for obstructive hypertrophic cardiomyopathy (oHCM) has not been studied. We hypothesized that prophylactic amiodarone would reduce the incidence of postoperative AF (POAF) following SM for oHCM. METHODS AND RESULTS: A single-centre, pre-post intervention open-label study of oral amiodarone (200 mg twice daily starting 7 days preoperatively and 200 mg once daily continuing for 30 days postoperatively) in patients without prior AF undergoing SM for oHCM from 2014 to 2018. The primary outcome was incident AF within 30 days. Secondary outcomes were unplanned readmission, AF treatment, total and intensive care unit (ICU) length of stay (LOS), and pacemaker implantation for high-grade atrioventricular (AV) block. 61 patients met inclusion criteria with 34 (55.8%) in the pre-intervention (control) group and 27 (44.2%) in the post-intervention (amiodarone) group. The incidence of POAF was 11.0% in the amiodarone group compared with 38.2% in the control group (P = 0.017). After adjusting for age, amiodarone was associated with less POAF [adjusted odds ratio (aOR) 0.21; 95% confidence interval (CI) 0.05, 0.76; P = 0.016]. ICU (2 days [IQR 1, 4] vs. 3 days [IQR 2, 4]; P = 0.165) and total (6 days [IQR 5, 6] vs. 6 days [IQR 5, 7]; P = 0.165) LOS were similar, as was the rate of pacemaker implantation (7.4% vs. 8.3%, P > 0.999). There were no adverse events associated with amiodarone. CONCLUSIONS: Perioperative oral amiodarone is safe and was associated with lower incidence of POAF following SM for oHCM.

Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes.

Heart failure remains a significant cause of morbidity and mortality following myocardial infarction. Cardiac remuscularization with transplantation of human pluripotent stem cell-derived cardiomyocytes is a promising preclinical therapy to restore function. Recent large animal data, however, have revealed a significant risk of engraftment arrhythmia (EA). Although transient, the risk posed by EA presents a barrier to clinical translation. We hypothesized that clinically approved antiarrhythmic drugs can prevent EA-related mortality as well as suppress tachycardia and arrhythmia burden. This study uses a porcine model to provide proof-of-concept evidence that a combination of amiodarone and ivabradine can effectively suppress EA. None of the nine treated subjects experienced the primary endpoint of cardiac death, unstable EA, or heart failure compared with five out of eight (62.5%) in the control cohort (hazard ratio = 0.00; 95% confidence interval: 0-0.297; p = 0.002). Pharmacologic treatment of EA may be a viable strategy to improve safety and allow further clinical development of cardiac remuscularization therapy.

Treatment of Postoperative New Onset Atrial Fibrillation with Repolarization Delaying Agents after Heart Surgery.

PURPOSE: The aim of this study was to evaluate the efficacy of the multichannel-blocker dronedarone for postoperative new onset atrial fibrillation (POAF) as compared to amiodarone. METHODS: Out of 990 patients who underwent cardiothoracic surgery between March 2011 and March 2012, 166 patients who developed POAF and treated with amiodarone or dronedarone were enrolled in this study. RESULTS: Eighty-nine patients were treated with amiodarone and 77 patients were treated with dronedarone at discharge. Seventy-five percent of patients with dronedarone were treated initially with intravenous amiodarone but quickly converted to oral dronedarone as soon as the mechanical ventilation was weaned off. The rate of conversion in sinus rhythm was not influenced by the resulting amiodarone-to-dronedarone crossover as compared to oral dronedarone only (p <0.247 at the ICU and p <0.640 at the normal care unit). At hospital discharge sinus rhythm was documented in 44% of the amiodarone patients and 99% of the dronedarone patients (p <0.001). The maintenance of sinus rhythm was demonstrated in 82% of the amiodarone patients versus 81% of the dronedarone patients at 6-month follow-up (p <0.804). CONCLUSIONS: Our data demonstrated the higher conversion rate to sinus rhythm in the early phase in the dronedarone group despite a comparable conversion rate in the mid-term phase compared to amiodarone.

Ivabradine Versus Amiodarone in the Management of Postoperative Junctional Ectopic Tachycardia: A Randomized, Open-Label, Noninferiority Study.

OBJECTIVES: This study sought to compare the efficacy of ivabradine and amiodarone in the management of postoperative junctional ectopic tachycardia (JET) after cardiac surgery in children. BACKGROUND: JET is a serious arrhythmia occurring in children after cardiac surgery and requires aggressive management. Amiodarone has been conventionally used in its treatment. Recent studies have reported the utility of ivabradine in this regard. METHODS: In this open-label randomized controlled trial, 94 children (age ≤18 years) who developed postoperative JET were allocated to receive either amiodarone or ivabradine. The primary endpoint was restoration of normal sinus rhythm. RESULTS: Sinus rhythm was achieved in 43 out of the 46 patients (93.5%) in the amiodarone group and 46 out of the 48 patients (95.8%) in the ivabradine group (mean difference of treatment effect: 2.3%; 95% confidence interval: -6.7% to 11.5%). The median (interquartile range) time taken to achieve sinus rhythm conversion was similar in both the groups: 21.5 (17-30.2) hours versus 22 (13.4-38.5) hours (p = 0.36)]. The time taken to rate control of JET was significantly less in the amiodarone group: median 7.0 (5.5-9.5) hours versus 8.0 (5.8-10.8) hours (p = 0.02)]. No drug-related adverse events were observed in the ivabradine group. CONCLUSIONS: Oral ivabradine is not inferior to intravenous amiodarone in converting postoperative JET to sinus rhythm. There was no difference in time taken to sinus rhythm conversion between the groups, although the rate control was earlier in patients who received amiodarone. Monotherapy with ivabradine may be considered as an alternative to amiodarone in the management of postoperative JET. (Comparison of Two Drugs, Ivabradine and Amiodarone, in the Management of Junctional Ectopic Tachycardia, an Abnormality in Cardiac Rhythm in Patients Under 18 years Who Undergo Cardiac Surgery: CTRI/2018/08/015182).

Prognostic benefits of prior amiodarone or ß-blocker use before the onset of ventricular arrhythmia with hemodynamic collapse.

Although antiarrhythmic drugs have long been used for the suppression of various types of arrhythmias, their prior use before the onset of ventricular arrhythmia with hemodynamic collapse and the effect on prognosis is not well known. Data from 1004 consecutive patients with cardiovascular shock in the Japanese Circulation Society's Shock Registry were analyzed. Eighty-four cases of ventricular arrhythmia-induced shock and ROSC (return of spontaneous circulation) were divided into the prior amiodarone or ß-blockers use group (Aß group, n = 27) and the non-amiodarone and non-ß-blockers use group (non-Aß group; n = 57) based on treatment before the onset of those arrhythmias. Clinical outcomes related to hemodynamic collapse such as OHCA (out-of-hospital cardiovascular arrest) was less in the Aß group [Aß group, 11/26 (42%) vs. non-Aß group, 41/56 (73%); p = 0.007]. Similarly, syncope was less common in the Aß group than in the non-Aß group [Aß group 4/27 (15%) vs. non-Aß group 27/57 (47%); p = 0.004]. Furthermore, prior amiodarone or ß-blockers use before the onset of ventricular arrhythmias was strongly associated with both survival at discharge (odds ratio 3.19; 95% confidence interval 1.06-9.67; p = 0.040) and neurological outcomes at discharge (odds ratio 3.96; 95% confidence interval 1.32-11.85; p = 0.014) based on multivariate logistic regression analysis. Prior amiodarone or ß-blockers use before the onset of malignant ventricular arrhythmia and maintaining appropriate blood concentrations in advance is associated with a good survival rate and better neurological outcomes after recovery from ventricular arrhythmia with hemodynamic collapse.

Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major.

INTRODUCTION: The aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy. METHODS: For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days. RESULTS: According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups. CONCLUSIONS: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.