-
Journal of Critical Care May 2024The echocardiography parameters may predict the maintenance of sinus rhythm after cardioversion of a supraventricular arrhythmia (SVA).
PURPOSE
The echocardiography parameters may predict the maintenance of sinus rhythm after cardioversion of a supraventricular arrhythmia (SVA).
MATERIALS AND METHODS
Patients in septic shock with onset of an SVA, normal to moderately reduced LV systolic function (EF_LV˃̳35%) and on a continuous noradrenaline of <1.0 μg/kg.min were included. Echocardiography was performed at the arrhythmia onset, 1 h and 4 h post cardioversion on an infusion of propafenone or amiodarone.
RESULTS
Cardioversion was achieved in 96% of the 209 patients within a median time of 6(1.8-15.6)h, 134(64.1%) patients experienced at least one SVA recurrence after cardioversion. At 4 h the left atrial emptying fraction (LA_EF, cut-off 38.4%, AUC 0.69,p˂0.001), and transmitral A wave velocity-time-integral (Avti, cut-off 6.8 cm, AUC 0.65,p = 0.001) showed as limited predictors of a single arrhythmia recurrence. The LA_EF 44(36,49)%, (p = 0.005) and the Avti 8.65(7.13,9.50)cm, (p < 0.001) were associated with sustained sinus rhythm and decreased proportionally to increasing numbers of arrhythmia recurrences (p < 0.001 and p = 0.007, respectively). The enlarged left atrial end-systolic diameter at the arrhythmia onset (p = 0.04) and elevated systolic pulmonary artery pressure at 4 h (p = 0.007) were weak predictors of multiple(˃3) recurrences.
CONCLUSION
The LA_EF and Avti are related to arrhythmia recurrences post-cardioversion suggesting potential guidance to the choice between rhythm and rate control strategies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03029169, registered on 24th of January 2017.
PubMed: 38759581
DOI: 10.1016/j.jcrc.2024.154832 -
Biomedicine & Pharmacotherapy =... Jun 2024Chagasic chronic cardiomyopathy (CCC) is the primary clinical manifestation of Chagas disease (CD), caused by Trypanosoma cruzi. Current therapeutic options for CD are...
Chagasic chronic cardiomyopathy (CCC) is the primary clinical manifestation of Chagas disease (CD), caused by Trypanosoma cruzi. Current therapeutic options for CD are limited to benznidazole (Bz) and nifurtimox. Amiodarone (AMD) has emerged as most effective drug for treating the arrhythmic form of CCC. To address the effects of Bz and AMD we used a preclinical model of CCC. Female C57BL/6 mice were infected with T. cruzi and subjected to oral treatment for 30 consecutive days, either as monotherapy or in combination. AMD in monotherapy decreased the prolonged QTc interval, the incidence of atrioventricular conduction disorders and cardiac hypertrophy. However, AMD monotherapy did not impact parasitemia, parasite load, TNF concentration and production of reactive oxygen species (ROS) in cardiac tissue. Alike Bz therapy, the combination of Bz and AMD (Bz/AMD), improved cardiac electric abnormalities detected T. cruzi-infected mice such as decrease in heart rates, enlargement of PR and QTc intervals and increased incidence of atrioventricular block and sinus arrhythmia. Further, Bz/AMD therapy ameliorated the ventricular function and reduced parasite burden in the cardiac tissue and parasitemia to a degree comparable to Bz monotherapy. Importantly, Bz/AMD treatment efficiently reduced TNF concentration in the cardiac tissue and plasma and had beneficial effects on immunological abnormalities. Moreover, in the cardiac tissue Bz/AMD therapy reduced fibronectin and collagen deposition, mitochondrial damage and production of ROS, and improved sarcomeric and gap junction integrity. Our study underlines the potential of the Bz/AMD therapy, as we have shown that combination increased efficacy in the treatment of CCC.
Topics: Animals; Nitroimidazoles; Female; Disease Models, Animal; Trypanosoma cruzi; Amiodarone; Mice, Inbred C57BL; Drug Therapy, Combination; Chagas Cardiomyopathy; Trypanocidal Agents; Mice; Chagas Disease; Reactive Oxygen Species; Chronic Disease; Parasitemia; Tumor Necrosis Factor-alpha; Parasite Load
PubMed: 38754265
DOI: 10.1016/j.biopha.2024.116742 -
Cureus Apr 2024Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to... (Review)
Review
Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively in cardiac surgeries. However, there is a lack of consensus on the use of amiodarone and other antiarrhythmic drugs as prophylaxis to reduce the occurrence of all types of postoperative arrhythmias in cardiac and non-cardiac surgeries. A comprehensive PubMed query yielded 614 relevant papers, of which 52 clinical trials were analyzed. The data collection included the class of antiarrhythmics, timing or method of drug administration, surgery type, type of arrhythmia and its incidence, and hospitalization length. Statistical analyses focused on prophylactic antiarrhythmics and their respective reductions in postoperative arrhythmias and hospitalization length. Prophylactic amiodarone alone compared to placebo demonstrated a significant reduction in postoperative arrhythmia incidence in cardiac and non-cardiac surgeries (24.01%, p<0.0001), and it was the only treatment group to significantly reduce hospitalization length versus placebo (p = 0.0441). Prophylactic use of class 4 antiarrhythmics versus placebo also demonstrated a significant reduction in postoperative arrhythmia incidence (28.01%, p<0.0001), and while there was no significant statistical reduction compared to amiodarone (4%, p=0.9941), a lack of abundant data provides a case for further research on the prophylactic use of class 4 antiarrhythmics for this indication. Amiodarone prophylaxis remains a prime cornerstone of therapy in reducing postoperative arrhythmia incidence and hospitalization length. Emerging data suggests a need for a broader exploration of alternative antiarrhythmic agents and combination therapies, particularly class 4 antiarrhythmics, in both cardiac and non-cardiac surgeries. This meta-analysis depicts the effectiveness of amiodarone, among other antiarrhythmics, in postoperative arrhythmia incidence and hospitalization length reduction in cardiac and non-cardiac surgeries.
PubMed: 38738095
DOI: 10.7759/cureus.57963 -
Scientific Reports May 2024Human liver organoids are in vitro three dimensionally (3D) cultured cells that have a bipotent stem cell phenotype. Translational research of human liver organoids for...
Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research.
Human liver organoids are in vitro three dimensionally (3D) cultured cells that have a bipotent stem cell phenotype. Translational research of human liver organoids for drug discovery has been limited by the challenge of their low hepatic function compared to primary human hepatocytes (PHHs). Various attempts have been made to develop functional hepatocyte-like cells from human liver organoids. However, none have achieved the same level of hepatic functions as PHHs. We here attempted to culture human liver organoids established from cryopreserved PHHs (PHH-derived organoids), using HYDROX, a chemically defined 3D nanofiber. While the proliferative capacity of PHH-derived organoids was lost by HYDROX-culture, the gene expression levels of drug-metabolizing enzymes were significantly improved. Enzymatic activities of cytochrome P450 3A4 (CYP3A4), CYP2C19, and CYP1A2 in HYDROX-cultured PHH-derived organoids (Org-HYDROX) were comparable to those in PHHs. When treated with hepatotoxic drugs such as troglitazone, amiodarone and acetaminophen, Org-HYDROX showed similar cell viability to PHHs, suggesting that Org-HYDROX could be applied to drug-induced hepatotoxicity tests. Furthermore, Org-HYDROX maintained its functions for up to 35 days and could be applied to chronic drug-induced hepatotoxicity tests using fialuridine. Our findings demonstrated that HYDROX could possibly be a novel biomaterial for differentiating human liver organoids towards hepatocytes applicable to pharmaceutical research.
Topics: Humans; Hepatocytes; Organoids; Cell Differentiation; Nanofibers; Cells, Cultured; Liver; Chemical and Drug Induced Liver Injury; Cell Survival; Cytochrome P-450 CYP3A
PubMed: 38736008
DOI: 10.1038/s41598-024-61544-y -
Journal of Cardiothoracic Surgery May 2024To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG)... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of intraoperative intravenous amiodarone in patients undergoing on-pump coronary artery bypass grafting surgery: a systemic review and PRISMA-compliant meta-analysis.
BACKGROUND
To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG) patients.
METHODS
A meta-analysis of randomized controlled trials was conducted. Pubmed, Embase, Cochrane Library, Ovid, China National Knowledge Infrastructure, and the Wan Fang database until July 1th, 2023. The primary outcomes of interest included the incidences of intra- and post-operative atrial fibrillation (POAF), ventricular fibrillation, or any arrhythmia, including atrial fibrillation, ventricular fibrillation, ventricular tachycardia, premature ventricular contraction, and sinus bradycardia. For continuous and dichotomous variables, treatment effects were calculated as the weighted mean difference (WMD)/risk ratio (RR) and 95% confidence interval (CI).
RESULTS
A database search yielded 7 randomized controlled trials including 608 patients, where three studies, including three treatments (amiodarone, lidocaine, and saline), contributed to the clinical outcome of atrial fibrillation, ventricular fibrillation, or any arrhythmia. Meta-analysis demonstrated that amiodarone can significantly reduce the incidence of POAF (RR, 0.39; 95%CI: 0.20, 0.77; P = 0.007, I = 0%) in patients undergoing on-pump CABG; there was no statistically significant influence on intra-operative atrial fibrillation, intra- and post-operative ventricular fibrillation, or any arrhythmia.
CONCLUSIONS
The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on-pump CABG. More well-designed clinical trials are needed to validate this result.
Topics: Humans; Amiodarone; Coronary Artery Bypass; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Intraoperative Care; Administration, Intravenous; Postoperative Complications; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38702789
DOI: 10.1186/s13019-024-02732-9 -
Journal of Medical Case Reports May 2024Amiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism... (Review)
Review
BACKGROUND
Amiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism can precipitate cardiac complications, including cardiac ischemia and myocardial infarction, although this has only been described in a few case reports.
CASE PRESENTATION
We present here a clinical scenario involving a 66-year-old male Caucasian patient under Amiodarone for atrial fibrillation, who developed AIT. In the presence of dyspnea, multiple cardiovascular risk factors and ECG abnormalities, a transthoracic echocardiogram was performed, showing inferobasal hypokinesia. This led to further investigations through a cardiac PET-CT, where cardiac ischemia was suspected. Ultimately, the coronary angiography revealed no abnormalities. Nonetheless, these extensive cardiologic investigations led to a delay in initiating an emergency endovascular revascularization for acute-on-chronic left limb ischemia. Although initial treatment using Carbimazole was not successful after three weeks, the patient reached euthyroidism after completion of the treatment with Prednisone so that eventually thyroidectomy was not performed. Endovascular revascularization was finally performed after more than one month.
CONCLUSIONS
We discuss here cardiac abnormalities in patients with AIT, which may be due to relative ischemia secondary to increased metabolic demand during hyperthyroidism. Improvement of cardiac complications is expected through an optimal AIT therapy including medical therapy as the primary approach and, when necessary, thyroidectomy. Cardiac investigations in the context of AIT should be carefully considered and may not justify delaying other crucial interventions. If considered mandatory, diagnostic procedures such as coronary angiography should be preferred to functional testing.
Topics: Humans; Amiodarone; Male; Aged; Anti-Arrhythmia Agents; Myocardial Ischemia; Atrial Fibrillation; Positron Emission Tomography Computed Tomography; Hyperthyroidism; Echocardiography
PubMed: 38698496
DOI: 10.1186/s13256-024-04552-w -
JTCVS Open Apr 2024Postoperative atrial fibrillation (POAF) is a prevalent complication following cardiac surgery that is associated with increased adverse events. Several guidelines and...
Enhanced Recovery After Surgery Cardiac Society turnkey order set for prevention and management of postoperative atrial fibrillation after cardiac surgery: Proceedings from the American Association for Thoracic Surgery ERAS Conclave 2023.
BACKGROUND
Postoperative atrial fibrillation (POAF) is a prevalent complication following cardiac surgery that is associated with increased adverse events. Several guidelines and expert consensus documents have been published addressing the prevention and management of POAF. We aimed to develop an order set to facilitate widespread implementation and adoption of evidence-based practices for POAF following cardiac surgery.
METHODS
Subject matter experts were consulted to translate existing guidelines and literature into a sample turnkey order set (TKO) for POAF. Orders derived from consistent class I or IIA or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the TKO in bold type. Selected orders that were inconsistently class I or IIA, class IIB, or supported by published evidence appear in italic type.
RESULTS
Preoperatively, the recommendation is to screen patients for paroxysmal or chronic atrial fibrillation and initiate appropriate treatment based on individual risk stratification for the development of POAF. This may include the administration of beta-blockers or amiodarone, tailored to the patient's specific risk profile. Intraoperatively, surgical interventions such as posterior pericardiotomy should be considered in selected patients. Postoperatively, it is crucial to focus on electrolyte normalization, implementation strategies for rate or rhythm control, and anticoagulation management. These comprehensive measures aim to optimize patient outcomes and reduce the occurrence of POAF following cardiac surgery.
CONCLUSIONS
Despite the well-established benefits of implementing a multidisciplinary care pathway for POAF in cardiac surgery, its adoption and implementation remain inconsistent. We have developed a readily applicable order set that incorporates recommendations from existing guidelines.
PubMed: 38690434
DOI: 10.1016/j.xjon.2024.02.008 -
Texas Heart Institute Journal Apr 2024Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart...
BACKGROUND
Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity.
METHODS
A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed.
RESULTS
The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included β-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months.
CONCLUSION
Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.
Topics: Humans; Dronedarone; Male; Retrospective Studies; Female; Adult; Heart Defects, Congenital; Anti-Arrhythmia Agents; Treatment Outcome; Heart Rate; Atrial Fibrillation; Amiodarone; Time Factors
PubMed: 38686681
DOI: 10.14503/THIJ-22-7993 -
International Journal of Molecular... Apr 2024Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper"...
Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. These studies provided a rationale for testing the effect of HJP272, an endothelin receptor antagonist (ERA), in hamster models of pulmonary fibrosis induced by intratracheal instillation of either bleomycin (BLM) or amiodarone (AM). To determine the temporal effects of blocking ET-1 activity, animals were given HJP272 either 1 h before initiation of lung injury or 24 h afterward. The results indicated that pretreatment with this agent caused significant reductions in various inflammatory parameters, whereas post-treatment was ineffective. This finding suggests that ERAs are only effective at a very early stage of pulmonary fibrosis and explains their lack of success in clinical trials involving patients with this disease. Nevertheless, ERAs could serve as prophylactic agents when combined with drugs that may induce pulmonary fibrosis. Furthermore, developing a biomarker for the initial changes in the lung extracellular matrix could increase the efficacy of ERAs and other therapeutic agents in preventing the progression of the disease. While no such biomarker currently exists, we propose the ratio of free to peptide-bound desmosine, a unique crosslink of elastin, as a potential candidate for detecting the earliest modifications in lung microarchitecture associated with pulmonary fibrosis.
Topics: Animals; Pulmonary Fibrosis; Endothelin Receptor Antagonists; Bleomycin; Cricetinae; Disease Models, Animal; Male; Lung; Humans; Endothelin-1
PubMed: 38673771
DOI: 10.3390/ijms25084184