dofetilide / Generic mfg. - LARVOL DELTA

Quinidine-Induced Microvolt Electrocardiographic Alternans. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc) - "The study population belongs to the "ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects" database. Furthermore, ECGA magnitude seemed to reveal transient changes better than amplitude, resulting in more post-dose time points, especially in the range 3.5-7 hours after quinidine administration, at which ECGA was statistically different than at the pre-dose time point. Thus, ECGA appears to disclose the higher risk of arrhythmia associated with quinidine.Clinical Relevance- The present study provides a contribution to guide therapy involving quinidine through the analysis of its proarrhythmic risk by electrocardiographic alternans."

Journal • Cardiovascular

Dofetilide in Atrial Fibrillation: A Comprehensive Review. (PubMed, Indian Pacing Electrophysiol J) - "However, its use is limited by concerns regarding torsades de pointes, mandatory in-hospital initiation, and stringent monitoring requirements. This review provides a comprehensive analysis of dofetilide, including its pharmacology, clinical trial evidence, safety profile, guideline recommendations, role in special populations, real-world application in India, and future perspectives."

Journal • Review • Atrial Fibrillation • Cardiovascular • Heart Failure

Integrating drug effects on individual cardiac ionic currents and cardiac action potentials to understand nonclinical translation to clinical ECG changes. (PubMed, Front Pharmacol) - "The results showed that hERG block-mediated QTC prolongation with dofetilide was shortened by co-administration of lidocaine or mexiletine-drugs that inhibit INaL...Consistent with this interpretation, nifedipine, which preferentially inhibits ICaL over hERG (ICaL: 13.2 nM; hERG: 35 μM; ratio = 2,651) caused APD shortening without AP triangulation. Results from this study thus support the following: 1) diltiazem failed to reduce moxifloxacin-induced QTC prolongation due to its concomitant hERG block at clinical exposure levels; and 2) the importance of using physiologically relevant protocols to generate ion channel pharmacology and obtaining functional recordings from myocytes to provide a better understanding of nonclinical data translation to clinical ECG signals. Data used in this manuscript, including the original electrophysiology records, may be found at: https://osf.io/69ght/."

Journal

Characteristics and Outcomes of Mavacamten Use in 2440 Patients With Obstructive Hypertrophic Cardiomyopathy. (PubMed, J Am Heart Assoc) - "Over an 8-month median follow-up on mavacamten in patients with obstructive hypertrophic cardiomyopathy, new AF/AFL and HF occurred in 5% and 4%, respectively. Further work is needed to better understand the expected incidence of AF/AFL, HF, and other long-term outcomes of mavacamten treatment in obstructive hypertrophic cardiomyopathy."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hypertrophic Cardiomyopathy • Obesity • Obstructive Hypertrophic Cardiomyopathy • Ventricular Tachycardia

Safety of Dofetilide Initiation Following a Shortened Amiodarone Washout Period (AHA 2025) - "In this cohort, dofetilide initiation less than 90 days after amiodarone discontinuation was not associated with increased torsades de pointes risk. These data challenge and support reconsideration of the blanket 3-month washout and suggest that a monitored, expedited rhythm-control transition is feasible and safe."

Clinical • Atrial Fibrillation • Cardiovascular

Comparative 1-Year Outcomes of Dofetilide Versus Amiodarone for Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Propensity-Matched Study. (AHA 2025) - "In this large, real-world, propensity-matched analysis of HCM patients with AF, dofetilide was associated with markedly improved one-year survival and reduced major adverse cardiovascular events compared to amiodarone, despite higher AF recurrence rates. These findings challenge conventional amiodarone preference in structural heart disease and support prospective randomized trials to optimize antiarrhythmic strategies in this high-risk population."

Atrial Fibrillation • Cardiomyopathy • Cardiovascular • CNS Disorders • Heart Failure • Hypertrophic Cardiomyopathy • Ischemic stroke • Myocardial Infarction • Nephrology • Renal Disease • Ventricular Tachycardia

Silent Fibrosis, Loud Signals: Early-Onset Atrial Arrhythmias as the Sentinel of Familial Restrictive Cardiomyopathy (AHA 2025) - "We present a compelling case of longstanding atrial fibrillation (Afib) and atrial flutter (AFL) culminating in refractory cardiogenic shock, ultimately revealing an undiagnosed restrictive cardiomyopathy.Case:A 40-year-old male with a history of persistent Afib and AFL, unremarkable cardiac MRI on first occurrence for atrial arrhythmias, presented with dyspnea, dizziness, fatigue, and palpitations while on dofetilide...Identifying RCM through advanced imaging or genetic screening is crucial, as it enables early consideration of interventions, such as evaluation for OHT, which may prevent catastrophic outcomes. Proactive screening and repeat imaging, such as cardiac MRI, in patients with incessant atrial arrhythmias who also have a significant familial burden, can mitigate delays in treatment and improve prognosis."

Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fatigue • Fibrosis • Heart Failure • Immunology • Pulmonary Disease

Longitudinal Evaluation of Anti-Arrhythmic Drug Use to Predict Hospitalization or Death in Patients with Ventricular Tachycardia (AHA 2025) - "From then, use of AADs (beta-blockers, sotalol, amiodarone, dofetilide, mexiletine) in the three years following were assessed on a quarterly basis. Linking AAD use with clinical outcomes is an important first step in identifying which patient profiles respond to which individual AADs and developing tailored VT treatment approaches. Here, we demonstrate profiles of VT patients at higher risk for hospitalization or death based on individual AADs."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Ventricular Tachycardia

Impact of Antiarrhythmic Use on Primary Graft Dysfunction in Orthotopic Heart Transplant Patients: A Single Center Retrospective Cohort Study (AHA 2025) - "Anti-arrhythmic medications such as amiodarone have been noted to increase the risk of PGD and thus normally discontinued when patients reach a UNOS level 1-3 status...Out of the patients who had OHT and antiarrhythmics up till the day of transplant; 11 were on mexiletine; 9 were on sotalol; 7 were on digoxin; 2 were on dofetilide; and 1 on quinidine, lidocaine, and disopyramide respectively... Patients on sotalol had 5.49 times more odds off having PGD post-transplant and this was statistically significant regardless of age, gender and race."

Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation

Deep Learning–Based Continuous QT Monitoring Identifies High-Risk Prolongation Events After Class III Antiarrhythmic Initiation (AHA 2025) - "A). We retrospectively analyzed 72,919 outpatient ECGs from 1,676 patients who were on dofetilide or sotalol across 2,083 unique outpatient encounters (Stanford, 2008–2024). One in six patients had documented QTc prolongation after discharge and had a fourfold increase of critical ventricular arrhythmia risk. 3DRECON-QT accurately identified these events from single-lead derived ICM signals, supporting its potential to close the outpatient surveillance gap in QT interval/risk monitoring."

Cardiovascular

The High Cost of Rhythm Control: A Rare Case of Dofetilide-Induced Liver Injury (ACG 2025) - "Introduction: Dofetilide, a class III antiarrhythmic agent, is generally regarded as having minimal hepatotoxicity compared to other drugs in its class, specifically amiodarone. In our patient, the Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 7, signifying a probable link between the drug and the observed liver injury. This case adds to limited literature and underscores the need for baseline and early post-initiation liver-function monitoring when prescribing dofetilide."

Clinical • Cholestasis • Gastroenterology • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Movement Disorders

Mexiletine as Adjunctive Therapy in Atrial Fibrillation Following Dofetilide Treatment Failure. (PubMed, Circ Arrhythm Electrophysiol) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Class III Antiarrhythmic Drug Cavutilide Does Not Increase the Susceptibility of the Ventricles to Phenylephrine-Induced Tachyarrhythmias Due to the Direct Dependence of the Effect on the Frequency of Myocardial Activation. (PubMed, Bull Exp Biol Med) - "The reference antiarrhythmic drug dofetilide under the same model conditions caused prolonged, multiple episodes of monomorphic ventricular tachycardia and frequent, repetitive paroxysms of high-frequency TdP. Thus, cavutilide demonstrates very low tendency to induce TdP under conditions of impaired myocardial perfusion, which can be explained by direct type of the dependence of its effect on the frequency of myocardium activation."

Journal • Anesthesia • Atrial Fibrillation • Cardiovascular • Ventricular Tachycardia

Sex-specific human electromechanical multiscale in-silico models for virtual therapy evaluation. (PubMed, J Mol Cell Cardiol Plus) - "Simulations predicted exacerbated QTc prolongation under Dofetilide in women (54-78 % higher than males) and T-wave amplitude reduction in men (max: -0.25 mV). Verapamil increased T-wave amplitude in females and decreased it in males, without affecting QTc...Sex differences in repolarisation reserve, calcium handling, and anatomy are key factors underpinning ECG and LVEF responses to drugs. Specifically, under calcium block, females showed more preserved LVEF, while under hERG block, females showed more QTc prolongation."

Journal • Cardiovascular

LQT-1213-0061: Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2). (clinicaltrials.gov) - P1/2 | N=42 | Terminated | Sponsor: Thryv Therapeutics, Inc. | N=28 ➔ 42 | Active, not recruiting ➔ Terminated; Advancing an alternative SGK1 inhibitor.

Enrollment change • Trial termination • Cardiovascular • KCNH2

The Time Course of Repolarization Effects of Intravenous Dofetilide: a Pure Class III Anti-Arrhythmic Agent. (PubMed, Am J Cardiol) - "The early effect of IV dofetilide on cardiac repolarization suggests dofetilide clinically utility with an immediate anti-arrhythmic action. Future clinical studies are indicated to determine optimum dosing, efficacy as well as safety."

Journal

Practical guide to concentration-QTc modeling: a hands-on tutorial. (PubMed, J Pharmacokinet Pharmacodyn) - "The tutorial uses real data from a previously published QT study by (Johannesen et al.Clin Pharmacol Ther 96(5):549-558 2014), focusing on two active treatments (dofetilide and verapamil) and placebo to illustrate positive and negative QT signals. Reproducibility of this workflow is ensured through the use of pkgr to manage R packages. The R codes provided as part of this tutorial were successfully used for several projects within the AstraZeneca portfolio and accepted by health authorities as part of QTc submissions."

Journal

Legacy hERG study data in contemporary integrated risk assessments - mitigating the risk of protocol and positive control article differences. (PubMed, J Pharmacol Toxicol Methods) - "The three key positive control articles, dofetilide, moxifloxacin and ondansetron were compared under the 'Legacy Protocol' and best practice 'Revised Protocol'. The inhibition of hERG current for 60 nM terfenadine in the 3627 historical examples was also consistent with predictions based on the hERG IC50 and Hill slope data under the two protocols. Based on the similarity between results collected under 'Legacy' and 'Revised' protocols we conclude that if the 'Legacy Protocol' has been used and the positive control examined was 60 nM terfenadine, there appears to be no need to repeat the hERG assessment."

Journal

Navigating Metastatic Thyroid Cancer in the Context of Amiodarone Induced Iodine Overload (ENDO 2025) - "Post-thyroidectomy hypothyroidism was treated with levothyroxine (175 mcg/day), maintaining TSH <0.1 mIU/L due to metastatic disease.Diagnostic RAI imaging was contraindicated by iodine saturation...Discontinuing amiodarone and initiating dofetilide to facilitate iodine clearance.2...Considering tyrosine kinase inhibitors if disease progressed while awaiting RAI eligibility.Currently, she remains clinically stable without significant progression, and future RAI eligibility is under reassessment.Clinical Lessons:This case highlights the unique complexities of managing metastatic PTC in the context of iodine excess from chronic amiodarone use. Key clinical lessons include:• Chronic amiodarone-induced iodine overload demands strategic tapering of amiodarone and the use of alternative antiarrhythmics.• Maintaining TSH suppression is critical to limiting tumor growth in metastatic PTC.• Close collaboration among endocrinology, cardiology, and oncology balances arrhythmia..."

Metastases • Atrial Fibrillation • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • NKX2-1 • PAX8

Arrhythmia Inducibility in the CAVB Dog Model, A Critical Analysis on Underlying Factors. (PubMed, Cardiovasc Toxicol) - "Differences in cardiac parameters disappeared upon dofetilide infusion. We discuss that prolonged repolarization and increased contractility may be early indications of calcium-mediated early after depolarization that may develop into TdP arrhythmias."

Journal • Cardiovascular

Characterization of a human wearable ECG device for continuous data collection in freely moving non-rodents. (PubMed, J Pharmacol Toxicol Methods) - "Mean Dofetilide-dependent QT changes over time were not different between devices and calculated Δ∆ QTci EC+10ms were < 2× between devices within species. Overall, these studies demonstrated the feasibility of using alternative devices and increasing options to collect in-cage ECG to collect nonclinical safety pharmacology and toxicology endpoints."

Journal • Preclinical

Exploring Public Interest in Atrial Fibrillation and Its Treatment Measures: A Google Trends Analysis. (PubMed, Cureus) - " This study demonstrates a rising public interest in AF. Searches related to medications such as amiodarone, metoprolol, diltiazem, and flecainide, as well as procedures including cardioversion, artificial cardiac pacemaker, and left atrial appendage occlusion, have all shown increasing trends."

Journal • Atrial Fibrillation • Cardiovascular • Respiratory Syncytial Virus Infections

NaV1.5 or KCa2 channel blockade does not increase arrhythmia risk in hypokalemic rabbit hearts, unlike KV11.1 inhibition with dofetilide. (PubMed, Int J Cardiol Heart Vasc) - "Neither of the KCa2 channel inhibitors (AP14145 or AP30663) or flecainide (NaV1.5 inhibitor) prolonged ventricular action potential duration (APD90) or increased pro-arrhythmic markers, whereas dofetilide (KV11.1 blocker) prolonged APD and increased the susceptibility to ventricular arrhythmia. These findings suggests that KCa2 channels have minimal importance for ventricular repolarization in healthy rabbit hearts under both normo- and hypokalemic conditions."

Journal • Preclinical • Atrial Fibrillation • Cardiovascular • NAV1

Sex-based Disparities in Class III Antiarrhythmic Drug-induced QT Prolongation: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (ATS 2025) - "Thus, we analyzed the FDA Adverse Event Reporting System (FAERS) to evaluate sex-based differences in QTc prolongation events associated with sotalol, dofetilide, and amiodarone. Female sex hormones estrogen and progesterone have been demonstrated to have varying effects on QT prolongation. FAERS data for class III antiarrhythmics presented above demonstrates a differential risk of QT prolongation and TdP amongst females, dependent on ADD. This may be partially explained by the proposed effects of estrogen and progesterone on rectifier potassium channels."

Adverse events • Atrial Fibrillation • Cardiovascular

Concomitant Usage of Contra-Indicated Medications in Patients With Atrial Fibrillation: A Comparison of Real-World Data Sources in the United States (ISPOR 2025) - "Rates of concomitant medication usage with Dofetilide and a contra-indicated medication (Cimetidine, Verapamil, Ketoconazole, Trimethoprim, or Hydrochlorothiazide) were analyzed within 12 months of Dofetilide initiation. The analysis shows an example of significant differences in open and closed claims sources when studying the same concomitant contra-indication medication usage. Selecting appropriate datasets is critical to accurately assess treatment patterns, minimize data biases, and ensure findings are relevant for real-world clinical decision-making."

Clinical • Real-world • Real-world evidence • Atrial Fibrillation • Cardiovascular