Brinavess (vernakalant) / Astellas, Merck (MSD), Correvio, EddingPharm, ATCO Laboratories - LARVOL DELTA

RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department (clinicaltrials.gov) - P4 | N=350 | Completed | Sponsor: Ottawa Hospital Research Institute | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

Identification of KCNJ5 gene an adverse prognosis associated novel onco-ionchannel in Indian pancreatic cancer cohort. (PubMed, Discov Oncol) - "An onco-channel gene, KCNJ5 significantly upregulated, and showing adverse survival in highly expressed KCNJ5 group in Indian cohort of PanCa, can be targeted with Amiloride, Vernakalant hydrochloride, Dalfampridine, Glyburide Levcromakalim and protodioscin. This understanding can lead to novel target identification for PanCa therapy development."

Journal • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • GABBR2

In-silico insights into personalised therapy selection of anti-arrhythmic drugs and ablation using patient-specific biatrial models for atrial fibrillation (ESC 2024) - "Four commonly used AADs were evaluated: vernakalant, acute and chronic amiodarone, flecainide, and digoxin. This study demonstrates the significance of personalised treatment selection in optimising patient outcomes. Combined therapeutic interventions have shown synergistic benefits in AF termination, surpassing individual therapies in this patient-specific model cohort. This shows the translational potential of using patient-specific stratification to inform treatment selection."

Clinical • Atrial Fibrillation • Cardiovascular

Effect of Obesity on the Use of Antiarrhythmics in Adults With Atrial Fibrillation: A Narrative Review. (PubMed, Clin Cardiol) - "Antiarrhythmics are not uniformly affected by obesity. This observation is based on heterogeneous studies of participants with an average BMI and poorly controlled confounding factors such as multimorbidity, concomitant medications, varying routes of administration, and assessment of obesity. Controlled trials with stratification at the time of recruitment for obesity are necessary to determine the significance of these findings."

Journal • Review • Atrial Fibrillation • Cardiovascular • Genetic Disorders • Obesity

Analysis of drug-induced and spontaneous cardioversions reveals similar patterns leading to termination of atrial fibrillation. (PubMed, Front Physiol) - "Five independent groups of goats were investigated: (1) spontaneous termination of AF, and drug-induced terminations of AF by various potassium channel inhibitors: (2) AP14145, (3) PA-6, (4) XAF-1407, and (5) vernakalant...AF termination is preceded by an increased organization of fibrillatory conduction. The termination itself is a sudden process with a critical role for the interplay between spatiotemporal organization and anatomical structure."

Journal • Atrial Fibrillation • Cardiovascular

Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development. (PubMed, J Pharmacol Toxicol Methods) - "We investigated the effects of GPCR agonists (acetylcholine and carbachol), a Ca2+ channel agonist (S-Bay K8644), an HCN channel antagonist (ivabradine) and K+ channel antagonists (4-AP and vernakalant). In the context of this chamber-specific pharmacology, we not only add to contractile characterization of hiPSC-CMs but propose a multi-well platform for medium-throughput early compound screening. Overall, these insights illustrate the key pharmacological differences between chamber-specific cardiomyocytes and their application on a multi-well contractility platform to gain insights for in vitro cardiac liability studies and disease modelling."

Journal • Atrial Fibrillation • Cardiovascular

in-Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: The i-STRATIFICATION study. (PubMed, Europace) - "In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool."

Journal • Atrial Fibrillation • Cardiovascular

External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method."

Clinical • Journal • Retrospective data • Review • Anesthesia • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure

Effectiveness and safety of vernakalant vs flecainide for cardioversion of atrial fibrillation in the emergency department: the VERITA study. (PubMed, Emergencias) - No abstract available

Clinical • Journal • Atrial Fibrillation • Cardiovascular

Efficacy and Safety of Intravenous Vernakalant in Rapid Cardioversion of Recent Onset Atrial Fibrillation: A Retrospective Single-Centre Study. (PubMed, Cureus) - "Vernakalant had 61% efficacy in the rapid cardioversion of paroxysmal AF to sinus rhythm, was well tolerated, and had a low rate of adverse events in our study population."

Journal • Retrospective data • Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis. (PubMed, Cardiovasc Drugs Ther) - "Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4 h; flecainide is definitely among the most effective for cardioversion within 24 h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended."

Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular • Hypotension

JAK2 as a surface marker for enrichment of human pluripotent stem cells-derived ventricular cardiomyocytes. (PubMed, Stem Cell Res Ther) - "Our study lays the groundwork for the identification of cardiac subtype surface markers that allow purification of cardiomyocyte sub-populations. Our findings suggest that JAK2 can be employed as a cell surface marker for enrichment of hPSC-derived ventricular-like CMs."

Journal • Atrial Fibrillation • Cardiovascular • Heart Failure • Transplantation • CD200 • JAK2 • SIRPA

Efficacy And Safety Outcome Of Intravenous Vernakalant For Recent-onset Atrial Fibrillation: A Systematic Review And Meta-analysis (AHA 2023) - "This hypothesis-generating study showed that intravenous vernakalant, though associated with a higher incidence of bradycardia and dysgeusia, is superior to placebo, Flecainide, and Amiodarone not Ibutilide in converting ROAF to sinus rhythm."

Retrospective data • Review • Atrial Fibrillation • Cardiovascular

Pharmacological cardioversion of atrial fibrillation: practical considerations. (PubMed, Pol Arch Intern Med) - "In patients without structural heart disease, complications occur rarely, hence traditional (propafenone, flecainide) or nonclassical Vaughan-Williams class I (antazoline) or class III (vernakalant, ibutilide or dofetilide) drugs are preferred. The presence of structural heart disease consistent with any left ventricular hypertrophy, heart failure, myocardial ischemia or valvular heart disease confines the choice of AAD to amiodarone. Given the risk of ventricular proarrhythmia of AAD, safety should always prevail over the enticing possibility of rhythm conversion. The present review aims to provide a comprehensible summary of proper qualification for PC, selection of suitable AAD and state-of-the-art periprocedural management of patients with recent-onset AF."

Journal • Anesthesia • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Ischemia

Amiodarone loading dosage in the treatment of postoperative atrial fibrillation: high versus standard dose treatment (ESC 2023) - "Although some drugs such as intravenous vernakalant, dofetilide, and ibutilide are effective in restoring sinus rhythm, but they are not common countries. Higher loading amiodarone dosage seems more effective than standard amiodarone protocol by the reason of earlier time in restoring sinus rhythm."

Atrial Fibrillation • Cardiovascular • Myocardial Infarction

Optical Mapping in Atrial Engineered Heart Tissues Reveals Proarrhythmic Potential of the Anti-AF Agent Vernakalant (AHA 2022) - "Optical mapping of chamber specific EHTs confirms atrial specific nature of VER as an atrial repolarization prolonging agent but raises unexpected concerns regarding potential proarrhythmic toxicity related to atrial conduction slowing."

Atrial Fibrillation

Utilizing human induced pluripotent stem cells to study atrial arrhythmias in the short QT syndrome. (PubMed, J Mol Cell Cardiol) - "Patient-specific hiPSC-based atrial cellular and tissue models of the SQTS were established, which provide examples on how this type of modeling can shed light on the pathogenesis and pharmacological treatment of inherited atrial arrhythmias."

Journal • Atrial Fibrillation • Cardiovascular • KCNH2

SELECTCARFAP: Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents (clinicaltrials.gov) - P4 | N=50 | Completed | Sponsor: David Filgueiras-Rama | Recruiting ➔ Completed

Biomarker • Trial completion • Atrial Fibrillation • Cardiovascular

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria. (PubMed, J Physiol) - "Vernakalant was effective in atria presenting long refractoriness (median I density 0.13 ± 0.05 S mF ). For short refractoriness, atria with fast Na current (I ) up-regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low I . The inward currents (I and I ) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics."

Journal • Atrial Fibrillation • Cardiovascular

"Acutely in PAF you can try Vernakalant as an alternative" (@FadyMFouad)

Characterization of electropharmacological profile of an anti-atrial fibrillatory drug vernakalant along with potential risk toward torsade de pointes: Translational studies using isoflurane-anesthetized dogs and isolated rat aortic preparations. (PubMed, J Pharmacol Sci) - "We compared them with those of known anti-atrial fibrillatory drugs; ranolazine, amiodarone, dronedarone, dl-sotalol and bepridil. The magnitude of vernakalant to alter those variables was the greater among those drugs except that the atrial selectivity was the lesser of those. Thus, vernakalant is expected to be efficacious against atrial fibrillation, but caution should be excised on its use for patients having labile ventricular function and repolarization."

Journal • Preclinical • Anesthesia • Atrial Fibrillation • Cardiovascular

Bayesian Network Meta-analysis of Randomized Controlled Trials on the Efficacy of Antiarrhythmics in the Pharmacological Cardioversion of Paroxysmal Atrial Fibrillation. (PubMed, Am J Cardiovasc Drugs) - "In comparing the antiarrhythmic agents used to restore sinus rhythm in the case of paroxysmal AF, vernakalant, amiodarone-ranolazine, flecainide, and ibutilide are the most effective medications. The verapamil-quinidine combination seems promising, though few RCTs have studied it. The incidence of side effects must be taken into account in the choice of antiarrhythmic in clinical practice."

Retrospective data • Review • Atrial Fibrillation • Cardiovascular

Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: University of Calgary | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Surgery • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

SELECTCARFAP: Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents (clinicaltrials.gov) - P4 | N=50 | Recruiting | Sponsor: David Filgueiras-Rama | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Biomarker • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

Effectiveness and Safety Profiles of Vernakalant for Cardioversion of acute-onset Atrial Fibrillation: A Systematic Review and Meta-analysis. (PubMed, Clin Ther) - "Vernakalant appears to be a good choice when AF is manifested postoperatively or exists with ischemic heart disease and valvular states. Tolerability-related data are promising, but a specific trial may be required to identify the causes of the deaths considered unrelated to vernakalant use. (Clin Ther. 2023;45:XXX-XXX)"

Clinical • Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular • Coronary Artery Disease • Heart Failure • Hypotension