Trial reportHeart rhythm2016
The positive frequency-dependent electrophysiological effects of the IKur inhibitor XEN-D0103 are desirable for the treatment of atrial fibrillation.
Trial report in Heart rhythm, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.Cardiovascular research · 2026Article
- The mechanism of electrical remodeling in atrial fibrillation and current research status of natural drugs and active ingredients inhibiting atrial electrical remodeling.Frontiers in cardiovascular medicine · 2026Review
- Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies.Current issues in molecular biology · 2025Review
- KFrontiers in physiology · 2025Article
- Effects of SZV-2649, a new multiple ion channel inhibitor mexiletine analogue.Scientific reports · 2024Article
- Ubiquitination is involved in PKC-mediated degradation of cell surface Kv1.5 channels.The Journal of biological chemistry · 2024Article
- Human induced pluripotent stem cell-derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents IKs to repolarization in the human atrium.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM.Stem cell reports · 2023Article
- Inhibitory effects of N-methyl-D-aspartate (NMDA) and αNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Targeting ion channels with ultra-large library screening for hit discovery.Frontiers in molecular neuroscience · 2023Review
- Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective.Frontiers in physiology · 2023Review
- The contribution of ion channels to shaping macrophage behaviour.Frontiers in pharmacology · 2022Review
- Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- New Strategies for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review.Diagnostics (Basel, Switzerland) · 2021Review
- Populations of in silico myocytes and tissues reveal synergy of multiatrial-predominant KBritish journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelective inhibitors of Kv1.5 channels are being developed for the treatment of atrial fibrillation (AF).
objectivesThe purpose of this study was to investigate the effects of the highly selective Kv1.5 inhibitor XEN-D0103 on human atrial action potentials (APs) at high excitation rates and to assess safety.
methodsIntracellular APs (stimulation rates 1-5 Hz) were measured in right atrial trabeculae from patients in sinus rhythm (SR), chronic AF (cAF; AF of >6 months duration), and paroxysmal AF (pAF). The safety and tolerability of XEN-D0103 were tested in a double-blind, randomized, placebo-controlled phase 1 study.
resultsDepending on its concentration, XEN-D0103 elevated the plateau potential. At 1 Hz, XEN-D0103 (3 µM) shortened action potential duration at 90% repolarization (APD90) and effective refractory period (ERP) in SR preparations, but prolonged these parameters in cAF preparations. In SR and pAF preparations, the shortening effects on APD90 and ERP turned into prolongation at high rates. In cAF trabeculae, XEN-D0103 prolonged APD90 and ERP at 2 and 3 Hz. At high rates, more SR and pAF preparations failed to capture excitation in the presence of the drug than in its absence. XEN-D0103 (10 µM) did not significantly affect human ventricular APs. Even with plasma concentrations reaching 7000 ng/mL, XEN-D0103 did not increase ∆∆QTcF (QT interval corrected by the Fridericia formula) in the analysis of electrocardiograms of healthy volunteers, and no subjects receiving an active treatment had a QT or QTcF interval >450 ms, or increase in QTcF from baseline >30 ms.
conclusionAPD prolongation and suppression of APs by XEN-D0103 at high stimulation rates in SR and pAF tissue, but not cAF, could be of therapeutic benefit for reducing AF burden. This concept needs to be confirmed in clinical trials.
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