ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2019
Mechanistic insights from targeted molecular profiling of repolarization alternans in the intact human heart.
Article in 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, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Detecting Local Myocardial Spatiotemporal Repolarization Gradients With Clinical Mapping Arrays.Circulation. Arrhythmia and electrophysiology · 2025Article
- Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.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 · 2023Article
- 25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies.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 · 2023Review
- Microvolt QRS Alternans in Hypertrophic Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.Journal of the American Heart Association · 2021Article
- A Method to Minimise the Impact of ECG Marker Inaccuracies on the Spatial QRS-T angle: Evaluation on 1,512 Manually Annotated ECGs.Biomedical signal processing and control · 2021Article
- Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KLipids in health and disease · 2020Article
- Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping.Heart rhythm · 2020Article
- Electrical Restitution and Its Modifications by Antiarrhythmic Drugs in Undiseased Human Ventricular Muscle.Frontiers in pharmacology · 2020Article
- Restitution and Stability of Human Ventricular Action Potential at High and Variable Pacing Rate.Biophysical journal · 2019Article
- The Effect of Emotional Valence on Ventricular Repolarization Dynamics Is Mediated by Heart Rate Variability: A Study of QT Variability and Music-Induced Emotions.Frontiers in physiology · 2019Article
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Authors and funding
13 authors at 5 institutions in 1 country.
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Abstract
aimsAction potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo. METHODS AND
resultsWe developed a novel approach combining intact heart electrophysiological mapping during cardiac surgery with rapid on-site data analysis to guide myocardial biopsies for laboratory analysis, thereby linking repolarization dynamics observed at the organ level with underlying ion channel expression. Alternans-susceptible and alternans-resistant regions were identified by an incremental pacing protocol. Biopsies from these sites (n = 13) demonstrated greater RNA expression in Calsequestrin (CSQN) and Ryanodine (RyR) and ion channels underlying IK1 and Ito at alternans-susceptible sites. Electrical restitution properties (n = 7) showed no difference between alternans-susceptible and resistant sites, whereas spatial gradients of repolarization were greater in alternans-susceptible than in alternans-resistant sites (P = 0.001). The degree of histological fibrosis between alternans-susceptible and resistant sites was equivalent. Mathematical modelling of these changes indicated that both CSQN and RyR up-regulation are key determinants of APD alternans.
conclusionCombined intact heart and cellular electrophysiology show that regions of myocardium in the in vivo human heart exhibiting APD alternans are associated with greater expression of CSQN and RyR and show no difference in restitution properties compared to non-alternans regions. In silico modelling identifies up-regulation and interaction of CSQN with RyR as a major mechanism underlying APD alternans.
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