Koertl, Thomas and Stehle, Thea and Riedl, Dominic and Trausel, Johanna and Rebs, Sabine and Pabel, Steffen and Paulus, Michael and Holzamer, Andreas and Marrouche, Nassir and Maier, Lars S. and Sohns, Christian and Streckfuss-Boemeke, Katrin and Sossalla, Samuel (2022) Atrial Fibrillation Burden Specifically Determines Human Ventricular Cellular Remodeling. JACC-CLINICAL ELECTROPHYSIOLOGY, 8 (11). pp. 1357-1366. ISSN 2405-500X, 2405-5018
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND Atrial fibrillation (AF) can either be a consequence or an underlying mechanism of left ventricular systolic dysfunction. Patients included in the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial who suffered from AF and left ventricular systolic dysfunction benefited from an AF burden <50% after catheter ablation compared with those patients with an AF burden >50%.OBJECTIVES This analysis tried to explain the clinical findings of the CASTLE-AF trial regarding AF burden in a "back-to-bench" approach. METHODS To study the ventricular effects of different AF burdens, experiments were performed using human ventricular induced pluripotent stem cell-derived cardiomyocytes undergoing in vitro AF simulation. Epifluorescence microscopy, action potential measurements, and measurements of sarcomere regularity were conducted.RESULTS Induced pluripotent stem cell-derived cardiomyocytes stimulated with AF burden of 60% or higher displayed typical hallmarks of heart failure. Ca2 thorn transient amplitude was significantly reduced indicating negative inotropic effects. Action potential duration was significantly prolonged, which represents a potential trigger for arrhythmias. A significant decrease of sarcomere regularity could explain impaired cardiac contractility in patients with high AF burden. These effects were more pronounced after 7 days of AF simulation compared with 48 hours.CONCLUSIONS Significant functional and structural alterations occurred at the cellular level at a threshold of w50% AF burden as it was observed to be harmful in the CASTLE-AF trial. Therefore, these translational results may help to understand the findings of the CASTLE-AF trial. (J Am Coll Cardiol EP 2022;8:1357-1366) (c) 2022 by the American College of Cardiology Foundation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEART-FAILURE; CATHETER ABLATION; DYSFUNCTION; MODEL; atrial fibrillation; CASTLE-AF; heart failure |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 11:49 |
| Last Modified: | 29 Jan 2024 13:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57548 |
Actions (login required)
 |
View Item |
