Abstract 12001: Atrial Fibrillation Induces Ventricular Dysfunction via Altered Ca 2+ Handling and Oxidative CaMKII Activation in the Human Heart

• DOI: 10.1161/circ.144.suppl_1.12001
• Publication Date: 2022-04-28T21:58:15Z
• Authors: Steffen Pabel; Maria Knierim; Thea Stehle; Felix Alebrand; Michael Paulus; Marcel Sieme; Melissa Herwig; Thomas Koertl; Brisca Wenner; Senka Ljubojevic-...; Nataliya Dybkova; Simon Sedej; Daniel Scherr; Christoph Brochha...; Gerd Hasenfuss; Lars S Maier; Nazha Hamdani; Katrin Streckfuss...; Samuel Sossalla
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Introduction: The effects of atrial fibrillation (AF) on left ventricular (LV) function are poorly understood. Clinical data indicate that the arrhythmic component AF may contribute to LV dysfunction. This study investigated human LV. Methods and Results: myocardium from patients with preserved (EF>50%) sinus rhythm (SR, n=31) or rate-controlled (n=24) obtained during surgery for aortic stenosis was studied. were mostly balanced without changes in remodeling. SR showed no fibrosis. In functional studies, systolic Ca 2+ transient amplitude cardiomyocytes (CM) reduced patients, while diastolic levels kinetics unaltered. These results confirmed CM non-failing donors (n=4) vs. (n=8). addition, normofrequent simulated vitro using rhythmic electrical culture pacing (both at 60 bpm). After 24h AF-simulation, (n=9) also an impaired amplitude. For a standardized chronic iPSC-CM (n=22 differentiations/5 individuals) tested. 7 days AF-simulation caused sarcoplasmic reticulum load, which could be explained by increased leak. Mechanistically, oxidative stress markers higher patients. /calmodulin-dependent protein kinase IIδ (CaMKII) found more oxidized Met281/282 leading CaMKII activity. Thus, RyR2 phosphorylation elevated, likely underlies depression handling AF. translational contractility experiments trabecula heart failure (n=8), 8h worsened contractile function. Conclusions: Here we firstly show impairs via activity different patient populations models. this demonstrates detrimental mechanisms absence tachycardia