Atrial Fibrillation Burden Specifically Determines Human Ventricular Cellular Remodeling

Area of Science:

• Cardiology
• Biomedical Engineering
• Stem Cell Biology

Background:

• Atrial fibrillation (AF) is linked to left ventricular systolic dysfunction.
• The CASTLE-AF trial indicated benefits for AF burden <50% post-ablation in patients with LV dysfunction.

Purpose of the Study:

• To investigate the cellular mechanisms behind AF burden's impact on ventricular function.
• To provide a "back-to-bench" explanation for CASTLE-AF trial findings.

Main Methods:

• Human ventricular induced pluripotent stem cell-derived cardiomyocytes were used for in vitro AF simulation.
• Techniques included epifluorescence microscopy, action potential, and sarcomere regularity measurements.

Main Results:

• High AF burden (≥60%) induced heart failure hallmarks in cardiomyocytes.
• Reduced Ca2+ transient amplitude and prolonged action potential duration were observed.
• Decreased sarcomere regularity correlated with impaired contractility, worsening over 7 days.

Conclusions:

• Cellular damage thresholds align with the CASTLE-AF trial's ~50% AF burden finding.
• These results elucidate the cellular basis for AF burden's detrimental effects on the left ventricle.