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Background: Atrial fibrillation (AF) is the most common clinically reported arrhythmia. It is associated with electrophysiological and structural alterations that promote the maintenance of the disease. The limited longevity of human cardiac samples has historically restricted mechanistic investigation into these remodeling processes of human atrial cardiomyocytes and has hampered antiarrhythmic-therapy development.

Objective: We aim to assess if classical AF-associated remodeling events can be elicited in atrial engineered human myocardium (EHM) constructed from atrial subtype-specific induced pluripotent stem cell derived cardiomyocytes (iPSC-CM).

Methods: To allow for long-term optical tachypacing at 3 Hz (TP), EHM were generated from cells expressing the light-gated ion-channel f-Chrimson (CRISPR-Cas9 technique). 24-hour or 7 day TP was applied to EHMs. Action potentials (AP) were acquired using …