Purpose and Method: Nilotinib has been reported to clinically cause QTc prolongation. We observed that nilotinib at 1 µg/mL induced repolarization delay showing early afterdepolarization (EAD) with electrical alternans under electrical pacing in human-induced pluripotent stem cell-derived cardiomyocytes sheets.  To characterize the alternans, we adopted field potential (FP), Ca²⁺ imaging, and motion vector analyses.
Results: Nilotinib induced EADs in every excitation for the most part, but excitation without EAD showed up intermittently, and EADs were sometimes terminated by electrical pacing via the MEA system, which depended on the pacing cycle lengths. Alternate phenomena of FP duration (FPD) were observed with and without EAD, which also caused alternans in the conduction speed, contraction velocity and peak amplitude of Ca peak along with Ca transient duration. During electrical pacing, electrical excitations with EADs induced conduction delays upon the next one without EAD. Transient loss of EAD increased the conduction speed, contraction velocity and Ca peak amplitude of the cell sheets upon the next electrical excitation, indicating that the shorter FPD enhanced the recovery of Ca and Na channels from their inactivation state. Alternans was not observed when only action potentials without EAD or with EAD were sustained.
Conclusion: Intermittent loss of EAD would enhance electrical, calcium, and mechanical alternans of the next beat in the in vivo heart.