Optical mapping of the interface between iPSC-derived grafts and swine myocardium suggests potential arrhythmia mechanisms

We used high-resolution optical mapping (~50 µm) to investigate potential arrhythmia mechanisms following transplantation of engineered cardiac tissue. We induced myocardial infarction in 6 immunosuppressed pigs and implanted cardiac spheroids into the border zone. One week later, 600-µm-thick cardiac slices containing implanted spheroids were harvested and electrical propagation was imaged. Histology showed low connexin-43 expression, scar, and misaligned muscle fibers at the graft-host interface. We observed propagation from host-to-graft in 10 slices from 3 pigs. Host-graft electrical bridges were spaced by millimeters. Propagation was ~4-fold slower in the graft than host. One graft beat spontaneously, but activation did not propagate from graft-to-host in this, or any other slice. We did not observe reentry, but slow in-graft conduction and sparse electrical bridges provided opportunity for reentry induction. These data reveal potential for reentrant or focal arrhythmias 1 week post-implant, which may resolve with maturation of the graft and the graft-host interface.