Loewe et al. (2014), in particular, demonstrated by simulating the effects of mutations on KCNH2 gene that APD and effective refractory period shortening combined to a more linear repolarization phase (triangular AP) were alone sufficient to induce a substrate for AF. The effects of these mutations was further investigated by extending that work to 3D anatomy with AF electrical remodeling, where the arrhythmogenic potential of the KCNH2 L532P and N588K mutations was confirmed (Heikhmakhtiar et al., 2020). The gene discussed is KCNH2; the disease is atrial fibrillation.