Electrophysiological analysis with multielectrode arrays shows repolarization durations consistent with LQTS and SQTS in 2D hiPSC-CM monolayers and in 3D cardiac tissue sheets (CTSs), while pharmacological inhibition of hERG with channel blockers reveals differential susceptibility of mutant 3D CTSs to arrhythmic events. Here, KCNH2 is linked to Familial short QT syndrome.