(A) Representative field potential (FP) recordings from WT (WT1) and the homozygous RYR2 duplication iPSC-CMs for both patients (RYR2 Dup 1 and RYR2 Dup 2) at baseline (top) and following ISO (100 nM) treatment (bottom). (B) A bar graph summary showing the erratic beating frequency (i.e., arrhythmic events) present at baseline and following ISO treatment in WT1 iPSC-CMs compared with RYR2 duplication iPSC-CMs for both patients. WT1-iPSC-CM baseline (n = 158, SEM = 1.25), WT-iPSC-CM ISO (n = 160, SEM = 1.5), RYR2 Dup 1-c1-iPSC-CM baseline (n = 165, SEM = 1.9), RYR2 Dup 1-c1-iPSC-CM ISO (n = 419, SEM = 1.7), RYR2 Dup 2-c1-iPSC-CM baseline (n = 129, SEM = 2.9), RYR2 Dup 2-c1-iPSC-CM ISO (n = 100, SEM = 3.8). (C) Representative FP recordings from WT1 control and RYR2 duplication iPSC-CMs from patient 2 (RYR2 Dup 2 clone 1) at baseline, following ISO (100 nM) treatment alone, and following ISO with nadolol (10 μM). (D) A bar graph summary of the erratic beating frequency (i.e., arrhythmic events) present in WT1 iPSC-CMs compared with RYR2 duplication iPSC-CMs from patient 2 (RYR2 Dup 2 clone 1) at baseline, following ISO (100 nM) and in response to pharmacotherapies (nadolol at 10 μM, propranolol at 1 μM, and flecainide at 6 μM). Data are shown as number of experiments, where each experiment includes data acquired from 250–500 electrode recordings each. WT1-iPSC-CM baseline (n = 4, SEM = 1.5), ISO (n = 12, SEM = 0.4), ISO + nadolol (n = 12, SEM = 0.20), ISO + propranolol (n = 12, SEM = 0.20), and ISO + flecainide (n = 12, SEM = 1.7). RYR2 Dup 2-c1-iPSC-CM baseline (n = 4, SEM = 3.9), ISO (n = 12, SEM = 1.5), ISO + nadolol (n = 12, SEM = 1.1), ISO + propranolol (n = 12, SEM = 0.72), and ISO + flecainide (n = 12, SEM = 1.2). Data are presented as mean ± SEM. The symbol *** represents P < 0.0001. A 1-way ANOVA with Tukey’s test was performed to determine statistical significance between multiple groups. P < 0.05 was considered significant.