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Thorough analysis of hiPSC-CM derived from a DSC2 patient, zebrafish and patient cohort, we identified abnormal repolarization dynamicity, prompting the discovery of a short QT interval in some ACM patients. By normalizing the increased repolarization reserve of ACM myocytes, class 3 AADs are likely to be the drugs of first choice for DSC2 patients. These findings may encourage randomized trials to evaluate class 3 antiarrhythmic drugs, alone or in combination with class I medications in ACM patients.