Based on these observations and preliminary data indicating increased ISK in patients with paroxysmal AF (69), we speculate that ISK upregulation can be an adaptive change to the increased propensity to DAD-mediated mediated cellular triggered activity that occurs during the early stage of AF when focal firing is thought to contribute to the periodic reinitiation of AF in the absence of clinically relevant ERP/APD abbreviation (70). Here, KCNE1 is linked to Paroxysmal atrial fibrillation.