For the characterization of the cardiovascular events, five main pathophysiological processes were found to be involved in the onset of AF induced by ibrutinib and acalabrutinib off-target binding: (1) inflammation; (2) structural remodeling and atrial fibrosis; (3) atrial fibrillation initiation electrophysiology and ectopic/triggering activity; (4) autonomic nervous system remodeling; and (5) overactivation of the renin-angiotensin-aldosterone system (RAAS). The gene discussed is REN; the disease is atrial fibrillation.