Ibrutinib-specific off-targets showed association with AF through structural remodeling (HCK, FGR, LYN, FYN, YES1, and FLT3) and electrophysiology activity (LYN and SRC), and with hypertension through inflammation (LCK, JAK3, and FLT3) and oxidative stress and endothelial dysfunction (ERBB2, BLK, SRC, and CSK). Here, ERBB2 is linked to endothelial dysfunction.