In the setting of heart failure (HF), reduction of Ito and increase of INaL prolong action potential duration (APD) which increases Ca2+ entry through LTCC and the subsequent SR Ca2+ release, leading to Ca2+ overload and CaMKII activation, and this process is facilitated by the enhanced β-AR adrenergic stimulation and oxidative stress, which causes excessive CaMKII activation. The gene discussed is CAMK2G; the disease is hydrops fetalis.