Given the expected long survivorship life in childhood cancer survivors, many of them would develop multiple cardiovascular risk factors later in their adult life, which can be considered as “second hits.” Since hypertension is the most significant cardiovascular risk factor for all adverse cardiac events, including heart failure and cardiac death, in anthracycline-treated childhood cancer survivors (10), we have recently developed a two-hit mouse model of juvenile DOX-induced latent cardiotoxicity that is exacerbated by adult-onset angiotensin II (ANGII)-induced hypertension (11). The gene discussed is AGT; the disease is heart failure.