While several mechanisms have been proposed, including enhanced natriuresis, better blood-pressure control, favorable changes in the renin–angiotensin–aldosterone axis, improved renal function and less oxidative stress [10,11], there is little, if any, evidence that any one of these or combination of these explain the magnitude of efficacy of this class of drugs in mitigating the progression of heart failure. The gene discussed is REN; the disease is heart failure.