Heart failure (HF) is one of the major health challenges in the 21st Century. Its prevalence is due a growing number of patients who survive heart attacks, who later develop heart failure; and the high incidence of diabetes leading to diabetic cardiomyopathy. Current treatments for HF only slow the progression of the disease; no treatment stops or reverses this adverse sequence. These limitations provoke the question Is HF purely a disease of cardiac myocytes, which seems to be the focus of current treatments; or is it a pathology involving both the coronary circulation and cardiac muscle? Answers to this question may facilitate a more complete understanding of the disease and a better treatment outcome.