Heart failure (HF) is a conundrum in that, current therapies only slow the progression of the disease. We posit, if the causal mechanism were targeted, progression of the disease could be stopped and potentially reversed. We hypothesize that insufficient myocardial blood flow (MBF) produces minute areas of ischemia, that lead to an accumulating injury culminating in HF. Accordingly, we determined the relationship between MBF and cardiac work (wall stress-rate product [WSRP]) in control C57Bl6/J mice (Control), mice with transaortic constriction to produce HF (TAC-HF) and HF mice treated with the coronary vasodilator, chromonar (4 weeks of treatment, TAC-Chromonar). MBF and WSRP were measured during norepinephrine infusion in anesthetized mice. In Controls, MBF increased when work/WSRP was increased with norepinephrine, however, when cardiac work was increased in TAC-HF, MBF did not increase. After chromonar treatment, when work increased, MBF increased. Changes in cardiac function paralleled MBF, i.e., decrement in cardiac function occurred in TAC-HF (ejection fraction), but 4 weeks of chromonar treatment reversed this functional decline. We also found in a model of cardiac hypoxia fate-mapping, a 5-fold increase in the number of hypoxic cardiac myocytes (TAC-HF vs Control), which was reversed by chromonar. Capillary densities also followed this trend with a decrease from Control in TAC-HF, which was restored by Chromonar. We propose that a cause of HF is inadequate MBF to meet the metabolic demands of the working heart. Pharmacological coronary vasodilation with chromonar to increase MBF in HF can reverse the functional decline and improve cardiac function.