Hydrogen sulfide, an endogenous gaseous 2nd messenger shown to mediate numerous physiological actions, is reduced in heart failure patients. We have recently developed a novel hydrogen sulfide precursor/donor, SG1002, which we have previous shown increases circulating hydrogen sulfide levels and improves cardiac function and decreases disease in murine models of heart failure. To test whether SG1002 is capable of overcoming sulfide deficits in heart failure patients, we have recently undertaken a double-blind, placebo-controlled Phase I dose escalation study. Doses ranging from 200–800mg BID for 1week were all well tolerated in normal healthy subjects, with side effects limited to nausea at the highest dose. Clinical blood chemistries, urinalysis and ECG were all unchanged. Analyses of pharmacokinetics and markers of oxidative stress are currently underway and will be reported. Based on the safety in this population, we are now repeating this study in heart failure subjects (Age 35–85, NYHA class II or III, EF<40%). Upon identifying an optimal dose we will undertake a Phase II study to further assess safety and the ability to overcome deficits in circulating hydrogen sulfide following 90days of treatment in heart failure subjects. Markers of oxidative stress and cardiac function will also be assessed in this study. We hypothesize that SG1002 will be safe and well tolerated in heart failure subjects and overcome the deficits in circulating hydrogen sulfide. By increasing circulating sulfide levels, we expect an overall improvement in cardiovascular health and decrease in indices of heart failure.