For a study, it was determined that heart failure with a maintained ejection fraction had few viable therapies (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations were proven to increase nitric oxide signaling, which could help HFpEF patients improve their aerobic capacity. The goal of the researchers was to determine how inhaled, nebulized inorganic nitrite affected exercise capacity in HFpEF after four weeks of treatment. About 105 individuals with HFpEF were enrolled in a multicenter, double-blind, placebo-controlled, 2-treatment, crossover experiment. Participants were enrolled at 17 US sites from July 22, 2016, to September 12, 2017, with a final follow-up date of January 2, 2018. Inorganic nitrate or placebo was inhaled with a micro nebulizer. During each 6-week phase of the crossover research, individuals were given no research drug for two weeks (baseline/washout), then 46 mg 3 times a day for a week, then 80 mg 3 times a day for 3 weeks. Peak oxygen consumption (ml/kg/min) was the primary endpoint. The Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability were all secondary endpoints. After 4 weeks of treatment, the results were evaluated. The experiment was completed by 98 (93%) of the 105 individuals who were randomized (median age, 68 years; 56% women). The mean peak oxygen consumption during the nitrite phase was not significantly different from the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95%CI, -0.56 to 0.16]; P=.27). There were no significant differences in daily activity levels (5,497 vs 5,503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P=.91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P=.39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P=.43) , echocardiographic E/e′ ratio (16.4 vs 16.6; difference, 0.1 [95% CI, −1.2 to 1.3]; P=.93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, −53 to 75]; P=.74). During the nitrite phase, 3 subjects (2.9%) experienced worsening heart failure, while 8 (7.6%) experienced worsening heart failure during the placebo period. In individuals with HFpEF, using inhaled inorganic nitrite for four weeks did not produce a significant improvement in exercise capacity when compared to placebo.