Inhaled inorganic nitrites do not improve exercise capacity in heart failure with preserved ejection fraction

1. In this randomized controlled trial, there was no difference in mean peak oxygen consumption between patients with Heart Failure with preserved Ejection Fraction (HFpEF) who received either inhaled nitrites or placebo.

2. There was no difference in daily activity levels between the nitrite and placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: There is no proven effective treatment available for patients with heart failure with preserved ejection fraction (HFpEF). As availability of nitric oxide may be compromised in HFpEF, some studies have suggested the possible utility of organic nitrates/inorganic nitrites in treating HFpEF. In this randomized control trial, HFpEF patients received inhaled, nebulized inorganic nitrites or placebo and had their exercise capacity assessed four weeks later. There was no significant difference found in mean peak oxygen consumption between the nitrite and placebo groups. Further, there were no between-treatment phase differences in daily activity levels, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, functional class, echocardiographic E/e’ ratio, and N-terminal fragment of the prohormone brain natriuretic peptide levels (NT-proBNP).

Overall, this study does not suggest a benefit of inorganic nitrites in patients with HFpEF. However, this study is limited by its primary hypothesis that assumes an improvement in hemodynamics would help patients with HFpEF become more active and obtain higher peak exercise capacity.

Click to read the study in JAMA

Relevant Reading: Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies

In-Depth [randomized controlled trial]: The study is a multicenter, randomized, double-blind, placebo-controlled, crossover study. 105 recruited participants included ambulatory patients that were 40 years or older and had HF while they were receiving stable medical therapy. Baseline studies including cardiopulmonary exercise testing and assessments of secondary end points, including quality-of-life scores, NYHA classification, and NT-proBNP levels, were obtained. During each 6-week phase of study, participants received no drug for 2 weeks (washout period) followed by a 4-week phase where nitrite or placebo was given at 46mg 3 times a day for 1 week, followed by 80mg 3 times a day for 3 weeks. Primary end point was peak oxygen consumption and secondary end points included daily activity levels, Kansas City Cardiomyopathy Questionnaire, NYHA functional class, cardiac filling pressures, and NT-proBNP levels. Overall, no significant difference was found in mean peak oxygen consumption (13.5 vs 13.7 mL/kg/min; p = 0.27). Further, there were no between-treatment phase differences in daily activity levels, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, functional class, echocardiographic E/e’ ratio, and N-terminal fragment of the prohormone brain natriuretic peptide levels (p > 0.05).

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