Sodium Nitrite May Improve Exercise Tolerance in Patients With HFpEF

Exercise machine equipped with an ergometer (apparatus for measuring the work performed and the effort and reaction of the patient) and spirometer (intrument for measuring the air entering and leaving the lungs)
Treatment of patients with HFpEF with sodium nitrite was found to have beneficial pulmonary, cardiac, and peripheral effects during exercise.

Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with sodium nitrite was found to have beneficial pulmonary, cardiac, and peripheral effects during exercise, according to a study published in the European Journal of Heart Failure.

In this analysis, data from 2 randomized, placebo-controlled trials ( Identifier: NCT01932606 and Identifier: NCT02262078) in which a total of 51 patients with HFpEF received intravenous or inhaled sodium nitrite or placebo for 5 minutes, were pooled and examined. Patients underwent a baseline assessment followed by a 5-minute exercise test prior to administration of assigned treatment.

Directly measured oxygen (O2) consumption (VO2) and levels of blood gas were measured to examine the impact of sodium nitrite during submaximal exercise test on skeletal muscle O2 conductance (Dm), alveolar capillary membrane O2 conductance (DL), VO2 kinetics, and O2 utilization.

Patients who received sodium nitrite vs placebo had greater improvements in Dm (+4.9±6.5 vs -0.9±4.3 ml/mmHg.min, respectively; P =.0008), and in VO2 kinetics, as measured by the average response time (-5.0±6.9 vs – 0.6±6.0 seconds, respectively; P =.03), and their O2 utilization was preserved even in the presence of increased convective O2 delivery via cardiac output (+0.4±0.7 vs -0.3±0.9 L/min, respectively; P =.02).

Treatment with sodium nitrite vs placebo was also associated with improvement in DL during exercise (-+2.5±6.3 vs -2.0±9.0 ml/mmHg.min, respectively; P =.05). This improvement correlated with lower pulmonary capillary pressures (r=-0.34; P =.02) as well as reduced pulmonary dead space ventilation fraction (-0.01±0.05 vs +0.02±0.05, respectively; P =.02).

While the data used in this study were from 2 trials, both trials were limited in their single-center design.

 “Future study is indicated to determine the precise mechanisms underlying these benefits at the tissue level, and to evaluate the efficacy of nitrite and other therapies targeting the nitric oxide-cGMP pathway to improve clinical status in patients with HFpEF,” concluded the study authors.


Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA. Peripheral and pulmonary effects of inorganic-nitrite during exercise in heart failure with preserved ejection fraction. Published online January 9, 2021. Eur J Heart Fail. doi:10.1002/ejhf.2093