A multicenter randomized clinical trial found that potassium nitrate supplementation may not improve exercise capacity or quality of life in patients with heart failure with preserved ejection fraction, although it may elevate blood nitric oxide metabolites.
In the double-blinded crossover trial, published in JAMA Cardiology, researchers included 84 participants who received either potassium nitrate (KNO3) or potassium chloride (KCl) for 6-week periods, with a 1-week washout between treatments.
The study population had a median age of 68 years, was predominantly female (69.0%), and mostly had New York Heart Association class II disease (69%). The mean 6-minute walk distance at baseline measured 335.5 m. The trial, conducted between October 2016 and July 2022 at the University of Pennsylvania, Philadelphia Veterans Affairs Medical Center, and Northwestern University, examined whether chronic inorganic nitrate supplementation could improve exercise tolerance in patients with heart failure with preserved ejection fraction patients.
The study showed no statistically significant difference in peak oxygen uptake between the KNO3 and KCl groups (10.23 vs 10.17 mL/min/kg, P = .73) or in total work performed (25.9 vs 23.63 kJ, P = .29). KNO3 administration increased trough levels of serum nitric oxide metabolites compared with KCl (418.4 vs 40.1 μM, P < .001).
Secondary endpoints, including quality of life assessed by the Kansas City Cardiomyopathy Questionnaire and exercise systemic vasodilatory reserve, showed no differences with KNO3 supplementation. The participants reported primarily minor gastrointestinal adverse effects.
KNO3 supplementation resulted in lower mean arterial pressure during peak exercise (122.5 vs 127.6 mmHg, P = .04). The researchers found no differences in various prespecified subgroups, including analyses by sex, race, diabetes status, hemoglobin levels, and calcium channel blocker use.
The study received support from the National Heart, Lung, and Blood Institute and was registered at ClinicalTrials.gov (NCT02840799). Conflict of interest disclosures can be found in the study.
