Potassium Nitrate Fails to Boost Exercise Capacity in HFpEF

TOPLINE:

The administration of potassium nitrate (KNO3) does not improve exercise capacity or quality of life in patients with heart failure with preserved ejection fraction (HFpEF), despite increasing levels of nitric oxide in blood.

METHODOLOGY:

• This multicenter crossover trial, conducted across three centers in the United States, assessed the effect of administering KNO3 on exercise capacity and quality of life.
• It included 84 patients with symptomatic HFpEF (median age, 68 years; 69% women; 76% White) who had a left ventricular ejection fraction over 50% and elevated intracardiac pressures. Participants had obesity (mean body mass index, 36.22), with a high prevalence of hypertension, diabetes, and obstructive sleep apnea.
• Patients were randomly assigned to receive either 6 mmol KNO3 first (n = 41) or 6 mmol potassium chloride (KCl) first (n = 43) three times daily for 6 weeks, with a 1-week washout period in between.
• At the end of each intervention phase, a test of incremental cardiopulmonary exercise was conducted using a supine cycle ergometer.
• Primary endpoints were the difference in peak oxygen uptake and total work performed during the exercise test; secondary endpoints included quality of life, left ventricular systolic and diastolic function, exercise systemic vasodilatory reserve, and parameters related to pulsatile arterial load.

TAKEAWAY:

• The administration of KNO3 vs KCl increased the levels of serum metabolites of nitric oxide significantly after 6 weeks (418.44 vs 40.11 μM; P
• Peak oxygen uptake or the total work performed did not improve significantly with the administration of KNO3 compared with KCl. Quality of life also did not improve with the administration of KNO3.
• Mean arterial pressure at peak exercise was significantly lower after the administration of KNO3 than after KCl (122.5 vs 127.6 mm Hg; P = .04), but the vasodilatory reserve and resting and orthostatic blood pressure did not differ.
• Adverse events were mostly minor, with gastrointestinal issues being the most common side effects reported.

IN PRACTICE:

“In this randomized crossover trial, chronic KNO3 [potassium nitrate] administration did not improve exercise capacity or quality of life, as compared with KCl [potassium chloride] among participants with HFpEF,” the authors of the study wrote.

SOURCE:

The study was led by Payman Zamani, MD, MTR, of the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia. It was published online on December 18, 2024, in JAMA Cardiology.

LIMITATIONS:

The potential activation of compensatory mechanisms by the chronic inorganic nitrate administration may have neutralized the short-term benefits. Various abnormalities in oxygen transport may be present simultaneously in patients with HFpEF, suggesting a combination of interventions may be required to improve exercise capacity.

DISCLOSURES:

This trial was supported by the National Heart, Lung, and Blood Institute. The study was supported by the National Center for Advancing Translational Sciences and National Institutes of Health. Some authors reported receiving grants, personal fees, and consulting fees and having patents from various pharmaceutical and medical device companies and institutes. One author reported having full-time employment with a healthcare company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.