Treatment of HFpEF With Nitrate Supplement: A Double-blind, Placebo Controlled Trial Including Patients With Atrial Fibrillation

Heart failure (HF) is the most common principal diagnosis for hospital admission in patients over 65 years old. There are two types of HF, those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Approximately half of patients with the clinical syndrome of HF have preserved systolic function. HEpEF is becoming more prevalent with aging of the population and obesity. There are only two class I recommendations for the treatment of HFpEF, which are controlling blood pressure and the use of diuretics to relieve symptoms. Exercise training is another approach to improving symptoms, however it may be poorly tolerated.

Nitrate supplement in the form of concentrated beetroot juice was recently shown to improve exercise tolerance in patients with HFpEF. (1) Beetroot juice contains high concentration of nitrate (NO3). This is metabolized to nitrite (NO2). It enters the blood stream, where it is further reduced to nitric oxide (NO) resulting in intense vasodilation.

Patients with diastolic dysfunction are often asymptomatic at rest but complain of dyspnea with exertion. Increase in heart rate with exercise causes reduced diastolic filling time and increases left sided filling pressure. Borloug, et al demonstrated this with right heart catheterization and supine exercise in patients with diastolic dysfunction. Infusion of NO2 resulted in decreased filling pressures and increased cardiac output. (2)

Neo40 is a new product made from concentrated beetroot juice in the form of a lozenge designed to dissolve on the tongue. NO3 supplement causes vasodilatation only in the setting of hypoxia and acidosis resulting in targeted vasodilatation.