Sodium Nitrite and Exercise Hemodynamics in HFpEF

Study Questions:

Does acute administration of sodium nitrite improve exercise hemodynamics and cardiac reserve in heart failure with preserved ejection fraction (HFpEF)?

Methods:

A total of 28 subjects with HFpEF were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects underwent cardiac catheterization with simultaneous expired gas analysis at rest and during supine exercise (20-W workload) for 5 minutes. Subjects were then randomized 1:1 to receive sodium nitrite (50 mcg/kg/min) infusion or placebo infusion. After 10 minutes, hemodynamics were repeated at rest and with exercise. In addition to central pressures, left ventricular stroke work (LVSW), cardiac output (CO), VO2, CaO2 – CVO2, VE/VCO2 slope, and CO/VO2 slope were assessed. The primary endpoint was the pulmonary capillary wedge pressure (PCWP) during exercise. Measures of vascular and ventricular function were pulmonary vascular resistance (PVR), pulmonary artery (PA) compliance, systemic vascular resistance (SVR), and LVSW, and integrated function and metabolism included VO2, CaO2 – CVO2, CO, and stroke volume.

Results:

There were no statistically significant baseline differences between treatment groups in characteristics and study measurements, including resting and exercise hemodynamics, expired gas data, and ventricular/vascular function. Nitrite infusion resulted in a modest decrease in resting right atrial, PA systolic, PA mean, and PCWP, but had no effect on other resting parameters. However, during exercise, nitrite resulted in a significant reduction in the primary endpoint PCWP (adjusted mean: 19 ± 5 mm Hg vs. 28 ± 6 mm Hg; p < 0.0003) and marked reductions in central pressures and SVR. In addition, nitrite improved LVSW, VO2, CO, and stroke volume, and had no effect on blood pressure and heart rate. PA systolic was reduced due to reduced PCWP, as PVR or PA compliance was not affected. The half-life of sodium nitrite in this study was calculated to be much lower than previously reported at 3.9 ± 6 minutes.

Conclusions:

The results of this study demonstrate that in patients with HFpEF, acute sodium nitrite infusion improves central pressures, measures of ventricular and vascular function, and metabolism during low-level exercise.

Perspective:

Patients with HFpEF have derangements in hemodynamics and impaired cardiac reserve with exercise. Currently, there are no effective treatment strategies for HFpEF. Based on the results of this study, inorganic nitrite specifically targets these exercise-induced abnormalities and may represent a potential therapy for HFpEF. Prospective trials are warranted.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Exercise

Keywords: Blood Pressure, Cardiac Catheterization, Exercise, Heart Failure, Nitrites, Pulmonary Artery, Pulmonary Wedge Pressure, Sodium Nitrite, Stroke Volume, Vascular Resistance, Ventricular Function


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