Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction

Subjects were studied on their long-term medications in the post-absorptive state and supine
position. Right heart catheterization was performed with simultaneous expired gas analysis
at rest and during supine exercise at a 20 Watts workload for 5 minutes. After the first
exercise phase (before any drug administration) and after return to steady-state baseline
hemodynamic values, subjects were randomized. Study drug or placebo was infused for 5
minutes. After a 10 minute observation period, hemodynamic measurements were repeated at
rest, followed by repeat supine exercise at a 20 Watts workload for 5 minutes, identical to
the study's first phase. Arterial and venous blood samples and hemodynamic and expired gas
data were acquired during each stage of the protocol.

Inclusion Criteria:

- Scheduled to undergo a cardiac catheterization procedure.

- Clinical symptoms of shortness of breath and fatigue

- Normal left ventricular ejection fraction (≥50%)

- Elevated left ventricular filling pressures at cardiac catheterization (defined as
resting pulmonary capillary wedge pressure (PCWP)>15 mmHg and/or PCWP≥25 mmHg during
exercise)

Exclusion Criteria:

- Systolic BP <120 mmHg

- Prior nitrate therapy (within previous 2 weeks)

- Glucose 6-phosphate dehydrogenase (G6PD) deficiency

- Other "non-HFpEF" specific causes of heart failure such as significant valvular
disease (>moderate left-sided regurgitation, >mild stenosis), severe pulmonary
disease, unstable coronary disease or coronary spasm, primary renal or hepatic
disease, constrictive pericarditis, or infiltrative, restrictive, or hypertrophic
cardiomyopathies