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

Barry Borlaug

Status and phase: Completed; Phase 2

Conditions: Heart Failure With Preserved Ejection Fraction; Exercise Intolerance; Heart Disease; Pulmonary Hypertension

Treatments: Drug: Nitrite; Drug: Saline Placebo for Nitrite

Study type: Interventional

Funder types: Other

Identifiers

NCT01932606

13-004077

Details and patient eligibility

About

Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that has no proven effective treatment. This study assessed the effects of acute nitrite administration on resting and exercise hemodynamics in patients with HFpEF.

Full description

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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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28 participants in 2 patient groups, including a placebo group

Nitrite

Experimental group

Description:

Study drug (NaNO_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.

Treatment:

Drug: Nitrite

Saline

Placebo Comparator group

Description:

Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure.

Treatment:

Drug: Saline Placebo for Nitrite