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NCT Number: NCT01932606

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

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.

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Key information

Conditions

Heart Disease Cardiovascular Diseases Exercise Intolerance Heart Diseases Heart Failure With Preserved Ejection Fraction Hypertension Hypertension, Pulmonary Lung Diseases Pulmonary Hypertension Respiratory Tract Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nitrite

Drug

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

Saline Placebo for Nitrite

Drug

Normal saline placebo will be infused for 5 minutes during the cardiac catheterization procedure. Hemodynamics will then be measured at baseline after study drug infusion and again during low level exercise (20 Watts).

Primary outcomes

  1. Exercise Pulmonary Capillary Wedge Pressure (PCWP)

    Time frame: during repeat exercise run, approximately 30 minutes after study drug administration

    Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.

Secondary outcomes

  1. Change in Central Pressures After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  2. Change in Heart Rate After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  3. Change in Blood Pressure After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  4. Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.

  5. Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.

  6. Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.

  7. Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.

  8. Change in Oxygen Consumption (VO_2) After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.)

  9. Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.

  10. Change in Cardiac Output After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) The volume of blood pumped per minute by each ventricle of the heart. Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.

  11. Change in Stroke Volume After Study Drug (Resting)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.

  12. Change in Central Pressures After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  13. Change in Heart Rate After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  14. Change in Blood Pressure After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  15. Change in PVR After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.

  16. Change in PA Compliance After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.

  17. Change in SVR After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.

  18. Change in LVSW After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.

  19. Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)

  20. Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.

  21. Change in Cardiac Output After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.

  22. Change in Stroke Volume After Study Drug (Exercise)

    Time frame: baseline, approximately 30 minutes after study drug administration

    Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.

Sponsors and collaborators

Lead sponsor

Barry Borlaug

Other

Registry information

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Aug 30, 2013
Registry last updated
Mar 14, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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