title: Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction.
abstract: BACKGROUND
  Abnormalities in nitric oxide signaling play a pivotal role in heart failure with preserved ejection fraction (HFpEF). Intravenous sodium nitrite, which is converted to nitric oxide in vivo, improves hemodynamics in HFpEF, but its use is limited by the need for parenteral administration. Nitrite can also be administered using a novel, portable micronebulizer system suitable for chronic use.
  
  
  OBJECTIVE
  Determine whether inhaled nitrite improves hemodynamics in HFpEF.
  
  
  RESULTS
  In a double-blind, randomized, placebo-controlled, parallel-group trial, subjects with HFpEF (n=26) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise before and after treatment with inhaled sodium nitrite (90 mg) or placebo. The primary end point was the pulmonary capillary wedge pressure during exercise. Before study drug administration, HFpEF subjects displayed an increase in pulmonary capillary wedge pressure with exercise from 20±6 to 34±7 mm Hg (P<0.0001). After study drug administration, exercise pulmonary capillary wedge pressure was substantially improved by nitrite as compared with placebo (baseline-adjusted mean 25±5 versus 31±6 mm Hg; analysis of covariance P=0.022). Inhaled nitrite reduced resting pulmonary capillary wedge pressure (-4±3 versus -1±2 mm Hg; P=0.002), improved pulmonary artery compliance (+1.5±1.1 versus +0.6±0.9 mL/mm Hg), and decreased mean pulmonary artery pressures at rest (-7±4 versus -3±4 mm Hg; P=0.007) and with exercise (-10±6 versus -5±6 mm Hg; P=0.05). Nitrite reduced right atrial pressures, with no effect on cardiac output or stroke volume.
  
  
  CONCLUSIONS
  Acute administration of inhaled sodium nitrite reduces biventricular filling pressures and pulmonary artery pressures at rest and during exercise in HFpEF. Further study is warranted to evaluate chronic effects of inhaled nitrite in HFpEF.
  
  
  BACKGROUND
  This single center randomized clinical trial is registered at clinicaltrials.gov (NCT02262078).
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN. borlaug.barry@mayo.edu.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
authors.affiliation: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN.
authors.forename: Katlyn E
authors.initials: KE
authors.lastname: Koepp
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012146:Rest / Q000502:physiology*; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology*
chemical_list: D012977:Sodium Nitrite
keywords: exercise; heart failure; hemodynamics; nitrate; nitric oxide