Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction

RATIONALE:Abnormalities in nitric oxide (NO) signaling play a pivotal role in heart failure with preserved ejection fraction (HFpEF). Intravenous sodium nitrite, which is converted to NO 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. METHODS AND 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, prior to and following treatment with inhaled sodium nitrite (90 mg) or placebo. The primary endpoint was the pulmonary capillary wedge pressure (PCWP) during exercise. Prior to study drug, HFpEF subjects displayed an increase in PCWP with exercise from 20±6 to 34±7 mmHg (p