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<0.0001). Following study drug administration exercise PCWP was substantially improved by nitrite as compared to placebo (baseline-adjusted mean 25±5 vs 31±6 mmHg, ANCOVA p=0.022). Inhaled nitrite reduced resting PCWP (-4±3 vs -1±2 mmHg, p=0.002), improved pulmonary artery compliance (+1.5±1.1 vs +0.6±0.9 ml/mmHg) and decreased mean pulmonary artery pressures at rest (-7±4 vs -3±4 mmHg, p=0.007) and with exercise (-10±6 vs -5±6 mmHg, 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.
- Received May 26, 2016.
- Revision received July 18, 2016.
- Accepted July 25, 2016.