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Sodium nitrite infusion improves exercise hemodynamics, cardiac reserve in patients with HFpEF
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Compared with placebo, sodium nitrite infusion improved exercise hemodynamics and enhanced cardiac reserve for patients with HF with preserved ejection fraction, according to data published in the Journal of the American College of Cardiology.
“Nitrite might more selectively target hemodynamic derangements developing during stress in people with [HF with preserved ejection fraction], with less risk of hypotension at rest,” Barry A. Borlaug, MD, associate professor of medicine, Mayo Clinic, Rochester, Minnesota, and colleagues wrote.
Barry A. Borlaug
The researchers studied 28 participants from January to September 2014 who had HF with preserved ejection fraction (HFpEF; mean age, 70 years; 61% women), most of whom also had hypertension.
Patients underwent cardiac catheterization and simultaneous expired gas analysis at rest and during exercise at a 20-W workload for 5 minutes. They were then randomly assigned to infusion of placebo or sodium nitrite (50 µg/kg/min; Hope Pharmaceuticals). Hemodynamic measurements were taken at rest, followed by a second exercise phase that was identical to the first. At each stage, researchers obtained central venous and arterial blood samples to measure the methemoglobin level and blood gases.
The primary endpoint was pulmonary capillary wedge pressure during exercise. Compared with placebo, nitrite infusion improved the primary endpoint (adjusted mean, 19 ± 5 mm Hg vs. 28 ± 6 mm Hg; P = .0003). Nitrite infusion also was associated with a greater effect on stress pulmonary capillary wedge pressure compared with resting pulmonary capillary wedge pressure (mean difference, 8.1 ± 1.4 mm Hg; P <.0001), according to the results.
Nitrite infusion slightly increased methemoglobin levels compared with placebo (0.5 ± 0.3% vs. 0.1 ± 0.4%; P = .002). No participant developed clinically meaningful methmoglobinemia (> 5%). Infusion also was associated with normalization of the increase in cardiac output relative to oxygen consumption.
While at rest, the nitrite group had modestly reduced right atrial pressure, pulmonary capillary wedge pressure and pulmonary artery pressures, the researchers wrote.
Nitrite infusion did not affect heart rate or systolic BP, but reduced BP during exercise compared with placebo (P = .05). Infusion also lowered exercise right atrial and pulmonary artery pressures. No hypotension or other events developed, according to the researchers.
The results “provide compelling rationale to pursue longer-term clinical trials of inorganic nitrites in patients with [HFpEF], a population for whom there is currently no effective treatment,” Borlaug and colleagues wrote.
“Longer-term studies of chronic nitrite administration need to be performed in much larger populations before we know more about how effective this treatment might be,” Borlaug told Cardiology Today. – by Trish Shea, MA
Disclosure: The study was supported by the Mayo Clinic Division of Cardiovascular Diseases. Borlaug reports receiving research support from Aires Pharmaceuticals. The other researchers report no relevant financial disclosures.
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