Introduction:
Pulmonary hypertension (PH) occurs in 35-83% of patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse outcomes. There are no effective therapeutic options for these patients. Oral nitrite has demonstrated promise in pre-clinical models of PH-HFpEF. Recently, a phase 2 clinical trial showed that a single dose of inhaled nitrite significantly lowered pulmonary, right atrial, and pulmonary artery wedge pressures and substantially increased pulmonary artery compliance in patients with PH-HFpEF. We are currently evaluating the efficacy of chronic oral nitrite as a novel therapeutic agent in PH-HFpEF. We report, for the first time, our initial findings of the acute hemodynamic effects of a single dose of oral nitrite.
Methods:
This is part of an ongoing blinded 10-week cross-over treatment trial of oral nitrite in PH-HFpEF (NCT03015402). Patients were defined as having PH-HFpEF based on an ejection fraction > 40% and right heart catheterization (RHC) with a mPAP≥ 25 mmHg, PAWP ≥15 mmHg and TPG ≥ 12 mmHg. Patients who met criteria based on a screening RHC were given a single open label dose of 40 mg of sodium nitrite. Cardiopulmonary hemodynamics were obtained by RHC at baseline and after a single dose of oral nitrite. We are actively enrolling patients with the intent to provide open label oral sodium nitrite to ten patients.
Results:
Eight patients have currently been enrolled in the cross-over trial, of which four have required a screening RHC and have been given open label oral nitrite. Oral nitrite was well tolerated in all patients without any adverse events. Acute cardiopulmonary hemodynamic are presented in Figure 1.
Conclusion:
Administration of oral nitrite acutely results in an improvement of right ventricular and left ventricular filling pressures without any significant reduction in cardiac output, cardiac index, or mean arterial pressure. Oral nitrite may be a novel therapeutic agent for patients with PH-HFpEF.
Inter-atrial dyssynchrony contributes to heart failure symptoms in patients with preserved ejection fraction: a potential novel therapeutic target
