The Effects of Inhaled Sodium Nitrite on Pulmonary Vascular Impedance in Patients with Pulmonary Hypertension Associated with HFpEF

Abstract

Purpose The severity and clinical response of pulmonary hypertension (PH) is monitored by measuring pulmonary vascular resistance (PVR). However, PVR is a steady-state measurement and ignores the pulsatile load encountered by the right ventricle (RV), which may be one-third of the total afterload. Pulmonary vascular impedance (PVZ) can depict both steady-state and pulsatile loads, thus may better predict clinical outcomes. We sought to calculate PVZ in patients with PH associated with HFpEF (PH-HFpEF), who were administered inhaled sodium nitrite to better understand the acute effects on afterload. Methods Patients with PH-HFpEF underwent right heart catherization (RHC) to obtain standard hemodynamics, and if eligible, were administered two doses of inhaled sodium nitrite at 45 and 90 mg. Concurrently, transthoracic Doppler spectral imaging was used to measure pulmonary artery velocity. A Fourier transform was used via MATLAB to calculate PVZ at the first ten harmonics for both pre and post-nitrite for comparison. Results Fourteen patients underwent RHC with simultaneous Doppler imaging and received at least one dose of inhaled sodium nitrite. Inhaled sodium nitrite decreased characteristic impedance (Zc, inversely related to compliance), and total work (WT) performed by the RV (Table 1). RV efficiency improved, defined by a reduction in the total work divided by cardiac output (WT/CO). There were trends towards decreases in pulmonary vascular resistance (Z0), first harmonic impedance (Z1), steady state work (Ws), and pulmonary vascular stiffness (Zs) after administration of this drug. Conclusion PVZ analysis showed inhaled sodium nitrite acutely improves pulmonary vascular compliance by reducing characteristic impedance (Zc) more so than PVR (Z0). This was associated with improved RV efficiency and total work. These results suggest inhaled sodium nitrite preferentially acts on the larger proximal compliance vessels to reduce the load on the RV.