Comparison of intravenous sildenafil with inhaled nitric oxide for acute vasodilator testing in pulmonary arterial hypertension

Abstract

Acute vasodilator testing (AVT) identifies acute responders for initiation of calcium channel blockers in pulmonary arterial hypertension (PAH) and operability in congenital heart disease (CHD). We sought to determine the feasibility of intravenous sildenafil (ivS) as an alternative to inhaled nitric oxide (iNO) in AVT. All patients with PAH undergoing cardiac catheterization for AVT (November 2015 to December 2020) were prospectively enrolled.Hemodynamic data were obtained at baseline, with iNO 20 ppm and ivS (0.25 mg/kg for children and 10 mg for adults). We studied 44 patients with a mean age of 20.5 ± 14.4 years (27 [61%] females and 20 [45%] children). There were 17 (38.6%) patients in the CHD group for operability assessment and 27 patients in non-CHD group (idiopathic pulmonary arterial hypertension-16[36.3%], residual PAH after shunt closure-7 [15.9%], and 2 cases [4.5%] each of familial PAH and portopulmonary hypertension). There was an excellent intraclass correlation for mean pulmonary artery pressures (0.903, 95% confidence interval, CI: 0.809-0.949, p < 0.001), mean aortic pressures (0.745, 95% CI: 0.552-0.858, p < 0.001), pulmonary vascular resistance index (0.920, 95% CI: 0.858-0.956, p < 0.001), systemic vascular resistance (SVR) index (0.828, 95% CI: 0.706-0.902, p < 0.001), and the ratio of pulmonary and SVR indices (0.857, 95% CI: 0.752-0.919, p < 0.001) between the two agents. There were two responders, both in non-CHD group, and were identified by iNO and ivS. The hemodynamic effects of ivS show excellent correlation with iNO and could be a potential alternative agent for identifying acute responders during AVT.

The effects of oxygenation on acute vasodilator challenge in pulmonary arterial hypertension

“… 10 iNO is delivered at variable concentrations and is often co‐administered with oxygen, although there is significant variability in how oxygen is utilized. 11 , 12 , 13 , 14 , 15 At present, there is no standardized protocol for the utilization of oxygen or the interpretation of the effects of oxygen on changes in mPAP during acute vasodilator challenge. In this study, we demonstrate that defining acute vasoresponsiveness after first adjusting for the effects of oxygenation identifies a group which has excellent long‐term responsiveness to CCBs.…”

“…iNO is a safe, well‐tolerated, and frequently utilized vasodilator agent in acute vasodilator challenge 10 . iNO is delivered at variable concentrations and is often co‐administered with oxygen, although there is significant variability in how oxygen is utilized 11–15 . At present, there is no standardized protocol for the utilization of oxygen or the interpretation of the effects of oxygen on changes in mPAP during acute vasodilator challenge.…”

“… 9 , 10 iNO can be delivered at variable concentrations and is often co‐administered with supplemental oxygen, however there is significant variability in the use of supplemental oxygen during acute vasodilator challenge, ranging from maintenance of fractional inspired oxygen (FiO 2 ) of 21% to use of 100% FiO 2 administered with iNO. 11 , 12 , 13 , 14 , 15 The effects of supplemental oxygen are not inert, as alveolar hypoxia has long been understood to induce pulmonary vasoconstriction and subsequent elevation in mPAP 16 , 17 , 18 and increased alveolar oxygen tension reduces mPAP 19 , 20 and pulmonary vascular resistance (PVR) 21 in PAH patients.…”