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Author(s): Rubabin Tooba [sup.1] , Allaa Almoushref [sup.2] , Adriano R. Tonelli [sup.3] [sup.4] Author Affiliations: (1) grid.239578.2, 0000 0001 0675 4725, Department of Internal Medicine, Cleveland Clinic, , 9500 [...], Background In patients with pulmonary arterial hypertension (PAH), it remains unknown if the response to the acute pulmonary vasoreactivity test changes over time and determines prognosis. Methods We included PAH patients who underwent two right heart catheterizations (RHC) with acute vasoreactivity challenge using inhaled nitric oxide (NO). The hemodynamic response was assessed by absolute or percentage change in mean pulmonary artery pressure (mPAP) or pulmonary vascular resistance (PVR). Results We included 54 patients, age 51 ± 17 years, and 44 (82%) female. The median (IQR) time between the two RHC was 24.5 months (14.8-42 months). The percentage drop in mPAP was less pronounced in the second RHC (- 8.6 ± 8.1 versus - 12.3 ± 13.8 mmHg, p = 0.02). A total of 8 (14%) patients met criteria for a positive vasodilatory test during the first RHC but only 1 during the second. Patients with increased vasoreactivity at second RHC were more likely to receive (a) treatment with phosphodiesterase-5 inhibitors (PDE5-inh) at first RHC (56% versus 27%, p = 0.04) and (b) more PAH-specific medications by second RHC (2.3 ± 0.8 versus 1.8 ± 0.9, p = 0.03). Cox survival analysis showed that change in mPAP or PVR during vasodilatory challenge at or between the first and second RHC had no impact on survival. Conclusions Pulmonary vascular reactivity to inhaled NO might decrease over time; however, there is great variability among patients. The use of PDE5-inh at first RHC and number of PAH-specific treatments by the second RHC were associated with an improvement in pulmonary vasoreactivity over time.