Background: Pulmonary fibrosis (PF) is made up of a wide variety of fibrotic lung diseases. Pulmonary hypertension (PH) frequently complicates pulmonary fibrosis (PH-PF) and is associated with worsening clinical outcomes. There are currently no approved therapies to treat PH-PF. PAC describes the pulsatile afterload that accounts for approximately 25% of the total RV afterload, and a reduction in PAC may initiate and/or exacerbate distal pulmonary vasculopathy and RV-PA uncoupling. PAC has been shown to be a strong predictor of outcomes in PAH. None of the currently available PAH pulmonary vasodilator therapies cause consistent and meaningful improvements in PAC. There is limited data on changes in PAC in PH-PF patients.
Aim: The aim of this study was to determine if increasing doses of iNO can improve PAC in patients with PH-PF.
Methods: PAC was evaluated in PF-PH patients undergoing RHC. PAC was derived as Stroke Volume /(Systolic PAP - Diastolic PAP). Increasing doses of pulsed inhaled nitric oxide (iNO) 30, 45 & 75 mcg/kg-IBW/hr, were administered over a 10-minute period, followed by a 10-minute washout. On completion of the RHC, subjects were offered the opportunity to go on to chronic iNO therapy in an extension study. Preliminary results are presented for the change from baseline in PAC for the first 4 subjects enrolled in the study (Total N = 8).
Results: Four subjects with PF-PH with a mPAP 34 mmHg, cardiac index 1.7 L/min/m2, PVR 584 dyne*sec/cm5, PCWP 10.8 mmHg, and PAC 2.2 ml/mmHg at baseline demonstrated a reduction in PAC with increasing doses of pulsed iNO (for table, see 'CTA- view full pdf').
Figure: The change in PAC (ml/mm Hg) by dose (for table, see 'CTA- view full pdf')
Conclusion: PAC improved after acute dosing with pulsed iNO. The iNO was safe and well tolerated. Subjects will be followed in an extension study where the acute change in PAC at baseline will be correlated with long term change in symptoms.