Level 3 Cardiopulmonary Exercise Testing to Guide Therapeutic Decisions in Non-Severe Pulmonary Hypertension with Lung Disease.

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group ( = 10), characterized by an increase in PVR with exertion, and a static PVR group ( = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, < 0.05), resting PVR (-1.04 WU, < 0.05), resting mean pulmonary arterial pressure (mPAP) (-5.8 mmHg, < 0.05), exercise PVR (-1.7 WU, < 0.05), exercise mPAP (-13 mmHg, < 0.05), and estimated right ventricular systolic pressure (-9.2 mmHg, < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil.