First approved by the US Food and Drug Administration in 2004, inhaled iloprost has become a mainstay of therapy for adults with pulmonary arterial hypertension (PAH) based on strong clinical trial evidence of its ability to improve symptoms and exercise capacity [1-3]. In 2023, however, the I-neb adaptive aerosol delivery system was discontinued, thereby limiting the availability of inhaled iloprost for new patients and promoting the ultimate discontinuation of the nebulized solution.

Pulmonary arterial hypertension (PAH) Group 1 from the World Health Organization (WHO) is a rare, severe chronic, and progressive condition. Patients with PAH have increased oxidative stress (OS) and diminished antioxidant capacity. Melatonin is a potent antioxidant hormone with reported benefits in PAH animal models. 

Cardiac output is essential to calculate pulmonary vascular resistance (PVR) and classify pulmonary hypertension (PH). Recent evidence has shown a lower agreement between thermodilution (COTD) and direct Fick (CODF) methods than historically estimated. The influence of the cardiac output measurement method on the classification of PH is poorly explored. 

While anxiety and depression are commonly reported in pulmonary hypertension (PH), limited evidence exists on how these conditions interact with the pathophysiological symptoms of PH. Fatigue and, to a lesser degree, pain are key symptoms of PH; however, they have rarely been examined as separate experiences associated with PH.