My Introduction to Pulmonary Hypertension

My journey into studying nitric oxide (NO) bioavailability developed as I explored the role of nitrite ions. The traditional view that nitrite was merely an inactive byproduct of NO oxidation was a perspective I sought to challenge. As I continued my research at Papworth and Addenbrooke's Hospitals under Professor Higenbottam, I hypothesized that nitrite ions could be a source of NO bioactivity.

The article, “Survival Outcomes and Impact of Targeted PAH Therapy in Portopulmonary Hypertension in the PVRI GoDeep Meta-Registry” by Jose et al. addresses the controversial question on the survival benefit of PAH drugs in portopulmonary hypertension (PoPH) [1]. Treatment strategies in PoPH are often extrapolated from other PAH subtypes as PoPH have largely been excluded from large PAH drug randomized trials. In this context, the present study represents an important contribution to the management of PoPH.

Pfizer initiated their Phase III trial of sildenafil for the treatment of PAH (SUPER study), which later led to the publication of the results [4] and the approval of sildenafil (20 mg, three times a day) in 2006 for the management of PAH. This period marked a pivotal moment in the medical history of treating PAH. I witnessed firsthand how this development transformed the landscape of treatment options for patients suffering from this severe condition.

In 1979, during my cardiology fellowship, a 16-year-old with primary pulmonary hypertension (PPH), a rare and severe condition at that time, spurred my research. There was limited literature then. My pediatric cardiology colleagues, who were experienced in dealing with pulmonary hypertension linked to congenital heart diseases, introduced me to vasoreactivity testing, a method involving the administration of oxygen and tolazoline to assess operability. Tolazoline administration resulted in a significant decrease in pulmonary artery (PA) pressure, suggesting potential therapeutic responsiveness, though diuretics were the only treatment for pulmonary hypertension and right heart failure at that time. This prompted my search for a viable solution.