PAH's Evolving Landscape: Pipeline Therapies, Diagnostic Gaps, and Older Patients

"PAH's Evolving Landscape: Pipeline Therapies, Diagnostic Gaps, and Older Patients" looks ahead to emerging therapies while revisiting who is actually being referred.

Dr. McLaughlin asks Dr. Channick what excites him about the future. He notes continued work on the established pathways, including a study of high-dose macitentan, 75 mg, that should report soon, and an inhaled guanylate cyclase activator within the nitric oxide pathway. Interest in inhaled routes is growing, and longer-acting inhaled prostacyclin formulations aim to avoid four-times-daily dosing. Beyond the existing pathways, an inhaled tyrosine kinase inhibitor is in development, with imatinib being repackaged after earlier toxicity concerns.

Dr. Kim identifies persistent gaps, including late diagnosis and risk assessment that omits the right ventricle and hemodynamics. A panelist adds that PAH is heterogeneous and that subgroups such as portopulmonary hypertension and congenital heart disease are underrepresented in studies. Optimizing proven pathways remains important, since expectations have shifted from keeping patients alive, to stable, to waiting for problems before adding therapy, and now to driving everyone toward low risk early.

Dr. McLaughlin observes that patients have changed. Clinicians once saw the 30-year-old woman clearly with PAH, and now they see older patients with elevated pressures on echo and several comorbidities. Dr. Channick says the demographics probably have not changed but recognition has, and treatments drive referral. Some older patients truly have PAH, though their response cannot be extrapolated from younger patients, so a proper diagnostic approach must exclude untreated sleep apnea, hypoventilation, and left heart disease.

Dr. Kim warns that the hemodynamic criteria are not a definition of PAH, particularly now that thresholds have been lowered. PAH remains a diagnosis of exclusion, and many referrals prove to be Group 2 or Group 3 disease. Dr. McLaughlin says only one or two of every ten new patients in her clinic have true PAH.

The next episode in this series, "PAH vs Left Heart PH: Echo Clues and Overlapping Physiology," features Dr. Vaidya on echo clues and a debate over spectrum versus buckets.