Management of Pulmonary Arterial Hypertension

Abstract

Purpose of Review This review focuses on the therapeutic management and individualized approach to Group 1 pulmonary arterial hypertension (PAH), utilizing Food and Drug Administration-approved PAH-specific therapies and various interventional and surgical options for PAH. Recent Findings The paradigm for the optimal management of PAH has shifted in recent years. Upfront combination therapy with an endothelin receptor antagonist and a phosphodiesterase 5 inhibitor is now widely accepted as standard of care. In addition, there is increasing emphasis on starting prostanoids early in order to delay time to clinical worsening. However, less is known regarding which prostanoid agent to initiate and the optimum time to do so. In order to facilitate shared decision-making, there is an increasing need for decision tools based on guidelines and collective clinical experiences to navigate between pharmacologic and interventional treatments, as well as explore innovative, therapeutic pathways for PAH. Summary The management of PAH has become increasingly complex. With a growing number of PAH-specific therapies, intimate knowledge of the therapeutics and the potential barriers to adherence are integral to providing optimal care for this high-risk patient population. While current PAH-specific therapies largely mediate their effects through pulmonary vasodilation, ongoing research efforts are focused on ways to disrupt the mechanisms leading to pulmonary vascular remodeling. By targeting aberrations identified in the metabolism and proliferative state of pulmonary vascular cells, novel PAH treatment pathways may be just on the horizon.

Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications

“…Currently, PDE5 inhibitors are an important therapeutic option in the treatment of pulmonary hypertension and their concentration is the highest in pulmonary circulation. PDE5 inhibitors are effective in the treatment of pulmonary arterial hypertension, both primary and associated with systemic connective tissue disease, in adults and children [ 76 , 77 , 78 , 79 ]. Pulmonary arterial hypertension is characterized by a reduction in the production of NO in the endothelium with a simultaneous increase in the expression and activity of PDE type 5 in smooth muscle cells of the pulmonary arteries [ 76 ].…”

Health Disparities in Pulmonary Arterial Hypertension and the Impact of the COVID-19 Pandemic

“…62 This is concerning for a disease such as PAH, which relies heavily on testing for diagnosing and treating patients, especially since early diagnosis and management in PAH are so critical to prognosis. 6 Whether this trend of decreased testing in minorities translates to less referrals to PAH specialists is worth investigating. If there is reduction in referrals to PAH specialists, then this would also result in less or delayed access to PAH-specific therapies.…”

“…WHO Groups 2-5 PH are common and serious. [4][5][6] WHO Group 1 PAH remains classified as an orphan disease associated with many underlying causes 5,6 and has an estimated 2.8-year median survival if left untreated. 7,8 Since 1980, hospital-ization and death rates from PAH have increased because of increased diagnosis and improved reporting patterns, but the total number of cases remains underestimated due to difficulties in disease detection.…”

“…2,12,13 With advances in PAH therapies, treatment is becoming more complex, requiring a more individualized approach. 6 By disproportionately impacting vulnerable patients, the delay to diagnosis and the barriers to introducing therapies have the potential to worsen health disparities in PAH, especially when compounded by the challenges facing patients and families during the COVID-19 pandemic.…”

Novel Advances in Modifying BMPR2 Signaling in PAH

“…Existing drugs target pulmonary vasodilation, proliferation and endothelial function by increasing nitric oxide (NO), inhibiting endothelin and voltage-gated calcium channels and by augmenting prostacyclin signaling pathways [ 8 ]. However, these drugs only partially increase survival and improve quality of life, while the majority of patients ultimately become resistant to medication and succumb to the disease [ 9 ]. With current treatments, the 5-year survival of PAH patients has been improved from 34% to 60%, yet these drugs are not capable of reducing the extent and progression of vascular and cardiac remodeling, resulting in eventual clinical deterioration of PAH patients over time [ 10 ].…”