Pulmonary Hypertension in 2021: Part I—Definition, Classification, Pathophysiology, and Presentation

Molecular Pathways in Pulmonary Arterial Hypertension

“…PH secondary to chronic thromboembolic pulmonary embolism (CTEPH) is categorized as group 4 PH. The 6th WSPH defined CTEPH as mPAP ≥ 20 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg diagnosed by right heart catheterization in the setting of flow limiting pulmonary artery thrombi/emboli [ 1 ]. Studies have reported an average annual incidence of CTEPH as 4%, higher than prior estimates of 0.1–0.5% [ 16 , 17 ], but this still might be an underrepresentation given that most patients are not evaluated for PH following an episode of pulmonary embolism and a majority of patients with CTEPH do not recall prior venous thromboembolism events [ 18 ].…”

“…Post-capillary PH is defined as mPAP > 20 mm Hg, PVR < 3 WU and PCWP > 15 mm Hg. This is seen in groups 2 and 5 PH (group 2 is due to left heart disease) [ 1 ]. Mixed pre- and post-capillary PH is mPAP > 20 mm Hg, PVR ≥ 3 WU and PCWP > 15 mm Hg and carries a worse prognosis [ 31 ].…”

“…Fibroblasts, in addition to some other interstitial cells, present in the arterial media are implicated in the fibrogenesis that underlies the pathologic vascular remodeling in PH. Given the inflammation in the disease process, pulmonary artery endothelium acquires an increasingly aberrant adhesive capacity with a dysregulated proliferative and anti-apoptotic growth constitution giving rise of in situ thrombosis [ 1 ].…”

“…Loss of BMPR2 mediated signaling has a predominant role in PAH pathogenesis. BMPR2 plays a role in endothelial growth and functional loss of BMPR2 tips the scale towards a pro-proliferative and anti-apoptotic endophenotype [ 1 , 110 ] that has since been described as the pathognomonic molecular change in PAH. In addition, BMPR2 functional deficit in the endothelium also facilitated the mitochondrial metabolic dysregulation and inflammation [ 89 ].…”

“…Pulmonary hypertension (PH) is a chronic condition characterized by a progressive pulmonary arterial pan-vasculopathy with consequent elevation in pulmonary arterial pressure and downstream hemodynamic and mechanical abnormalities in the pulmonary vessels and right ventricle. The first World Symposium on Pulmonary Hypertension (WSPH) in 1973 arbitrarily defined PH as a resting mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg, as measured by right heart catheterization [ 1 ]. However, in a 2016 retrospective review of 21,727 veterans undergoing right heart catheterization, Maron and colleagues noted higher clinical risk and mortality hazard emerging at mPAP of approximately 19 mm Hg [ 2 ].…”