2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS).

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.

C hronic thromboembolic pulmonary hypertension (CTEPH) is a complication of acute pulmonary emboli with uncertain prevalence, ranging from 0.57% to 9.1%. 1The diagnosis is strongly associated with a history of acute venous thromboembolism.2 CTEPH results from incomplete Editorial, see p 1731 Clinical Perspective on p 1771resolution of pulmonary emboli that become organized into vessel walls and cause different degrees of obstruction to Background-Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli.Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. Methods and Results-Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-toevent) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s -1 ·cm -5 at reassessment correlated with worse long-term survival. Conclusions-Our data confirm excellent long-term survival and maintenance of good functional status post-PEA.Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery. 4 It is recognized that there is a steep surgical and institutional learning curve at the start of a PEA program, but, in experienced centers, the operative mortality rate is <5%.5-7 A number of reports have confirmed improved short-term outcome in terms of hemodynamics, right ventricular function, quality of life, functional status, and exercise capacity after surgery. [7][8][9][10][11][12][13][14][15][16][17][18] Fewer reports describe long-term outcome post-PEA, and those that have been published are mainly retrospective and either only had small numbers of patients [19][20][21][22][23][24][25][26] or limited information of factors correlated with long-term outco...

We showed, for the first time, that the incidence of IPAH is lower in children than adults and that the clinical features can be different. Most children present with clinical evidence of advanced disease and clinical status at presentation is predictive of outcome. This 7-year experience confirms the significant improvement in survival over historical controls.

provides new genetic evidence for the association of GDF2 mutations with PAH and confirms that these mutations cause impaired BMP9 function