The diagnosis and management of pulmonary arterial hypertension (PAH) includes several advances, such as a broader recognition of extrapulmonary vascular organ system involvement, validated point-of-care clinical assessment tools, and focus on the early initiation of multiple pharmacotherapeutics in appropriate patients. Indeed, a principal goal in PAH today is an early diagnosis for prompt initiation of treatment to achieve a minimal symptom burden; optimize the patient’s biochemical, hemodynamic, and functional profile; and limit adverse events. To accomplish this end, clinicians must be familiar with novel risk factors and the revised hemodynamic definition for PAH. Fresh insights into the role of developmental biology (i.e., perinatal health) may also be useful for predicting incident PAH in early adulthood. Emergent or underused approaches to PAH management include a novel TGF-β ligand trap pharmacotherapy, remote pulmonary arterial pressure monitoring, next-generation imaging using inert gas–based magnetic resonance and other technologies, right atrial pacing, and pulmonary arterial denervation. These and other PAH state of the art advances are summarized here for the wider pulmonary medicine community.

To characterise the clinical features of diseases associated with paediatric pulmonary hypertension, including natural history, evaluation and therapeutic interventions, longitudinal data from 1500 children from major PH programmes were analysedhttps://bit.ly/3ff3zjV

Paediatric pulmonary arterial hypertension (PAH) shares common features with adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for caring for infants and children with PAH, as presented by the paediatric task force of the 7th World Symposium on Pulmonary Hypertension. We provide updates on diagnosing, classifying, risk-stratifying and treating paediatric pulmonary hypertension (PH) and identify critical knowledge gaps. An updated risk stratification tool and treatment algorithm is provided, now also including strategies for patients with associated cardiopulmonary conditions. Treatment of paediatric PH continues to be hindered by the lack of randomised controlled clinical trials. The challenging management of children failing targeted PAH therapy is discussed, including balloon atrial septostomy, lung transplantation and pulmonary-to-systemic shunt (Potts). A novel strategy using a multimodal approach for the management of PAH associated with congenital heart diseases with borderline pulmonary vascular resistance is included. Advances in diagnosing neonatal PH, especially signs and interpretation of PH by echocardiography, are highlighted. A team approach to the rapidly changing physiology of neonatal PH is emphasised. Challenges in drug approval are discussed, particularly the challenges of designing accurate paediatric clinical trials with age-appropriate end-points and adequate enrolment.

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by failure of the lung circulation to achieve or sustain the normal drop in pulmonary vascular resistance (PVR) at birth. Past laboratory studies identified the important role of nitric oxide (NO)-cGMP signaling in the regulation of the perinatal lung circulation, leading to the development and application of inhaled NO therapy for PPHN. Although inhaled NO therapy has improved the clinical course and outcomes of many infants, pulmonary hypertension can be refractory to inhaled NO, suggesting the need for additional approaches to severe PPHN. To develop novel therapeutic strategies for PPHN, ongoing studies continue to explore basic mechanisms underlying the pathobiology of PPHN in experimental models, including strategies to enhance NO-cGMP signaling. Recent studies have demonstrated that impaired vascular endothelial growth factor (VEGF) signaling may contribute to the pathogenesis of PPHN. Lung VEGF expression is markedly decreased in an experimental model of PPHN in sheep; inhibition of VEGF mimics the structural and functional abnormalities of PPHN, and VEGF treatment improves pulmonary hypertension through upregulation of NO production. Other studies have shown that enhanced NO-cGMP activity through the use of cGMP-specific phosphodiesterase inhibitors (sildenafil), soluble guanylate cyclase activators (BAY 41-2272), superoxide scavengers (superoxide dismutase), and rho-kinase inhibitors (fasudil) can lead to potent and sustained pulmonary vasodilation in experimental PPHN. Overall, these laboratory studies suggest novel pharmacologic strategies for the treatment of refractory PPHN.