David B. Badesch

Neonates and infants with FOXF1 mutation develop alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), which is typically considered a uniformly fatal neonatal lung disorder due to marked hypoxemic respiratory failure with severe pulmonary hypertension (PH). Survival beyond infancy is exceedingly rare, with limited reports of FOXF1 genetic abnormalities in older children or adult cases of severe PH. Here, we report the case of a male patient with a pathogenic FOXF1 variant who presented with severe PH in early infancy whose disease stabilized and improved with early and aggressive PH therapy. The patient subsequently died at the age of 30 years, however, due to severe right ventricular failure due to the acute onset of pneumonia. This case highlights that survival into adulthood is feasible in patients with FOXF1‐related pulmonary vascular disease and supports the inclusion of FOXF1 in pulmonary hypertension genetic panels for subjects who develop PH across the lifespan.

Pulmonary arterial hypertension (PAH) was historically viewed as a disease of young adults; however, emerging evidence suggests rising prevalence in the elderly, which is an insufficiently characterized population. We evaluated clinical and sociodemographic features of PAH patients over 80 years and compared their outcomes with younger patients. We performed a prospective cohort study utilizing the Pulmonary Hypertension Association Registry to compare clinical characteristics, functional capacity, and quality of life measures between octogenarians (≥ 80 years) and non‐octogenarians (< 80 years) at enrollment and follow‐up visits. Associations between age subgroups and outcomes were assessed using linear, binomial, and Cox regression. The cohort comprised 113 octogenarians and 3,094 non‐octogenarians with PAH. Smoking history was more common in octogenarians, who also more frequently had idiopathic or connective tissue disease–related PAH. Octogenarians had lower right atrial pressure and mean pulmonary artery pressure ( p < 0.001) than younger patients. At baseline, octogenarians had a lower absolute 6‐min walk distance and higher World Health Organization functional class ( p < 0.001). Octogenarians were more often initially treated with monotherapy and less likely to receive a prostacyclin analog. Octogenarians had a 57% higher risk of all‐cause hospitalization and twice the mortality of younger adults after covariate adjustment (IRR 1.57, 95%CI 1.06–2.33, p < 0.05 and HR 2.38, 95%CI 1.62–3.52, p = 0.001, respectively). The oldest PAH patients exhibit distinct clinical profiles, therapies, and outcomes compared to younger adults, though it remains uncertain whether these differences reflect a unique phenotype, reduced therapy response, or the cumulative effects of aging and comorbid conditions.