BackgroundThe knowledge of hereditary predisposition has changed our understanding of Pulmonary Arterial Hypertension. Genetic testing has been widely extended and the application of Pulmonary Arterial Hypertension specific gene panels has allowed its inclusion in the diagnostic workup and increase the diagnostic ratio compared to the traditional sequencing techniques. This is particularly important in the differential diagnosis between Pulmonary Arterial Hypertension and Pulmonary Venoocclusive Disease. MethodsSince November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of Pulmonary Arterial Hypertension or Pulmonary Venoocclusive Disease included in the Spanish Registry of Pulmonary Arterial Hypertension. Herein, we present the clinical phenotype and prognosis of all Pulmonary Arterial Hypertension patients with disease-associated variants in TBX4. ResultsOut of 579 adults and 45 children, we found in eight patients from seven families, diseasecausing associated variants in TBX4. All adult patients had a moderate-severe reduction in

Background and aims Protein‐losing enteropathy (PLE) after Fontan surgery carries significant morbimortality. Its pathophysiology and association with other Fontan complications are poorly understood. Our aims were to examine whether Fontan‐PLE is associated with greater liver damage and to assess the presence of systemic and intestinal inflammation. Methods Fontan patients with PLE and Fontan controls without PLE matched for age and Fontan surgery procedure were included. Data were prospectively compiled on blood and stool tests, liver imaging, elastography, cardiac‐MRI and cardiac catheterization. Results Twenty‐nine Fontan patients were enrolled (14 with PLE and 15 controls without PLE). Patients with PLE had more advanced liver disease estimated by non‐invasive methods: blunt liver margins on ultrasonography (71.4% vs 26.7%, P = .027), greater median liver stiffness (25.4 vs 14.5 kPa, P = .003) and higher FIB‐4 (P = .016). Portal hypertension‐related signs were more common in patients with PLE including ascites (P = .035), larger spleen size (P = .005), oesophageal varices/splanchnic collateral shunts (P = .03), higher liver stiffness‐spleen size‐to‐platelet ratio risk score (P < .001) and lower platelet count (P = .01). Systemic proinflammatory cytokines (TNF‐α, interleukin‐6), biomarkers of intestinal permeability (intestinal fatty‐acid binding protein) and faecal calprotectin concentrations were also significantly increased in Fontan‐PLE (P < .05). Faecal calprotectin directly correlated with alpha‐1 antitrypsin clearance and inversely with cardiac index, total serum proteins and body mass index. Conclusion Fontan‐PLE is associated with advanced liver disease and increased markers of systemic inflammation and intestinal permeability. Faecal calprotectin is elevated and correlates with Fontan‐PLE severity. Liver assessment is mandatory in all Fontan patients, and especially in those with PLE.