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

No abstract

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension that shares some clinical and haemodynamic features with idiopathic pulmonary arterial hypertension (PAH). However, suspicion of PVOD is crucial, considering that PAH-specific treatment may precipitate life-threatening pulmonary oedema and lung transplant should be considered from diagnosis [1,2].The absence of pathogenic variants in the EIF2AK4 gene and the prohibitive risk of performing a lung biopsy in these patients often prevents a definitive diagnosis of PVOD [3][4][5]. Therefore, PVOD diagnosis frequently relies on the identification of other indicators with a high associated likelihood of PVOD, namely: decreased diffusing capacity of the lung for carbon monoxide (D LCO ) and typical high-resolution computed tomography (HRCT) features [5][6][7]. However, their sensitivity and specificity are far from perfect and additional diagnostic tools are missing. We hypothesise that cardiopulmonary exercise testing (CPET) might reveal characteristic patterns of exercise performance in PVOD patients, strengthening its suspicion and diagnosis.We studied 23 patients diagnosed with PVOD, referred to a national referral centre for pulmonary hypertension. Among them, 16 patients carried pathogenic biallelic variants in EIF2AK4; two presented the three typical HRCT features; two developed pulmonary oedema on PAH-specific treatment; and, in the remaining three, PVOD diagnosis was only possible by histological examination of lung specimens after transplantation. The control group consisted of 52 consecutive PAH patients on regular follow-up (24 idiopathic PAH and 28 heritable PAH associated with BMPR2).Patients underwent symptom-limited incremental CPET on a cycle ergometer. Exercise variables were measured at rest, ventilatory threshold and peak exercise. Oxygen saturation was monitored by pulse oximeter. Clinical and haemodynamic data closest to CPET were analysed.The mean±SD age was 39.8±11.9 years, without differences between PVOD and PAH groups (37.7±11.7 versus 40.7±12; p=0.28). PVOD patients did not show female sex predominance (43.5% versus 76.9%, p=0.08). They presented worse functional class (FC) (FC I: none PVOD versus 13 PAH; FC II: 11 PVOD versus 31 PAH; and FC III: 12 PVOD versus eight PAH; p<0.01) and lower D LCO levels (32.8±7.8 versus 78.7±13.2%; p<0.01) than PAH patients. Most CPET (85.3%) was performed in patients receiving PAHspecific treatment, including 32% on systemic prostacyclins. 11 patients were not receiving any PAHspecific medication: nine (seven PAH and two PVOD) who underwent CPET at diagnosis and two PVOD who did not tolerate it.PAH patients achieved higher work rates than PVOD patients. There was a significant reduction in predicted peak oxygen uptake (V O 2 ), oxygen pulse and V O 2 levels at ventilatory threshold in PVOD patients compared to PAH (table 1).The main exponents of ventilatory efficiency were increased to a greater extent in PVOD when compared to PAH patients, both minute ventilation (V E )/carbon di...

No abstract

No abstract