Background: Pulmonary arterial hypertension (PAH) is a heterogeneous entity with important genetic background. Risk assessment is essential to evaluate the probability of death or lung transplantation. Nevertheless, current risk scores neglect genetic predisposition, which can reclassify PAH group and risk. Our aim was to create a simplified risk score including genetics.
Methods: Our aim was to create a simplified risk score including genetics. Patients with idiopathic, heritable and toxin-induced PAH and patients with heritable or sporadic pulmonary veno-oclusive disease (PVOD) were included from the REHAP registry. Cox regression analysis including baseline variables of the validated French Pulmonary Hypertension Registry (FPHR) score was compared with the same model with addition of the presence of a pathogenic/likely pathogenic variant. Harrel’s C statistic compared scores.
Results: Three hundred and four adult patients were included from a cohort of 493 patients belonging to the REHAP registry between 2011 and 2021. Median age was 42.5 (34.0–57.0) years, and 70.7% were women.
At least one pathogenic/likely pathogenic variant was discovered in each patient in group 1, composed of 20 PVOD patients and 43 heritable PAH cases. Group 2 included 28 sporadic PVOD cases (representing 11.6%), 193 idiopathic or familiar without genetic variants PAH and 20 cases of toxin-induced PAH. Despite the higher prevalence of PVOD in group 1, diffusing capacity of the lung for carbon monoxide was similar (61.0 vs. 62.0% in the latter; P = 0.568). Variant carriers were significantly younger (36.0 vs. 46.0 years in non-carriers; P < 0.001) and had a more severe haemodynamic disease (mean pulmonary artery pressure 55.0 vs 50.0 mmHg in non-carriers; P = 0.029).
The presence of a genetic variant was associated with a higher risk of death or lung transplantation (hazard ratio 1.57; 1.01–2.46; P = 0.047). Harrel’s C statistic was 0.634 after applying the FPHR score. The addition of the genetic testing results increased the goodness of fit of the multivariable model up to 0.666.
Conclusions: A simple risk score including genetics strengthens the prognostic value of current multivariable models.
KEY CONTRIBUTORS
Alejandro Cruz-Utrilla. Pulmonary Hypertension Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Natalia Gallego. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability. Mauro Lago-Docampo Williams Hinojosa. Pulmonary Hypertension Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Carmen Pérez Olivares-Delgado. Pulmonary Hypertension Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Jair Tenorio Castaño. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability. Julián Palomino Doza. Unit of Familial and heritable Cardiomyopathies, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Fernando Arribas Ynsaurriaga. Chief of the Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. María Pilar Escribano Subias. Pulmonary Hypertension Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
