TY - JOUR
T1 - Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry
AU - Utrilla, Alejandro Cruz
AU - Gallego, Natalia
AU - Tenorio, Jair Antonio
AU - Guillén, Inmaculada
AU - Torrent-Vernetta, Alba
AU - Moya-Bonora, Amparo
AU - Labrandero, Carlos
AU - MARÍA, ELVIRA GARRIDO-LESTACHE RODRÍGUEZ-MONTE
AU - Rodríguez-Ogando, Alejandro
AU - Rey, Maria del Mar Rodriguez Vazquez del
AU - López, Juana María Espín
AU - Izquierdo, Beatriz Plata
AU - Álvarez-Fuente, María
AU - Moreno-Galdó, Antonio
AU - Escribano, Pilar
AU - Cerro, Maria jesus del
N1 - This project was funded by project “Bases Genético-Moleculares de la Medicina de Precisión en la Hipertensión Arterial Pulmonar”. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Gobierno de España. Co-funded by “Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014–2020” (Award number: PI 18/01233). A.C.-U. holds a research-training contract “Rio Hortega” (CM20/00164) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III). REHIPED is supported by unrestricted grants of Janssen and Ferrer.
PY - 2022/9
Y1 - 2022/9
N2 - Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications.
AB - Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications.
KW - Pediatric pulmonary hypertension
KW - Genetics
KW - Heritable pulmonary arterial hypertension
KW - Pulmonary veno-occlusive disease
UR - https://www.mdpi.com/1422-0067/23/18/10433
U2 - 10.3390/ijms231810433
DO - 10.3390/ijms231810433
M3 - Article
C2 - 36142358
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 18
M1 - 10433
ER -