ESC Congress 2026 Abstract · Oct 26, 2026
Clonal hematopoiesis-related genes in patients with atrial septal defect associated with pulmonary arterial hypertension
By Li SL, Lu XT, He ZY et al.
Background: The cause of atrial septal defec associated with pulmonary arterial hypertension(ASD-PAH) remains largely unknown. Recently, clonal hematopoiesis (CH) has been reported to be associated with cardiovascular and PAH. Objective: To investigate the mutation profiles of CH-related genes in patients with atrial septal defect associated with pulmonary arterial hypertension (ASD-PAH). Methods: 88 patients with atrial septal defect (ASD) who were treated at our institution were enrolled in this study, including the isolated ASD without PAH group (n=37) and ASD-PAH group (n=51). All selected patients were confirmed to have isolated ASD without other types of congenital heart disease (CHD) through comprehensive diagnostic imaging, including echocardiography, right heart catheterization, and CTA. Following enrollment, peripheral venous blood samples were collected from all patients, whole-genome DNA sequences were extracted and performed whole exome sequencing. The sequencing data were processed using bioinformatics tools such as GATK, Samtools, and Varscan, and compared against major human genomic databases including refGene, rmsk, gwasCatalog, 1000g, and HGMD. The quality of coverage in the target regions was assessed, ultimately identifying mutations in CH-related genes.All data analyses were conducted using SPSS 27, p-value <0.05 was considered statistically significant for all analyses. Results: In the ASD without PAH group, including 31 females (83.8%), aged 38 (26, 52.50) years; in the ASD-PAH group, including 38 females (74.5%), aged 41 (30, 53) years. Among the 88 ASD patients, 48 (54.5%) were found to carry at least one CH mutation. In the ASD without PAH group, 15 (40.5%) had CH mutations, and in the ASD-PAH group, 33 (64.7%) had CH mutations, there was a statistically significant difference between the two groups (P < 0.05). In the ASD without PAH group, the most frequently mutated CH-related genes were SETD2. In the ASD-PAH group, the predominant CH mutations occurred in SETD2 and TNFAIP3, followed by NOTCH1、SETBP1、KANSL1、SH2B3、ASXL1、PTPRF and CBLB genes. Conclusion: Clonal hematopoiesis may play a role in the pathogenesis of ASD-PAH.