A second-hit conceptual framework for pulmonary arterial hypertension in adult congenital heart disease: genetics, hemodynamics, and treat-and-repair
Abstract
Pulmonary arterial hypertension (PAH) complicates a clinically important subset of adult congenital heart disease (ACHD) and contributes to substantial morbidity and premature mortality. This narrative review synthesizes direct and indirect evidence within a second-hit conceptual framework for ACHD-associated PAH. In this framework, baseline pulmonary vascular susceptibility interacts over time with sustained hemodynamic or hypoxemic exposure and with superimposed biological or clinical stressors. SOX17 has the clearest direct genetic association with ACHD-PAH, whereas evidence involving BMPR2-related metabolic, inflammatory, and proliferative pathways is derived predominantly from heritable PAH, broader PAH populations, and experimental models. Experimental and computational studies also suggest that disturbed flow and mechanobiological signaling may contribute to endothelial dysfunction and endothelial-to-mesenchymal transition, although these mechanisms have not been established as a causal sequence in longitudinal ACHD cohorts. Four-dimensional flow magnetic resonance imaging and cardiopulmonary exercise testing may characterize abnormal flow patterns and impaired pulmonary vascular reserve in research settings, but neither is validated for screening patients with borderline ACHD hemodynamics or for selecting therapy. Evidence supporting treat-and-repair remains observational and defect-specific, with the most developed adult data derived from carefully selected patients…
Read the paper
Related studies
- Protective effects of tadalafil and N-acetyl cysteine therapy on cisplatin-induced testicular toxicity
- The Use of Generative AI for Scientific Literature Searches for Systematic Reviews: ChatGPT and Microsoft Bing AI Performance Evaluation
- Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons
- Ozone-modified properties of pumpkin seed oil as anti-H. pylori, anticancer, anti-diabetic and anti-obesity agent
- Effectiveness of Low-Intensity Extracorporeal Shock Wave Therapy in Erectile Dysfunction: An Analysis of Sexual Function and Penile Hardness at Erection: An Umbrella Review
- Molecular Docking of Silymarin as a Ligand for Aromatase Enzyme and HIV-1 Reverse Transcriptase Using Molegro Virtual Docker
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.