Yasuhara Jun, Schultz Karlee, Bigelow Amee M, Garg Vidu
Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, United States.
Heart Center, Nationwide Children's Hospital, Columbus, OH, United States.
Front Cardiovasc Med. 2023 Apr 28;10:1142707. doi: 10.3389/fcvm.2023.1142707. eCollection 2023.
Congenital aortic valve stenosis (AVS) is one of the most common valve anomalies and accounts for 3%-6% of cardiac malformations. As congenital AVS is often progressive, many patients, both children and adults, require transcatheter or surgical intervention throughout their lives. While the mechanisms of degenerative aortic valve disease in the adult population are partially described, the pathophysiology of adult AVS is different from congenital AVS in children as epigenetic and environmental risk factors play a significant role in manifestations of aortic valve disease in adults. Despite increased understanding of genetic basis of congenital aortic valve disease such as bicuspid aortic valve, the etiology and underlying mechanisms of congenital AVS in infants and children remain unknown. Herein, we review the pathophysiology of congenitally stenotic aortic valves and their natural history and disease course along with current management strategies. With the rapid expansion of knowledge of genetic origins of congenital heart defects, we also summarize the literature on the genetic contributors to congenital AVS. Further, this increased molecular understanding has led to the expansion of animal models with congenital aortic valve anomalies. Finally, we discuss the potential to develop novel therapeutics for congenital AVS that expand on integration of these molecular and genetic advances.
先天性主动脉瓣狭窄（AVS）是最常见的瓣膜异常之一，占心脏畸形的3%-6%。由于先天性AVS通常呈进行性发展，许多患者，包括儿童和成人，一生中都需要经导管或手术干预。虽然成人群体中退行性主动脉瓣疾病的机制已部分阐明，但成人AVS的病理生理学与儿童先天性AVS不同，因为表观遗传和环境风险因素在成人主动脉瓣疾病的表现中起重要作用。尽管对先天性主动脉瓣疾病（如二叶式主动脉瓣）的遗传基础有了更多了解，但婴幼儿先天性AVS的病因和潜在机制仍不清楚。在此，我们回顾先天性狭窄主动脉瓣的病理生理学、其自然病史和疾病进程以及当前的管理策略。随着先天性心脏病遗传起源知识的迅速扩展，我们还总结了关于先天性AVS遗传因素的文献。此外，对分子层面的进一步了解促使先天性主动脉瓣异常动物模型不断增加。最后，我们讨论开发先天性AVS新型疗法的潜力，并阐述如何整合这些分子和遗传学进展以推动该领域发展。
