Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
College of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
PLoS One. 2023 Feb 7;18(2):e0280163. doi: 10.1371/journal.pone.0280163. eCollection 2023.
Congenital heart defects are the most common type of birth defects in humans and frequently involve heart valve dysfunction. The current treatment for unrepairable heart valves involves valve replacement with an implant, Ross pulmonary autotransplantation, or conventional orthotopic heart transplantation. Although these treatments are appropriate for older children and adults, they do not result in the same efficacy and durability in infants and young children for several reasons. Heart valve implants do not grow with the. Ross pulmonary autotransplants have a high mortality rate in neonates and are not feasible if the pulmonary valve is dysfunctional or absent. Furthermore, orthotopic heart transplants invariably fail from ventricular dysfunction over time. Therefore, the treatment of irreparable heart valves in infants and young children remains an unsolved problem. The objective of this single-arm, prospective study is to offer an alternative solution based on a new type of transplant, which we call "partial heart transplantation." Partial heart transplantation differs from conventional orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. Similar to Ross pulmonary autotransplants and conventional orthotopic heart transplants, partial heart transplants contain live cells that should allow it to grow with the recipient child. Therefore, partial heart transplants will require immunosuppression. The risks from immunosuppression can be managed, as seen in conventional orthotopic heart transplant recipients. Stopping immunosuppression will simply turn the growing partial heart transplant into a non-growing homovital homograft. Once this homograft deteriorates, it can be replaced with a durable adult-sized mechanical implant. The protocol for our single-arm trial is described. The ClinicalTrials.gov trial registration number is NCT05372757.
先天性心脏缺陷是人类最常见的出生缺陷类型,常涉及心脏瓣膜功能障碍。目前,对于无法修复的心脏瓣膜,治疗方法包括瓣膜置换植入、Ross 肺动脉自体移植或传统的原位心脏移植。尽管这些治疗方法适用于年龄较大的儿童和成人,但由于多种原因,在婴儿和幼儿中并不具有相同的疗效和耐久性。心脏瓣膜植入物不会随身体生长而生长。Ross 肺动脉自体移植在新生儿中的死亡率较高,如果肺动脉瓣功能障碍或缺失,则不可行。此外,随着时间的推移,原位心脏移植不可避免地会因心室功能障碍而失败。因此,婴儿和幼儿无法修复的心脏瓣膜的治疗仍然是一个未解决的问题。本单臂前瞻性研究的目的是提供一种基于新型移植的替代解决方案,我们称之为“部分心脏移植”。部分心脏移植与传统的原位心脏移植不同,因为只有包含心脏瓣膜的心脏部分被移植。与 Ross 肺动脉自体移植和传统的原位心脏移植类似,部分心脏移植包含活细胞,这应该使其能够随受者儿童生长。因此,部分心脏移植将需要免疫抑制。如常规原位心脏移植受者所见,免疫抑制的风险是可以管理的。停止免疫抑制只会使正在生长的部分心脏移植变成非生长的同种异体同基因移植物。一旦这种同基因移植物恶化,可以用耐用的成人尺寸机械植入物替换。描述了我们的单臂试验方案。ClinicalTrials.gov 试验注册号为 NCT05372757。