Removable Stents for Neonates with Cyanotic Congenital Heart Disease(CCHD)

描述(申请人提供)：目前许多形式的先天性心脏病的治疗需要在出生后不久就开始多次手术，伴随而来的是高发病率和潜在的死亡率。一种有希望的替代治疗方法是在动脉导管未闭(PDA)处放置支架，以推迟最终修复，直到孩子长大并降低风险。提出了一种专门为新生儿PDA植入而设计的新型支架，以克服临床医生在新生儿PDA中使用这种新方法所遇到的困难，以及由于所使用的支架不是为此目的而设计的并发症。由工程师和儿科心脏病专家组成的跨学科团队将(1)确定/记录新生PDA中植入支架的要求，包括移除；(2)利用模体进行分析性和体外研究，以确定支架和移除器械最有希望的候选设计；(3)在合适的动物模型中进行体内试点研究，以评估部署、可再捕获、可跟踪性和放射不透明度；以及(4)进行试验性的长期动物研究，以评估安全性和有效性。在后一项研究中，建议的支架设计将与目前使用的支架在维持PDA的通畅性、组织炎症以及在有粘连的内皮组织存在的情况下从PDA安全取出方面进行比较。这些研究将为完成治疗新生儿青紫型先天性心脏病的PDA支架的开发奠定令人信服的基础。 与公共卫生相关：虽然在冠心病的治疗方面已经取得了重大进展，包括在过去十年中死亡率下降了30%，但仍有很长的路要走，而且作为一个整体，这一领域的资金严重不足。一种专门为新生儿PDA植入而设计的新型支架的成功开发将是对这一目标的重大贡献，为治疗青紫型先天性心脏病提供了一种更安全、侵入性更小的方法，包括左心发育不良综合征(HLHS)，这是所有出生一年内最致命的先天性心脏病。目前，这些新生儿的幸存者要求他们在出生后不久接受侵入性和高风险的心内直视手术，而安全有效的PDA支架的可用性将允许将侵入性手术推迟到儿童风险低得多的年龄。

DESCRIPTION (provided by applicant): Current treatment of many forms of congenital heart disease requires multiple surgical procedures starting shortly after birth, with attendant high morbidity and potential mortality. A promising alternative treatment calls for placing a stent in te patent ductus arteriosus (PDA), in order to delay definitive repair until the child is older and wil have a lower risk. A novel stent specifically designed for implantation in the neonate PDA is proposed, in order to overcome the difficulties that clinicians have experienced with this new procedure in newborns, complications arising from the fact that the stents used were not designed for this purpose. An interdisciplinary team of engineers and pediatric cardiologists will (1) identify/document the requirements for a stent to be implanted in the newborn PDA, including removal; (2) perform analytical and in vitro studies with phantoms to identify the most promising candidate designs for the stent and removal instrumentation; (3) conduct an in vivo pilot study in a suitable animal model to evaluate deployment, recaptureability, trackability and radiopacity; and (4) conduct a pilot long-term animal study to assess safety and efficacy. In this latter study, proposed stent designs will be compared with stents currently being used, in regard to maintenance of patency of the PDA, tissue inflammation, and safe removal from the PDA in the presence of adherent endothelial tissue. These studies will form a compelling foundation for completing development of a PDA stent for treatment of Cyanotic Congenital Heart Disease in neonates. PUBLIC HEALTH RELEVANCE: While significant improvement in treatment of CHD has already been made, including a 30% reduction in mortality over the past decade, there is a still a long way to go and as a whole this area has been significantly underfunded. Successful development of a new stent, specifically designed for implantation in the PDA in neonates, would represent a major contribution toward this end, providing a safer and less invasive means for treating cyanotic congenital heart disease, including hypoplastic left heart syndrome (HLHS), the deadliest of all congenital heart diseases during the first year of life. Currently, the survivl of these neonates requires that they undergo invasive and highly risky open-heart procedures shortly after birth, whereas the availability of a safe and effective PDA stent for would permit delay of invasive surgery until an age when the child is at much lower risk.