Coronary Post-Dilatation Catheter

描述（由申请人提供）：冠状动脉疾病（CAD）给美国医疗保健系统带来了巨大的临床负担（约1600万美元）和财政负担（到2030年约1060亿美元）。许多冠心病患者急性和稳定冠状动脉疾病的标准护理包括经皮冠状动脉介入支架置入。支架置入术后的临床结果直接关系到支架/血管面积是否足够小（即完全支架部署），支架是否完全贴合血管壁。大量研究表明，高达85%的冠状动脉支架部署不足，因此需要球囊后扩张以达到适当的支架扩张。尽管在扩张后，高达58%的支架仍未到位。虽然多种因素影响支架部署，但只有血管/支架反冲和球囊扩张不足被证明是导致支架扩张不足的主要因素。球囊扩张不足导致大部分支架部署不足，这并不奇怪，因为在体内依赖于固有的不准确的制造商离体压力-直径关系。在我们的I期资助（R43 HL120517 -冠状动脉扩张后导管）中，描述了一种新型设备，它作为标准的冠状动脉扩张后导管，但在膨胀期间根据欧姆定律而不是经验压力-直径关系提供实时球囊尺寸。第一阶段的研究结果在两个方面都非常成功。在Aim #1中更新了显示台和CB导管，在Aim #2中对受损猪冠状动脉导管的验证显示了非常准确的扩张后（即，体内CB球囊测量精度偏差= 0.05mm，这在临床上是高度可接受的，因为这至少比0.5mm的标准支架分割小一个数量级（即小10倍））。在这个II期申请中，我们建议下一步获得研究性器械豁免（IDE）的批准，以进行一项人体试点研究，该研究将主要用于评估一组CAD患者的器械安全性和次要器械有效性。为了实现这些II期目标，提出了以下具体目标：1)最终动物验证：在良好实验室规范（GLP）环境中评估CB导管系统在一组患病动物中的安全性和有效性，用于向FDA和机构审查委员会（irb）提交数据；2)人体验证：在一项双中心研究中，在一小群人（30例患者）中评估安全性和有效性。这项II期研究解决了一个非常重要的国家和世界范围的临床需求，不仅可以影响NHLBI，而且可以影响NIH的许多其他任务领域。这些目标的成功完成将使我们能够将我们的研究成果转化为可商用的设备，从而大大改善CAD患者的预后。

DESCRIPTION (provided by applicant): Coronary artery disease (CAD) places a major clinical (~16M) and financial (~$106B by 2030) burden on the U.S. healthcare system. The standard of care for many CAD patients with acute and stable coronary conditions involves percutaneous coronary intervention with stenting. Clinical outcomes following stenting are directly related to the achievement of adequate minimal stent/vascular area (i.e., full stent deployment) with full stent apposition against the vascular wall. Numerous studies have shown that up to 85% of all coronary stents are under-deployed and therefore require balloon post-dilatation to achieve proper stent expansion. Despite post-dilatation, up to 58% of stents still remain under-deployed. Although various factors affect stent deployment, only vascular/stent recoil and balloon under-expansion were shown to be the major factors causing stent under-expansion. Balloon under-expansion contributes to the majority of the stent under- deployment, which is not surprising given the in vivo reliance on inherently inaccurate manufacturer ex vivo pressure-diameter relationships. In our Phase I grant (R43 HL120517 - Coronary Post-Dilatation Catheter), a novel device was described which operates as a standard coronary post-dilatation catheter, but also provides real-time balloon dimension during inflation based on Ohm's law instead of empirical pressure-diameter relationships. The results of the Phase I study were extremely successful for both aims. The display console and CB catheter were updated in Aim #1 and validation of the CB catheter in injured swine coronary vessels showed extremely accurate post-dilatation in Aim #2 (i.e., in vivo CB balloon measurement accuracy bias = 0.05mm, which is highly acceptable clinically given this is at least an order of magnitude smaller (i.e., 10x smaller) than the 0.5mm standard stent divisions). In this Phase II application, we propose the next step of obtaining approval for an investigational device exemption (IDE) to conduct a human pilot study which will be used to assess primarily the device safety and secondarily device efficacy in a group of CAD patients. To accomplish these Phase II objectives, the following specific aims are proposed: 1) Final Animal Validation: To assess the safety and efficacy of the CB catheter system in a set of diseased animals in a good-laboratory practice (GLP) setting to be used for data submission to the FDA and institutional review boards (IRBs); and 2) Human Validation: To assess the safety and efficacy in a small group of humans (30 patients) in a two-center study. This Phase II study addresses a highly significant national and worldwide clinical need that can impact not just NHLBI, but many other mission areas of NIH. Successful completion of these proposed Aims will allow us to translate our research findings to a commercially available device that could drastically improve CAD patient outcomes.