Device for Treatment of Cardiac No-Option Patients

用于治疗心脏病患者的装置

• 批准号: 9761580
• 负责人: Terry Hubbard
• 金额: $ 99.19万
• 依托单位: 3DT HOLDINGS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761580
• 关键词: Acute; Address; Agonist; Animal Model; Animals; Anterior; Arteriosclerosis; Award; Bypass; Cardiac; Cardiovascular system; Cause of Death; Centers for Disease Control and Prevention (U.S.); Chest Pain; Chronic; Clinic; Clinical; Clinical Data; Comorbidity; Congestive Heart Failure; Coronary; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary artery; Data; Development; Device Safety; Devices; Diabetes Mellitus; Diffuse; Edema; Epidemic; Exposure to; Family suidae; Fatigue; Foundations; Health Care Costs; Healthcare; Healthcare Systems; Heart Transplantation; Heart failure; Hemorrhage; Hypertension; Incidence; Infrastructure; Institutes; Intervention; Investigation; Ischemia; Left; Metabolic syndrome; Metals; Myocardial Infarction; Myocardial Revascularization; Myocardium; Nature; Operative Surgical Procedures; Organ Transplantation; Outcome; Patients; Perfusion; Peripheral; Pharmacology; Phase; Preparation; Process; Reporting; Risk; Safety; Shortness of Breath; Smooth Muscle Myocytes; Stents; Structure of left gastric vein; Surgeon; System; Technology; Therapeutic; Thick; Translating; United States; United States National Institutes of Health; Validation; Veins; Venous; Venous Pressure level; Venous system; Wedge Pressures; Western Europe; World Health Organization; animal safety; clinically relevant; cost; design; first-in-human; human study; hypercholesterolemia; implantation; novel; patient population; percutaneous coronary intervention; performance tests; phase 1 study; phase 2 study; pre-clinical; preconditioning; pressure; repaired; restenosis; stem

ABSTRACT Of the nearly 1 million US patients suffering from myocardial infarction each year, 15-20% are poor candidates for CABG or PCI because of diffuse CAD, multiple stents, and failed CABG and are therefore considered "no- option" patients. These patients suffer daily from severe angina, shortness of breath, fatigue, and the like and are frequently untreatable by CABG or PCI which has been shown to have very poor outcomes under these conditions. Without a heart transplant, the no-option patient typically progresses to CHF. The Company’s technology enables a revascularization therapy for the no-option patient that is not reliant on repairing the arterial system. The therapy is a staged approach which uses a novel venous pressure preconditioning (VPP) device to prime the coronary vein for retroperfusion via coronary vein bypass graft (CVBG). Development of the VPP device has focused on overcoming limitations associated with coronary retroperfusion that have stemmed from abrupt increases in perfusion pressure, leading to edema and hemorrhage of the myocardium. Our approach avoids acutely raising the pressure in the coronary veins from venous (10-20 mmHg) to arterial values (100-120 mmHg) in a single step and instead, regulates the pressure at an intermediate level (between arterial and venous levels). Importantly, results from our Phase I studies have shown safe and selective pre-arterialization of the left anterior descending coronary vein using the percutaneously delivered VPP devices. This proof-of-concept was demonstrated by thicker vessel walls and with greater degree of functional smooth muscle cells (i.e., respond to pharmacological agonist and antagonist) in the preconditioned vessels occluded by the VPP device compared to normal veins. Our previous studies have demonstrated that veins with this degree of remodeling safely enable retroperfusion at full arterial pressure without edema or hemorrhage. To advance these outstanding findings, the chronic retroperfusion therapeutic approach must be challenged under clinically relevant conditions that resemble the multiple comorbidities of “no-option” patients. Accordingly, this Phase II proposal advances this promising technology in two specific aims: 1) To demonstrate efficacy of chronic retroperfusion enabled by the VPP device in a chronic animal study of a translational animal model of DCAD and focal ischemia comorbidities; and 2) To collect GLP safety data in a chronic animal study for an IDE submission to the FDA. This Phase II study addresses a highly significant clinical need for providing revascularization for “no-option” patients and can reach across various NIH Institutes and Centers.

抽象的 在近100万美国患有心肌梗塞的患者中，有15-20％是候选人 对于CABG或PCI，由于弥漫性CAD，多个支架和失败的CABG，因此被认为是“没有 - 选择“患者。这些患者每天患有严重的心绞痛，呼吸急促，疲劳等 CABG或PCI经常无法治疗，这在这些下面非常有结果 没有心脏移植的条件 技术可以为无选患者进行血运重建疗法 系统。 冠状动脉静脉通过冠状动脉旁路移植（CVBG）。 设备的重点是克服与冠状动脉折后灌注有关的限制，这些局限性 突然增加灌注压力，导致我们的方法的水肿和出血 避免从静脉（10-20 mmHg）到动脉值（100-120）急性升高冠状静脉的压力 MMHG）在一个步骤中，而是调节中间水平的压力（在替代和静脉之间 级别）。 使用经皮递送的VPP设备的前静脉静脉静脉 由较厚的容器壁和更大程度的功能平滑肌细胞证明 与VPP装置遮住的预处理容器中的药理学激动剂和拮抗剂比较 正常的静脉 在全部压力下进行递归灌注，并出血。 在临床相关条件下，必须对慢性返回灌注治疗方法受到质疑 类似于“无选”患者的多种合并症。 有前途的技术有两个具体的目标：1）证明您实现了慢性返回灌注 VPP装置在DCAD和局灶性缺血合并症的翻译动物模型的慢性动物研究中； 2）在一项慢性动物研究中收集GLP安全数据，以提交给FDA 研究解决了为“无选”患者提供重新体重的重新体重的临床需求，并且可以 到达各种NIH机构和中心。

项目成果

Pre-arterialization of coronary veins prior to retroperfusion of ischemic myocardium: percutaneous closure device.

• DOI: 10.3389/fcvm.2023.1208903
• 发表时间: 2023
• 期刊: FRONTIERS IN CARDIOVASCULAR MEDICINE
• 影响因子: 3.6
• 作者: Choy, Jenny S.;Hubbard, Terry;Golts, Eugene M.;Bhatt, Deepak L.;Navia, Jose A.;Kassab, Ghassan S.
• 通讯作者: Kassab, Ghassan S.