Novel Micro-Implant to Measure Intracardiac Pressure in Congenital Heart Patients

描述（由申请人提供）：具有功能性单心室（FSV）解剖结构的先天性心脏病患者通常需要在婴儿期和儿童期进行一系列手术，以便为他们提供存活至成年的机会。第二阶段手术称为半Fontan手术（HFP），将全身静脉血从上半身和头部重新引导到肺循环中，而不通过介入的心室腔。由于血液流入肺部在很大程度上是一个被动过程，肺血管系统内的任何解剖阻塞、肺血管阻力升高或显著心室功能障碍都可能导致患者的半Fontan压升高。在分阶段姑息治疗过程中早期在半Fontan通路内出现的问题可能导致Fontan手术期间和Fontan患者一生中并发症的风险增加。因此，保持最佳的半Fontan解剖结构和生理学对于FSV患者的长期成功和生存非常重要。目前，在大多数机构中，在术后即刻或在等待Fontan的门诊环境中常规测量半Fontan通路压力不是标准做法。术后监测半Fontan压力需要在上身或颈部静脉留置导管。这有可能导致全身静脉的完全血栓形成，这对于半Fontan患者是毁灭性的并发症。此外，连续门诊心脏导管术测量半Fontan压力的婴儿在手术并发症的风险。因此，为了给ICU和门诊的临床医生提供测量半Fontan压力的方法，研究人员正在开发一种小型化的压力传感器，可以在第二阶段手术时直接植入半Fontan通路。申报的植入式压力监测器将在术后即刻提供半Fontan通路的血流动力学评估，而不会产生全身静脉血栓形成风险。在门诊环境中半Fontan通路压力的间隔测试将允许临床医生观察压力上升趋势，这可能提供正在发展的问题的早期指示，并允许在不可逆损伤发生之前进行早期干预。这将在没有心导管插入术相关风险的情况下完成。在这项研究中，研究人员将完成微型植入式无线压力传感器的开发。将实现最终设计冻结，并完成设计控制要求，包括风险分析、生物相容性试验、无菌性和制造过程，以满足FDA要求。将进行临床前动物研究，包括慢性GLP动物研究，以确定器械的体内生物相容性、功能性和安全性。最后，本研究将在申请过程中为研究者提供支持，以获得FDA的研究器械豁免，用于这些复杂形式的先天性心脏病婴儿的初步可行性研究。 公共卫生相关性：先天性心脏病是所有出生缺陷中最常见的类型。先天性心脏病的最严重和高风险形式是那些出生时只有一个功能心室或泵室的患者。虽然每天出生的患有这些疾病的患者的绝对数量相对较低，但这些患者在出生后立即开始的护理期间消耗了大量的医疗资源和资金。如果被批准用于婴儿和儿童，所提出的压力监测系统将使临床医生能够测量患有这些功能性单心室心脏病的儿童的动态肺动脉压。这种新的能力可以通过允许医生优化药物并在不可逆损伤发生之前检测并发症的发作来极大地改善向这些患者提供的医疗护理，这最终可以大大改善与这种高风险患者人群相关的发病率和死亡率，并减少医疗资源的利用。

DESCRIPTION (provided by applicant): Congenital heart disease patients with functional single ventricle (FSV) anatomy usually require a series of surgeries during infancy and childhood in order to provide them with a chance to survive into adulthood. The second stage surgery, termed the hemi-Fontan procedure (HFP) re-routes systemic venous blood from the upper body and head into the pulmonary circulation without passing through an intervening ventricular chamber. Because blood flow into the lungs is largely a passive process, any anatomic obstruction within the pulmonary vasculature, elevated pulmonary vascular resistance, or significant ventricular dysfunction can result in patients having elevated hemi-Fontan pressures. Problems that develop within the hemi-Fontan pathway early in the staged palliation process can result in an increased risk for complications during the Fontan operation and throughout a Fontan patient's life. Therefore, maintaining optimal hemi-Fontan anatomy and physiology is important for long term success and survival for FSV patients. Currently, it is not standard practice at most institutions to routinely measure hemi-Fontan pathway pressures in the immediate post- operative period or in the ambulatory setting while awaiting the Fontan. Post-operative monitoring of the hemi- Fontan pressures requires an indwelling catheter in an upper body or neck vein. This has the potential to lead to complete thrombosis of the systemic vein, which is a devastating complication for the hemi-Fontan patient. Furthermore, serial outpatient cardiac catheterizations to measure hemi-Fontan pressures place infants at risk for procedural complications. Therefore, to provide clinicians in the ICU and in the ambulatory setting with the means to measure hemi-Fontan pressures, investigators are developing a miniaturized pressure sensor that can be implanted directly into the hemi-Fontan pathway at the time of the second stage operation. The proposed implantable pressure monitor will provide readily available hemodynamic assessment of the hemi- Fontan pathway during the immediate post-operative period without the risk of systemic venous thrombosis. Interval testing of the hemi-Fontan pathway pressure in the ambulatory setting will allow clinicians to observe for rising pressure trends, which may provide early indication of a problem that is developing and allow for earlier intervention before irreversible damage has occurred. This will be accomplished without the risk associated with cardiac catheterization. During this study investigators will complete the development of a miniature implantable wireless pressure sensor. Final design freeze will be achieved, and design control requirements, including risk analysis, biocompatibility testing, sterility, and manufacturing processes, will be completed to satisfy FDA requirements. Preclinical animal studies will be carried out, including a chronic GLP animal study, to determine the device's in vivo biocompatibility, functionality, and safety profile. Finally, this study will support investigators during the application process to obtain Investigational Device Exemption from the FDA for the initial feasibility studies in infants with these complex forms of congenital heart disease. PUBLIC HEALTH RELEVANCE: Congenital heart disease is the most common type of all birth defects. The most severe and high risk forms of congenital heart disease are those patients born with only one functional ventricle or pumping chamber. Although the absolute number of patients born each day with these conditions is relatively low, these patients consume a tremendous amount of healthcare resources and funding during their lifetime of care, which starts immediately after birth. If approved for use in infants and children, the proposed pressure monitoring system would enable clinicians to measure ambulatory pulmonary artery pressures in children with these functional single ventricle heart conditions. This new ability could greatly improve the medical care provided to these patients by allowing physicians to optimize medications and detect the onset of a complication before irreversible damage has occurred, which could ultimately result in greatly improved morbidity and mortality associated with this high risk patient population and a reduction in healthcare resource utilization.