Novel Catheter for Treatment of Ventricular Tachycardia

描述（由申请人提供）：缺血性室性心动过速（VT）是导致美国每年发生的30万例心脏性猝死中一半以上的原因。植入式心律转复除颤器（ICD）是标准的治疗方法，但它们很昂贵，ICD植入物的总成本接近5万美元，美国每年在这些植入物上的花费超过22亿美元。除颤器是有效的，但不能治愈，因为接受除颤器的患者中有一半会出现新的室速，对除颤器没有反应，这需要他们以额外的费用服用抗心律失常药物。在过去几年中，由于设计和可靠性问题，已经召回了55,000个icd。热消融治疗是ICD植入的一种有吸引力的替代或辅助治疗方法，因为它对许多类型的室上性心动过速的成功率超过90%，但它在治疗缺血性室性心动过速方面尚未成功。普遍认为消融治疗不成功是因为它不能治疗较大的、我们已经开发了一种能够做到这一点的方法，使用盐增强射频（SERF）消融。我们通过在射频消融的同时向组织内注射温生理盐水来治疗室速。注入的盐水在细胞外空间流动，传递能量。这使组织的有效导热系数增加了20多倍。我们已经使用可操纵的SERF消融导管和可伸缩电极在犬梗死模型中证明，SERF消融产生足够大的热病变来治疗室室，病变是可靠的跨壁，即使存在梗死疤痕，多个病变可以放置以提供一条阻断线。我们也证明了这种疗法是安全的，导管符合安全性和可靠性要求，并且具有生物相容性。我们建议完成用于治疗缺血性VT的盐增强射频（SERF）消融系统的开发。我们将完成系统和导管的设计，并验证它们符合医疗安全标准（EN60601-1）、生物相容性（ISO-10993），并验证灭菌达到10-6的无菌保证水平（SAL）。我们将在梅奥诊所、洛约拉大学、宾夕法尼亚大学和布里格姆妇女医院的大型动物梗死模型中开展广泛的临床前生存试验。然后，我们将申请并获得研究器械豁免（IDE），以开展多中心临床试验。我们开发的SERF消融治疗室性心动过速（VT）与公共卫生相关，因为我们正在解决一个日益增长和昂贵的问题，即患者接受的用于治疗这些潜在致命心律失常的植入式心律转复除颤器（ICDs）既不能治愈也不可靠。美国每年花费超过20亿美元放置ICD，而一半的患者出现了对ICD无反应的额外室性心动过速。至少，这些病人受到的电击严重降低了他们的生活质量。在最坏的情况下，病人仍然容易发生心源性猝死。迫切需要一种有效和廉价的方法来治疗这些患者的静脉血栓。

DESCRIPTION (provided by applicant): Ischemic ventricular tachycardia (VT) is a contributing cause to more than half of the 300,000 sudden cardiac deaths that occur annually in the United States. Implantable cardioverter defibrillators (ICDs) are the standard therapy but they are expensive the total cost of an ICD implant approaches $50,000 and the United States spends more than $2.2B on these implants annually. ICDs are effective, but not curative up to half of the patients who receive ICDs develop new sites of VT that are unresponsive to the defibrillator, requiring them to be put on antiarrhythmia drugs at additional cost. And 55,000 ICDs have been recalled in the last few years for design and reliability problems. Thermal ablation therapy is an attractive alternative or adjunctive therapy to ICD implantation as it has a success rate of more than 90% for many classes of supraventricular tachycardias, but it has not been successful in treating ischemic VT. It is generally agreed that ablation therapy has been unsuccessful because it is not capable of treating the large, deep arrhythmogenic foci that cause ischemic VT. We have developed a method capable of doing so using saline-enhanced radiofrequency (SERF) ablation. We treat VT by injecting warm saline into the tissue simultaneous with RF ablation. The infused saline flows through the extracellular space convecting energy. This increases the effective thermal conductivity of the tissue by a factor of more than 20. We have used our steerable SERF ablation catheter with a retractable electrode to demonstrate in a canine infarct model that SERF ablation creates thermal lesions large enough to treat VT the lesions are reliably transmural, even in the presence of infarct scars, and multiple lesions can be placed to provide a line of block. We have also shown that the therapy is safe, that the catheter meets safety and reliability requirements, and that it is biocompatible. We propose to complete the development of our saline-enhanced radiofrequency (SERF) ablation system for treating ischemic VT. We will complete the design of our system and catheter and validate that they comply with medical safety standards (EN60601-1), biocompatibility (ISO-10993), and validate the sterilization to a sterility assurance level (SAL) of 10-6. We will carry out extensive preclinical survival testing in large-animal infarct models at the Mayo Clinic, Loyola University, The University of Pennsylvania, and the Brigham and Women's Hospital. We will then apply for and obtain an Investigational Device Exemption (IDE) to carry out a multi-center clinical trial. PUBLIC HEALTH RELEVANCE Our development of SERF ablation to treat ventricular tachycardia (VT) is relevant to public health in that we are addressing a growing and expensive problem the implantable cardioverter defibrillators (ICDs) that patients receive to treat these potentially fatal arrhythmias are neither curative nor reliable. The United States spends over $2B annually placing ICDs, and half of the patients develop additional VTs that are unresponsive to their ICD. At minimum the shocks these patients receive severely reduce their quality of life. At worst the patient remains susceptible to sudden cardiac death. An effective and inexpensive method of treating these patients VTs is urgently needed.