Wireless Vagal Nerve Stimulation System for Treating Atrial Fibrillation

描述（由申请人提供）：房颤（AF）是最常见的心律失常，与发病率和死亡率的重大风险相关。AF目前影响着超过250万美国人，随着我们的老龄化社会，受影响的人口正在稳步增长。AF独立地使卒中风险增加4- 5倍，是卒中复发的独立风险因素，并且至少占所有缺血性卒中的15-20%。除了相关的健康风险和生活质量下降外，AF还是一种经济负担 美国医疗保健系统，目前每年的医疗保险费用估计为160亿美元。在过去的十年中，神经调节剂作为抗心律失常药物和消融手术的替代品出现，用于治疗某些形式的AF。对迷走神经施加低水平的电刺激可抑制AF诱导。这种创新形式的神经心脏控制是一种用于治疗AF的非药物、非消融方式，可维持健康的心肌。该项目的最终目标是通过将最近的前沿研究转化为临床可行的技术来提高AF患者的生活质量。迄今为止，大多数研究神经调节作为AF治疗的研究都是急性手术。为了将这种方法推向临床应用，将需要开发能够进行慢性刺激的合适装置。Rosellini Scientific与Stimwave Technologies Inc.合作。将他们的无线脊髓刺激技术应用于适合于低水平迷走神经刺激（LL-VNS）治疗AF的形状因子和治疗方案。拟议研究的目的是在长期研究中评价LL-VNS治疗AF的治疗价值。为了实现这一目标，我们将我们的系统植入到高产量的AF犬模型中，并评估由于LL-VNS持续4周而导致的AF频率的变化。在实验期间，植入式脉冲发生器（IPG）将向左心耳输送快速心房起搏（RAP），持续6小时/天 与RAP同时，实验组将接受来自Rosellini Scientific VNS系统的LL-VNS，而对照组将接受假刺激。将计算每周AF负荷，定义为未使用RAP期间所有自发性AF发作的持续时间总和，并在组间进行比较。为了使我们的治疗可行，我们必须看到治疗组与对照组相比AF负担减少50%。如果可行，我们将向NIH申请2期资金，以确定慢性研究中适当的治疗方案，并将提交U44以进一步开发该设备。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is associated with substantial risk of morbidity and mortality. AF currently affects more than 2.5 million Americans and the affected population is steadily growing with our aging society. AF independently increases the risk of stroke by 4- to 5-fold, is an independent risk factor for stroke recurrence, and is responsible for at least 15-20% of all ischemic strokes. In addition to its associated health risks and diminished quality of life, AF is a financial burden on the US Healthcare system, with annual Medicare costs currently estimated at $16 billion. Over the past decade, neuromodulator emerged as an alternative to antiarrhythmic medications and ablative procedures for the treatment of some forms of AF. Applying low levels of electrical stimulation to the vagus nerves inhibits AF inducibility. This innovative form of neural cardiac control is a non-pharmacological, non- ablative modality for the treatment of AF that maintains healthy myocardium. The ultimate goal of this project is to enhance the quality of life for individuals with AF by translating this recent cutting edge research into a clinically viable technology. To date the majority of studies investigating neuromodulation as a treatment for AF were acute procedures. To progress this approach towards clinical application will require the development of suitable devices capable of chronic stimulation. Rosellini Scientific has partnered with Stimwave Technologies Inc. to apply their wireless spinal cord stimulation technology to a form factor and therapeutic treatment protocol suitable for low-level vagus nerve stimulation (LL-VNS) to treat AF. The goal of the proposed study is to evaluate the therapeutic value of LL- VNS for treating AF in a long-term study. To accomplish this goal, we will implant our system in a high-yield canine model of AF and evaluate changes in AF frequency as a result of LL-VNS for a period of 4 weeks. During the experimental period, an implantable pulse generator (IPG) will deliver rapid atrial pacing (RAP) to the left atrial appendage for 6 hours/day to induce AF. Concurrent with RAP, the experimental group will receive LL-VNS from the Rosellini Scientific VNS system, while the control group will receive sham stimulation. The weekly AF burden, defined as the sum of the duration of all spontaneous AF episodes during the period without RAP, will be calculated and compared between groups. For our treatment to be indicated as feasible, we must see e 50% reduction in AF burden for the treatment group versus control. If feasibility is achieved, we will apply to the NIH for Phase 2 funding to determine the appropriate treatment protocol in a chronic study and will submit a U44 to further develop the device.