Low energy ventricular defibrillator

描述（由申请人提供）：心源性猝死是世界各地的主要死因，在美国每年约有40万人猝死，超过肺癌、乳腺癌或艾滋病。它通常由心室颤动（VF）和室性心动过速（VT）引起。VF是猝死的最常见机制。植入式心脏复律器（ICD）治疗经过二十年的发展，已成为有猝死风险患者的标准治疗。终止VF的最常见策略是使用ICD进行大电击。尽管ICD在挽救生命方面的有效性已得到证实，但至少有三个主要问题与其高压（HV）电击有关。首先，高压电击会产生大量疼痛，这通常与焦虑、恐惧、抑郁和生活质量下降有关。其次，估计有20%的植入ICD的患者在植入后三年内可能会因设备内的非致命性心律失常或电噪声而经历不适当的电击。在一级预防时代，不适当的电击甚至更麻烦，因为适当的电击发生率正在下降;电击被递送给没有症状性心律失常病史的患者。第三，电击与心力衰竭和死亡的风险增加有关。Sweeney等人的一份新报告清楚地表明，与仅接受抗心动过速起搏治疗的患者相比，休克患者的室性心律失常发作负担显著更高，生存率更差。“虚拟电极极化”（VEP）概念已被提出作为维持心房颤动（AF）的机制，并在体外和体内跨膜电位研究的实验光学标测中得到证实。最近的犬研究结果表明，多阶段治疗（MST）显著降低了心房除颤所需的能量。具体而言，三阶段治疗通过应用三个不同阶段的治疗显著降低了AF心脏复律的能量，我们在机械上将其与以下相关：（1）维持AF的波前的解除固定，（2）防止波前对组织异质性（如疤痕）的重新固定，以及（3）剩余波前的湮灭。我们假设，使用多阶段算法进行心室内除颤将是有效的，该算法需要比当前单次双相电击少得多的能量水平。为了评估这种新的方法，我们建议开发一种有效的外部除颤系统的基础上的视觉诱发电位的概念，结合两种不同的工程方法：1）可变脉冲调制和2）单场效应管功率放大器系统。然后，我们将在急性犬研究中进行测试，以比较单一固定载体与可变载体的性能。预计拟议的新研究将为多相低能量电击可以安全实现内部心室除颤的假设提供根本性的重要见解。我们期望本研究是从“VEP和拔钉”理论到心室除颤器临床发展的一大步。如果增强型系统对心室除颤有效且安全，它将推动低能量多脉冲植入式除颤器设备的商业产品开发，并鼓励更高比例的合格患者考虑这种挽救生命的治疗。 公共卫生相关性：心源性猝死是世界范围内的主要死因，在美国每年约有40万人猝死。心室颤动（VF）是最常见的原因。终止VF的最常见策略是通过植入式心脏除颤器（ICD）进行单次大规模双相电击。尽管其有效性，但由于高电压电击可能引起的心脏组织损伤、不适当电击引起的疼痛以及电池寿命短，对当前ICD设计的担忧越来越多。目前，只有约1/3的合格患者人群植入了除颤器。电击波形的重新设计和优化对于开发低能量除颤器至关重要，该除颤器提供多级治疗并结合患者和临床医生更容易接受的可变脉冲波形。目前全球ICD市场约为66亿美元，预计到2014年将增长到78亿美元， 用颠覆性技术打入这个市场。

DESCRIPTION (provided by applicant): Sudden cardiac death is a major cause of death around the world, with approximately 400,000 sudden deaths per year in the United States, more than are attributed to lung cancer, breast cancer, or AIDS. It is often caused by ventricular fibrillation (VF) and ventricular tachycardia (VT). VF is the most frequent mechanism of sudden death. Implantable cardiac defibrillators (ICDs) have become the standard of care for patients at risk for sudden death following two decades of advancement in ICD therapy. The most common strategy for terminating VF is with a large electric shock by ICDs. Despite the proven efficacy of ICDs in saving lives, at least three major issues have been linked with their high voltage (HV) shocks. First, high voltage shocks produce substantial pain, which is often associated with anxiety, fear, depression, and reduced quality of life. Secondly, an estimated 20 percent of patients with ICDs may experience inappropriate shocks within three years of implant in response to a non-lethal arrhythmia or electrical noise within the device. In the primary prevention era, inappropriate shocks are even more troublesome, since appropriate shocks are decreasing in incidence; shocks are being delivered to patients with no history of symptomatic arrhythmias. Thirdly, shocks have been associated with an increased risk of heart failure and death. A new report by Sweeney, et al clearly demonstrated that shocked patients have substantially higher ventricular arrhythmia episode burden and poorer survival compared with anti-tachycardia pacing-only-treated patients. The "virtual electrode polarization" (VEP) concept has been proposed as a mechanism sustaining atrial fibrillation (AF) and demonstrated in experimental optical mapping of transmembrane potential studies in vitro and in vivo. Recent canine results have revealed that multiple-stage therapy (MST) significantly lowers the energy required for atrial defibrillation. Specifically, the three-stage therapy significantly lowers the energy for cardioversion of AF by application of three different stages of therapy, which we mechanistically relate to the: (1) unpinning of wave fronts that maintain AF, (2) prevent repinning of wave fronts to tissue heterogeneities such as scar, and (3) annihilation of remaining wave fronts. We hypothesize that internal ventricular defibrillation will be effective using a mult-stage algorithm that will require much less energy level than the current single biphasic shock. To evaluate this novel method, we propose to develop an efficient external defibrillation system based on the VEP concept incorporating two different engineering approaches; 1) variable pulse modulation and 2) single FET power amplifier system. We will then test in an acute canine study to compare performance with a single fixed vector versus a variable vector. It is anticipated that the proposed new study will provide fundamentally important insights into the hypothesis that multiple phased low-energy shocks can safely achieve internal ventricular defibrillation. We expect the study is a big step forward from the "VEP and unpinning" theory to ventricular defibrillator clinical development. If the enhanced system is effective and safe for ventricular defibrillation, it should advance commercial product development of low-energy multiple pulse implantable defibrillator devices and will also encourage a higher percentage of eligible patients to consider this life-saving treatment. PUBLIC HEALTH RELEVANCE: Sudden cardiac death is a major cause of death around the world, with approximately 400,000 sudden deaths per year in the United States. Ventricular fibrillation (VF) is the most frequent cause. The most common strategy for terminating VF is with a single, large, biphasic electric shock by an implantable cardiac defibrillator (ICD). Despite ther effectiveness, there have been increasing concerns with current ICD design, due to cardiac tissue damage likely induced by high voltage shocks, pain caused by inappropriate shocks, and short battery life. Currently, only about 1/3 of the eligible patient population has a defibrillato implanted. Redesign and optimization of shock waveforms is critical for developing a low-energy defibrillator delivering multistage therapy and incorporating variable pulse-shaped waveforms that will be more acceptable to patients and clinicians. The current global market for ICDs is approximately $6.6 billion and is projected to grow to $7.8 billion by 2014, offering opportunities to break into this market with disruptive technology.