Ultrasound Guided Mitral Valve Ablation

 描述(申请人提供)：心脏瓣膜疾病是心血管疾病的第三大流行来源，仅在美国每年就导致约20,000人死亡。此外，据估计，美国每年进行的瓣膜手术有95,000例，其中43%是二尖瓣手术。这些数字在未来几年将大幅增加，因为我们的人口将继续长寿。在接下来的50年里，美国65岁以上的人口将增加一倍以上，从3400万增加到7900万。事实上，年龄最大的老年人(85岁以上)目前是人口增长最快的部分，到2050年将翻两番以上。鉴于已知的心脏瓣膜疾病，特别是MV中的心脏瓣膜疾病，这些数字令人震惊。如今，导致二尖瓣反流(MR)的MV脱垂长期治疗的黄金标准是开胸修复或置换手术，这对老年患者来说是非常不可取的。对于MMVD患者，有强烈的临床需求将其作为开胸手术的替代方案。这项建议的目的是开发一种综合导管的成像策略，以缩小扩大的粘液瘤MV叶的大小，为开胸手术叶切除提供一种经皮替代方案。这种一体化导管的新奇之处在于，它同时使用冷冻锚定来 在射频(RF)能量消融的同时，附着在移动的MV叶上，以改变叶组织的大小和内在生物力学特性。这项建议的主要进步将是成功地引导导管，并在体内通过超声成像定量测量MV几何形状和血流动力学的实时变化。首先，我们将开发一种成像策略来量化猪模型中MV叶几何形状和血流动力学功能的变化(目标1)。然后，我们将展示这一策略的能力，以治疗粘液瘤MV小叶导致MR的犬模型(目标2)。这项研究的终点将是在影像引导下传递射频能量，并验证减少的MR用于粘液瘤MV小叶的经皮治疗。此外，每个目标的成功完成将使这一战略转化为临床。

 DESCRIPTION (provided by applicant): Heart valve disease is the 3rd most prevalent source of cardiovascular disease, leading to ~20,000 deaths per year in the U.S. alone. Moreover, there are an estimated 95,000 valve procedures performed each year in the U.S. and 43% of these are mitral valve (MV) procedures. These numbers will increase substantially in the coming years as our population continues to live longer. Over the next 50 years, the population of Americans age 65+ will more than double - from 34 to 79 million. In fact, the oldest of the old (85+) are currently the fastest growing segment of the population and will more than quadruple by 2050. These numbers are alarming in light of what is known of heart valve disease, particularly in the MV. Today, the 'gold standard' for long-term treatment for MV prolapse, leading to mitral regurgitation (MR), is open-chest repair or replacement surgery, which is highly undesirable for elderly patients. There is a strong clinical need for percutaneous treatment for patients with MMVD as an alternative to open-chest surgery. The goal of this proposal is to develop an imaging strategy for an integrated catheter to reduce the size of enlarged, myxomatous MV leaflets, providing a percutaneous alternative to open-chest surgical leaflet resection. The novelty of this integrated catheter is that it simultaneously uses cryo-anchoring to adhere to a moving MV leaflet, while ablating with radiofrequency (RF) energy to alter the size and intrinsic biomechanical properties of the leaflet tissue. The primary advancements of this proposal will be to successfully guide the catheter and quantify real-time changes of MV geometry and hemodynamics with ultrasound imaging in vivo. First, we will develop the imaging strategy to quantify changes to MV leaflet geometry and hemodynamic function in a swine model (Aim 1). Then, we will demonstrate this strategy's ability to treat myxomatous MV leaflets that lead to MR in a canine model (Aim 2). The endpoint of this research will be demonstration of image-guided delivery of RF energy and validation of reduced MR for the percutaneous treatment of myxomatous MV leaflets. Further, successful completion of each aim will position this strategy for translation into the clinic.