Endovascular Cardiac Optical Mapping

描述（申请人提供）：全国有500多万人患有心律失常，每年有120多万人住院治疗，40万人死亡。心脏消融术的发展显著改善了治疗效果。传统的消融依赖于电子解剖测绘，这可能是繁琐的，通常需要使用复杂的导航系统。即便如此，当前测绘模式的时空分辨率仍然很低。这些限制导致消融是一个高度专业化和昂贵的程序，只有在选定的中心提供。此外，由于传统测绘技术的限制，在消融过程中难以评估消融的有效性。在初始手术时无法准确预测最终的成功导致心律失常复发和反复消融。与传统的电解剖测绘工具相比，直接可视化导管提供了简单性，因为心脏解剖可以直接可视化，而不需要复杂的测绘系统。然而，直接可视化导管的一个主要限制是不能直接映射电生理。例如，在房颤的肺静脉隔离中，虽然这在很大程度上是一种基于解剖学的手术，但仅靠直接可视化不能轻易地促进生理定向消融（例如，基于复杂心房分房电图的消融或焦旋翼的识别）。同样，当对室性心动过速进行底物修饰消融时，从视觉上识别消融目标是有问题的。此外，正如……的情况一样

DESCRIPTION (provided by applicant): Cardiac arrhythmias affect more than 5 million people nationwide, resulting in more than 1.2 million hospitalizations and 400,000 deaths yearly. The development of cardiac ablation has significantly improved treatment outcomes. Ablation traditionally has relied on electroanatomic mapping which can be tedious and often requires the use of complex navigation systems. Even so, the spatiotemporal resolution of current mapping modalities remains low. These limitations cause ablation to be a highly specialized and costly procedure offered only at select centers. In addition, the effectiveness of ablation is difficult t evaluate during the procedure due to limitations of traditional mapping technologies. The inability to accurately predict ultimate success at the time of initial procedure leads to recurren arrhythmia and repeat ablations. Direct visualization catheters offer simplicity compared to traditional electroanatomic mapping tools in that cardiac anatomy can be directly visualized without the need for complex mapping systems. However, a major limitation of direct visualization catheters is that electrophysiology cannot be directly mapped. For example, in pulmonary vein isolation for atrial fibrillation, although this is largely an anatomically based procedure, direct visualization alone cannot readily facilitate physiologically directed ablation (e.g. ablation based on complex atrial fractionated electrograms or identification of focal rotors) Likewise, when performing substrate modification ablation for ventricular tachycardia, identification of ablation targets visually is problematic at best. Furthermore, as is the case for traditional mapping/ablation systems, ablation efficacy cannot be directly verified, and relies on surrogate endpoints such as electrical block which can be confounded intra-procedurally by tissue edema. Here we propose to combine the simpler approach of a direct visualization catheter with novel, inexpensive, and scalable electrophysiological mapping technology, using voltage sensitive fluorescent dyes to intuitively visualize both anatomy and electrophysiology. In particular, photostable dyes with emissions in the near-infrared spectrum can be optimized for safe in vivo imaging. This system will be applicable to all forms of arrhythmia, including atrial fibrillation, and promises to reduce costs by reducing procedural complexity, procedure time, and arrhythmia recurrence rates. During Phase I the following three specific aims will be addressed: 1. Demonstrate technical feasibility of fluorescence imaging using an affordable light-emitting- diode/single camera system. 2. [Establish preliminary deliverability and safety of optimized near-infrared voltage sensitive dye(s) for clinical use.] 3. Demonstrate the feasibility f a balloon-tipped endovascular visualization catheter to minimally invasively optically map ratiometric voltage in a live animal. In subsequent work, the device and dye designs will be further optimized, dye safety profile will be characterized in more detail, we will refine a clinicl procedural approach in animal models, and the software analysis approach will be expanded, all while pushing toward the ultimate goal of a commercial product.