SKNA as a biomarker for cardiovascular events

项目总结 此应用程序的目的是验证皮肤交感神经活动(SKNA)可用于 作为生理事件的生物标志物，包括在治疗期间预测神经恢复 低温治疗心脏骤停，并对房颤(房颤)术后复发的患者进行风险分层 导管消融术。交感神经活动(SNA)可以从录音中确定的概念 来源于皮肤的研究表明交感神经张力在心脏中很重要 心律失常。Krannert心脏病研究所的研究实验室已经成功地开发出 方法从皮下组织或皮下组织中记录自主神经活动。 在皮肤表面(SKNA)。我们发现皮下神经活动与SKNA密切相关。 星状神经节神经活动在动态犬模型中的作用。然后对SKNA录音进行验证，并 翻译到人类患者身上，最近有文献证明交感神经活动与 房性和室性心律失常的发作。在本提案中，我们现在将应用SKNA录音作为 正在接受靶向温度管理(TTM)治疗的患者的神经状态的生物标志物 并对接受消融治疗后房颤复发的患者进行风险分层。 每年有超过35万例院外心脏骤停，它们是 存活率低，可电击节律为31%，所有节律加在一起为11%。缺氧 在心脏骤停患者中，脑损伤是发病率和死亡率的主要原因。在这 背景，TTM是已被证明具有神经保护和改善神经学的仅有的干预措施之一 心脏骤停后的转归。尽管如此，脑缺血可能会持续几个小时，并准确地 接受TTM治疗的患者的神经结局的短期评估仍然是一个挑战。显著 在TTM期间，SKNA降低或SKNA与心率的关系改变可能意味着自主神经调节障碍。 房颤(房颤)是一种进行性疾病，通常进展为持续性，然后 永久自动对焦。房颤持续的时间越长，任何相关治疗方案的结果都会变得越少 有利的。经皮导管消融是治疗房颤的常用方法，但房颤复发 消融后仍然是一个问题。有了SKNA的记录，我们现在可以可视化和分析 可以触发房颤，并对消融后房颤复发的风险进行分层。 本项目的目的是使用SKNA记录作为(1)神经学结果的生物标记物 心脏骤停后接受TTM治疗的患者；(2)对导管消融后房颤复发的风险分层。 目前的研究拨款申请旨在检验SKNA是一个有用的生物标记物和 是未来常见心血管疾病临床研究的潜在替代终点，并 为疾病的神经机制提供了新的见解。

PROJECT SUMMARY The objective of this application is to test the hypothesis that skin sympathetic nerve activity (SKNA) can be used as a biomarker for physiological events including predicting neurological recovery during therapeutic hypothermia for cardiac arrest, and to risk stratify patients for recurrence of atrial fibrillation (AF) following catheter ablation. The concept that sympathetic nerve activity (SNA) could be determined from recordings obtained from the skin originated from studies that have shown that sympathetic tone is important in cardiac arrhythmogenesis. The research labs at the Krannert Institute of Cardiology have successfully developed methods to record autonomic nerve activity in ambulatory canine models from either subcutaneous tissues or on the surface of the skin (SKNA). We found that both subcutaneous nerve activity and SKNA closely correlated with stellate ganglia nerve activity in ambulatory canine models. SKNA recordings were then validated and translated to human patients and it was recently documented that sympathetic nerve activity correlates to the onset of atrial and ventricular arrhythmias. In this proposal, we will now apply SKNA recordings to be used as a biomarker for neurological status in patients that are undergoing targeted temperature management (TTM) for cardiac arrest and to risk stratify patients for AF recurrence after undergoing ablation therapy. There are more than 350,000 out-of-hospital cardiac arrests taking place every year and they are associated with poor survival rates, with 31% for shockable rhythms and 11% for all rhythms combined. Anoxic brain injury accounts for a significant majority of morbidity and mortality in post-cardiac arrest patients. In this context, TTM is one of the only interventions that has been shown to be neuroprotective and improve neurologic outcomes after cardiac arrest. Despite this, cerebral ischemia may persist for several hours and an accurate short-term assessment of neurological outcome in patients undergoing TTM remains a challenge. Significantly low SKNA or an altered SKNA relationship with heart rate during TTM could signify autonomic dysregulation. Atrial fibrillation (AF) is a progressive disease that commonly advances into persistent and then permanent AF. The longer AF continues, the outcome of any associated therapeutic options becomes less favorable. Percutaneous catheter ablation is commonly used as a therapy for AF, however recurrence of AF after ablation remains an issue. With SKNA recordings, we can now visualize and analyze the nerve activity that can trigger AF, and risk stratify patients for AF recurrence post ablation. The purpose of this project is to use SKNA recordings as a biomarker for (1) neurologic outcome in patients undergoing TTM post-cardiac arrest; (2) to risk stratify patients for AF recurrence after catheter ablation. This present research grant application is designed to test the hypothesis that SKNA is a useful biomarker and a potential surrogate end point for future clinical investigations in common cardiovascular diseases, and to provide new insights into the neural mechanisms of diseases.