SKNA as a biomarker for cardiovascular events

SKNA 作为心血管事件的生物标志物

• 批准号: 10614542
• 负责人: Thomas H Everett
• 金额: $ 50.57万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614542
• 关键词: Ablation; Anoxic Encephalopathy; Applications Grants; Arrhythmia; Atrial Fibrillation; Biological Markers; Canis familiaris; Cardiac; Cardiac ablation; Cardiology; Cardiopulmonary Resuscitation; Cardiovascular Diseases; Cardiovascular system; Cerebral Ischemia; Circulation; Consent; Data; Disease; Electrocardiogram; Electrodes; Event; Future; Guidelines; Heart Arrest; Heart Atrium; Heart Diseases; Heart Rate; Heart failure; Hospitalization; Hour; Human; Hybrids; Intervention; Left; Measures; Methods; Morbidity - disease rate; Nerve; Neurological outcome; Neurological status; Outcome; Patients; Percutaneous Catheter Ablation; Physiological; Procedures; Prognostic Marker; Progressive Disease; Protocols documentation; Public Health; Pulmonary veins; Recurrence; Research; Research Project Grants; Sinus; Skin; Source; Structure of stellate ganglion; Subcutaneous Tissue; Surface; Surrogate Endpoint; Survival Rate; Temperature; Testing; Therapeutic; Translating; Ventricular Arrhythmia; Visit; Visualization; autonomic nerve; canine model; clinical investigation; design; follow-up; heart rate variability; improved; insight; mortality; natural hypothermia; neurological recovery; neuromechanism; neuroprotection; neuroregulation; out-of-hospital cardiac arrest; patient stratification; programs; prospective; risk stratification; subcutaneous; success

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.

项目摘要 本申请的目的是测试皮肤交感神经活动（SKNA）可以用于 作为生理事件的生物标志物，包括预测治疗期间的神经恢复， 降低心脏骤停体温，并对患者进行心房颤动（AF）复发风险分层， 导管消融术交感神经活动（SNA）可以从记录中确定的概念 来自皮肤的研究表明，交感神经张力在心脏 胚胎发生Krannert心脏病研究所的研究实验室已经成功地开发了 记录来自皮下组织或皮下组织的非卧床犬模型中自主神经活动的方法 皮肤表面（SKNA）。我们发现皮下神经活动和SKNA密切相关， 星状神经节神经活动。然后对SKNA记录进行验证， 翻译到人类患者中，最近有记录表明，交感神经活动与 房性和室性心律失常发作。在本提案中，我们现在将SKNA记录用作 接受目标温度管理（TTM）的患者神经系统状态的生物标志物， 心脏骤停和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， 与低存活率相关，可电击节律为31%，所有节律组合为11%。缺氧 脑损伤占心脏骤停后患者发病率和死亡率的绝大多数。在这 在上下文中，TTM是已被证明具有神经保护作用并改善神经功能的唯一干预措施之一。 心脏骤停后的结果。尽管如此，脑缺血可能持续数小时， 对接受TTM治疗的患者的神经学结果进行短期评估仍然是一个挑战。显著 低SKNA或TTM期间SKNA与心率的关系改变可能意味着自主神经失调。 心房颤动（AF）是一种进行性疾病，通常进展为持续性， 永久性房颤。房颤持续时间越长，任何相关治疗选择的结果就越少。 有利的。经皮导管消融术通常用作房颤的治疗，但房颤复发 消融后仍然是一个问题。通过SKNA记录，我们现在可以可视化和分析神经活动， 可触发房颤，并对消融术后房颤复发的患者进行风险分层。 本项目的目的是使用SKNA记录作为（1）神经学结果的生物标志物， 心脏骤停后接受TTM的患者;（2）对导管消融术后房颤复发的患者进行风险分层。 本研究资助申请旨在测试SKNA是一种有用的生物标志物的假设， 一个潜在的替代终点，用于未来常见心血管疾病的临床研究， 为疾病的神经机制提供新的见解。

项目成果

Time and frequency domain analysis of physiological features during autonomic dysreflexia after spinal cord injury.

• DOI: 10.3389/fnins.2023.1210815
• 发表时间: 2023
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Kirby, Ana Karina;Pancholi, Sidharth;Anderson, Zada;Chesler, Caroline;Everett, Thomas H.;Duerstock, Bradley S.
• 通讯作者: Duerstock, Bradley S.