Quantitative Detection of Coronary Microvascular Dysfunction in Long COVID Patients using a Comprehensive, Rapid, Free-Breathing Cardiovascular MRI

使用全面、快速、自由呼吸的心血管 MRI 定量检测长期新冠肺炎患者的冠状动脉微血管功能障碍

• 批准号: 10671235
• 负责人: Daniel Kim
• 金额: $ 77.73万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671235
• 关键词: Acute; Age; Americans with Disabilities Act; Arrhythmia; Biological Markers; Blood; Blood Vessels; Blood flow; Breathing; COVID-19; COVID-19 patient; COVID-19 survivors; Cardiopulmonary; Cardiovascular Abnormalities; Cardiovascular system; Chest Pain; Chronic; Cicatrix; Classification; Clinical; Clinical Trials; Contrast Media; Control Groups; Coronary; Coronary Arteriosclerosis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic tests; Diffuse; Endothelium; Enrollment; Ethnic Origin; Exercise Test; Fibrosis; Functional disorder; Future; Gadolinium; Goals; Grant; Healthcare; Heart; Heart Diseases; Image; Infection; Inflammation; Injury; Ionizing radiation; Ischemia; Knowledge; Left Ventricular Ejection Fraction; Long COVID; Lung; Magnetic Resonance; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Matched Case-Control Study; Measures; Medical Imaging; Microvascular Dysfunction; Modality; Myocardial; Myocardial perfusion; Oxygen; Patients; Perfusion; Pericardial body location; Positioning Attribute; Post-Acute Sequelae of SARS-CoV-2 Infection; Protocols documentation; Race; Radioactive Tracers; Recording of previous events; Resources; Risk Factors; SARS-CoV-2 infection; Severities; Stress; Symptoms; Testing; Time; United States National Institutes of Health; Vaccines; asymptomatic COVID-19; cardiovascular health; coronavirus disease; cost; disability; exercise capacity; exercise intolerance; extracellular; heart imaging; hemodynamics; imaging facilities; imaging modality; improved; indexing; pain patient; pain symptom; perfusion imaging; persistent symptom; post SARS-CoV-2 infection; prevent; pulmonary function; sex; tomography

Project Summary/Abstract: Post-acute sequelae of SARS-CoV-2 (PASC), which occurs up to 30% of COVID- 19 infections, has emerged as a significant healthcare issue in the US. The mechanisms, diagnostic imaging tests, and therapies for persistent symptoms caused by PASC remain unknown. The CDC describes PASC symptoms as difficult to explain and manage due to lack of knowledge and reliable test. This study seeks to define the mechanism of persistent chest pain caused by PASC and establish an effective cardiac imaging test for guiding therapy. To minimize the influence of confounders, this project focuses on well-characterized patients with persistent chest pain, which occurs in about 20% of PASC patients. Endothelial inflammation and injury are important manifestations of acute COVID-19 infection, which may result in chronic coronary microcirculatory dysfunction (CMD). Stress cardiovascular magnetic resonance (CMR) is the ideal “one-stop-shop” imaging test for PASC patients with persistent chest pain, because it does not involve ionizing radiation (i.e. safe for repetitive surveillance), is a proven modality for CMD, and uses standard clinical MRI hardware and contrast agents. Furthermore, it affords a comprehensive assessment of cardiovascular abnormalities, including: obstructive coronary artery disease (coronary magnetic resonance angiography), pulmonary hemodynamics (4D flow), myocardial inflammation (T2, T1), scar (late gadolinium enhancement), diffuse fibrosis (extracellular volume fraction [ECV]), and contractile dysfunction (left ventricular ejection fraction [LVEF], RVEF, strain). Recognizing the need to account for potential confounders, we have assembled a powerful, comprehensive, CMR protocol for imaging PASC patients. Our central hypothesis is that CMD is the mechanism for chest pain in a substantial proportion of symptomatic PASC patients, despite having normal lung function and no history of heart disease prior to COVID infection. To test our hypothesis, we will conduct a matched case-control study comparing MPRs between well-characterized PASC patients with persistent chest pain, asymptomatic COVID-19 survivors matched for sex, age, race/ethnicity, CAD risk factors, vaccine status, and severity of acute COVID illness, and matched healthy controls. The goals of this study are: (1) to determine whether CMR-derived MPR quantification is accurate and precise; to determine whether MPR quantification and coronary MRA adds incremental value for diagnosing CMD; (2) to determine whether MPRs are reduced in PASC patients with chest pain due to symptom status and/or prior COVID infection; to determine whether MPRs predict chest pain better than other CMR indices, clinical profiles, and blood biomarkers; (3) to determine whether temporal changes in MPRs differ between treated and untreated PASC patients; whether temporal changes in MPRs correlate with temporal changes in angina status. This proposal has high potential impact on PASC patients suffering from chest pain by identifying and quantifying the mechanism of persistent chest pain, informing future development and applications of mechanism-directed therapies for CMD, and improving cardiovascular health.

项目摘要/摘要：SARS-CoV-2 (PASC) 的急性后遗症发生率高达 30% 19 感染已成为美国的一个重大医疗保健问题。其机制、诊断成像。 PASC 引起的持续症状的测试和治疗方法仍然未知。 CDC 对 PASC 的描述仍然未知。 由于缺乏知识和可靠的测试，这些症状难以解释和管理。 明确 PASC 引起持续性胸痛的机制并建立有效的心脏影像检查 为了最大限度地减少混杂因素的影响，该项目重点关注特征明确的患者。 约 20% 的 PASC 患者会出现持续性胸痛。 急性COVID-19感染的重要表现，可能导致慢性冠状动脉微循环障碍 应激性心血管磁共振 (CMR) 是理想的“一站式”成像测试。 对于持续性胸痛的 PASC 患者，因为它不涉及电离辐射（即重复性安全） 监测），是一种经过验证的 CMD 方式，并使用标准临床 MRI 硬件和造影剂。 此外，它还可以对心血管异常进行全面评估，包括： 冠状动脉疾病（冠状动脉磁共振血管造影）、肺血流动力学（4D 血流）、 心肌炎症（T2、T1）、疤痕（钆晚期增强）、弥漫性纤维化（细胞外体积 分数 [ECV]）和收缩功能障碍（左心室射血分数 [LVEF]、RVEF、应变）。 由于需要考虑潜在的混杂因素，我们组装了一个强大、全面的 CMR 协议 我们的中心假设是 CMD 是导致胸痛的重要机制。 尽管肺功能正常并且没有心脏病史，但有症状的 PASC 患者的比例 为了检验我们的假设，我们将进行一项比较 MPR 的匹配病例对照研究。 在具有持续性胸痛的明确 PASC 患者与无症状的 COVID-19 幸存者之间进行 匹配性别、年龄、种族/民族、CAD 风险因素、疫苗状况和急性新冠肺炎严重程度，以及 本研究的目标是：（1）确定 CMR 衍生的 MPR 定量。 准确且精确；确定 MPR 量化和冠状动脉 MRA 是否增加了增量价值 诊断 CMD；（2）确定 PASC 患者因症状而出现胸痛时 MPR 是否降低 状态和/或既往 COVID 感染；确定 MPR 是否比其他 CMR 更好地预测胸痛 (3) 确定MPR的时间变化是否不同 治疗和未治疗的 PASC 患者之间 MPR 的时间变化是否与时间相关 该提案对患有胸痛的 PASC 患者具有很大的潜在影响。 通过识别和量化持续性胸痛的机制，为未来的发展提供信息 应用机制导向疗法治疗 CMD，并改善心血管健康。