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（PASC），该后遗症最多发生在COVID-的30％ 19种感染已成为美国的重大医疗问题。机制，诊断成像 测试和由PASC引起的持续症状的疗法尚不清楚。疾病预防控制中心描述了PASC 由于缺乏知识和可靠测试而难以解释和管理的症状。这项研究试图 定义由PASC引起的持续性胸痛的机制，并建立有效的心脏成像测试 用于指导疗法。为了最大程度地减少混杂因素的影响，该项目专注于特征良好的患者 持续的胸痛，大约有20％的PASC患者发生。内皮感染和受伤是 急性共同19感染的重要表现，这可能导致慢性冠状动脉微循环 功能障碍（CMD）。应力心血管磁共振（CMR）是理想的“一站式”成像测试 对于持续胸痛的PASC患者，因为它不涉及电离辐射（即安全重复 监视），是CMD的一种经过验证的方式，并使用标准的临床MRI硬件和对比剂。 此外，它对心血管异常进行了全面评估，包括：阻塞性 冠状动脉疾病（冠状动脉共振血管造影），肺血液动力学（4D流）， 心肌炎症（T2，T1），疤痕（加多林晚期增强），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）。认可 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 用于成像PASC患者。我们的中心假设是CMD是胸痛的机制 有症状的PASC患者的比例，肺部功能正常，没有心脏病病史 在感染联盟之前。为了检验我们的假设，我们将进行比较MPRS的匹配的病例对照研究 在持续胸痛的良好表征的PASC患者之间，不对称的Covid-19幸存者 匹配性别，年龄，种族/种族，CAD危险因素，疫苗状况以及急性共同疾病的严重程度以及 匹配的健康对照。这项研究的目标是：（1）确定CMR衍生的MPR定量是否 是准确而精确的；确定MPR量化和冠状动脉MRA是否增加了增量值 诊断CMD； （2）确定由于症状而患有胸痛的PASC患者的MPRS是否减少 状态和/或事先的共同感染；确定MPRS是否比其他CMR更好地预测胸痛 指数，临床轮廓和血液生物标志物； （3）确定MPRS中的暂时变化是否不同 在治疗和未治疗的PASC患者之间； MPRS的暂时变化是否与临时变化相关 心绞痛状态的变化。该建议对患有胸痛的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，告知未来发展和 用于CMD的机制指导疗法的应用，并改善心血管健康。