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

项目摘要/摘要：SARS-CoV-2（PASC）的急性后后遗症，发生率高达COVID-19的30%。 19例感染，已成为美国的一个重大医疗问题。机制，诊断成像 PASC引起的持续症状的测试和治疗仍然未知。CDC描述了PASC 由于缺乏知识和可靠的测试，症状难以解释和管理。本研究旨在 明确PASC引起持续性胸痛的机制，建立有效的心脏影像学检查方法 来指导治疗为了最大限度地减少混杂因素的影响，该项目侧重于特征良好的患者 持续性胸痛，发生在大约20%的PASC患者中。内皮炎症和损伤是 急性COVID-19感染的重要表现，可能导致慢性冠状动脉微循环 功能障碍（CMD）。压力心血管磁共振（CMR）是理想的“一站式”成像检查 对于持续性胸痛的PASC患者，因为它不涉及电离辐射（即重复使用安全）。 监测），是CMD的经证实的模态，并且使用标准临床MRI硬件和造影剂。 此外，它还可以全面评估心血管异常，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）、瘢痕（晚期钆增强）、弥漫性纤维化（细胞外容积 收缩功能障碍（左心室射血分数[LVEF]，RVEF，应变）。认识 考虑到考虑潜在混杂因素的需要，我们制定了一个功能强大、全面的CMR方案， 用于PASC患者的成像。我们的中心假设是CMD是胸痛的机制， 有症状的PASC患者比例，尽管肺功能正常且无心脏病史 在感染COVID之前。为了验证我们的假设，我们将进行一项配对病例对照研究， 在具有持续性胸痛特征的PASC患者、无症状COVID-19幸存者 在性别、年龄、人种/种族、CAD风险因素、疫苗状态和急性COVID疾病严重程度方面匹配，以及 匹配的健康对照。本研究的目的是：（1）确定CMR衍生的MPR定量是否 MPR定量和冠状动脉MRA是否增加了 诊断CMD;（2）确定PASC患者是否因症状引起胸痛而降低MPR 状态和/或既往COVID感染;以确定MPR是否比其他CMR更好地预测胸痛 指标、临床特征和血液生物标志物;（3）确定MPR的时间变化是否与 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 心绞痛状态的变化。这一建议对患有胸痛的PASC患者有很大的潜在影响 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，改善心血管健康。

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.