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

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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.