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.
