Rapid Cardiovascular MRI for Screening Microvascular Angina in COVID-19 Survivors

Post-acute sequelae of SARS-CoV-2 (PASC), which occurs following 10-20% of COVID-19 infections, with persistent cardiovascular symptoms (dyspnea up to 43%, chest pain up to 22%, and fatigue up to 53%) has emerged as a significant healthcare issue in the US. The mechanisms, optimal screening tests, and therapies for PASC patients remain unknown. On December 2021, the American Heart Association released an RFA for studying mechanisms underlying cardiovascular effects of COVID-19 and PASC. In direct response, this study seeks to discover the mechanism and establish the optimal screening for a subgroup of PASC patients suffering from chest pain. Regarding screening, stress cardiovascular magnetic resonance (CMR) is the ideal “one-stop-shop” imaging test for phenotyping patients with a wide variety of cardiovascular manifestations, including virus-mediated coronary endothelial and myocardial injuries. Stress CMR affords a comprehensive assessment of said injuries, including evaluation of coronary microvascular dysfunction (CMD), myocardial inflammation, necrosis or scar, diffuse fibrosis, contractile function, and pulmonary hemodynamics. Leveraging our access to a library of rapid, arrhythmia-insensitive, free-breathing CMR acquisitions that we have developed with support from the parent study, we have assembled a powerful comprehensive, free-breathing (45-min) stress CMR protocol. Compared with standard stress CMR protocols provided by MRI vendors, our advanced protocol delivers increased diagnostic information (standard CMR content + rest-CPT-stress MBF quantification + coronary MRA + 4D flow) per unit time, extends the applicability to patients with arrhythmia and/or dyspnea, and improves patient comfort and clinical workflow. The specific aims are: (1) to determine whether continuous CMR indices of CMD (endothelial-dependent myocardial perfusion reserve), myocardial inflammation (T2), fibrosis (extracellular volume fraction), and contractile function (ejection fraction, strain) are worse in PASC patients with chest pain (abnormal vs. normal CPET result groups) than matching healthy controls; (2) to determine whether continuous CMR indices predict exercise intolerance measured with CPET (peak VO2, continuous) and symptom survey (ordinal) in PASC patients with angina. This proposal has high potential impact because it aligns with the RFA: to study mechanisms underlying cardiovascular effects of long COVID.