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Principal Investigator: Daniel Kim
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $741,023
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <Age><Americans with Disabilities Act><Arrhythmia><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Vessels><Blood flow><Breathing><COVID infected patient><COVID patient><COVID positive patient><COVID survivors><COVID-19><COVID-19 infected patient><COVID-19 infection><COVID-19 infection survivors><COVID-19 patient><COVID-19 positive patient><COVID-19 survivors><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><CV-19><Cardiac Arrhythmia><Cardiac Diseases><Cardiac Disorders><Cardiopulmonary><Cardiovascular><Cardiovascular Abnormalities><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Chest Pain><Chronic><Cicatrix><Classification><Clinical><Clinical Trials><Contrast Agent><Contrast Drugs><Contrast Media><Control Groups><Coronary><Coronary Arteriosclerosis><Coronary Artery Disease><Coronary Artery Disorder><Coronary Atherosclerosis><Coronavirus Infectious Disease 2019><Data><Detection><Development><Diagnosis><Diagnostic><Diagnostic Imaging><Diagnostic tests><Diffuse><Dysfunction><Endothelium><Enrollment><Ethnic Origin><Ethnicity><Exercise Test><Fibrosis><Functional disorder><Future><Gadolinium><Gd element><Goals><Grant><Healthcare><Heart><Heart Arrhythmias><Heart Diseases><Heart Vascular><History><Image><Inflammation><Injury><Ionizing Electromagnetic Radiation><Ionizing radiation><Ischemia><Knowledge><LVEF><Left Ventricular Ejection Fraction><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lung><Lung Respiratory System><MR Imaging><MR Tomography><MRI><MRI Angiography><MRIs><Magnetic Resonance><Magnetic Resonance Angiography><Magnetic Resonance Imaging><Matched Case-Control Study><Measures><Medical Imaging><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Microvascular Dysfunction><Modality><Myocardial><Myocardial perfusion><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Nuclear Magnetic Resonance Imaging><O element><O2 element><Oxygen><PASC><Patients><Perfusion><Pericardial><Pericardial body location><Physiopathology><Position><Positioning Attribute><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Protocol><Protocols documentation><Race><Races><Radiation-Ionizing Total><Radioactive Tracers><Radiopaque Media><Recording of previous events><Research Resources><Resources><Respiratory Aspiration><Respiratory Inspiration><Risk Factors><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 survivors><SARS-CoV2 infection><Scars><Severe acute respiratory syndrome coronavirus 2 infection><Severities><Stress><Symptoms><Systematics><Testing><Time><United States National Institutes of Health><Vaccines><Zeugmatography><acute 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patient><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus infectious disease-19><coronavirus patient><cost><developmental><disability><enroll><exercise capacity><exercise intolerance><extracellular><facilities for imaging><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><health care><heart disorder><heart imaging><heart scanning><hemodynamics><histories><image-based method><imaging><imaging center><imaging facilities><imaging method><imaging modality><imaging-related facilities><improved><indexing><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><injuries><inspiration><ionizing output><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><lung function><microvascular complications><microvascular disease><pain patient><pain symptom><painful symptom><pathophysiology><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><perfusion imaging><persistent COVID-19><persistent symptom><post COVID syndrome><post COVID-19 sequelae><post COVID-19 syndrome><post SARS-CoV-2 infection><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute sequelae following COVID-19><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><prevent><preventing><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prolonged COVID-19 symptoms><pulmonary><pulmonary function><racial><racial background><racial origin><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><sex><small vessel disease><survive COVID-19><survive SARS-CoV-2><tomography><vascular>