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Principal Investigator: Jiwon Kim
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $625,046
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY / ABSTRACT
Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Despite substantial short term mortality
risk, the overwhelming majority of infected patients survive acute illness, resulting in a growing population at risk
for long term events. Cardiopulmonary symptoms are common after COVID-19, as shown by survey data
reporting fatigue (53%), dyspnea (43%), and worsened quality of life (44%) 60 days after acute infection, but
mechanism and time course of symptoms are unknown. Recent studies and our own preliminary data have
shown myocardial tissue abnormalities on cardiac magnetic resonance (CMR) to be common in COVID-19
survivors – raising the possibility that symptoms stem from viral effects on the heart. However, CMR findings to
date are limited by small size and clinical data susceptible to referral bias, raising uncertainty as to
generalizability. It is also unknown whether altered myocardial tissue properties (fibrosis, edema) impact clinical
outcomes.
The central hypothesis of our research is that CMR tissue characterization will be incremental to clinical
assessment and cardiac contractile function for prediction of long-term cardiopulmonary symptoms, effort
tolerance, and prognosis among COVID-19 survivors. To test this, we will study patients from an active multi-
ethnic NYC registry of COVID-19 survivors: We have already leveraged echocardiographic imaging data from
this registry to show that (1) adverse cardiac remodeling (dilation, dysfunction) markedly augments short term
mortality, (2) COVID-19 acutely alters left and right ventricular remodeling, and (3) many patients who survive
initial hospitalization for COVID-19 have adverse cardiac remodeling – including 40% with left ventricular (LV)
dysfunction and 32% with adverse RV remodeling (dilation, dysfunction): Our current proposal will extend
logically on our preliminary data to test whether CMR tissue characterization provides incremental predictive
utility with respect to reverse remodeling and prognosis. At least 510 COVID-19 survivors will be studied. Echo
will be analyzed at time of and following COVID-19 for longitudinal remodeling, as will CMR at pre-specified (6-
12, 36 month) follow-up timepoints. Established and novel CMR technologies will be employed, including
assessment of cardiac and lung injury, high resolution (3D) myocardial tissue characterization, and
cardiopulmonary blood oxygenation. In parallel, QOL, effort tolerance (6-minute walk test), biomarkers, and
rigorous follow-up will be obtained to discern clinical implications and relative utility of imaging findings. Aim 1
will identify determinants of impaired quality of life and effort intolerance among COVID-19 survivors. Aim 2 will
test whether myocardial tissue injury on CMR is associated with impaired contractility, and whether fibrosis
predicts contractile recovery. Aim 3 will determine whether myocardial tissue injury is independently associated
with adverse prognosis (new onset clinical heart failure, hospitalization, mortality). Results will address key
knowledge gaps regarding COVID-19 effects on the heart necessary to guide surveillance, risk stratification, and
targeted therapies for millions of COVID-19 survivors at risk for myocardial injury, cardiopulmonary symptoms,
and adverse prognosis.
Terms: <3-D><3-Dimensional><3D><Active Follow-up><Acute><Address><Affect><Arrhythmia><Biological Markers><Blood><Blood Reticuloendothelial System><Body Tissues><Breathlessness><COVID infected patient><COVID patient><COVID positive patient><COVID survivors><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 infected patient><COVID-19 infection survivors><COVID-19 patient><COVID-19 positive patient><COVID-19 related risk><COVID-19 risk><COVID-19 risk factor><COVID-19 survivors><COVID19 patient><COVID19 positive patient><CV-19><Cardiac><Cardiac Arrhythmia><Cardiopulmonary><Chest Pain><Clinical><Clinical Data><Clinical assessments><Coronavirus Infectious Disease 2019><Data><Data Reporting><Dropsy><Dysfunction><Dyspnea><Echocardiogram><Echocardiography><Edema><Event><Fatigue><Fibrosis><Fibrosis in the heart><Fibrosis in the myocardium><Fibrosis within the heart><Fibrosis within the myocardium><Fibrotic myocardium><Functional disorder><General Population><General Public><Groups at risk><Heart><Heart Arrhythmias><Heart Injuries><Heart Muscle tissue><Heart Research><Heart failure><Histopathology><Hospital Admission><Hospitalization><Hydrops><Image><Impairment><Infection><Inflammation><Knowledge><LV remodeling><Lack of Energy><Left><Left Ventricular Dysfunction><Left Ventricular Remodeling><Long-term Follow-up><Longterm Follow-up><Lung><Lung Diseases><Lung Respiratory System><Lung damage><Magnetic Resonance><Measures><Methods><Myocardial depression><Myocardial dysfunction><Myocardial tissue><Myocardium><New York City><Outcome><Patients><People at risk><Persons><Persons at risk><Physiologic><Physiological><Physiopathology><Population><Populations at Risk><Predisposition><Prognosis><Property><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Pathology><QOL><Quality of life><Recovery><Registries><Reporting><Research><Resolution><Right Ventricular Dysfunction><Right heart dysfunction><Right ventricle dysfunction><Right-sided heart dysfunction><Risk><SARS-CoV-2 infected patient><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 survivors><Specific qualifier value><Specified><Structure><Survey Instrument><Surveys><Survivors><Susceptibility><Symptoms><Technology><Testing><Thrombosis><Time><Tissues><Transthoracic Echocardiography><Treatment Failure><Uncertainty><United States><Ventricular><Viral><Walking><active followup><acute COVID-19><acute SARS-CoV-2 infection><acute infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adverse consequence><adverse outcome><bio-markers><biologic marker><biomarker><cardiac MRI><cardiac dysfunction><cardiac failure><cardiac fibrosis><cardiac injury><cardiac magnetic resonance imaging><cardiac muscle><cardiac research><clinical predictors><clinical prognosis><clinical relevance><clinically relevant><common symptom><coronary fibrosis><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 infected patient><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 risk><coronavirus disease 2019 risk factor><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 impact><coronavirus disease-19 patient><coronavirus infectious disease-19><coronavirus patient><data registry><data representation><data representations><death risk><develop therapy><disease of the lung><disorder of the lung><doubt><fibrotic heart><follow up><follow-up><followed up><followup><functional status><heart dysfunction><heart fibrosis><heart muscle><heart sonography><imaging><improved><indexing><injury to the myocardium><injury to tissue><intervention development><left ventricle abnormality><left ventricle remodeling><long-term followup><longterm followup><lung disorder><lung injury><lung pathology><mortality><mortality risk><multi-ethnic><multiethnic><myocardial fibrosis><myocardial injury><novel><pandemic><pandemic disease><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><predict clinical outcome><pulmonary><pulmonary damage><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><resolutions><response><right ventricle remodeling><right ventricular remodeling><risk associated with COVID-19><risk factor associated with COVID-19><risk factor related to COVID-19><risk related to COVID-19><risk stratification><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><stem><stratify risk><study population><survive COVID-19><survive SARS-CoV-2><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapy development><therapy failure><three dimensional><thrombotic disease><thrombotic disorder><tissue injury><treatment development>