Cardiac Magnetic Resonance Tissue Characterization in COVID-19 Survivors

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Cardiac MRI

Patients participate in an NIH funded cardiac MRI to assess their symptoms.

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Echocardiogram

Patients participate in an NIH funded cardiac echocardiogram to assess their symptoms.

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6-minute walk test

Patients participate in a 6-minute walk test to assess their symptoms.

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Questionnaire

Patients answer a survey-based questionnaire to assess their symptoms.

Participants with focal fibrosis based on cardiac imaging (MRI and echocardiogram) > 3 months post-COVID-19 (coronavirus disease 2019) diagnosis, at first study visit

Time frame: Day of first study visit, > 3 months post acute COVID-19 infection

Focal fibrosis scored on LGE(late gadolinium enhancement) CMR in affected LV segment based on transmural extent of hyperenhanced myocardium at \> 3 months post-COVID-19 diagnosis. Further categorized in accordance with established criteria (ischemic: subendocardial or transmural, non-ischemic: mid or epicardial). Total size (% LV myocardium) measured based on segmental scores, further quantified using the full-width half maximum method.

Participants with focal fibrosis based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Focal fibrosis scored on LGE-CMR in affected LV segment based on transmural extent of hyperenhanced myocardium at 12-36 months post first study visit. Further categorized in accordance with established criteria (ischemic: subendocardial or transmural, non-ischemic: mid or epicardial). Total size (% LV myocardium) measured based on segmental scores, further quantified using the full-width half maximum method.

Blood oxygenation of participants at > 3 months post-COVID-19 diagnosis, first study visit

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

Blood oxygenation in both the heart (LV/RV) and pulmonary arteries measured on QSM (quantitative susceptibility mapping) at \> 3 months post-COVID-19 diagnosis, first study visit: conversion from susceptibility to blood oxygenation. Compute left-right heart oxygen saturation difference (ΔSO2) for which venous saturation will be measured in the RV outflow tract/pulmonary artery (PA) junction (analogous to invasive cath), left and right pulmonary artery differential saturation and relative saturation (in relation to the RV), and mixed venous oxygen saturation (SvO2), which will be calculated by subtracting ΔSO2 (on QSM) from arterial oxygen saturation measured by pulse oximetry (obtained at conclusion of CMR exam).

Blood oxygenation of participants at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Blood oxygenation in both the heart (LV/RV) and pulmonary arteries measured on QSM (quantitative susceptibility mapping) at 12-36 months post first study visit: conversion from susceptibility to blood oxygenation. Compute left-right heart oxygen saturation difference (ΔSO2) for which venous saturation will be measured in the RV outflow tract/pulmonary artery (PA) junction (analogous to invasive cath), left and right pulmonary artery differential saturation and relative saturation (in relation to the RV), and mixed venous oxygen saturation (SvO2), which will be calculated by subtracting ΔSO2 (on QSM) from arterial oxygen saturation measured by pulse oximetry (obtained at conclusion of CMR exam).

Lung abnormalities in participants at > 3 months post-COVID-19 infection

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

Lung abnormalities at \> 3 months post-COVID-19 infection graded on high resolution 3D MRA (magnetic resonance angiography) as (1) consolidative or ground glass signal abnormality or (2) linear areas of scarring and fibrosis. A validated semi-quantitative scoring system is then be applied as follows: each of the 5 lung lobes scored based on extent of anatomic involvement where 0=no involvement: 1=\<5% involvement; 2=5-25% involvement; 3=26-59% involvement; 4=51-75% involvement; and 5=\>75% involvement. The resulting global score is the sum of each individual lobar score (range 0-25).

Lung abnormalities in participants at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Lung abnormalities at 12-36 months post first study visit graded on high resolution 3D MRA (magnetic resonance angiography) as (1) consolidative or ground glass signal abnormality or (2) linear areas of scarring and fibrosis. A validated semi-quantitative scoring system is then be applied as follows: each of the 5 lung lobes scored based on extent of anatomic involvement where 0=no involvement: 1=\<5% involvement; 2=5-25% involvement; 3=26-59% involvement; 4=51-75% involvement; and 5=\>75% involvement. The resulting global score is the sum of each individual lobar score (range 0-25).

Quality of life (QOL) in participants at > 3 months post-COVID-19 diagnosis, at first study visit based on clinical indices and symptoms assessed by the (Patient-Reported Outcomes Measurement Information System) PROMIS-29 questionnaire.

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

QOL at \> 3 months post-COVID-19 diagnosis evaluated based on scores from the (Patient-Reported Outcomes Measurement Information System) PROMIS-29 questionnaire (0-10 scale per 7 categories) which is represented by a standardized T-score (mean=50, Standard Deviation=10). QOL data will be analyzed as a continuous variable.

Quality of life (QOL) in participants at 12-36 months post first study visit based on clinical indices and symptoms assessed by the (Patient-Reported Outcomes Measurement Information System) PROMIS-29 questionnaire.

Time frame: 12-36 months post first study visit

QOL at 12-36 months post first study visit evaluated based on scores from the (Patient-Reported Outcomes Measurement Information System) PROMIS-29 questionnaire (0-10 scale per 7 categories) which is represented by a standardized T-score (mean=50, Standard Deviation=10). QOL data will be analyzed as a continuous variable.

Effort tolerance as measured by a 6-minute walk test at > 3 months post-COVID-19 diagnosis, at first study visit

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

Effort tolerance \> 3 months post-COVID-19 diagnosis quantified via 6-minute walk test, measured as a continuous variable based on total duration walked (during 6-minute test time, or time of patient requested test termination), as well as a age and gender based binary cutoffs employed in prior literature. Impaired effort tolerance will be tested both as a binary (\<85% predicted) and continuous variable (distance) for statistical analysis.

Effort tolerance as measured by a 6-minute walk test at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Effort tolerance at 12-36 months post first study visit quantified via 6-minute walk test, measured as a continuous variable based on total duration walked (during 6-minute test time, or time of patient requested test termination), as well as a age and gender based binary cutoffs employed in prior literature. Impaired effort tolerance will be tested both as a binary (\<85% predicted) and continuous variable (distance) for statistical analysis.

Participants with edema based on cardiac imaging (MRI and echocardiogram) at > 3 months post-COVID-19 diagnosis, at first study visit

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

Edema at \> 3 months post-COVID-19 diagnosis: Identified on T2 mapping assessed on a segmental basis corresponding to LGE-CMR. Elevated T2 (i.e. edema) will defined in accordance with established criteria. Myocardial T2 relaxation times extracted from T2 maps after contouring of endocardial and epicardial borders, T2 maps will be analyzed using a 16 segment AHA (American Heart Association) model. T2 values above an established threshold will be indicate presence or absence of edema where T2 value of \>80 ms will be used to distinguish edema from healthy myocardium. Global edema assessed as sum of number of affected LV segments. Exploratory analyses test additional indices of edema severity, as assessed based on maximal and mean T2 in all LV segments.

Participants with edema based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Edema at 12-36 months post first study visit : Identified on T2 mapping assessed on a segmental basis corresponding to LGE-CMR. Elevated T2 (i.e. edema) will defined in accordance with established criteria. Myocardial T2 relaxation times extracted from T2 maps after contouring of endocardial and epicardial borders, T2 maps will be analyzed using a 16 segment AHA (American Heart Association) model. T2 values above an established threshold will be indicate presence or absence of edema where T2 value of \>80 ms will be used to distinguish edema from healthy myocardium. Global edema assessed as sum of number of affected LV segments. Exploratory analyses test additional indices of edema severity, as assessed based on maximal and mean T2 in all LV segments.

Participants with diffuse fibrosis based on cardiac imaging (MRI and echocardiogram) at > 3 months post-COVID-19 diagnosis, at first study visit

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

Diffuse fibrosis at 6-12 months post-COVID-19 diagnosis assessed based on extracellular volume (ECV) measured by T1 values in co-registered regions on pre- and post-contrast Modified Look-Locker Inversion (MOLLI): ECV will be calculated via an established formula ECV = (1-hematocrit) \* \[(1/T1myo post - 1/T1myo pre) / (1/T1blood post - 1/T1bloodpre)\].

Participants with diffuse fibrosis based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Diffuse fibrosis at 12-36 months post first study visit assessed based on extracellular volume (ECV) measured by T1 values in co-registered regions on pre- and post-contrast Modified Look-Locker Inversion (MOLLI): ECV will be calculated via an established formula ECV = (1-hematocrit) \* \[(1/T1myo post - 1/T1myo pre) / (1/T1blood post - 1/T1bloodpre)\].

Quality of life (QOL) in participants at > 3 months post-COVID-19 diagnosis, at first study visit based on clinical indices and symptoms assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ)

Time frame: Day of first study visit, > 3 months post- acute COVID-19 infection

The Minnesota Living with Heart Failure (MLHFQ) scores at \> 3 months post-COVID-19 diagnosis range from 0-105 where a higher score indicates more significant impairment in health related quality of life. QOL data will be analyzed as a continuous variable.

Quality of life (QOL) in participants based on clinical indices and symptoms assessed by the Seattle Angina (SAQ) questionnaire at 12-36 months post first study visit

Time frame: 12-36 months post first study visit

Seattle Angina (SAQ) questionnaires scored at 12-36 months post first study visit between 0-100 where higher scores indicate better functional status. QOL data will be analyzed as a continuous variable.

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