Cardiac Magnetic Resonance Tissue Characterization in COVID-19 Survivors

NCT05164744 | Recruiting

• 2 other identifiers: 21-02023362R01HL159055-01
• Study Type: observational
• Target: 510
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test if visualizing the heart with cardiac MRI/echo will be important in the understanding cardiac function and prediction of cardiopulmonary symptoms, physical effort tolerance, and outcomes in COVID-19 survivors. If successful, the research will allow us to identify the causes of lasting cardiopulmonary symptoms and begin developing cardiac and lung directed therapies accordingly.

Conditions

COVID-19; COVID-19 Acute Respiratory Distress Syndrome; COVID-19 Lower Respiratory Infection; COVID-19 Acute Bronchitis; Coronavirus Disease 2019; COVID-19 Pneumonia; COVID-19 Respiratory Infection

Keywords

coronavirus disease 2019,

Outcome Measures

Primary Outcomes (16)

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

  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.

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

• Participants with focal fibrosis based on cardiac imaging (MRI and echocardiogram) at 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.

  12-36 months post first study visit

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

  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).

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

• Blood oxygenation of participants at 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).

  12-36 months post first study visit

• Lung abnormalities in participants at > 3 months post-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).

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

• Lung abnormalities in participants at 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).

  12-36 months post first study visit

• 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.

  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.

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

• 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.

  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.

  12-36 months post first study visit

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

  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.

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

• Effort tolerance as measured by a 6-minute walk test at 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.

  12-36 months post first study visit

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

  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.

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

• Participants with edema based on cardiac imaging (MRI and echocardiogram) at 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.

  12-36 months post first study visit

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

  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) \* \[(1/T1myo post - 1/T1myo pre) / (1/T1blood post - 1/T1bloodpre)\].

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

• Participants with diffuse fibrosis based on cardiac imaging (MRI and echocardiogram) at 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) \* \[(1/T1myo post - 1/T1myo pre) / (1/T1blood post - 1/T1bloodpre)\].

  12-36 months post first study visit

• 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)

  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.

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

• 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

  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.

  12-36 months post first study visit

Study Arms (1)

Diagnosed with COVID-19

Participants in the study cohort will have been diagnosed with COVID-19 by a PCR (polymerase chain reaction) positive test

Diagnostic Test: Cardiac MRI; Diagnostic Test: Echocardiogram; Diagnostic Test: 6-minute walk test; Diagnostic Test: Questionnaire

Interventions

Echocardiogram DIAGNOSTIC_TEST

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

Diagnosed with COVID-19

6-minute walk test DIAGNOSTIC_TEST

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

Diagnosed with COVID-19

Questionnaire DIAGNOSTIC_TEST

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

Diagnosed with COVID-19

Cardiac MRI DIAGNOSTIC_TEST

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

Diagnosed with COVID-19

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study Population will be comprised of 510 patients (Men and women ≥ 18 years old) with documented (SARS-CoV-2 RT-PCR+) COVID-19 infection, inclusive of patients with residual cardiopulmonary symptoms (shortness of breath, fatigue, chest pain) and asymptomatic patients.

You may qualify if:

• Emergency room presentation and/or hospitalization with COVID-19 infection defined in accordance with established criteria as follows: SAR-CoV2 RT-PCR+ (severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction) and at least one of the following symptoms: dyspnea, cough, dysphagia, rhinorrhea, diarrhea, nausea/vomiting, myalgias, fever, syncope/presyncope.

You may not qualify if:

• Contraindication to CMR (i.e. non-compatible pacemaker/defibrillator) or gadolinium (known hypersensitivity, eGFR (estimated globular filtration rate) \<30 ml/min/1.73m2).
• Inability to provide informed consent (e.g. cognitive impairment).
• Unrelated condition (e.g. neoplasm) with life expectancy \<12 months prohibiting follow-up.
• Patients with contraindications to gadolinium (known or suspected hypersensitivity, glomerular filtration rate \< 30 ml/min/1.73m2) will undergo non-contrast MRI but will not be excluded from this study.
• Patients with known or suspected pregnancy based on Weill Cornell Radiology intake surveys (reviewed by a clinical RN (registered nurse), as well as research personnel) will be excluded from the protocol.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Weill Medical College of Cornell University: lead

Study Sites (3)

New York Presbyterian-Brooklyn Methodist Hospital

Brooklyn, New York, 11215-3609, United States

RECRUITING

New York Presbyterian Queens

New York, New York, 10021, United States

RECRUITING

Weill Cornell Medicine/New-York Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood Samples will be collected (30-50mL) to examine biomarkers which will be collected by venesection into citrate or anti-coagulated tubes, and comprised of the following: troponin, ferritin, C reactive protein, D dimer, white blood count, hematocrit, hepatic transaminases, erythrocyte sedimentation rate. In addition, blood samples will be partitioned via differential centrifugation, frozen (-80C) and stored for future research (informed by the current protocol) to further test emerging hematological markers reflective of cardiac injury.

MeSH Terms

Conditions

COVID-19

Interventions

Echocardiography; Walk Test; Pain Measurement

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Exercise Test; Neurologic Examination; Physical Examination

Study Officials

• Jiwon Kim, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth Manowitz, BS

CONTACT

2127462627; elm4036@med.cornell.edu

Mahniz Reza, BA

CONTACT

2127462627; CovidHeartStudy@med.cornell.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: December 21, 2021
• Study Start: July 1, 2021
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (3)