Clinical trial NCT05164744: Cardiac Magnetic Resonance Tissue Characterization in COVID-19 Survivors
Official title: Cardiac Magnetic Resonance for Tissue Characterization-Based Risk Stratification of Cardiopulmonary Symptoms, Effort Tolerance, and Prognosis Among COVID-19 Survivors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: COVID-19 Pneumonia
COVID-19
COVID-19 Respiratory Infection
COVID-19 Acute Respiratory Distress Syndrome
COVID-19 Lower Respiratory Infection
COVID-19 Acute Bronchitis
Coronavirus Disease 2019
Keywords: coronavirus disease 2019,
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-12-21
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: 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 the investigator's 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 the 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, the investigators will study patients from an active multiethnic New York City registry of COVID-19 survivors: the investigators 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): the investigator's current proposal will extend logically on the 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion criteria:

* 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.

Primary outcomes:
measure: Participants with focal fibrosis based on cardiac imaging (MRI and echocardiogram) > 3 months post-COVID-19 (coronavirus disease 2019) diagnosis, at first study visit
timeFrame: Day of first study visit, > 3 months post acute COVID-19 infection
measure: Participants with focal fibrosis based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: Blood oxygenation of participants at > 3 months post-COVID-19 diagnosis, first study visit
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: Blood oxygenation of participants at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: Lung abnormalities in participants at > 3 months post-COVID-19 infection
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: Lung abnormalities in participants at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: 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.
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: 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.
timeFrame: 12-36 months post first study visit
measure: Effort tolerance as measured by a 6-minute walk test at > 3 months post-COVID-19 diagnosis, at first study visit
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: Effort tolerance as measured by a 6-minute walk test at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: Participants with edema based on cardiac imaging (MRI and echocardiogram) at > 3 months post-COVID-19 diagnosis, at first study visit
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: Participants with edema based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: Participants with diffuse fibrosis based on cardiac imaging (MRI and echocardiogram) at > 3 months post-COVID-19 diagnosis, at first study visit
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: Participants with diffuse fibrosis based on cardiac imaging (MRI and echocardiogram) at 12-36 months post first study visit
timeFrame: 12-36 months post first study visit
measure: 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)
timeFrame: Day of first study visit, > 3 months post- acute COVID-19 infection
measure: 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
timeFrame: 12-36 months post first study visit
Secondary outcomes:
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: New York Presbyterian-Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Queens
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine/New-York Presbyterian Hospital
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Jiwon Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: