Cardiovascular Implications of COVID-19
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|ClinicalTrials.gov Identifier: NCT04435457|
Recruitment Status : Recruiting
First Posted : June 17, 2020
Last Update Posted : February 4, 2021
|Condition or disease|
|SARS-CoV 2 SARS Pneumonia COVID-19 SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere Cardiac Complication|
This will be a cross-sectional cohort study of participants who will undergo a detailed cardiovascular imaging evaluation and blood draw once they have recuperated from a prior index-hospitalization at Clements University Hospital or Parkland Memorial Hospital in Dallas, Texas, USA for COVID-19 and are no longer contagious (~4-6 weeks post hospitalization). Due to the uncertainty with which the extent of cardiac injury represents phenotypic cardiac manifestations in COVID-19, the investigators plan to enroll individuals according to their highest, in-hospital, (high sensitivity - cardiac troponin T) hs-cTnT. The following proposed stratification scheme will afford testing a spectrum hs-cTnT levels.
Table: Enrollment strata by hs-cTnT (N=70)
hs-cTnT [ng/L] < 50 50-100 101-500 > 500
Enrollment N=20 N=20 N=20 N=10
The investigators propose the following exploratory protocol for deep phenotyping to characterize surviving patients with COVID-19 and elevated hs-cTnT during hospitalization.
All participants will undergo a protocolized multiparametric cardiac magnetic resonance imaging (CMR) assessment with an electrocardiography-gated breath hold protocol under the oversight of study personnel and read by a reader blinded to hs-cTnT data from the COVID-19 index hospitalization. Conventional 1H CMR evaluations will include T2 maps, native and post-contrast T1 maps, as well as extracellular volume index calculation and late gadolinium for inflammatory injury. Standardized adenosine hyperemic stress perfusion CMR will be performed for quantitative myocardial blood flow analysis. In addition to conventional 1H CMR a subset of 5 patients from the highest and lowest troponin groups, age- and BMI-matched, will undergo hyperpolarized 13C metabolic CMR with infusion of [1-13C] pyruvate under fasting conditions to assess inflammation and post carbohydrate load to assess a decrease in myocardial mitochondrial oxidative metabolism.
Biospecimens will be collected by study personnel at the time of CMR or preliminary study site visit. A fasting venous blood sample (50 cc) will be collected, maintained on ice and transported to the Mammen Laboratory, which is located on the campus of UT Southwestern. Both serum and plasma will be isolated and aliquoted for storage and immediately frozen and stored until use and will not undergo any freeze-thaw cycles. RNA and protein will be extracted from the samples for biomarker and autoantibody (AAb) assays. The presence of cardiac-specific AAbs has been shown to be involved in both the manifestation and development of cardiac disease manifestation and predicting disease development. Utilizing a customized ELISA-based detection assay, ~20 circulating cardiac-specific AAbs that have been reported to be associated with heart failure will be assessed and quantified during the early (1-2 months post-hospitalization) phases of the patient post COVID-19 hospitalization course.
Leukocytes will be isolated from the biospecimens samples and genomic DNA will be extracted from the cells to perform Next Generation Whole Exome Sequencing (WES). These studies will be undertaken in the Next-Generation Sequencing Core on campus. Capitalizing on a well-established research collaboration between the Mammen Laboratory and the McDermott bioinformatics group, the WES data will be analyzed for genetic mutations associated with cardiomyopathy as well as autoimmunity.
If funds are available, both the imaging and molecular assessments will be duplicated in individuals with paired data after an additional 10-12 months from hospitalization.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||70 participants|
|Target Follow-Up Duration:||1 Year|
|Official Title:||Uncovering the Cardiac Phenotype of Individuals With SARS-COV-2 and Cardiac Injury|
|Actual Study Start Date :||September 1, 2020|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||June 30, 2021|
- Prevalence of Myocarditis [ Time Frame: Up to 4 weeks ]Patterns of late gadolinium enhancement and T1 and T2 mapping consistent with myocarditis on a post-hospitalization cardiac magnetic resonance imaging examination
- Prevalence of cardiac abnormalities by cardiac magnetic resonance imaging [ Time Frame: Up to 4 weeks ]This includes categorically abnormal structural, mechanical functional, vascular, and metabolic using cardiac magnetic resonance imaging
- Prevalence of molecular and genetic immune system abnormalities [ Time Frame: Up to 4 weeks ]Presence of cardiac autoantibodies and defects within the immune system as detected by Whole Exome Sequencing making an individual susceptible to subacute cardiac injury during COVID-19 infection
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04435457
|Contact: Carolyn Kelly, RN, MPH, CCRC||214-645-8040||Carolyn.Kelly@utsouthwestern.edu|
|United States, Texas|
|University of Texas Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Carolyn Kelly, RN MPH Carolyn.Kelly@utsouthwestern.edu|
|Principal Investigator:||Justin L Grodin, MD, MPH||UT Southwestern Medical Center at Dallas|