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November 16, 2023

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National COVID Cohort Collaborative (N3C) Cardiovascular Disease Domain Team Makes Early Discoveries in Link Between COVID-19 and Cardiovascular Disease

The Cardiovascular Diseases Domain Team (CVDT) is composed of individuals with a variety of backgrounds including clinicians, analysts, biostatisticians, and scientists from many institutions across the country, working collaboratively towards new discoveries of the impact of COVID-19 on cardiovascular diseases. Since the first meeting in February 2021, this group has been productive in researching COVID-19-related clinical cardiovascular health problems, learning about the relationship between COVID-19 and cardiovascular disease, and disseminating findings through manuscripts and abstract presentations at national meetings. In addition, CVDT members have been involved in supporting the N3C community in a number of activities including concept set creation and quality review of concept sets that have led to supporting the creation of N3C recommended concept sets and serving as beta-testers for the new publications intent platform.

Early efforts by the CVDT focused on investigating the impact of COVID-19 on patients with active cancers and measuring differences in major adverse cardiovascular events (MACE). This work resulted in three abstract presentations at the American College of Cardiology (ACC) 2022 Annual Meeting (Patel B, et al, Visaria A, et al, Visaria A, et al) and a recent publication in the journal Cardio-Oncology (Patel B, et al.). Additional work resulting in abstract presentations at ACC include an evaluation of outcomes and complications in patients with CVD infected with COVID-19 (Khodaverdi M, et al.) and the impact of health disparities in vaccinated CVD patients infected with COVID-19 (Khodaverdi M, et al).

More recent work has been related to exploring the impact of CVD-related comorbidities on MACE outcomes in COVID-19-infected patients with pre-existing heart failure (Jacob Neumann, project lead) and myocarditis/pericarditis diagnosis trends during the pre-COVID-19 era (Jan 2018-March 2020), the COVID-19/pre-vaccine era (April-December 2020), and COVID-19 and vaccine era (January 2021-March 2023). The CVDT has also explored the incidence of new cardiovascular complications between COVID-19 infection and receiving an mRNA vaccine (Scott Chapman and Sameh Hozayen, project leads).

Findings from Selected Research Projects Includes:

  • Outcomes of Patients with active cancers and pre-existing cardiovascular diseases infected with SARS-CoV-2
    • We examined patients who were had a history of cardiovascular disease (CVD) who did or did not have active cancer (defined as last record of receiving a cancer treatment within 30 days of and the outcome of MACE were compared across 4 groups (CVD (-), CVD (+), Cardioonc (-) and Cardioonc (+).  The research objective was to determine the impact of COVID-19 infection on patients with concomitant active cancers.  Patients with both CVD and active cancer suffered relatively worse outcomes when they had acute COVID-19 infection during early and alpha surges in the United States. These findings highlight the need for improved management strategies and further research to better understand the impact of the virus on vulnerable populations during the COVID-19 pandemic.


  • COVID-19 Related Major Adverse Cardiovascular Events in Patients with Pre-Existing Heart Failure.
    • Patients with heart failure are at increased risk for COVID-19 related complications.  In this study, we evaluated patients with pre-existing heart failure and risk factors associated with MACE.  COVID-19 infection resulted in increased risk of MACE in patients with underlying CV co-morbidities. Patients with prior kidney disease had increased risk of 90 day mortality.


  • Myocarditis and Pericarditis Diagnosis Trends from 2018-2023 and the Influence of COVID-19 Infection and mRNA COVID-19 Vaccines.
    • Myocarditis and pericarditis diagnosis trends were explored from 2018-2023 to compare incidence during pre-COVID-19 era (Time 1: January 2018-March 2020), COVID-19 era without mRNA vaccine (Time 2: April -December 2020) and during COVID-19 era with mRNA vaccine (Time 3: January 2021-March 2023).  We also sought to explore differences in the incidence across the 3 time periods between no COVID or vaccine, COVID-19, and mRNA vaccine.  We found myocarditis and pericarditis increased during the COVID-19 pandemic relative to pre-pandemic levels (2.21 vs. 4.31 vs. 3.86 %/month/1000 patients for Time periods 1, 2, and 3, respectively), and was highest in those who did not have a COVID-19 infection or received an mRNA vaccine within 21 days of myo/pericarditis diagnosis (Time 2: 3.89; Time 3: 3.47) compared to COVID-19 infected patients (Time 2: 0.42, Time 3: 0.32), and lowest in the mRNA vaccine (Time 3: 0.056).


  • Comparison of Cardiovascular Complications Associated with Myocarditis and Pericarditis Between COVID-19 Infection and mRNA COVID-19 Vaccines.
    • We evaluated myo/pericarditis incidence and compared new cardiovascular diagnoses and severity of illness between COVID-19 and mRNA vaccine patients with myo/pericarditis.  Myo/pericarditis diagnosis was considerably more common in COVID-19 infection compared to mRNA vaccine (84.2% vs. 15.8%).  There were more patients who had new heart failure diagnosis (29% vs. 24%), and cardiomyopathy (20% vs. 14%) with COVID-19 infection compared to mRNA vaccine recipients.   Atrial arrhythmias were more common in mRNA vaccine (14% vs. 17%). Hospitalization was similar (54% vs. 52%) but severity of illness was more common in the COVID-19 cohort (25% vs. 12%).


  • Methodological Quality Checks for OMOP Drug Concept Set Creation; Patel S et al.
    • Quality of concept sets is a key aspect of the N3C and researcher reliability in the accuracy and intended reflection of the tools used by N3C researchers.  CVDT members collaborated with members of the RECOVER Long COVID initiative to review and develop a framework for iterative quality checks and clinician verification within the OMOP CDM vasoactive agents concept set.  This work will be presented at the upcoming AMIA Annual Symposium.


The CVDT welcomes new team members and project ideas and has offered collaborative support for new projects. To learn more about the Cardiovascular Diseases Domain Team or to join our Domain Team, please visit https://covid.cd2h.org/cardiology or email n3c-dt-cardiology@googlegroups.com.


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Coordination, Communication, and Operations Support (CCOS) is funded by theNational Center for Advancing Translational Sciences, National Institutes of Health.

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