Cardiovascular Manifestations of COVID-19

Significance:

Coronavirus disease 2019 (COVID-19) is a rapidly spreading infection that has already
affected close to a million patients around the world. It is estimated that COVID-19 will be
lethal for up to 200,000 Americans. Several cardiovascular manifestations have been reported
to be associated with the disease or its treatment and might be contributing to its high
mortality rates.1,2 The National Health Commission of China (NHC) documented that
approximately 12% of patients without prior cardiovascular disease (CVD) who expired in the
setting of COVID-19 had either elevated cardiac troponin I levels or a cardiac arrest during
hospitalization.3 Furthermore, patients with underlying cardiovascular comorbidities
experience worse outcomes when infected with SARS-CoV-2.1 Acute myocarditis, acute myocardial
injury, and heart failure have been associated with COVID-19.3 However, most of these
associations come from small observational studies or from comparisons with other
coronaviruses.3 The hypothesized pathogenetic mechanism of CVD in COVID-19 includes either
direct effects of the virus to the cardiac cells expressing the angiotensin- converting
enzyme 2 (ACE2) receptor, or indirect effects from the severe systemic inflammatory response,
cytokine surge and immune system activation. The exact effect of COVID-19 on the
cardiovascular system though is still not well known. This study seeks to identify the
prevalence of CVD and its role in clinical outcomes of hospitalized patients diagnosed with
COVID-19 in a large tertiary center of Houston, TX. CVD associated with COVID-19 might be
contributing to the high mortality rates and its recognition will allow for prevention, early
diagnosis and appropriate treatment. This will be the first, large, case-control study
assessing cardiovascular involvement of COVID-19 in a well-defined cohort of patients.

Methods:

Study population and data handling:

A retrospective observational case-control study will be performed. Multiple hospitals will
participate in the current study and the study protocol will be submitted separately to each
local IRB for approval. Subjects admitted to the participating hospitals from March 30th,
2020 to March 30th, 2021, who were tested for SARS-CoV-2 by PCR will be identified through
the microbiology lab registry. Subjects who were tested positive for SARS-CoV-2 by PCR will
be age- and gender-matched with subjects admitted to the hospital with similar symptoms but
negative PCR tests for SARS-CoV-2 (one negative PCR test for patients of low clinical
suspicion and two negative tests, 24 hours apart from each other, for patients of high
clinical suspicion). Demographic, clinical, laboratory and imaging findings will be collected
by retrospective electronic chart review. The current study will not involve face-to-face
patient contact and does not intent to alter the usual care of the patients involved. The
collected data will be deidentified and stored in a HIPAA approved, password-secured
designated folder of the UTH-share drive of the University of Texas Health Science Center at
Houston. No patient information will be stored or processed in any personal electronic
devices. A total of 500 study subjects are estimated to be included in the study. Upon
completion of the study, the data will be stored for an additional 5 years; following that
all research-related files will be permanently deleted.

Data collection:

Demographic characteristics including age at the time of diagnosis, gender, race and body
mass index will be collected. Past medical history including coronary artery disease, heart
failure with reduced or preserved ejection fraction, atrial fibrillation, hypertension,
dyslipidemia, diabetes mellitus, smoking status as well as home medications will be
abstracted. The name and daily dose of ACE inhibitors or angiotensin receptor blockers will
be recorded. Laboratory values including cardiac enzymes, electrolytes, hemoglobin and
creatinine will be collected. Available electrocardiograms (EKGs) and transthoracic
echocardiograms (TTEs) will be individually reviewed by an independent cardiovascular disease
fellow or a cardiovascular disease faculty member who will be blinded to the SARS-CoV-2 PCR
results. Finally, clinical outcomes including need for mechanical ventilation, length of
intensive care unit stay, length of hospitalization, arrhythmias, cardiac arrest and
in-hospital mortality will be abstracted from the electronic charts.

Statistical analysis:

Continuous variables will be tested for distribution. Normally distributed variables will be
presented as mean values +/- standard deviation (SD) and compared using the student's t test.
Non-normally distributed variables will be presented as median values with interquartile
ranges and compared using the Mann-Whitney test. Categorical variables will be presented as
percentages and compared using chi-square test. Multivariable regression analysis will be
performed to control for possible cofounder. A two-sided p-value of less than 0.05 will be
considered statistically significant. All statistical analyses will be performed using STATA
15 (StataCorp, College Station, TX).