Introduction
Since the initial outbreak of the novel coronavirus disease
(SARS-CoV-2/COVID-19) in December, 2019 (from Wuhan, China), there have
been 693,282 confirmed cases and 33,106 deaths worldwide as of March,
30,
2020.1,2Symptomatic patients usually present with fever, dry cough, and
shortness of breath, which may appear 2-14 days after
infection.3While it has been demonstrated that this virus has a predilection for
the lungs and that respiratory complications are strongly associated
with mortality, emerging reports show that cardiac involvement can be
present in COVID-19 patients. Here, we synthesize the literature to
describe the various cardiac findings in COVID-19 that have been made in
relation to risk factors, predictors of progression, and complications
during and post COVID-19 infection. We aim to provide a comprehensive
review on this matter to assist physicians and researchers in their
efforts to efficiently update their understanding to better address the
various burdens of the current global pandemic.
Cardiac risk factors have been identified that predict the
susceptibility to COVID-19 infection and illness severity. According to
the Centers for Disease Control and Prevention (CDC), elderly patients
with comorbidities at a higher risk to become infected with COVID-19,
especially those with coronary heart disease, hypertension, or
diabetes.4Cardiovascular diseases are also associated with worse prognosis and
more severe progression of COVID-19. A study that investigated infected
patients who received care in the intensive care unit (ICU) reported the
frequency of cardio-cerebrovascular diseases, hypertension, and diabetes
to be 3 folds, 2 folds, and 2 folds, respectively, higher than
counterparts receiving non-ICU
care.5 A
different investigation focusing on patients with severe symptoms
described that 25% had heart diseases, 44% had arrhythmia, and 58%
had
hypertension.6Cardiac injury has been associated with COVID-19 mortality as well. One
study found that patients with cardiac injury had higher mortality than
those without (51.2% vs. 4.5%,
respectively).7In this same study, Cox regression model showed that patients with
cardiac injury were at a higher risk of death both from time of symptom
onset (hazard ratio, 4.26 [95% CI 1.92-9.49]) and from the time of
hospital admission to end point (hazard ratio, 3.41 [95% CI,
1.62-7.16]).7 Taken together, there is mounting
evidence that underlying cardiovascular conditions lead to higher
likelihood of infection, more severe disease progression, and greater
risk for mortality from COVID-19.
Interestingly, recent evidence suggests that cardiac signs can be useful
predicting factors in distinguishing mild versus severe COVID-19 disease
progression. While the virus does have a predilection for the lungs, the
infection also involves damage to the heart, vessels, liver, kidney, and
other
organs.8This suggests that there may be pathological signs pertaining to organ
systems other than lungs that could be relevant in the generation of a
reliable prognosis. Indeed, it has been found that Troponin I levels are
only marginally increased in all patients with COVID-19, but values
exceeding the 99th percentile in the upper reference limit are only
observed in 8-12% of positive
cases.9Early measurement of biomarkers for cardiac damage upon a suspected
infected patient’s admission to the hospital could help identify cardiac
injury, which ultimately predicts a more severe prognosis.
Cardiac injury in COVID-19 may result from direct effects of the virus
itself. In general, viral infections are one of the most common causes
of infectious
myocarditis.10Evidence also suggests that common infections trigger acute coronary
events and
strokes.11,12Following this vein, researchers have aimed to describe the mechanisms
of COVID-19-mediated cardiac injury. The virus infects host cells
through angiotensin-converting enzyme-2 (ACE2) receptors which can lead
to pneumonia, acute myocardial injury, and chronic cardiovascular
damage.13ACE2 receptors, which are important in the cardiovascular and immune
systems, are membrane bound aminopeptidases. These receptors are highly
expressed in the heart and lungs, and they have been confirmed to be the
functional receptors for the novel
coronavirus.14These findings indicate that myocardial injury caused in COVID-19 might
be ACE2 related. Given this mechanism of action, there has been
substantial discussion and controversy on the use of antihypertensive
ACE inhibitors in COVID-19 infected patients. Updates from the AHA
suggest that, based on mortality data, ACE inhibitors should be
maintained or initiated in patients with myocardial infections, heart
failure, or
hypertension.15Multiple review articles have echoed this guideline, indicating that
withdrawal of RAAS inhibitors in patients with COVID-19 may be
harmful.16,17
Recent studies and case reports have shed light on the potential of
acute cardiac injury occurring in COVID-19 infected patients. Middle
east respiratory syndrome related coronavirus (MERS-CoV) can cause
myocarditis and heart
failure.18Both COVID-19 and MERS-CoV have relatively similar pathogenicity, with
myocardial damage being associated in both diseases, leading to
increased complexity in patient
treatment.13One case report discussed a COVID-19 patient with left ventricular
dysfunction and acute pericarditis who presented without any respiratory
tract signs or
symptoms.19An investigation of the clinical features of patients with COVID-19
found myocardial injury in 5 out of 41 patients, and it mainly
manifested as an increase in high sensitivity cardiac troponin 1
levels.20Importantly, cardiac involvement has not only been present in adults but
shown to be present in infants as well. A case of a 55 day old infant
who presented with pneumonia, liver injury, and myocardial injury has
been reported in
China.21This pediatric patient had an abnormal myocardial zymogram on admission,
occasional tachycardia (150-170 bpm) on hospital days 2-6, and increased
troponin I levels (0.025 microgram/L) on hospital day
4.21 These findings suggest that myocarditis as a
complication of COVID-19 should be considered and might help improve
management and treatment of infected patients.
Cardiac issues in COVID-19 may also be related to the pharmacologic
interventions. Antiviral medications are a common treatment, and an
investigation of 138 COVID-19 infected patients reported that 89.9% of
patients were given such
medications.6It has been previously established that antiviral drugs can cause
cardiac insufficiency, arrhythmias, and other cardiovascular
disorders.22Therefore, cardiac injuries caused by pharmacological treatments must be
kept in mind while managing COVID-19 infected patients.
The question of whether chronic cardiac issues are present post COVID-19
recovery still remains. Although much about this question is currently
not well known, studies from chronic cardiac outcomes of SARS-CoV, which
is structurally similar to SARS-CoV-2, provides evidence that these
outcomes are important considerations. A longitudinal study following
patients that recovered from SARS-CoV reported that 68% had
hyperlipidemia, 4% had cardiovascular system abnormalities, and 60%
had glucose metabolism disorders post
recovery.23Furthermore, lipid metabolism dysregulation in patients with a history
of SARS-CoV infection and serum concentration of free fatty acids,
lysophosphatidylcholine, lysophosphatidylethanolamine, and
phosphatidylglycerol were significantly increased compared with people
without history of SARS-CoV
infection.23These results suggest that SARS-CoV is associated with cardiovascular
diseases and serum metabolic alterations. Based on these findings,
chronic cardiac diseases as a coronavirus-associated pathology must be
considered and further investigations of cardiac conditions post
COVID-19 are required.
When do the pathology processes of the COVID-19 affect patient care, in
addition to an obvious detrimental effect on myocardial function leading
to heart failure? If a patient presents with underlying congestive heart
failure, COVID-19 can markedly increase the severity of the illness.
Furthermore, COVID-19 does not preclude coronary artery plaque rupture
and myocardial infarction or progression of coronary artery disease.
Patients needing urgent coronary artery bypass grafting, aortic valve
replacement, repair of an aortic dissection, other urgent or emergent
operation may be more prone to myocardial dysfunction after the surgery,
especially if cardioplegic arrest is used. There is no data on the
effect of COVID-19 on myocardial protection during cardiac surgery.
Patients undergoing percutaneous coronary intervention (PCI) or coronary
stenting, may have a similar poor outcome due to the additive effect of
myocardial ischemia and poor underlying myocardial function.