Keywords
coronavirus - COVID-19 - cardiovascular disease
Epidemiology of Cases
On December 31, 2019, 27 cases of pneumonia of unknown cause first surfaced in Wuhan,
Hubei province, which were reported to the World Health Organization (WHO) country
office in China. Investigators in Wuhan published their initial experience with this
infection in the recent March edition of Journal of the American Medical Association (JAMA).[1] After identification and isolation of the pathogen, this virus was originally called
2019 novel coronavirus (2019-nCoV) and officially renamed severe acute respiratory
syndrome CoronaVirus 2 (SARS-CoV-2) by the WHO.[2] The virus has since then spread throughout the world with the first case in India
reported on January 30, 2020 in Thrissur, Kerala. Taking into cognizance the alarming
rate of spread and severity of the disease, WHO characterized COVID-19 as a pandemic
on March 11, 2020. To date, nearly 5 million people have been reported to be infected
worldwide, with over 300000 deaths, and the numbers are rapidly rising every day.
Although the main symptoms of COVID-19 appear to be respiratory, some infected patients
suffer, in addition, from severe cardiovascular damage. This is especially true for
patients with underlying cardiovascular diseases who are more prone to infection and
might have an increased risk of death.[3]
Pathophysiology of COVID-19 Infection
Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound aminopeptidase which is
highly expressed in the heart and lung. Infection is triggered by the binding of the
spike protein of the virus to ACE2 and consequent invasion of lung (alveolar epithelial
cells) and heart, resulting in respiratory and cardiac complications. ACE2 is a homolog
of ACE and converts angiotensin II to angiotensin 1–7. It thus protects the heart/lungs
from the harmful effect of angiotensin II which is mediated via systemic vasoconstriction.
The exact mechanism of cardiac involvement is speculated to be either direct myocardial
damage or via an imbalance between subtypes of T helper cells, leading to a cytokine
storm and shock-like state.
Cardiovascular complications occur in a significant proportion of patients and are
an important independent risk factor for mortality. It has been observed that there
is a vulnerable population prone to develop serious complications, which includes
patients with comorbid conditions, namely, advanced age, diabetes mellitus, hypertension,
coronary artery disease, heart failure, chronic lung disease, and patients with cancer
or with immune compromised status.[4]
Cardiovascular Manifestations
Myocarditis Related Myocardial Injury
The severity of myocardial involvement after COVID-19 infection varies, with patients
presenting with chest pain, arrhythmias, dyspnea or acute left ventricular (LV) failure.[1]
[3] The electrocardiogram (ECG) abnormalities include nonspecific ST-T abnormalities,
T wave inversions, PR segment and ST segment depression, and elevations mimicking
acute coronary syndrome (ACS) in some cases. Differentiating ACS from COVID-19 related
myocarditis by ECG and clinical presentation may be challenging. Echocardiography
may be helpful in this situation, with regional wall motion abnormality demonstrated
in ACS, and either no wall motion abnormality or global hypokinesia seen in COVID-19
related myocarditis.
Acute myocardial injury associated with COVID-19 mainly manifests as an increase in
high-sensitivity cardiac troponin I (hs-cTn I), requiring admission to the intensive
care unit (ICU). Patients with severe symptoms often have complications involving
acute myocardial injury.[1] ECG, echocardiography abnormalities and troponin elevation correlate with severity
of the infection and denote worse outcomes in patients with severe infection.[5]
[6] There is usually raised CRP, CD4, CD8 and interleukin 6 (IL-6), pointing to an inflammatory
response. This inflammatory response may result in myocarditis. Hu et al reported
a patient with fulminant myocarditis, following SARS-CoV-2 infection. The patient
showed remarkable improvement in LV function with methylprednisolone and immunoglobulins
in addition to other symptomatic therapy.[7]
Acute Coronary Syndrome
Some patients with SARS-Cov-2 present with ACS and ST-elevation myocardial infarction
(STEMI) or non-STEMI picture.
Treatment of STEMI in COVID-19 patients is controversial in nature. In patients presenting
with “low-risk STEMI,” defined as inferior STEMI without right ventricular involvement
or lateral wall MI and also without hemodynamic compromise, thrombolytic therapy has
been suggested to be the preferred option by American College of Cardiology (ACC)
when compared with percutaneous coronary intervention (PCI) to avoid exposure to staff.
If PCI is pursued, appropriate personal protective equipment (PPE) for staff is mandatory,
with full decontamination of the catheterization laboratory after completion of the
procedure.[8]
In a recent study published in Circulation, Stefanini et al[9] reported a review of their 29 COVID-19 patients with STEMI. Emergent coronary angiography
confirmed culprit lesions in 60% of patients. The author emphasized that delay in
reperfusion to provide adequate protection to the staff and fibrinolytic therapy may
be an alternative approach. The obvious limitation of this approach is that nearly
40% will also receive fibrinolytic therapy in the absence of any underlying culprit
lesion. These patients either have myocarditis or stress cardiomyopathy. In the absence
of endomyocardial biopsy, it remains difficult to be sure of underlying pathology
in such cases.
In the setting of non-STEMI, conservative therapy may be appropriate in low-risk patients
with COVID-19 infection. High-risk patients or those with hemodynamic instability
should be managed with invasive approach.[8]
ACS in infected patients portends a poor prognosis. Myocardial ischemia or necrosis
compromises underlying functional cardiac reserve, precipitating cardiac insufficiency.
Arrhythmias and Acute Heart Failure
Patients infected with COVID-19 may present with palpitations, most commonly sinus
tachycardia and, rarely, atrial fibrillation, resulting from hypoxia, inflammatory
stress and abnormal metabolism. Dysrhythmias with elevated troponin levels should
alert the clinician toward underlying acute myocarditis or ACS.[10] Rarely, ventricular tachycardia may occur secondary to QT prolongation either as
result of underlying myocarditis or some drug, namely, use of hydroxychloroquine and
azithromycin.
COVID-19 infection can present with acute heart failure as the primary manifestation
in 24% of patients and is associated with an increased risk of mortality.[11]
Venous Thromboembolism
Patients infected with the virus are also at increased risk of venous thromboembolism,
resulting from systemic inflammation and abnormalities of the coagulation pathways,
leading to elevations of D-dimer levels.[10]
[12]
[13] In one study, all 25 patients infected with COVID-19 had elevated D-dimer levels
out of which 10 patients had CT pulmonary angiography-proven pulmonary embolism.[3] Low-molecular weight heparin has been used in a study to reduce mortality in severe
COVID-19 infection.[14]
COVID-19 and Chronic Cardiovascular Disease
The increased metabolic demand as a result of infection imposes a burden on patients
with underlying chronic cardiovascular disease, who have reduced cardiac reserve,
leading to decompensation of stable state. Widespread systemic inflammation may be
linked to increased risk of plaque rupture, worsening heart failure and stent thrombosis,
and rigorous use of plaque stabilizing agents, antifailure measures and antiplatelet
therapy should be considered.[15]
Furthermore, symptoms of COVID-19 infection tend to be more severe in these patients
and a large proportion of deaths occur in patients with cardiovascular disease. The
mortality may be nearly 10 times higher in these patients as compared with those without
such comorbid conditions. Thus, it is important to optimally control the comorbid
cardiac condition and take all preventive steps to avoid COVID-19 infection in this
vulnerable group.
Conclusion
The COVID-19 pandemic with uncertain clinical characteristics has caused an unprecedented
level of burden on healthcare systems across the world. SARS-CoV-2 possibly infects
the host cells through ACE2 receptors, causing myocardial damage and leading to adverse
prognosis in patients with underlying cardiovascular disease. Therefore, careful monitoring
of infected patients for cardiovascular complications becomes paramount to provide
timely treatment in order to reduce overall mortality.
