This is a sketch I did as a part of a pilot study examining the anatomical features of the heart in intricate detail. Thought this may make a nice opening visual for this article.
Navigating the myriad of academic literature may be challenging to decipher for some individuals. Thus, via sharing this on this blogging platform I hope to increase and consolidate the public and/or professional understanding of this niche topic of the surging pandemic. Any feedback is as always welcomed and appreciated.
Covid-19 predominantly being a respiratory condition for the majority of the population, some cardiac pathology may be manifested in vulnerable populations. This article aims to examine the underlying mechanisms and the associated ailments implicated in heart diseases owing to Covid-19.
PATHOPHYSIOLOGY
ACE2 is a receptor binding site for coronaviruses, which is expressed in blood vessels, heart and lungs. This binding causes the virus to be engulfed (taken inside) into the pneumocytes. It then releases its RNA in to the cytoplasm of the cell and uses the cell’s ribosomes to make more copies of its RNA.
This proliferation of the virus in the lung parenchyma may be characterized by mild symptoms such as dry cough and fever, which leads to the recruitment of macrophages.
This in turn damages the cells, which release inflammatory mediators. This causes macrophage recruitment. The macrophages secrete specific cytokines such as interleukin-1, interleukin-6 and tumour necrotic factor alpha. The cytokines may trigger a cytokine storm in some cases of covid-19. The cytokine storm can reach systemic circulation and also affect the heart.
ACUTE CORONARY SYNDROME
Acute coronary syndrome describes an array of clinical heart conditions such as acute myocardial ischaemia, unstable angina, non ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
Figure 3: Types of ischaemia.
HEART FAILURE
Heart failure is when the heart becomes unable to pump blood around the body. This may be presented as shortness of breath and fatigue in patients. A possible mechanism by which the heart might fail to pump blood in COVID-19 infection is via myocarditis. Myocarditis is known as inflammation of cardiac cells. COVID-19 can bind to ACE2 receptors on the heart and directly affect the cardiomyocytes. Initially, the virus proliferates in the cardiac cells upon gaining entry, and destroying the irreplaceable myocytes. It may then trigger the innate immune response by the recruitment of macrophages and cytokines, leading to a cytokine storm which is characterised by elevated levels of interleukin 6 and 7. This damages the cardiac cells. Myocarditis can also be caused the hyperinflammation in the lungs travelling in the blood and reaching the heart cells, impairing their function. In patients, myocarditis can have mild symptoms such as palpitations and chest pains to severe presentations like cardiogenic shock or ventricular arrhythmias. Direct infiltration of the virus into the heart can also cause electrical instabilities. For example, it can affect the pacemaker cells in the Sino-Atrial (SA) node along with the Atrioventricular (AV) node, impairing their electrical excitability and conductivity. When the virus directly destroys the myocardial cells (which is characterised by elevated levels of Troponin I and Lactate Dehydrogenase) it reduces the number of cells participating in electrical conductivity, which can lead to other cardiac conditions like arrhythmias.
Figure 4: the activation of the viral spike protein of COVID-19 by TMPRSS2 and the subsequent binding to the ACE2 receptor in the cardiomyocytes.
Figure 5: internalisation of the virus in the cardiomyocyte.
ARRHYTHMIAS
Arrhythmias can be a consequence of myocarditis in COVID-19. They may arise due to the damaged contractile cells. Hypoxemia induced by lung dysfunction may activate the sympathetic nervous system, which result in enhanced automaticity. This is an increase in the frequency of action potentials. After depolarisations can also occur. These are depolarisations of the cardiomyocytes which occur during, or immediately after the repolarisation phase as a result of calcium entry into the cardiomyocytes in the repolarisation phase. This can cause tachyarrhythmias. This means that the heart is continuously contracting in succession, without allowing time for it to fill with blood. It reduces the stroke volume and the ejection fraction, also reducing the cardiac output as a result. Another type of arrhythmia caused by COVID-19 is Delayed After Depolarisation (DAD). These can occur when there is intracellular calcium overload. As a result, resting membrane potential becomes less negative. DADs occur after the normal repolarisation of the heart but before a normal depolarisation would occur. This happens because of sodium entry causing another cellular contraction.
Figure 6: the types of electrical abnormalities that can occur as a consequence of direct infiltration of the virus into the heart, or as a result of myocarditis or lung inflammation.
CARDIAC BIOMARKERS
Myocardial injury can be as a consequence cytokine storm (uncontrolled proliferation of macrophages and lymphocytes) mediated by increased inflammatory biomarkers such as interleukin-6 (IL-6), ferritin, lactate dehydrogenase (LDH), and D-dimer. D-dimer is a small protein in the blood produced as product of blood clot degradation, when fibrin is destroyed by the process of fibrinolysis. If the inflammation from the lungs reaches the vascular system, it causes vasodilation and increases vascular permeability throughout the body = decreasing the blood volume and total peripheral resistance and therefore decreasing blood pressure. In severe cases, the low levels of perfusion to other organs as a result of the low blood pressure can cause multiple organ failure. The cytokine storm may also trigger myocarditis via interleukin 1, 7 and 22. This may cause myocardial cell death leading to decreased contractility of the heart and adverse remodelling of the left ventricle. Adverse remodelling refers to the structural changes in the heart as a result of loss of myocardial cells.
Other than inflammatory biomarkers of myocardial injury, levels of protein and hormones also indicate the level of cardiac injury. Both troponin T and ventricular natriuretic peptide were elevated in patients who ultimately died of covid-19, as compared to the survivors in which no such elevations were seen. Troponin T is a protein and damage to the heart releases troponin T into the bloodstream. Natriuretic peptide is a peptide that is released during heart failure. It decreases blood pressure by fluid excretion from the kidneys. Hypoxia induced hypertension in patients with COVID-19 may increase ventricular wall stress and leads to the release of B-type natriuretic peptide. A possible reason for B-type natriuretic peptide elevation could be the lung inflammation and consolidation resulting from hypoxemia activates the peripheral chemoreceptors located in the carotid sinus. The carotid bodies respond to this hypoxia by increasing the firing rate from the carotid sinus nerve to the respiratory centre in the medulla oblongata. This in turn stimulates the sympathetic nervous system and increases blood pressure.
CONCLUSION
It is important for healthcare professionals to be aware of the cardiac consequences of covid-19 as some patients with SARS COV 2 infection went to the doctor because of heart palpitations and chest tightness rather than respiratory symptoms, but were later diagnosed with COVID-19. In addition, 5 of the first 41 patients diagnosed with COVID-19 in Wuhan suffered a myocardial injury. Out of those 5 patients, 4 where admitted to the ICU with significantly higher blood pressure than those not treated in the ICU. This indicates that cardiac involvement in covid-19 is associated with a worse prognosis.
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