The Cardiac Implications of COVID-19

Although COVID-19 is primarily a respiratory condition, many patients may suffer from cardiovascular consequences which range from arrhythmia to heart failure, especially in those with pre-existing cardiovascular diseases and advanced age. Understanding the mechanisms behind why cardiovascular consequences are higher in COVID-19 compared to flu is important in bettering our understanding of the disease and how to treat it effectively.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection typically results in either asymptomatic or mild-moderate COVID-19 severity in the vast majority of people. However, in specific age groups (especially those over 65) and those with pre-existing health conditions (including cardiovascular diseases, diabetes, hypertension, etc), the risk of severe disease is much higher and can require intensive care unit admission in hospital, or in some cases death.

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Cardiovascular/cardiac implications in COVID-19

In severe disease, multi-organ system failure and acute respiratory distress syndrome (ARDS) can lead to death. At the center of the most severe clinical manifestation of COVID-19 is the presence of substantially elevated cytokines (cytokine-release syndrome) which include granulocyte colony-stimulating factor (GCSF), interferon-inducible protein 10, macrophage inflammatory protein-1A and tumor necrosis factor (TNF)-alpha. In addition, those who have myocardial injury also show substantially elevated interleukin-6 (IL-6) levels, suggesting the severity of disease corresponds to the levels of circulating cytokines.

As discussed, the severity of the disease may be related to the levels of cytokines circulating in patients which can lead to an array of multi-organ damage, including to the heart and cardiovascular system. Specifically, cytokines acting on the heart can lead to stress cardiomyopathy and/or cytokine-related myocardial dysfunction in the most severe cases of COVID-19.

A key component that is implicated in cardiovascular dysfunction in COVID-19 is the renin-aldosterone-angiotensin system (RAAS). SARS-CoV-2 binds to ACE2 receptors in the body which in turn leads to a downregulation of ACE2 receptors. This downregulation of ACE2 can lead to decreased rates of the conversion of angiotensin II (ATII) to angiotensin I (ATI) which leads to elevated levels of ATII that can have a direct effect on the cardiovascular system such as increased sympathetic activity, vasoconstriction, aldosterone secretion (causing renal sodium and water reabsorption), pulmonary vascular permeability, and fibrosis.

COVID-19 in patients with cardiovascular disease

One of the biggest risk factors for severe COVID-19 and fatality from COVID-19 is cardiovascular disease comorbidity. For example, out of nearly 45,000 patients in China (case-fatality rate of 2.3%), the highest mortality rates were in patients with cardiovascular disease (10.5%), followed by diabetes (7.3%) and hypertension (6%), and these effects were similarly observed in Italy.

A majority of patients with cardiovascular disease tend to be older (over the age of 65), where most of the deaths from COVID-19 occur. Furthermore, 2 or more comorbidities are usually present in many patients with cardiovascular disease, including hypertension and diabetes which increase the risk of severe disease and death substantially, combined with advanced age. Patients with heart failure and diseases such as ischaemic heart disease may suffer from potentially severe and devastating cardiac implications with COVID-19.

The causes of mortality in hospitalized COVID-19 patients with pre-existing cardiovascular disease can be attributed to several different factors, including those mentioned previously. Several studies have shown that elevated troponin levels are associated with severe disease and mortality from COVID-19. Elevated troponin levels are associated with myocarditis, systemic infection and cytokine storm, arrhythmias and ischemia. Thus, troponin and cytokine measurements may serve to be crucial prognostic markers in disease outcomes.

Patients with pre-existing cardiovascular diseases (especially heart failure) are at an increased risk of severe disease and mortality from COVID-19 (especially older patients), but COVID-19 may also cause the development of new cardiovascular implications (including cardiomyopathy/myocarditis) in patients without pre-existing cardiovascular diseases.

These may be related to cytokine storm levels causing systemic damage (severe disease), or perhaps even direct SARS-CoV-2 infection of cardiac tissues. Whilst this is rare in healthy younger individuals, older patients with other comorbidities may be at an increased risk of developing new cardiac implications from COVID-19.

For example, patients with COVID-19 have a higher incidence of arrhythmias such as long-QT syndrome and torsades des pointes (found in many COVID-19 patients who die) which may be caused by metabolic abnormalities including cytokine storms, hypoxemia and acidosis. Many of these patients also have elevated troponin levels, thus serum measurements of troponin and other cytokines are an excellent prognostic tool in patients with severe COVID-19, and for assessment of cardiac conditions such as myocarditis.

Management of pre-existing comorbidities (health conditions) such as the aggressive treatment of heart failure, cardiac and cardiovascular diseases is important in reducing the risk of severe COVID-19 complications and mortality. These include antiarrhythmics (for arrhythmias/atrial fibrillation/tachycardia), vasopressors/diuretics (heart failure/cardiogenic shock), statins/heparin/beta-blockers (coronary syndromes) and thrombolysis (in pulmonary embolism).

Flu vs COVID-19

Compared to flu, COVID-19 has a higher case mortality rate (CMR) in addition to a higher prevalence of complications in COVID-19 compared to flu, especially in patients with pre-existing cardiovascular disease. However, this information must be taken with caution as testing for seasonal flu and reporting to health authorities is done in a limited way compared to COVID-19 and different health authorities have different ways of reporting death from both diseases.

Despite that, many countries have used these statistical parameters to compare between COVID-19 and flu. In China, official statistics place COVID-19 to have almost 15 times higher CMR compared to flu. Furthermore, deaths in patients with cardiac abnormalities/cardiovascular diseases and COVID-19 are substantially higher than the same existing comorbidities in flu. It is important to note that cardiac diseases predispose more severe disease and risk of death (primarily from myocarditis) in both flu and COVID-19, but the rates are higher in COVID-19 compared to flu.

Summary

In summary, people with pre-existing cardiovascular and cardiac diseases are at an increased risk of more severe disease and mortality from COVID-19 as they would be from flu also. However, compared to flu, COVID-19 has a higher death rate for patients with cardiovascular diseases.

Such patients should be very cautious in preventing getting infected (e.g., shielding), and should ensure they stay on top of medications and treatments, especially in the context of heart failure. Cytokine storms and troponin levels may be important pathological and prognostic markers in severe COVID-19 and could serve to be important treatment targets.

References

• Nishiga et al, 2020. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 17(9):543-558. https://pubmed.ncbi.nlm.nih.gov/32690910/
• Ranard et al, 2020. Approach to Acute Cardiovascular Complications in COVID-19 Infection. Circ Heart Fail. 13(7):e007220. https://pubmed.ncbi.nlm.nih.gov/32500721/
• Thakkar et al, 2020. Cardiovascular Implications of COVID-19 Infections. Methodist Debakey Cardiovasc J. 16(2):146-154. https://pubmed.ncbi.nlm.nih.gov/32670475/
• Boukris et al, 2020. Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective. Can J Cardiol. 36(7):1068-1080. https://pubmed.ncbi.nlm.nih.gov/32425328/
• Khan et al, 2020. Cardiovascular implications of COVID-19 versus influenza infection: a review. BMC Med. 18(1):403. https://pubmed.ncbi.nlm.nih.gov/33334360/

Further Reading

• All Coronavirus Disease COVID-19 Content
• Plasma Donation and COVID-19
• COVID-19 and Diabetes
• COVID-19 and Headache
• COVID-19 and Diarrhea

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.