COVID-19 and Heart Disease

The 2019-2020 coronavirus (COVID-19) has infected hundreds of thousands of people worldwide. Although anyone can be infected and anyone can be seriously ill, there is a specific risk factor that predicts a poor prognosis. This main risk factor is that of heart disease, which ranges from the common condition of hypertension to myocardial injury. The drugs used to treat heart disease may also play a role in the mechanics of COVID-19. This article will look into the relationship between heart disease and COVID-19 as well as touch on the impact of the medications used in the treatment of heart disease.

The first issue with heart disease is not its adverse outcome risk, but that it has been shown to predispose patients to the COVID-19 infection. In a meta-analysis done by Driggin et al. (2020), it was shown that, of 1527 patients diagnosed with COVID-19, 17.1% had existing hypertension and 16.4% had some form of cardiac disease. It is also suggested that angiotensin-converting enzyme-2 (ACE-2) inhibitors (ACE-i) and angiotensin receptor blockers (ARB), used in the treatment of heart disease, may up-regulate ACE-2. This thereby increases the susceptibility to the virus as the pathogen uses the ACE-2 receptors to enter the human cell and use its replication machinery (Driggen et al., 2020). Therefore patients with heart disease are at an increased risk of contracting the infection.

COVID-19 is predominantly a disease of the lungs, however the immediate cause of death for some patients may actually be the heart. According to Warraich (2020), cardiac injury was reported in 59% of patients who died in a hospital in Wuhan vs. only 1 % in survivors. Another study, done by Roser, Ritchie and Ortiz-Ospina (2020), showed that 10.5% of patients diagnosed with both COVID-19 and heart disease died. This is thought to be due to the massive inflammatory response that occurs in COVID-19 throughout the body, including the heart (Warraich, 2020). Fast, abnormal heart rates were responsible for 44% of Wuhan patients being transferred to the intensive care units (Warraich, 2020). Cardiomyopathy was documented in 23% of COVID-29 cases in a study done by Diggin et al. (2020). These changes in the heart, that occur in the presence of COVID-19 infection, seem to have a worse effect in those already predisposed to heart issues. This is evident biochemically in that the levels of troponins (a marker for myocardial inflammation and damage) were increased substantially in patients with coronavirus and a comorbid heart condition (Warraich, 2020).

There are many important mechanisms that lead to the overlap seen between COVID-19 and heart disease. These mechanisms are mainly related to the pathways that regulate the immune system. The first important factor is that of age. As patients age, there is an increased prevalence of heart disease and decreased immune activity, which increases their susceptibility to infections and increases the likelihood of adverse outcomes (Driggin et al., 2020). This decreased immunity was proven in a study with the influenza virus, where inadequately low protective titres were shown after the administration of the influenza vaccine (Driggin et al., 2020). Another factor playing into the overlap between cardiac disease and the immune system is that of hyperlipidaemia and diabetes. Patients with heart disease are more likely to have these two comorbidities and these are known to cause a dysregulation of the immune system (Driggin et al., 2020). It is therefore clear that cardiovascular disease may be a marker of accelerated immunological aging and dysregulation and thus directly relate to COVID-19 prognosis.

Another major risk factor for patients with circulatory disease and COVID-19 is that that come with hyperlipidaemia and atherosclerosis. Patients with atherosclerotic plaques are at risk of an acute myocardial infarction, stroke, or pulmonary embolism as the profound inflammatory response and haemodynamic changes seen in COVID-19 can cause a plaque rupture (Driggin et al., 2020) and subsequent thrombosis. The virus itself can also disrupt the plaque leading to those same fatal outcomes (StopAfib.org, 2020).

A more common type of heart disease, hypertension, has also been specifically shown to worsen outcomes in patients with COVID-19. Roser, Ritchie and Ortiz-Ospina (2020) showed in their study that 6% of patients diagnosed with COVID-19 and hypertension died. It was also not only the worse outcome that was a problem in patients with hypertension, but also that hypertensive patients had an increased susceptibility to the infection due to an increase in the expression of ACE-2 receptors in the lungs (Driggin et al., 2020).

A unique and major concern for patients who contract COVID-19 with an underlying cardiac disease is myocardial injury. This can occur due to myocardial ischaemia or myocarditis and is indicated by increased troponin levels in the blood (Driggin et al., 2020). The ischaemia is directly related to lung function, as the severe respiratory state seen in patients with COVID-19 worsens the already vulnerable heart muscle and therefore causes hypoxic injury to the muscle (Driggin et al., 2020). Amongst 68 deaths in a case series of 150 patients, 7% died due to myocarditis and circulatory failure and 33% had myocarditis and circulatory failure contribute to their death (Driggin et al., 2020). On autopsy of these patients, there were clear inflammatory mononuclear infiltrates in the myocardial tissue (Driggin et al., 2020).

Another concern for patients with COVID-19 is that of arrhythmias, a common manifestation in patients with the infection. Diggin et al. (2020) showed in a study that in 138 hospital patients in Wuhan, 16.7% had arrhythmias and 44% of the patients in the intensive care unit had arrhythmias. This is attributed to the metabolic disarray, hypoxia, and inflammatory stress in the setting of a viral infection (Diggin et al., 2020). An important factor that all healthcare professionals need to remember is that COVID-19 with an arrhythmia and raised troponins must raise concern for a myocarditis (Diggin et al., 2020).

Myocarditis in COVID-19 patients is an indicator for poor prognostic. In a rabbit study done by Edwards et al. (2020), it was shown that coronavirus can induce a myocarditis, especially in patients with underlying cardiac diseases. In the acute phase of the study (days 2 – 5), the histological investigations showed degradation and necrosis of myocytes, myocytolysis, interstitial oedema, and haemorrhage (Edwards et al., 2020). It was also shown that the virus was isolated in the myocardial tissue at this early stage (Edwards et al., 2020). Severity of these changes increased in the subacute phase (days 6 – 12) and dilation of the left ventricle occurred along with pleural effusions and congestion of the liver and lungs (Edwards et al., 2020). The myocarditis itself was detected on day 9 and peaked on day 12, after which heart weights and heart weight to body weight ratio increased and congestive heart failure resulted with the death of all the test rabbits (Edwards et al., 2020). The coronavirus also causes respiratory distress and the oedema and effusions seen in the lungs in heart failure patients only compounds the problem (StopAfib.org, 2020), leading to profound hypoxia and cardiogenic shock (Diggin et al., 2020).

The final issue in COVID-19 patients and heart disease is that of medications. As previously stated, ACE-I and ARBs may increase susceptibility to the virus (Diggin et al., 2020). It is not only the drugs for heart disease that causes negative outcomes for COVID-19 patients but the drugs to treat COVID-19 may cause negative outcomes in heart disease patients. Lopinavir-Ritonavir are under investigation as possible treatment options for COVID-19 and have been used to treat HIV infection for years (Diggin et al., 2020). These drugs, however, have been shown to cause QT and PR prolongation, especially in patients with baseline abnormalities or those taking other prolongation drugs (Diggin et al., 2020). HMG-CoA reductase inhibitors (statins) used in hyperlipidaemia and circulatory disease also have the potential to interact with the combination of lopinavir/ritonavir and can result in myopathy due to elevated statin levels when administered together (Diggin et al., 2020). Lovastatin and simvastatin, in particular, are contraindicated for co-administration with lopinavir/ritonavir due to risk of rhabdomyolysis (Diggin et al., 2020), which can lead to kidney damage. Another drug being explored for the treatment of COVID-19 is chloroquine and hydroxychloroquine. These are antimalarial drugs that have shown in vitro antiviral activity (Diggin et al., 2020) but have also shown to have the potential for immediate to delayed myocardial toxicity (Diggin et al., 2020). Chloroquine cardiac toxicity presents as restrictive or dilated cardiomyopathy or conduction abnormalities thought to be due to intracellular inhibition of lysosomal enzymes in the myocytes (Diggin et al., 2020). The potential treatment for COVID-19 may therefore put heart disease patients at an increased risk for adverse outcomes and even death.

Heart disease and COVID-19 co-infection is therefore a predictor of poor outcomes when the infection is contracted. It is vital that heart disease patients are quarantined and remain as socially isolated as possible to avoid exposure to the virus.

References

Driggin, E., Madhavan, M., Bikdeli, B., Chuich, T., Laracy, J., Bondi-Zoccai, G., Brown, T., Nigoghossian, C., Zidar, D., Haythe, J., Brodie, D., Beckman, J., Kirtane, A., Stone, G., Krumholz, H. and Parikh, S., 2020. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic. Journal of the American College of Cardiology, 3(31).

Edwards, S., Small, J., Geratz, J., Alexander, L. and Baric, R., 1992. An Experimental Model for Myocarditis and Congestive Heart Failure after Rabbit Coronavirus Infection. Journal of Infectious Diseases, [online] 165(1), pp.134-140. Available at: <https://www.ncbi.nlm.nih.gov/pubmed/1309370> [Accessed 23 March 2020].

Roser, M., Ritchie, H. and Ortiz-Ospina, E., 2020. Coronavirus Disease (COVID-19) – Statistics And Research. [online] Our World in Data. Available at: <https://ourworldindata.org/coronavirus> [Accessed 23 March 2020].

StopAfib.org. 2020. Coronavirus Resources For Those With Afib. [online] Available at: <https://www.stopafib.org/newsitem.cfm/NEWSID/671/atrial%20fibrillation/afib> [Accessed 23 March 2020].

Warraich, H., 2020. Coronavirus Is Especially Threatening For People With Heart Disease | ACL Administration For Community Living. [online] Acl.gov. Available at: <https://acl.gov/news-and-events/news/coronavirus-especially-threatening-people-heart-disease> [Accessed 23 March 2020].