COVID-19 is a viral infection that has caused a global pandemic, infecting millions of people worldwide. As the pandemic progressed, the medical community discovered that COVID-19 is not just a respiratory illness, but it can also affect other organs in the body, including the heart. In this article, we will discuss Major adverse cardiac events (MACE) as a frequently diagnosed complication of COVID-19.
What are Major Adverse Cardiac Events (MACE)?
Major adverse cardiac events (MACE) are a group of serious cardiovascular complications that can occur as a result of a heart-related disease or condition. These events are usually classified into three main categories: myocardial infarction (MI), stroke, and cardiovascular death. MACE are considered major because they can cause significant morbidity and mortality, and often require urgent medical attention.
How does COVID-19 cause MACE? COVID-19 is caused by the SARS-CoV-2 virus, which primarily affects the respiratory system. However, the virus can also cause inflammation and damage to other organs, including the heart. COVID-19 can cause MACE through several mechanisms:
- Direct viral infection of heart cells: Studies have shown that SARS-CoV-2 can directly infect heart cells, causing myocarditis (inflammation of the heart muscle). Myocarditis can weaken the heart muscle, leading to heart failure, arrhythmias, and MACE.
- Indirect damage to the heart: COVID-19 can cause a severe inflammatory response in the body, known as a cytokine storm. This can cause damage to the heart and blood vessels, leading to plaque rupture, thrombosis, and MI.
- Exacerbation of underlying heart conditions: Patients with pre-existing heart conditions, such as hypertension, coronary artery disease, and heart failure, are at higher risk of developing MACE from COVID-19. COVID-19 can exacerbate these conditions, leading to MACE.
Epidemiology of MACE in COVID-19: Several studies have reported the incidence of MACE in COVID-19 patients. A study conducted in New York City reported that 19% of hospitalized COVID-19 patients had cardiac injury, defined as elevated cardiac biomarkers (troponin or BNP) or new electrocardiogram (ECG) abnormalities. Another study conducted in Wuhan, China, reported that 12% of COVID-19 patients had cardiac injury, and these patients had a higher risk of mortality compared to those without cardiac injury.
A meta-analysis of 21 studies including 12,459 COVID-19 patients reported that the overall incidence of MACE was 9.5%. The incidence of MI was 3.3%, stroke was 2.3%, and cardiovascular death was 5.5%. The incidence of MACE was higher in patients with severe COVID-19 compared to those with mild or moderate disease.
Clinical Manifestations of MACE in COVID-19: MACE can present with a wide range of clinical manifestations in COVID-19 patients. These include:
- Chest pain or discomfort: This is the most common symptom of MI and is caused by the blockage of blood flow to the heart muscle.
- Shortness of breath: This is a common symptom of heart failure and can be caused by fluid buildup in the lungs.
- Palpitations: This is a common symptom of arrhythmias, which can be caused by inflammation or direct viral infection of the heart.
- Confusion or slurred speech: These are common symptoms of stroke, which can be caused by blood clots or hemorrhage in the brain.
- Sudden cardiac arrest: This is a rare but potentially fatal complication of COVID-19, which can be caused by arrhythmias or heart failure.
Diagnosis and Management of MACE in COVID-19: Diagnosis of MACE in COVID-19 patients requires a high index of suspicion, especially in those with pre-existing cardiovascular risk factors or symptoms suggestive of cardiac disease. The following diagnostic tests can be helpful in the diagnosis of MACE:
- Cardiac biomarkers: Troponin and BNP are markers of cardiac injury and can be elevated in patients with MACE.
- Electrocardiogram (ECG): ECG can detect abnormalities suggestive of MI or arrhythmias.
- Echocardiogram: Echocardiogram can detect structural abnormalities of the heart, such as myocarditis or heart failure.
The management of MACE in COVID-19 patients is similar to that of non-COVID-19 patients. Treatment options include medications, such as antiplatelet agents, beta-blockers, and ACE inhibitors, and invasive procedures, such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for MI, and thrombolysis or thrombectomy for stroke. In patients with severe COVID-19, treatment should be individualized based on the patient’s overall clinical status and the risk-benefit ratio of invasive procedures.
Prevention of MACE in COVID-19: Prevention of MACE in COVID-19 patients involves a comprehensive approach to reduce the risk of cardiovascular complications. The following measures can be helpful in preventing MACE:
- Prevention of COVID-19 infection: This can be achieved by following public health measures, such as wearing masks, practicing social distancing, and getting vaccinated.
- Control of pre-existing cardiovascular risk factors: This includes managing hypertension, diabetes, and hyperlipidemia.
- Early recognition and management of cardiac symptoms: COVID-19 patients with pre-existing cardiovascular disease or symptoms suggestive of cardiac disease should receive prompt evaluation and management.
Recent studies have suggested that necroptosis, a form of programmed cell death, may play a role in the pathogenesis of cardiovascular complications in COVID-19. In this article, we will review the current literature on the association between necroptosis and MACE in severe COVID-19.
Necroptosis and its Role in COVID-19: Necroptosis is a regulated form of cell death that is characterized by the rupture of the plasma membrane and the release of cellular contents, leading to inflammation and tissue damage. It is mediated by the activation of receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), and mixed lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in various pathological conditions, including viral infections.
Several studies have reported that SARS-CoV-2 can induce necroptosis in different cell types, including cardiomyocytes and endothelial cells. The viral proteins, such as the envelope protein and the ORF3a protein, have been shown to activate RIPK1 and RIPK3, leading to necroptosis. Necroptosis can also be triggered by the dysregulated immune response to the virus, including the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which can activate RIPK1 and RIPK3.
MACE and Necroptosis in COVID-19: Emerging evidence suggests that necroptosis may play a role in the development of MACE in severe COVID-19 cases. Several studies have reported increased levels of RIPK1, RIPK3, and MLKL in the hearts and blood of COVID-19 patients who experienced MACE. These findings suggest that necroptosis may contribute to myocardial injury and vascular damage, leading to the development of MACE.
Myocardial Infarction: Myocardial infarction, or heart attack, is a common MACE in severe COVID-19 patients. Necroptosis has been implicated in myocardial injury during COVID-19. Studies have shown that RIPK1, RIPK3, and MLKL are upregulated in the hearts of COVID-19 patients who suffered myocardial infarction. Activation of necroptosis can lead to cardiomyocyte death and subsequent inflammation, contributing to myocardial injury and impaired cardiac function.
Heart Failure: Heart failure, characterized by the inability of the heart to pump enough blood to meet the body’s needs, has also been reported in severe COVID-19 cases. Necroptosis has been implicated in the pathogenesis of heart failure during COVID-19. Studies have shown that necroptosis markers, such as RIPK1 and MLKL, are elevated in the hearts of COVID-19 patients with heart failure. Necroptosis-induced cardiomyocyte death and subsequent inflammation may contribute to the development and progression of heart failure in severe COVID-19 cases.
Stroke: Stroke, a cerebrovascular event caused by the disruption of blood flow to the brain, has been reported in severe COVID-19 patients. Necroptosis has also been implicated in the pathogenesis of stroke during COVID-19. Studies have shown that RIPK1 and RIPK3 are upregulated in the brain tissue of COVID-19 patients who suffered stroke. Necroptosis-induced neuronal death and subsequent inflammation may contribute to the development and progression of stroke in severe COVID-19 cases.
Potential Therapeutic Targets: The association between necroptosis and MACE in severe COVID-19 cases highlights the potential for targeting necroptosis as a therapeutic strategy. Several compounds have been shown to inhibit necroptosis, including necrostatin-1, a specific inhibitor of RIPK1, and GSK’872, a specific inhibitor of RIPK3. Studies have shown that the administration of necrostatin-1 can reduce myocardial injury and improve cardiac function in animal models of myocardial infarction. Additionally, the administration of GSK’872 has been shown to reduce brain injury and improve neurological function in animal models of stroke.
Conclusion: In conclusion, MACE are frequently diagnosed complications of severe COVID-19 cases, and necroptosis has been implicated in their pathogenesis. The activation of necroptosis in cardiomyocytes and endothelial cells can contribute to myocardial injury and vascular damage, leading to the development of MACE such as myocardial infarction, heart failure, and stroke. Targeting necroptosis may represent a potential therapeutic strategy for reducing the incidence and severity of MACE in severe COVID-19 cases. Further research is needed to better understand the mechanisms of necroptosis in COVID-19 and to develop effective therapeutic interventions.
reference link :https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04423-8