Practical Approach to Acute Coronary Syndrome in Patients with COVID-19

Rafael Bellotti Azevedo Bruna Gopp Botelho João Victor Gonçalves de Hollanda Leonardo Villa Leão Ferreira Letícia Zarur Junqueira de Andrade Stephanie Si Min Lilienwald Oei Tomás de Souza Mello Elizabeth Silaid Muxfeldt About the authors

Abstract

Acute cardiac injury is associated with higher mortality in patients with the novel coronavirus disease-2019 (COVID-19) and the exact etiology can be challenging to diagnose in the emergency setting during the pandemic. From a pathophysiological perspective, SARS-CoV-2 infection is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha) that leads to systemic inflammation and consequent increased risk of acute myocardial infarction (AMI) caused by atheromatous plaque rupture and significant myocardial oxygen supply-demand imbalance. Moreover, SARS-CoV-2 tropism to the renin-angiotensin-aldosterone system through the ACE2 receptor induces myocarditis that may rapidly progress to left ventricular dysfunction and hemodynamic instability. Myocardial inflammation with pericardial involvement, i.e. , myopericarditis, can progress to cardiac tamponade and obstructive shock. These cardiovascular complications, which are associated with a worse prognosis and higher mortality, can be associated with clinical manifestations, electrocardiographic changes, and troponin values similar to AMI. Thus, the diagnosis and treatment of patients with acute chest pain and dyspnea admitted to the emergency department is a significant challenge during the COVID-19 pandemic. Here, we provide a review of the literature focusing on a practical approach to acute coronary syndrome patients with confirmed or suspected COVID-19.

Acute Coronary Syndrome; Betacoronavirus; COVID-19; Infection; Pandemics; Troponin; Electrocardiography/methods

Introduction

In December 2019, a new positive-strand RNA virus,11. Astuti I, Ysrafil , Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2): An overview of viral structure and host response. Diabetes Metab Syndr. 2020; 14(4): 407-12. belonging to the family Coronaviridae , began to circulate in Wuhan, China. The new virus shares characteristics with the SARS-CoV and MERS-CoV, both responsible for epidemics in past decades. It was named SARS-CoV-2, which is the cause of the current pandemic announced by the World Health Organization (WHO) in March 2020. In Brazil, at the end of June 2020, the number of confirmed cases had already surpassed 1,5 million, with 65,000 deaths from the disease.22. Ministério da Saúde - Coronavírus Brasil. Disponível em: <https://covid.saude.gov.br/>. Acesso em: 30 junho. 2020.
https://covid.saude.gov.br/>...
The fatality rate in the country reaches 6.9%, similar to other countries with similar diagnostic approaches.33. Johns Hopkins University of Medicine. Coronavirus Resource Center. <https://coronavirus.jhu.edu/map.html>. Acesso em: 30 junho 2020.
https://coronavirus.jhu.edu/map.html>...
Unlike the other six phylogenetically similar viruses, the etiological agent of coronavirus disease-2019 (COVID-19) is highly infectious, with a basic reproduction number (R0) between 2 and 3.5.44. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N Engl J Med. 2020; 382(13):1199-207.

5. Riou J, Althaus CL. Pattern of early human‐to‐human transmission of Wuhan 2019 novel coronavirus (2019‐nCoV), December 2019 to January 2020. Euro Surveill. 2020; 25(4):2000058.
- 66. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019‐nCoV outbreak originating in Wuhan, China: a modelling study. Lancet. 2020; 395:689‐97. Moreover, some studies have identified high viremias in patients who do not present any symptoms, emphasizing the relevance and the direct impact of this finding on the global spread of the disease.77. Tong Z-D, Tang A, Li K-F, Li P, Wang H-L, Yi J-P et al. Potential presymptomatic transmission of SARS‐CoV‐2, Zhejiang Province, China, 2020. Emerg Infect Dis. 2020; 26(5): 1052-4.

8. Bai SL, Wang JY, Zhou YQ, Yu DS, Gao XM, Li LL et al. Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province. ZhonghuaYu Fang Yi Xue Za Zhi. 2020; 54(5):491-3.
- 99. Rocklöv J, Sjödin H, Wilder-Smith A. COVID‐19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures. J Travel Med. 2020; 27(3):taaa030.

Acute coronary syndrome is a clinical condition with high prevalence, morbidity, and mortality. Acute chest pain is a usual complaint in the emergency units, with well-defined protocols and differential diagnosis from other (fatal or not) diseases, aiming to establish a rapid and effective treatment. In the current global health crisis, scientific evidence has revealed significant cardiovascular involvement in COVID-19, which makes the management of acute chest pain even more complex and challenging in the emergency setting, urging the need for reviewing these protocols. Cardiac involvement in SARS-CoV-2 patients seems to affect mainly those with typical cardiovascular risk factors and to incorporate several pathophysiological mechanisms, such as a direct cardiac injury by the viral cytopathic effect, myocardial injury due to a pro-inflammatory state and systemic inflammation, and decompensation of pre-existing cardiovascular disease.1010. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System A Review. JAMA Cardiol. 2020 Mar 27; doi: 10.1001/jamacardio.2020.1286. [Epub ahead of print].
https://doi.org/10.1001/jamacardio.2020....

11. Zheng Y-Y, Ma Y-T, Z J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5):259-60.

12. Xiong T-Y, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020; 41(19):1798-800.
- 1313. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020; e200950.

A meta-analysis with 341 patients associated myocardial injury with severe COVID-19 infection since patients with high troponin serum levels required intensive care more often.1414. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): evidence from a meta-analysis. Prog Cardiovasc Dis. 2020 Mar 10. doi: 10.1016/j.pcad.2020.03.001. [Epub ahead of print].
https://doi.org/10.1016/j.pcad.2020.03.0...
Myocardial injury is also a predictor of higher mortality in patients with COVID-19. Furthermore, cardiovascular complications such as acute myocardial infarction (AMI) are frequent in these patients and may cause irreversible myocardial damage1515. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. or even rapidly progress to cardiogenic shock and death.1616. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11):1061-9. , 1717. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-62.

Therefore, it is imperative to understand the main mechanisms involved in the development of myocardial ischemia in SARS-CoV-2 infection, and its diagnosis, to implement appropriate clinical interventions aiming to prevent unfavorable outcomes and possibly permanent sequelae.

Methodology

This study is an extensive scoping review. The bibliographical survey was performed in the PubMed platform using the descriptors “COVID-19”, “2019-nCoV”, “Myocardial Infarction”, “Acute Coronary Syndrome” and “Echocardiography” in the advanced search function. Articles diverging or not related to the main theme, and articles not written in English were excluded from the review. After exclusions, 59 articles were selected and thoroughly reviewed to compose the present study and were cited either directly or via cross-reference.

Discussion

Cardiovascular Risk Factors

Hypertension and diabetes mellitus has been described as the most prevalent comorbidities among individuals with COVID-19, particularly in the more severe forms of the disease requiring hospitalization. On average, 30% and 10% of severe COVID-19 patients are hypertensive and diabetics, respectively,1616. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11):1061-9. and these conditions are also related to higher mortality in these patients, varying amongst different populations.1818. Yanai H. A significance of high prevalence of Diabetes and Hypertension in Severe COVID-19 patients. J Clin Med Res 2020; 12(6):389-92. A meta-analysis including 12 studies demonstrated that the prevalence of diabetes and hypertension in patients with severe COVID-19 was significantly higher compared to those with non-severe forms of the disease (OR: 3.52; 95% CI: 2.65-4.67 and OR: 2.69; 95% CI: 2.16-3.34, respectively). Three studies showed that uncontrolled glucose levels are related to higher severity. However, regarding blood pressure control, the results were controversial.1818. Yanai H. A significance of high prevalence of Diabetes and Hypertension in Severe COVID-19 patients. J Clin Med Res 2020; 12(6):389-92.

In a case study performed in New York City, United States with 5,700 patients (mean age of 63 years; 39.7% female), the most frequent comorbidities were hypertension (56.6%), obesity (41.7%), and diabetes mellitus (33.8%).1919. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020; 323(20):2052-9. In a meta-analysis with 419 patients (61.8% male, mean age of 55.6 years), the most prevalent comorbidity was hypertension (24.3%), followed by diabetes mellitus (15.2%) and heart disease (6.2%).2020. Zuin M, Rigatelli G, Zuliani G, Rigatelli A, Mazza A, Roncon L. Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis. J Infect. 2020; 81(1):e84-e86. In general, patients with COVID-19 and hypertension had a higher mortality risk compared to those without hypertension.2121. Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients with COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension 2020; 76(1):51-8.

It is worth highlighting that patients with hypertension and diabetes, from a pathophysiological perspective, have higher inflammation levels. Therefore, these patients are at higher risk for complications due to immune hyperactivity and severe inflammatory response caused by the SARS-CoV-2 infection, heightening pre-existing endothelial dysfunction and inflammation, leading to more adverse outcomes. It is still unclear if the risk of infection among these patients is greater than in the general population. However, hypertension and diabetes are comorbidities associated with the highest morbidity and mortality among patients with COVID-19.1818. Yanai H. A significance of high prevalence of Diabetes and Hypertension in Severe COVID-19 patients. J Clin Med Res 2020; 12(6):389-92. Additionally, chronic cardiovascular disease may become unstable as a consequence of the imbalance between the disease-induced increase of metabolic demand and decrease in cardiac reserve.2222. Moccia F, Gerbino A, Lionetti V, Miragoli M, Munaron LM, Pagliaro P et al. COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches. Geroscience. 2020; 1-29.

Yang et al.,2121. Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients with COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension 2020; 76(1):51-8. in a retrospective study assessing the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) on clinical parameters and inflammatory profile of 126 patients with pre-existing hypertension and COVID-19, reported that hypertensive patients had higher mortality rates (10.3% vs. 6.4%) and higher incidence of critical illness (18.3% vs. 11.2%) when compared to normotensive patients, but without statistical significance. Moreover, hypertensive patients with COVID-19 showed higher plasma concentrations of ultra-sensitive C-reactive protein (25.4 [4.6-100.8] vs. 12.6 [2.6-53.3]; p=0.024), procalcitonin (0.092 [0.049-0.223] vs. 0.062 [0.035-0.134]; p=0.017), and IL-6 (13.8 [4.8-51.3] vs. 8.2 [1.8-22.8]; p=0.017) in comparison to non-hypertensive patients of the control group. It is possible that patients with COVID-19 and pre-existing hypertension experience a greater increase in inflammatory markers when compared to non-hypertensive patients, developing, therefore, a more exacerbated immune hyperactivity and more pronounced systemic inflammation.2121. Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients with COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension 2020; 76(1):51-8.

In addition to a pro-inflammatory state at baseline, which per se is a risk factor for a severe form of COVID-19, it must be noted that older age is associated with a higher prevalence of hypertension and diabetes than the general population.2222. Moccia F, Gerbino A, Lionetti V, Miragoli M, Munaron LM, Pagliaro P et al. COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches. Geroscience. 2020; 1-29. , 2323. Boukhris M, Hillani A, Moroni F, Annabi MS, Addad F, Ribeiro MH et al. Cardiovascular implications of the COVID-19 pandemic: a global perspective. Can J Cardiol. 2020; S0828-282X(20)30464-5. Previous studies revealed that older patients with underlying diseases have a higher likelihood of progressing to a more severe form of the disease. Also, exacerbated immune and inflammatory responses associated with a cytokine storm may have a significant role in the progression of COVID-19 in hypertensive patients since increased IL-6 levels and a higher degree of inflammation were identified in this population.2323. Boukhris M, Hillani A, Moroni F, Annabi MS, Addad F, Ribeiro MH et al. Cardiovascular implications of the COVID-19 pandemic: a global perspective. Can J Cardiol. 2020; S0828-282X(20)30464-5.

24. Wang L, Zhang Y, Zhang S. Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy. Front Cardiovasc Med. 2020; 7:78.
- 2525. Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Intern J Infect Dis.2020; 95:332-9.

It is still unclear if individuals with diabetes mellitus are more susceptible to COVID-19, but studies have reported a higher risk of unfavorable progression in this group of patients. Huang et al.,2626. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403. in a meta-analysis including 30 retrospective and cohort studies with 6,452 patients, evidenced that diabetes mellitus was associated with unfavorable clinical outcomes (RR 2.38 [1.88,3.03], p<0.001; I2: 62%), with a subgroup composed of higher mortality (RR 2.12 [1.44, 3.11], p<0.001; I2: 72%), higher risk of severe COVID-19 (RR 2.45 [1.79, 3.35], p<0.001; I2: 45%), and higher incidence of ARDS (RR 4.64 [1.86, 11.58], p=0.001; I2: 9%] in patients with COVID-19. However, diabetes mellitus was not associated with a greater need for hospitalization in intensive care units (RR 1.47 [0.38, 5.67], p=0.57; I2: 63%, p=0.07).2626. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403.

From a pathophysiological perspective, the relationship between diabetes and higher virulence of SARS-CoV-2 has not been well elucidated in the medical literature. However, authors have postulated that pathophysiological mechanisms, such as: a higher expression of ACE2 favoring viral endocytosis; an increased expression of furin, a type-1 membrane-bound protease belonging to the proprotein convertase subtilisin/kexin class (PCSK), optimizing viral entry and replication; and basal hypercytokinaemia at the expense of IL-6, enhancing the systemic inflammatory state observed in the severe forms of the disease, are all factors potentially responsible for increased risk, virulence, and severity of SARS-CoV-2 infection among patients with diabetes.2727. Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr 2020;14(4):303-10. Moreover, diabetic individuals have a higher risk of respiratory infection due to an impaired immune system response.2727. Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr 2020;14(4):303-10. Thus, it is postulated that ACE2 may have an important role in aggravating COVID-19 infection among patients with diabetes.2626. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403.

Furthermore, it is known that the damage caused by COVID-19 to the cardiovascular system is probably multifactorial, caused by metabolic imbalance, systemic inflammation (cytokine storm), coagulation disorders characterized by a pro-thrombotic state, and direct myocardial injury due to a viral cytopathic effect.2323. Boukhris M, Hillani A, Moroni F, Annabi MS, Addad F, Ribeiro MH et al. Cardiovascular implications of the COVID-19 pandemic: a global perspective. Can J Cardiol. 2020; S0828-282X(20)30464-5.

24. Wang L, Zhang Y, Zhang S. Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy. Front Cardiovasc Med. 2020; 7:78.
- 2525. Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Intern J Infect Dis.2020; 95:332-9. Several studies have shown that patients with cardiovascular risk factors (advanced age, hypertension, and diabetes) and pre-existing cardiovascular disease (coronary arterial disease, cardiomyopathies, and cerebrovascular disease) have a higher risk of progressing to more severe forms of COVID-19, and are consequently more susceptible to cardiac complications.1010. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System A Review. JAMA Cardiol. 2020 Mar 27; doi: 10.1001/jamacardio.2020.1286. [Epub ahead of print].
https://doi.org/10.1001/jamacardio.2020....
, 1818. Yanai H. A significance of high prevalence of Diabetes and Hypertension in Severe COVID-19 patients. J Clin Med Res 2020; 12(6):389-92. , 2828. Costa IBS, Bittar CS, Rizk SI, Filho AEA, Santos KAQ, Machado TIV and al. The Heart and COVID-19: What Cardiologists Need to Know. Arq Bras Cardiol. 2020; doi: 10.36660/abc.20200279. [Epub ahead of print]
https://doi.org/10.36660/abc.20200279...
Hence, the association between SARS-CoV-2, coronary artery disease, and acute coronary syndromes is most likely related to the ability of these several mechanisms to destabilize previous coronary artery plaques and cause complications.2929. Hendren NS, Drazner MH, Bozkurt B, Cooper LT. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020; 141(23):1903-14. , 3030. Pinto DS. Coronavirus disease 2019 (COVID-19): Coronary artery disease issues. UpToDate. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-myocardial-infarction-and-other-coronary-artery-disease-issues.
https://www.uptodate.com/contents/corona...
Therefore, patients with heart disease present greater susceptibility to viral infection and cardiac complications related to COVID-19.

Pathophysiology

The fourth definition of AMI published by the American Heart Association (AHA), American College of Cardiology (ACC), and European Society of Cardiology (ESC) is characterized by acute myocardial injury associated with clinical, electrocardiographic, and laboratory findings suggestive of ischemia, being classified in five types according to the underlying pathophysiological mechanism.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64.

Individuals with previous cardiovascular disease and cardiovascular risk factors are at higher risk for type 1 AMI and atherothrombosis when infected by the coronavirus.3232. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5. Patients with severe COVID-19 develop cytokine storm with consequent systemic inflammation, which increases the predisposition to thrombosis due to a hypercoagulability state, causing atherosclerotic plaque instability and rupture, coronary thrombosis, and subsequent ischemia and necrosis of the myocardial segment irrigated by the occluded coronary artery.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. , 3333. Long B, Brady W, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7):1504-7. Previous epidemiological studies about influenza have already demonstrated an association between the viral infection and an increased risk for acute coronary syndrome during the first seven days of the disease.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. , 3333. Long B, Brady W, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7):1504-7.

Type 2 AMI, characterized by an oxygen supply-demand imbalance, has also been described in patients with SARS-CoV-2 infection with or without previous cardiovascular diseases.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. , 3232. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5. The pathogenic hypothesis for the correlation between COVID-19 and type 2 AMI derives from the increase of metabolic demand generated by viral infection and the decrease of oxygen supply due to hypoxemia in patients with severe respiratory failure in more advanced stages of the disease.3434. Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr 2020; 14(3):247-50. Furthermore, a Chinese study suggests that some proteins in the viral structure of SARS-CoV-2 may bind to the hemoglobin beta chain, reducing the oxygen supply to tissues.3535. Liu W, Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv 2020. www.https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
www.https://chemrxiv.org/articles/COVID-...

Despite its scarce description in the medical literature, the existence of another type of AMI, the type 4b, should be mentioned. This type is restricted to patients with previous coronary disease who already underwent primary angioplasty, which in the context of SARS-CoV-2 infection, might progress to stent thrombosis and myocardial ischemia.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. The pathophysiological correlation between AMI type 4b and COVID-19, as previously mentioned, seems to be associated with a hypercoagulability state due to endothelial dysfunction caused by inflammatory hyperactivity and hypercytokinaemia observed in SARS-CoV-2 infection. Also, it is worth reinforcing the chronic pro-inflammatory state of these patients due to coronary artery disease, which exacerbates the expression of cytokines and contributes to the formation of new thrombus.3636. Lacour T, Semaan C, Genet T, Ivanes F. Insights for increased risk of failed fibrinolytic therapy and stent thrombosis associated with COVID ‐19 in ST ‐segment elevation myocardial infarction patients. Catheter. Cardiovasc Interv 2020; doi:10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...

The Role of Troponin and Electrocardiography

Several studies have demonstrated that myocardial injury, diagnosed by the increase in troponin levels, is associated with higher mortality in patients with COVID-19.1313. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020; e200950. , 3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...
In a meta-analysis that included 13 studies, patients with acute myocardial injury required more hospitalization in intensive care units (RR 7.945, p<0.01) and presented higher mortality (RR 7.95, p<0.001).3838. Santoso A, Pranata R, Wibowo A, Al-Farabi MJ, Huang I, Antariksa B. Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis. Am J Emerg Med 2020; S0735-6757(20)30280-1. In a retrospective study which analyzed 187 patients hospitalized with COVID-19, serum troponin levels presented a significant positive linear correlation with C-reactive protein and NT-proBNP levels, evidencing an important association between myocardial injury and ventricular stress with systemic inflammation, which is mainly present in the more severe stages of the disease.3939. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27;e201017. Therefore, these findings suggest that troponin is an important prognostic marker in patients infected with SARS-CoV-2.1313. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020; e200950. , 3838. Santoso A, Pranata R, Wibowo A, Al-Farabi MJ, Huang I, Antariksa B. Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis. Am J Emerg Med 2020; S0735-6757(20)30280-1. , 3939. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27;e201017.

Infection by SARS-CoV-2 increases the risk of AMI particularly because it induces instability and rupture of pre-existing atherosclerotic plaque and causes significant oxygen supply-demand imbalance in the myocardium.3232. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5. Moreover, there are case reports describing the development of acute myocarditis, due to a likely viral tropism or association with the hypercytokinaemia and systemic inflammation triggered by viral infection, with clinical and laboratory presentations suggestive of AMI, becoming, therefore, an important differential diagnosis in patients with COVID-19.4040. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 27 Mar; doi:10.1001/jamacardio.2020.1096. [Epub ahead of print]
https://doi.org/10.1001/jamacardio.2020....

Due to the significant clinical similarity between myocarditis and acute coronary syndrome, it is vital to determine the pre-test probability through the elucidation of risk factors, physical examination, and complementary exams such as serum troponin dosage and electrocardiography (ECG). Due to their practicality, these exams are feasible to perform in an adverse hospital environment, where the risk of disease transmission is high and complex logistics for invasive exams would otherwise be required.3232. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5. , 4141. Siddamreddy S, Thotakura R, Dandu V, Kanuru S, Meegada S. Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction. Cureus, 2020; 12(4):e7782.

The ECG may be a useful tool to elucidate cardiovascular complications related to COVID-19. Electrocardiographic changes such as convex ST-segment elevation or depression and ischemic T-wave, respecting the anatomic topography of the culprit coronary artery, especially when associated with mirrored reciprocal images in anatomically opposed electrocardiographic leads, corroborate the diagnosis of AMI. However, it does not completely exclude the possibility of a myopericarditis,4141. Siddamreddy S, Thotakura R, Dandu V, Kanuru S, Meegada S. Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction. Cureus, 2020; 12(4):e7782. which usually presents with diffuse ST-segment changes not anatomically correlated with a certain coronary bed, absence of mirrored reciprocal images, and concave morphology.4242. Irabien-Ortiz A, Carreras-Mora J, Sionis A, Pàmies J, Montiel J, Tauron M. Fulminant myocarditis due to COVID-19. Rev Esp Cardiol (Engl Ed) 2020; 73(6):503-4. , 4343. Hua A, O’Gallager K, Sado D, Byrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J. 2020; 41(22):2130. Furthermore, there are reports of myocarditis associated with pericardial inflammation with unspecific ECG repolarization abnormalities, presence of alternating QRS amplitude and low voltage, accentuating the importance to investigate concomitant pericardial effusion in these patients.4040. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 27 Mar; doi:10.1001/jamacardio.2020.1096. [Epub ahead of print]
https://doi.org/10.1001/jamacardio.2020....

The fourth global definition of AMI postulates that the diagnosis of atherothrombotic type 1 AMI is established based on the increase or decrease of troponin serum levels, with at least one measurement above the 99th percentile of the upper reference limit in a healthy population, in association with a compatible clinical state.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. Nevertheless, it is worth noting that patients with acute myocarditis may also present increased troponin levels besides similar clinical manifestations during hospital admission. Thus, although increased troponin values reflect myocardial injury, it does not indicate the etiology and the underlying pathophysiological mechanism.3131. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64. On the other hand, troponin curve and delta may help to diagnose patients with precordial pain and suspected COVID-19, since myocardial injury associated with ischemia usually reaches its peak in 12-24 hours, while non-ischemic etiologies such as myocarditis present a late peak and a longer plateau.1414. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): evidence from a meta-analysis. Prog Cardiovasc Dis. 2020 Mar 10. doi: 10.1016/j.pcad.2020.03.001. [Epub ahead of print].
https://doi.org/10.1016/j.pcad.2020.03.0...
, 3232. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5.

A retrospective study including 6,557 patients assessed ultrasensitive troponin variability in emergency rooms and reported that an absolute delta of 16 ng/L presented a specificity and sensitivity of 94.2% and 83.2% for AMI, respectively, being a significant AMI predictor in patients with basal troponin between 14 and 50 ng/L.4444. Douville P, Thériault S. Variability of High-Sensitivity Troponin T Concentrations in Emergency Settings: Impact for the Diagnosis of Myocardial Infarction Am J Clin Pathol. 2018; 150(1):51-7. This result reinforces that, although the analysis of troponin curve and absolute delta may be useful for the differential diagnosis between AMI and myocarditis in patients with acute precordial pain and suspected COVID-19 in the emergency setting, it does not have the capacity for diagnostic exclusion.

The European Society of Cardiology4545. The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESCCOVID-19-Guidance. (Last update: 10 June 2020).
https://www.escardio.org/Education/COVID...
guidance advocates that mild elevations in troponin serum levels in patients with suspected COVID-19, 2-3 times higher than the upper limit, particularly in older patients with pre-existing cardiovascular disease, do not require a more profound investigation for type I AMI unless the patient has suggestive clinical manifestations or electrocardiographic changes. However, a significant increase ( i.e . five times the upper limit) indicates a more severe myocardial injury in patients with COVID-19, potentially reflecting cardiac complications such as Takotsubo syndrome, myocarditis, or COVID-19-induced type I AMI. It is noteworthy that due to its prognostic value in patients with COVID-19, major centers have recommended the measurement of serum troponin levels in every patient, with suspected or confirmed COVID-19, with cardiovascular risk factors, established cardiovascular disease, or symptoms indicating a more severe form of the disease.2828. Costa IBS, Bittar CS, Rizk SI, Filho AEA, Santos KAQ, Machado TIV and al. The Heart and COVID-19: What Cardiologists Need to Know. Arq Bras Cardiol. 2020; doi: 10.36660/abc.20200279. [Epub ahead of print]
https://doi.org/10.36660/abc.20200279...

Nonetheless, in emergency rooms, diagnostic uncertainty may persist even after performing ECG and measurement of serum troponin levels in patients with precordial pain and suspected SARS-CoV-2 infection. In these cases, point-of-care echocardiography may be a useful tool to clarify the diagnosis. Moreover, in the absence of symptoms or electrocardiographic findings suggestive of type I AMI with a significant increase in troponin, an echocardiographic evaluation may be also beneficial to define the underlying cause of cardiac injury.

Role of Echocardiography

Echocardiographic assessment may also help in the differential diagnosis between myocarditis and acute coronary syndrome in COVID-19. Transthoracic echocardiography is more likely to detect contractility changes in the ventricular segment perfused by the culprit coronary artery of patients with acute coronary syndrome. On the other hand, the usual finding in myocarditis is diffuse hypokinesia with a reduction in the ejection fraction, maybe associated with a discrete pericardial effusion, although segmental dyskinesia and even a hyperdynamic state may also occur. However, acute myocarditis may also occur with preserved ventricular function without any segmental ventricular contractility changes evidenced by echocardiography. Thus, abnormal electrocardiographic and echocardiographic findings, combined with the patient’s clinical manifestations may guide the differential diagnosis and outcome of COVID-19 patients.3333. Long B, Brady W, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7):1504-7.

The main echocardiographic findings described in the more severe forms of COVID-19 are: (1) hyperdynamic state, represented by an increase in cardiac output and left ventricular ejection fraction with reduced peripheral vascular resistance; (2) stress-induced acute cardiomyopathy, characterized by abnormalities in segmental contraction and left ventricular apical ballooning (Takotsubo cardiomyopathy); (3) right ventricular hypertrophy and acute pulmonary hypertension; and (4) global systolic and/or diastolic dysfunction, caused by severe hypoxia, long-term anoxia and/or systemic inflammation. It is worth noting that circulatory failure in these patients is usually associated with a state of significant ventricular dysfunction and reduced peripheral vascular resistance secondary to concomitant lactic acidosis.4646. Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
https://doi.org/10.1186/s13054-020-02856...

Another significant aspect of the echocardiographic evaluation of these patients is the assessment of pulmonary vascular resistance and the presence of right ventricular dysfunction due to hypoxia, vasospasm of the pulmonary arteries, hypercapnia, and inflammation.4646. Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
https://doi.org/10.1186/s13054-020-02856...
This finding may point to the presence of pulmonary thromboembolism (PTE), which is often described in patients with more severe SARS-CoV-2 infection. The presence of echocardiographic findings such as interventricular septum protrusion towards the left ventricle, right ventricular systolic and/or diastolic dysfunction, changes in pulmonary artery flow, and acute tricuspid valve regurgitation indicate the presence of pulmonary hypertension and right ventricular dysfunction in patients with COVID-19.4646. Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
https://doi.org/10.1186/s13054-020-02856...
The association between pneumonia caused by COVID-19 and pulmonary embolism is a challenge for frontline intensive care physicians since the symptoms overlap. Bedside echocardiography may be a useful tool to early detect PTE.4747. Sulemane S, Baltabaeva A, Barron AJ, Chester R, Rahman-Haley S. Acute pulmonary embolism in conjunction with intramural right ventricular thrombus in a SARS-CoV-2-positive patient. Eur Heart J Cardiovasc Imaging. 2020; jeaa115. https://doi.org/10.1093/ehjci/jeaa115.
https://doi.org/10.1093/ehjci/jeaa115...

In a study evaluating 120 patients with COVID-19, right ventricular global longitudinal strain (RVGLS) was shown to be a significant predictor of mortality in these patients. Lower RVGLS values were associated with higher serum levels of D-dimer and C-reactive protein, in addition to a higher incidence of ARDS and greater need for mechanical ventilation.4848. Li Y, Li H, Zhu S, Xie Y, Wang B, He L et al. Prognostic Value of Right Ventricular Longitudinal Strain in Patients with COVID-19. JACC Cardiovasc Imaging 2020; DOI: 10.1016/j.jcmg.2020.04.014.
https://doi.org/10.1016/j.jcmg.2020.04.0...
It is worth noting that the severe forms of COVID-19 associated with cytokine storm result in systemic inflammation and hypercoagulability. Thus, acute right ventricular dysfunction in patients with COVID-19 may be secondary to an abrupt right ventricular pressure overload caused by increased pulmonary vascular resistance in PTE and/or pulmonary artery vasospasm resulting from severe hypercapnia and/or hypoxemia in patients with severe respiratory failure.4646. Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
https://doi.org/10.1186/s13054-020-02856...
Clinically, a suddenly increased dyspnea associated with pleuritic chest pain requires PTE investigation in patients with COVID-19.4646. Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
https://doi.org/10.1186/s13054-020-02856...
, 4848. Li Y, Li H, Zhu S, Xie Y, Wang B, He L et al. Prognostic Value of Right Ventricular Longitudinal Strain in Patients with COVID-19. JACC Cardiovasc Imaging 2020; DOI: 10.1016/j.jcmg.2020.04.014.
https://doi.org/10.1016/j.jcmg.2020.04.0...

It is noteworthy that coronary computed tomography angiography and cardiac magnetic resonance imaging (CMR) may be useful to clarify the diagnosis. Regarding magnetic resonance imaging, the presence of interstitial myocardial edema without anatomical correlation, early myocardial gadolinium enhancement (EGE), and multifocal late myocardial enhancement with subepicardial or mesocardial distribution suggest myocarditis. On the other hand, myocardial ischemia presents a subendocardial or transmural distribution, respecting the anatomical topography of the obstructed coronary artery.4949. Pozo E, Sanz J. Differentiating infarction from myocarditis. Heart Metab. 2014; 62:13-7. Furthermore, coronary computed tomography angiography can assess the presence or absence of coronary obstruction in a non-invasive manner, having, however, limitations due to the need for heart rate control and coronary vasodilation during the exam. Thus, since neither CMR nor coronary computed tomography angiography is not very feasible due to the high transmission rate of COVID-19, increased risk of health-care personnel contamination during patient transportation, and prolonged-time of these exams, these tests should be considered in stable patients, as additional diagnostic methods when the diagnosis cannot be established by echocardiography.3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...

Transthoracic echocardiography should ideally be performed in an emergency setting, by point-of-care or dynamic method, as an early assessment method of patients with COVID-19. The method provides hemodynamic evidence to guide clinical management. In critically ill patients, it is recommended a daily echocardiographic evaluation for a strict assessment of the ventricular function and hemodynamic parameters, and guidance of treatment with inotropic and/or circulatory support.2828. Costa IBS, Bittar CS, Rizk SI, Filho AEA, Santos KAQ, Machado TIV and al. The Heart and COVID-19: What Cardiologists Need to Know. Arq Bras Cardiol. 2020; doi: 10.36660/abc.20200279. [Epub ahead of print]
https://doi.org/10.36660/abc.20200279...

Clinical Approach

During the current pandemic, patients presenting to the emergency department with chest pain, dyspnea, and hyperdynamic state, are highly suspected cases of COVID-19. However, due to its high prevalence, acute coronary syndrome must also be considered as a differential diagnosis.5050. Yousefzai R, Bhimaraj A. Misdiagnosis in the COVID era: When Zebras are Everywhere, Don’t Forget the Horses. JACC Case Rep 2020 Apr 27. doi: 10.1016/j.jaccas.2020.04.018. [Epub ahead of print]
https://doi.org/10.1016/j.jaccas.2020.04...
Moreover, in the most severe forms of COVID-19, there are cardiovascular complications such as myocarditis, acute myocardial infarction, and right ventricular overload due to severe pulmonary involvement.3333. Long B, Brady W, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7):1504-7. , 4141. Siddamreddy S, Thotakura R, Dandu V, Kanuru S, Meegada S. Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction. Cureus, 2020; 12(4):e7782. , 5151. Loghin C, Chauhan S, Lawless S. Pseudo acute myocardial infarction in a young COVID-19 patient. JACC Case Rep 2020 Apr 27. doi:10.1016/j.jaccas.2020.04.015. [Epub ahead of print]
https://doi.org/10.1016/j.jaccas.2020.04...

Thus, clinical reasoning is based on clinical assessment, appropriate propaedeutic, risk stratification, and complementary diagnostic exams (ECG, cardiac enzymes, and bedside echocardiography) ( Figure 1 ), taking into consideration that a diagnostic error in this context has a strong iatrogenic effect regarding the patient – due to the risks of an unnecessary procedure – and the healthcare team – due to the exposure to a potential infection without the appropriate protection and caution.3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...

Figure 1
– Flowchart of the clinical approach to patients with chest pain during the coronavirus disease-2019 (COVID-19) pandemic COVID-19: coronavirus disease-2019; STEMI: acute ST-elevation myocardial infarction; NSTEMI: acute non-ST-elevation myocardial infarction; PCI: percutaneous coronary intervention.

Several scientific societies and institutions have positioned themselves on the relocation of the scarce medical supplies in face of the increased demand for hospital care and adjustments in the management of acute coronary syndrome during the COVID-19 pandemic.3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...
, 5252. Welt FGP, Shah PB, Aronow HD, Bortnick AE, Henry TD, Sherwood MW. et al. Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From ACC’s Interventional Council and SCAI. J Am Coll Cardiol 2020; 75(18):2372-5.

An initial guidance – Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From ACC’s Interventional Council and SCAI5252. Welt FGP, Shah PB, Aronow HD, Bortnick AE, Henry TD, Sherwood MW. et al. Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From ACC’s Interventional Council and SCAI. J Am Coll Cardiol 2020; 75(18):2372-5. – proposed the first hospital protocols for the management of AMI in the COVID-19 pandemic. The paper suggests a preference for fibrinolysis over primary percutaneous intervention (PCI) aiming to avoid contamination of healthcare professionals. However, this strategy has generated undesirable results.5353. Stefanini GG, Montorfano M, Trabattoni D, Andreini D, Ferrante G, Ancona M et al. ST-Elevation Myocardial Infarction in Patients with COVID-19: Clinical and Angiographic Outcomes. Circulation. 2020; 141(25:2113-6.

A second guidance – Management of Acute Myocardial Infarction During the COVID-19 Pandemic – published by the Society for Cardiovascular Angiography and Interventions (SCAI), American College of Cardiology (ACC), and American College of Emergency Physicians (ACEP) has been used as a foundation for most of the new current protocols. The document proposes that patients should be classified into five distinct groups: definitive diagnosis of acute ST-elevation myocardial infarction (STEMI), possible diagnosis of STEMI, acute non-ST-elevation myocardial infarction (NSTEMI) and unstable angina, patients out of the therapeutic window, and patients in cardiogenic shock/out-of-hospital cardiac arrest.3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...
Regardless of the category to which the patient is assigned, a COVID-19 rapid test must be performed if available, to define the patient’s infectious state.3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...
Furthermore, the adoption of individual protection procedures while providing care to any patient with suggestive symptoms of COVID-19 is imperative, including hemodynamic and other invasive procedures. The guidance on the diagnosis and management of acute coronary syndrome proposed for the COVID-19 pandemic is summarized on Table 1 .

Table 1
– Clinical approach to patients with acute coronary syndrome during the coronavirus disease-2019 (COVID-19) pandemic

It is worth mentioning that this guidance3737. Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
https://doi.org/10.1002/ccd.28948...
and several other similar institutional protocols,5454. Di Uccio FS, Valente S, Colivicchi F, Murrone A, Caldarola P, Di Lenarda A et al. Position paper ANMCO: Organizzazione della Rete per il trattamento dei pazienti con sindrome coronarica acuta durante emergenza pandemica COVID-19. G Ital Cardiol 2020;21(5):332-5. published based on a smaller set of evidence, contrast with those that recommend performing fibrinolysis as a preferable therapeutic strategy to STEMI with primary angioplasty reserved only for patients with contraindications to this pharmacological procedure,5555. Jing Z-C, Zhu H-D, Yan X-W, Chai W-Z, Zhang S. Recommendations from the Peking Union Medical College Hospital for the management of acute myocardial infarction during the COVID-19 outbreak. Eur Heart J. 2020; 41(19):1791-4. , 5656. Zeng J, Huang J, Pan L. How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People’s Hospital. Intensive Care Med. 2020; 46(6):1111-3. patients without a confirmed SARS-CoV-2 infection,5757. Abdelaziz H, Patel B, Chalil S, Choudhury T. (2020). COVID-19 Pandemic and Acute Myocardial Infarction. Crit Pathw Cardiol. 2020; 19(2):55-7. and AMI patients with hemodynamic and/or electrical instability.5858. Sadeghipour P, Talasaz AH, Eslami V, Geraiely B, Vojdanparast M, Sedaghat M et al. Management of ST‐segment‐elevation myocardial infarction during the coronavirus disease 2019 (COVID ‐19) outbreak: Iranian“247” National Committee's position paper on primary percutaneous coronary intervention. Catheter Cardiovasc Interv. 2020; 10.1002/ccd.28889.
https://doi.org/10.1002/ccd.28889...

Nevertheless, the request for cardiac catheterization (38% in the United States) during the SARS-CoV-2 pandemic has decreased. This fact may be explained by: 1) reluctance of patients with symptomatic AMI to seek health care due to fear of contracting COVID-19, resulting in a longer therapeutic window; 2) higher frequency of diagnostic errors due to the burden of healthcare logistics; 3) increased use of fibrinolytic therapy as the main therapeutic intervention, due to its presumed safety regarding the risk of SARS-CoV-2 transmission.5959. Garcia S, Albaghdadi MS, Meraj PM, Schmidt C, Garberich R, Jaffer FA et al. Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States during COVID-19 Pandemic. J Am Coll Cardiol. 2020; 75(22):2871-2.

Conclusion

Acute myocardial injury is significantly associated with in-hospital mortality, and a marker of worse prognosis in patients infected with SARS-CoV-2. Risk stratification and assessment of the pre-test probability are essential to improve the diagnostic accuracy of cardiovascular complications of COVID-19, with as accurate as possible differentiation of myocarditis from acute coronary syndrome, careful indication of invasive diagnostic tests, and consequent implementation of appropriate therapies.

References

  • 1
    Astuti I, Ysrafil , Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2): An overview of viral structure and host response. Diabetes Metab Syndr. 2020; 14(4): 407-12.
  • 2
    Ministério da Saúde - Coronavírus Brasil. Disponível em: <https://covid.saude.gov.br/> Acesso em: 30 junho. 2020.
    » https://covid.saude.gov.br/>
  • 3
    Johns Hopkins University of Medicine. Coronavirus Resource Center. <https://coronavirus.jhu.edu/map.html> Acesso em: 30 junho 2020.
    » https://coronavirus.jhu.edu/map.html>
  • 4
    Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N Engl J Med. 2020; 382(13):1199-207.
  • 5
    Riou J, Althaus CL. Pattern of early human‐to‐human transmission of Wuhan 2019 novel coronavirus (2019‐nCoV), December 2019 to January 2020. Euro Surveill. 2020; 25(4):2000058.
  • 6
    Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019‐nCoV outbreak originating in Wuhan, China: a modelling study. Lancet. 2020; 395:689‐97.
  • 7
    Tong Z-D, Tang A, Li K-F, Li P, Wang H-L, Yi J-P et al. Potential presymptomatic transmission of SARS‐CoV‐2, Zhejiang Province, China, 2020. Emerg Infect Dis. 2020; 26(5): 1052-4.
  • 8
    Bai SL, Wang JY, Zhou YQ, Yu DS, Gao XM, Li LL et al. Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province. ZhonghuaYu Fang Yi Xue Za Zhi. 2020; 54(5):491-3.
  • 9
    Rocklöv J, Sjödin H, Wilder-Smith A. COVID‐19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures. J Travel Med. 2020; 27(3):taaa030.
  • 10
    Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System A Review. JAMA Cardiol. 2020 Mar 27; doi: 10.1001/jamacardio.2020.1286. [Epub ahead of print].
    » https://doi.org/10.1001/jamacardio.2020.1286
  • 11
    Zheng Y-Y, Ma Y-T, Z J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5):259-60.
  • 12
    Xiong T-Y, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020; 41(19):1798-800.
  • 13
    Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020; e200950.
  • 14
    Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): evidence from a meta-analysis. Prog Cardiovasc Dis. 2020 Mar 10. doi: 10.1016/j.pcad.2020.03.001. [Epub ahead of print].
    » https://doi.org/10.1016/j.pcad.2020.03.001
  • 15
    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506.
  • 16
    Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11):1061-9.
  • 17
    Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-62.
  • 18
    Yanai H. A significance of high prevalence of Diabetes and Hypertension in Severe COVID-19 patients. J Clin Med Res 2020; 12(6):389-92.
  • 19
    Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020; 323(20):2052-9.
  • 20
    Zuin M, Rigatelli G, Zuliani G, Rigatelli A, Mazza A, Roncon L. Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis. J Infect. 2020; 81(1):e84-e86.
  • 21
    Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients with COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension 2020; 76(1):51-8.
  • 22
    Moccia F, Gerbino A, Lionetti V, Miragoli M, Munaron LM, Pagliaro P et al. COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches. Geroscience. 2020; 1-29.
  • 23
    Boukhris M, Hillani A, Moroni F, Annabi MS, Addad F, Ribeiro MH et al. Cardiovascular implications of the COVID-19 pandemic: a global perspective. Can J Cardiol. 2020; S0828-282X(20)30464-5.
  • 24
    Wang L, Zhang Y, Zhang S. Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy. Front Cardiovasc Med. 2020; 7:78.
  • 25
    Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Intern J Infect Dis.2020; 95:332-9.
  • 26
    Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403.
  • 27
    Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr 2020;14(4):303-10.
  • 28
    Costa IBS, Bittar CS, Rizk SI, Filho AEA, Santos KAQ, Machado TIV and al. The Heart and COVID-19: What Cardiologists Need to Know. Arq Bras Cardiol. 2020; doi: 10.36660/abc.20200279. [Epub ahead of print]
    » https://doi.org/10.36660/abc.20200279
  • 29
    Hendren NS, Drazner MH, Bozkurt B, Cooper LT. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020; 141(23):1903-14.
  • 30
    Pinto DS. Coronavirus disease 2019 (COVID-19): Coronary artery disease issues. UpToDate. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-myocardial-infarction-and-other-coronary-artery-disease-issues
    » https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-myocardial-infarction-and-other-coronary-artery-disease-issues
  • 31
    Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al. What’s new in the Fourth Universal Definition of Myocardial infarction? J Am Coll Cardiol. 2018;72(18):2231-64.
  • 32
    Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail 2020; 26(6):470-5.
  • 33
    Long B, Brady W, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38(7):1504-7.
  • 34
    Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr 2020; 14(3):247-50.
  • 35
    Liu W, Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv 2020. www.https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
    » www.https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
  • 36
    Lacour T, Semaan C, Genet T, Ivanes F. Insights for increased risk of failed fibrinolytic therapy and stent thrombosis associated with COVID ‐19 in ST ‐segment elevation myocardial infarction patients. Catheter. Cardiovasc Interv 2020; doi:10.1002/ccd.28948.
    » https://doi.org/10.1002/ccd.28948
  • 37
    Mahmud E, Dauerman HL, Frederick GP et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic. J Am Coll Cardiol 2020; 10.1002/ccd.28948.
    » https://doi.org/10.1002/ccd.28948
  • 38
    Santoso A, Pranata R, Wibowo A, Al-Farabi MJ, Huang I, Antariksa B. Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis. Am J Emerg Med 2020; S0735-6757(20)30280-1.
  • 39
    Guo T, Fan Y, Chen M, Wu X, Zhang L, He T et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27;e201017.
  • 40
    Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 27 Mar; doi:10.1001/jamacardio.2020.1096. [Epub ahead of print]
    » https://doi.org/10.1001/jamacardio.2020.1096
  • 41
    Siddamreddy S, Thotakura R, Dandu V, Kanuru S, Meegada S. Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction. Cureus, 2020; 12(4):e7782.
  • 42
    Irabien-Ortiz A, Carreras-Mora J, Sionis A, Pàmies J, Montiel J, Tauron M. Fulminant myocarditis due to COVID-19. Rev Esp Cardiol (Engl Ed) 2020; 73(6):503-4.
  • 43
    Hua A, O’Gallager K, Sado D, Byrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J. 2020; 41(22):2130.
  • 44
    Douville P, Thériault S. Variability of High-Sensitivity Troponin T Concentrations in Emergency Settings: Impact for the Diagnosis of Myocardial Infarction Am J Clin Pathol. 2018; 150(1):51-7.
  • 45
    The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESCCOVID-19-Guidance (Last update: 10 June 2020).
    » https://www.escardio.org/Education/COVID-19-and-Cardiology/ESCCOVID-19-Guidance
  • 46
    Peng Q-Y, Wang X-T, Zhang L-N. Using echocardiography to guide the treatment of novel coronavirus pneumonia. Crit Care 24, 143 (2020). https://doi.org/10.1186/s13054-020-02856-z
    » https://doi.org/10.1186/s13054-020-02856-z
  • 47
    Sulemane S, Baltabaeva A, Barron AJ, Chester R, Rahman-Haley S. Acute pulmonary embolism in conjunction with intramural right ventricular thrombus in a SARS-CoV-2-positive patient. Eur Heart J Cardiovasc Imaging. 2020; jeaa115. https://doi.org/10.1093/ehjci/jeaa115
    » https://doi.org/10.1093/ehjci/jeaa115
  • 48
    Li Y, Li H, Zhu S, Xie Y, Wang B, He L et al. Prognostic Value of Right Ventricular Longitudinal Strain in Patients with COVID-19. JACC Cardiovasc Imaging 2020; DOI: 10.1016/j.jcmg.2020.04.014.
    » https://doi.org/10.1016/j.jcmg.2020.04.014
  • 49
    Pozo E, Sanz J. Differentiating infarction from myocarditis. Heart Metab. 2014; 62:13-7.
  • 50
    Yousefzai R, Bhimaraj A. Misdiagnosis in the COVID era: When Zebras are Everywhere, Don’t Forget the Horses. JACC Case Rep 2020 Apr 27. doi: 10.1016/j.jaccas.2020.04.018. [Epub ahead of print]
    » https://doi.org/10.1016/j.jaccas.2020.04.018
  • 51
    Loghin C, Chauhan S, Lawless S. Pseudo acute myocardial infarction in a young COVID-19 patient. JACC Case Rep 2020 Apr 27. doi:10.1016/j.jaccas.2020.04.015. [Epub ahead of print]
    » https://doi.org/10.1016/j.jaccas.2020.04.015
  • 52
    Welt FGP, Shah PB, Aronow HD, Bortnick AE, Henry TD, Sherwood MW. et al. Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From ACC’s Interventional Council and SCAI. J Am Coll Cardiol 2020; 75(18):2372-5.
  • 53
    Stefanini GG, Montorfano M, Trabattoni D, Andreini D, Ferrante G, Ancona M et al. ST-Elevation Myocardial Infarction in Patients with COVID-19: Clinical and Angiographic Outcomes. Circulation. 2020; 141(25:2113-6.
  • 54
    Di Uccio FS, Valente S, Colivicchi F, Murrone A, Caldarola P, Di Lenarda A et al. Position paper ANMCO: Organizzazione della Rete per il trattamento dei pazienti con sindrome coronarica acuta durante emergenza pandemica COVID-19. G Ital Cardiol 2020;21(5):332-5.
  • 55
    Jing Z-C, Zhu H-D, Yan X-W, Chai W-Z, Zhang S. Recommendations from the Peking Union Medical College Hospital for the management of acute myocardial infarction during the COVID-19 outbreak. Eur Heart J. 2020; 41(19):1791-4.
  • 56
    Zeng J, Huang J, Pan L. How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People’s Hospital. Intensive Care Med. 2020; 46(6):1111-3.
  • 57
    Abdelaziz H, Patel B, Chalil S, Choudhury T. (2020). COVID-19 Pandemic and Acute Myocardial Infarction. Crit Pathw Cardiol. 2020; 19(2):55-7.
  • 58
    Sadeghipour P, Talasaz AH, Eslami V, Geraiely B, Vojdanparast M, Sedaghat M et al. Management of ST‐segment‐elevation myocardial infarction during the coronavirus disease 2019 (COVID ‐19) outbreak: Iranian“247” National Committee's position paper on primary percutaneous coronary intervention. Catheter Cardiovasc Interv. 2020; 10.1002/ccd.28889.
    » https://doi.org/10.1002/ccd.28889
  • 59
    Garcia S, Albaghdadi MS, Meraj PM, Schmidt C, Garberich R, Jaffer FA et al. Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States during COVID-19 Pandemic. J Am Coll Cardiol. 2020; 75(22):2871-2.

  • Study Association
    This study is not associated with any thesis or dissertation work.

  • Sources of Funding .There were no external funding sources for this study.

Publication Dates

  • Publication in this collection
    08 Jan 2021
  • Date of issue
    Jan-Feb 2021

History

  • Received
    31 May 2020
  • Reviewed
    06 July 2020
  • Accepted
    15 Aug 2020
Sociedade Brasileira de Cardiologia Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil
E-mail: sbc@cardiol.br