ABC | Volume 114, Nº6, June 2020

Review Article Figueiredo Neto et al. Coronavirus and Myocardium Arq Bras Cardiol. 2020; 114(6):1051-1057 increasing the chance that this reflects a cytokine storm or secondary hemophagocytic lymphohistiocytosis, rather than isolated myocardial injury. Mechanisms of myocardial injury and COVID -19 Themechanisms of myocardial injury are not well established, but they probably involve an increase in cardiac stress due to respiratory failure and hypoxemia, acute coronary syndrome (ACS), indirect lesion from the systemic inflammatory response, direct myocardial infection by SARS-CoV-2, and other factors (Figure 2). 10 Myocardial injury secondary to imbalance between oxygen supply and demand Situations of severe physiological stress, such as sepsis and respiratory failure, which are present in patients with COVID-19, are associated with increased biomarkers of myocardial injury, leading to worse prognosis in some patients. 11 The most likely mechanism is an imbalance between oxygen supply and demand, without rupture of the atheromatous plaque, consistent with diagnosis of type 2 myocardial infarction. 12,13 These patients have higher rates of mortality when compared to those with type 1 myocardial infarction, likely as a result of a greater number of comorbities. 14 Due to age and the comorbidity profile of patients hospitalized with severe COVID-19, it may be inferred that this population has a higher risk of underlying non-obstructive CAD and that the occurrence of type 2 myocardial contributes to increased troponin and worse outcomes. 7 Microvascular injury The likely mechanism of myocardial injury results from the formation of microthrombi in the myocardial vasculature, in the presence of a state of hypercoagulability as in disseminated intravascular coagulation (DIC). Changes in the coagulation and fibrinolytic systems are important in patients with COVID-19, and DIC has been observed in the majority patients who died. 15 The mechanisms of DIC in the context of sepsis and acute respiratory distress syndrome present in these patients are complex; it is believed to be related to an exhaustion of the coagulation and fibrinolytic systems causing both bleeding and thrombosis. 16 The increase in inflammatory cytokines, such as IL-6 and tumor necrosing factor-alpha (TNF- α ), as well as endothelial injury, increase the expression of tissue factor, leading to a pro-thrombotic state. 17 On the other hand, dysregulation of antithrombin III, plasminogen activator inhibitor type 1 (PAI-1), and protein C in significant situations of inflammation and sepsis promotes a state of anticoagulation. 18 Furthermore, platelet activation also occurs in the context of sepsis and inflammation, changing the delicate balance of the coagulation system. 19 In this manner, the presence of inflammation and the immune activation present in severe COVID-19 infectionmay lead toDIC, microvascular dysfunction, and myocardial injury. Systemic inflammatory response One of the likely mechanisms related to cardiac injury in patients with severe COVID-19 involves the intense systemic Figure 2 – Potential mechanisms of myocardial injury in COVID-19. DIC: disseminated intravascular coagulation; MI: myocardial infarction. Source: Atri D, Siddidi HK, Lang J, et al. COVID-19 for the Cardiologist: ACurrent Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies. JACC Basic Transl Sci. 2020 Apr 10. doi: 10.1016/j.jacbts.2020.04.002. [Epub ahead of print] 1053