ABC | Volume 114, Nº5, May 2020

Review Article Costa et al. The heart and COVID-19 Arq Bras Cardiol. 2020; 114(5):805-816 ACE2 receptor and the virus enters the host cell (Figure 2), where ACE2 inactivation occurs, favoring pulmonary damage. Because of the high ACE2 concentrations in the heart, potentially severe damage to the cardiovascular system can occur. 13,21 Patients with preexisting CVD apparently have increased serum levels of ACE2, which might contribute to the more severe manifestations in that population. 22-24 Similarly, individuals with hypertension would have a higher ACE2 expression secondary to the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB), which would potentially increase the susceptibility to SARS-CoV-2 infection. 4 However, current studies on humans have some limitations: a) assessment of a small number of individuals using those drugs, and b) the advanced age of a large part of the patients assessed, which is an important confounder, because advanced age increases the susceptibility to infection and is the major factor of poor prognosis. 25 It is worth noting that, despite substantial structural homology between ACE2 and ACE, their enzyme active sites are distinct, and, as a result, ACE inhibitors in clinical use do not directly affect ACE2 activity. In addition, that enzyme plays a well-known role in the recovery of ventricular function of patients with myocardial injury, because it inhibits angiotensin II activity. 26 On the other hand, angiotensin II has been suggested to account for the cardiac injury by the coronavirus, and the administration of recombinant ACE2 would normalize angiotensin II levels. Studies with recombinant ACE2 and losartan are being conducted. 25 The current recommendation is that ACEI and ARB should be continued in patients on regular use of those drugs, because of the clear benefit of blood pressure control and mortality decrease in those with HF, as evidenced in randomized studies. 27,28 In the severe forms of COVID-19, hemodynamic stability and renal function should be assessed individually before deciding on the continuation or withdrawal of the drugs. Cardiovascular disease as a risk for the severe form of COVID-19 Patients with cardiovascular risk factors (advanced age, hypertension and diabetes), as well as those with CVD (coronary artery disease, cardiomyopathies and cerebrovascular disease), have susceptibility to the severe form of COVID-19 and cardiovascular complications, being classified as a risk group. Approximately 80% of the patients with the severe form of COVID-19 have a comorbidity. 29 Table 1 summarizes the major studies that characterize the clinical comorbidities of patients with COVID-19. 9-12,17,29-32 A recent meta-analysis including eight studies from China, with 46,248 infected individuals, has shown that the most prevalent comorbidities were hypertension (17 ± 7%), diabetes mellitus (8 ± 6%) and CVD (5 ± 4%). Wang et al., assessing only hospitalized patients with COVID-19, have reported a higher prevalence of hypertension (31.2%), CVD (19.6%) and diabetes (10.1%), 9 emphasizing that individuals with those comorbidities have the most severe form of COVID-19, usually requiring hospitalization. These patients more often had hypoxemia and need for ICU admission. 9,30 Likewise, advanced age is related to the severe form of disease. In those studies, the median age has ranged from 42 to 64 years, 11,30 being higher in severely ill patients (64 vs 51.5). 29 In addition, patients admitted to ICU and those with hypoxemia were older. 9,30 Cardiovascular complications were also frequent among patients from the risk group. Those with CVD had troponin elevation and higher rates of shock and arrhythmias. 10-12 Guo et al., assessing a cohort with 187 patients, have observed that those with myocardial injury had a high prevalence of hypertension (63%vs 28%), diabetes (30.8% vs 8.9%), coronary artery disease (32.7% vs 3%) and HF (15.4% vs 0%), and were older (median age, 71.4 years). 10 In a cohort of 191 patients, Zhou et al. have assessed the characteristics of the deceased ones as compared to those of the discharged ones. In that cohort, the deceased patients had a higher prevalence of hypertension (48%), diabetes (31%) and CVD (24%). Advanced age was an independent predictor of mortality. 12 Mortality rate increases with increasing age as follows: 1.3% in patients aged 50-59 years; 3.6% in patients aged 60-69 years; 8% in patients aged 70- 79 years; and 14.8% in patients aged 80 years and older. 31 Population studies have reported an overall mortality rate of 6% in patients with hypertension, 7.3% in patients with diabetes and 10.5% in patients with CVD. 33 Patients with cancer have a higher risk for COVID-19 because of their impaired defense and their sequelae from the antineoplastic treatment. In China, among the confirmed cases of COVID-19, the prevalence of cancer has ranged from 1% to 7%, which is higher than the overall incidence of cancer in that country (0.2% - 201.7/100,000 individuals). 2,10,34 Patients with cancer more often developed the severe form of COVID-19 as compared to those without cancer (39% vs 8%). 35 Of the patients with cancer submitted to recent chemotherapy or surgery, 75% developed severe disease as compared to 43% of those with no recent treatment. 35 Algorithm of cardiovascular assessment Although not formally, cardiovascular assessment of patients with suspected or confirmed SARS-CoV-2 infection is recommended in the following situations: a) preexisting CVD or cardiovascular risk factors; b) cardiovascular signs and symptoms (dyspnea, shock, chest pain, electrocardiographic alterations or increased cardiac area); c) alterations on biomarkers, such as d-dimer, troponin, NT-proBNP and ferritin; and d) need for hospitalization. Those with CVD are prone to experience myocardial injury after SARS-CoV-2 infection, in addition to being at a higher risk of death. 10 Cardiologists should be part of the team caring for critical patients, aiding in clinical discussions and treatment. The initial cardiovascular assessment should comprise clinical history, physical examination, troponin levels, and electrocardiogram (ECG). Troponin levels above the 99th- percentile upper reference limit and acute alterations on ECG support the identification of patients at higher cardiovascular 808