ABC | Volume 114, Nº5, May 2020

Review Article Costa et al. The heart and COVID-19 Arq Bras Cardiol. 2020; 114(5):805-816 algorithm of cardiovascular assessment for the early detection of complications, in addition to recommending protocols to treat cardiovascular complications in those patients. Complications of COVID-19 on the cardiovascular system Recent data of the COVID-19 pandemic have shown that the virus can affect the cardiovascular system with several manifestations, such as myocardial injury, HF, Takotsubo syndrome (TS), arrhythmias, myocarditis and shock. 4,11-14 The damage due to COVID-19 to the cardiovascular system is probably multifactorial and can result from an imbalance between high metabolic demand and low cardiac reserve, systemic inflammation and thrombogenesis, in addition to direct cardiac damage from the virus. 13 This damage to the cardiovascular system occurs mainly in patients with cardiovascular risk factors (advanced age, hypertension and diabetes) or preexisting CVD. 10,11 Figure 1 summarizes the inflammatory response to the viral infection, which leads to damage to the cardiovascular system and lungs, with elevation in the levels of d-dimer, procalcitonin, C-reactive protein, ferritin, troponin and NT-proBNP, culminating in cardiovascular complications and death. The systemic inflammatory response to SARS-CoV-2 is accompanied by higher concentrations of cytokines related to injury to the cardiovascular system. 15 The increase in troponin levels is accompanied by an elevation in other inflammatory markers, such as d-dimer, ferritin, interleukin 6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein, procalcitonin and leukocyte count. 1,11 Zhou et al. have shown higher levels of d-dimer, IL-6, ferritin and LDH, as well as lymphopenia, in patients who died, suggesting that those inflammatory markers might have prognostic implications. A d-dimer level at admission greater than 1µg/mL was an independent predictor of mortality in that population. 12 In addition to elevated inflammatory markers, patients with COVID-19 show increased BNP or NT- proBNP levels, markers of myocardial dysfunction. Patients with myocardial injury showed higher NT-proBNP levels, with positive linear correlation. 10,11 This finding reinforces that those with myocardial injury are prone to cardiac function impairment. 10 A meta-analysis with four studies, including 341 COVID-19 patients, has reported significantly higher troponin I levels in patients with severe disease as compared to those with non- severe disease. 16 Patients with myocardial injury more often required admission to the intensive care unit (ICU) (22.2% vs. 2.0%), had a higher incidence of HF (52% vs 12%) and a higher death rate (59% vs. 1%). 1,9 Shi et al., assessing 416 hospitalized patients with COVID-19, have reported that myocardial injury, defined as troponin levels above the 99th- percentile upper reference limit, is a frequent complication (19.7%) in those patients, being associated with increased mortality and ARDS. 11 On multivariate analysis, myocardial injury and ARDS were independent predictors of mortality (HR Figure 1 - Coronavirus and the heart. Patients with risk factors and/or cardiovascular disease are prone to develop severe forms of COVID-19 and its complications. Pulmonary impairment manifests initially as an influenza syndrome (cough and fever), progressing to pneumonia (dyspnea, hypoxemia, tachypnea) and, in some cases, to ARDS. Host response to the virus leads to systemic inflammation findings, with elevation of markers of inflammation (CRP, procalcitonin, d-dimer, IL-6, ferritin, LDH) and of myocardial injury / cardiac dysfunction (troponin/NT-proBNP), which predisposes to acute heart failure, myocarditis, thrombosis and arrhythmias. Cardiovascular complications hinder the host response to the virus, leading to shock, failure of multiple organs and death. CAD: coronary artery disease; LDH: lactate dehydrogenase; LVEF: left ventricular ejection fraction; CRP: C-reactive protein; IL-6: interleukin-6; ARDS: acute respiratory distress syndrome. 806