ABC | Volume 115, Nº2, August 2020

Brief Communication Martins-Filho et al. Cardiac biomarkers in patients with COVID-19 Arq Bras Cardiol. 2020; 115(2):273-277 the population. In addition, none of the studies performed analysis for adjustment of confounding factors. Results of meta-analysis showed differences in age between groups. Non-survivors of COVID-19 were older compared to survivors (MD = 14.3 years, 95% CI 9.2 to 19.4). Male sex (RR = 1.3, 95% CI 1.2 to 1.4), the presence of existing hypertension (RR = 1.7, 95% CI 1.2 to 2.4), and cardiovascular disease (RR = 3.3, 95% CI 1.4 to 7.8) were also associated with increased risk of mortality. The meta-analysis of myocardial injury biomarkers showed a large increase in hs-cTnI (SMD = 1.0, 95% CI 0.8 to 1.2), NT-proBNP (SMD = 1.1, 95% CI 0.7 to 1.4), and CK-MB (SMD = 1.0, 95% CI 0.2 to 1.8) in non-survivor patients. Elevated hs-cTnI values above the 99 th percentile URL were associated with 8-fold increase in the risk of in-hospital death (RR = 8.0, 95% CI 2.2 to 28.5). No evidence of substantial publication bias was observed for hs-cTnI. Cardiac complications, including acute cardiac injury (RR= 8.9, 95%CI 4.2 to 19.3), heart failure (RR = 5.1, 95% CI 2.5 to 10.7), and arrhythmias (RR= 4.9, 95% CI 1.2 to 10.9) were found to be risk factors for COVID-19 related death. Comparisons of clinical data, myocardial injury biomarkers, and cardiac complications between non-survivors and survivors of COVID-19 are displayed in Table 2. Forest plots and funnel plots are shown in the supplemental digital content (e-Figures 1 – 3). Discussion Surveillance of cardiovascular events associated with COVID-19 seems very warranted. 12 This study confirms and better quantifies the association between myocardial injury biomarkers and/or acute cardiac complications with in-hospital death in patients with COVID-19. However, it remains unclear whether acute cardiac involvement is primarily provoked by SARS-CoV-2 or whether it is a multifactorial non-specific cardiac involvement of a severe systemic infection. 13 It has been proposed that SARS-CoV-2 may lead to cardiac injury via multiple mechanisms including direct viral invasion of cardiomyocytes and subsequent myocarditis, since viral particles have been identified in myocardial cells. 14 However, changes in cTnI over time and the absence of typical signs on echocardiography and ECG in patients with COVID-19 have suggested that myocardial injury in patients with COVID-19 is more likely related to systemic consequences of disease. 15 Other plausible mechanisms that have been suggested to explain troponin elevation in this scenario include type 1 and, mainly, type 2 myocardial infarction due to acute respiratory distress syndrome, sepsis, cytokine storm, and even Takotsubo syndrome. 16 Therefore, SARS-CoV-2 infection may either induce new cardiac injuries and/or act as a precipitating factor to worsen underlying cardiovascular diseases and lead to death. In this meta-analysis, we analyzed well-established biomarkers for myocardial injury diagnosis and outcome prediction. Elevation of hs-cTnI, NT-proBNP, and CK-MB were associated with increased risk of death in patients with SARS-CoV-2 infection. Management of patients with myocardial injury biomarkers and acute cardiovascular decompensation is primarily based on supportive care and individualized approach to better guide treatment. Unfortunately, we do not have evidence to Table 2 - Comparison of clinical data, myocardial injury biomarkers, and cardiac complications between non-survivors and survivors of COVID-19 Parameter MD (95% CI) between non- survivors and survivors SMD (95% CI) between non- survivors and survivors RR (95% CI) p value I 2 Clinical Age, years 14.3 (9.2 to 19.4) - - < 0.001 88% Male - - 1.3 (1.2 to 1.4) < 0.001 0% Comorbidities Hypertension - - 1.7 (1.2 to 2.4) 0.001 74% Cardiovascular disease - - 3.3 (1.4 to 7.7) 0.005 70% Myocardial injury biomarkers hs-cTnI - 1.0 (0.8 to 1.2) - < 0.001 42% hs-cTnI (> 99th percentile) - - 8.0 (2.2 to 28.5) 0.001 93% NT-proBNP - 1.1 (0.7 to 1.4) - < 0.001 50% CK-MB - 1.0 (0.2 to 1.8) - 0.010 81% Cardiac complications Acute cardiac injury - - 8.9 (4.2 to 19.1) < 0.001 79% Heart failure - - 5.1 (2.5 to 10.7) < 0.001 75% Arrhythmias - - 4.9 (1.2 to 19.0) 0.020 85% MD: mean difference; SMD: standardized mean difference; RR: risk ratio; CI: confidence interval. Positive results for SMD indicate increased levels of biomarkers in non-survivor patients. 275