Cardiac Injury Biomarkers and the Risk of Death in Patients with COVID-19: A Systematic Review and Meta-Analysis

Abstract

Background. Cardiac complications may develop in a proportion of patients with the novel coronavirus disease (COVID-19), which may influence their prognosis. Objectives. To assess the role of cardiac injury biomarkers measured on admission and during hospitalization as risk factors for subsequent death in COVID-19 patients. Methods. A systematic review and meta-analysis was carried out involving cohort studies that compared the levels of cardiac injury biomarkers in surviving and dead COVID-19 patients. Cardiac injury is defined as an elevation of the definitive markers (cardiac troponin (cTnI and cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) above the 99th percentile upper reference limit. Secondary markers included creatine kinase-myocardial bound (CK-MB), myoglobin, interleukin-6 (IL-6), and C-reactive protein (CRP). The risk of death and the differences in marker concentrations were analyzed using risk ratios (RRs) and standardized mean differences (SMDs), respectively. Results. Nine studies met the inclusion criteria (1799 patients, 53.36% males, 20.62% with cardiac injury). The risk of death was significantly higher in patients with elevated cTn than those with normal biomarker levels (RR = 5.28, $P<0.0001$ ). Compared to survivors, dead patients had higher levels of cTn (SMD = 2.15, $P=0.001$ ), IL-6 (SMD = 3.13, $P=0.03$ ), hs-CRP (SMD = 2.78, $P<0.0001$ ), and CK-MB (SMD = 0.97, $P<0.0001$ ) on admission and a significant rise of plasma cTnT during hospitalization. Conclusion. COVID-19 patients with elevated cTn on admission, possibly due to immune-mediated myocardial injury, are at increased risk for mortality. This requires further radiographic investigations, close monitoring, and aggressive care to reduce the risk of severe complications and death.