Elevated N-terminal pro-brain natriuretic peptide is associated with increased mortality in patients with COVID-19: systematic review and meta-analysis

Pranata, Raymond; Huang, Ian; Lukito, Antonia Anna; Raharjo, Sunu Budhi

OBJECTIVES: This systematic review and meta-analysis aimed to assess the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in patients with COVID-19. METHODS: Systematic literature search from several electronic databases were performed. The outcome was mortality (non-survivor) in patients with COVID-19 pneumonia. NT-proBNP data were in continuous variable (pg/mL), dichotomous data (elevated/non-elevated) and effect estimate adjusted to cardiac injury/elevated biomarkers of cardiac injury. RESULTS: A total of 967 patients from six studies were included in this analysis. NT-proBNP was higher in non-survivor group (standardised mean difference 0.75 (0.44, 1.07), p<0.001; I(2): 61%). Elevated NT-proBNP was associated with increased mortality (RR 3.63 (92.21, 5.95), p<0.001; I(2): 60%). Sensitivity analysis by removing a study reduces heterogeneity (risk ratio 3.47 (2.36, 5.11), p<0.001; I(2): 49%). Pooled adjusted HR (adjusted to cardiac injury/elevated biomarkers of cardiac injury) showed that elevated NT-proBNP was independently associated with mortality (HR 1.37 (1.19, 1.57), p<0.001; I(2): 0%, p=0.77). Pooled analysis of multiple cut-off point resulted in a sensitivity of 76% (46%–92%) and specificity of 88% (71%–96%). Summary receiver operating characteristic curve analysis demonstrates an area under curve of 0.90 (0.87–0.93). Elevated NT-proBNP has a likelihood ratio (LR) +6.4 and LR -0.3. CONCLUSION: Elevated NT-proBNP level was associated with increased mortality in COVID-19 pneumonia.