Prediction of clinical outcomes in patients with coronavirus disease 2019 using high-sensitive troponin I and N-terminal pro-B-type natriuretic peptide
Authors: Sano M , Toyota T , Morimoto T , Okada T , Sasaki Y , Taniguchi T , Kim K , Kobori A , Ehara N , Kinoshita M , Doi A , Tomii K , Kihara Y , Furukawa Y 
Published: October 2022

Abstract

Background
Several comorbidities, including cardiovascular diseases or myocardial injury, are reported to be associated with poor prognosis in patients with Coronavirus disease 2019 (COVID-19). However, detailed prognostic analysis of myocardial injury by various biomarkers in COVID-19 patients is limited.

Purpose
This study aims to explore the prognostic values of high-sensitive Troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for COVID-19 patients using Japanese real-world data.

Methods
The COVID-MI study is a retrospective cohort study that enrolls consecutive laboratory-confirmed COVID-19 patients admitted to the hospital from July 2020 to September 2021. We collected clinical data, including cardiac biomarker values, by chart review. If the prespecified biomarkers in concern were not available, we measured them using the institutional serum blood bank, which enrolled patients prospectively from July 2020. Patients with available biomarkers were analyzed according to the values of hsTnI or NT-proBNP, using the clinically relevant thresholds (hsTnI: 5 ng/L and 99th percentile of the upper reference limit [99%ile URL], and NT-proBNP: 125 pg/mL and 900 pg/mL). The primary outcome measure was all-cause death. Secondary outcome measures included acute respiratory distress syndrome, myocardial infarction, myocarditis/pericarditis, venous thromboembolism, cerebral infarction, and bleeding events.

Results
We enrolled 917 patients with COVID-19 confirmed by viral nucleic acid amplification test. The mean age was 61 years, and 591 patients (64%) were men. On admission, the number of patients classified as severe or critical COVID-19 was 515 (56%) and 85 (8.7%), respectively. Among the 544 patients with hsTnI values, 365 (67%) patients had elevated hsTnI of ≥5 ng/L, and 134 patients (25%) had TnI of ≥99%ile URL. Besides, among 546 patients with NT-proBNP values, 295 patients (54%) had elevated NT-pro-BNP of ≥125 pg/mL, and 93 patients (17%) had NT-proBNP of ≥900 pg/mL. The median follow-up period was 31 days (interquartile range: 11–90 days). In cumulative incidence analysis, higher levels of hsTnI and NT-proBNP were associated with significantly higher mortality (hsTnI: &lt;5 ng/L group; 8.8%, 5 ng/L to 99%ile URL group; 19%, and ≥99%ile URL group; 37%, P&lt;0.001, and NT-proBNP: &lt;125 pg/mL group; 7.8%, 125 to 900 pg/mL group; 21%, and ≥900 pg/mL group; 45%, P&lt;0.001). The adjusted risk for all-cause death remained significant for each threshold of cardiac biomarkers (hsTnI ≥99%ile URL: hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.11–3.54, P=0.02, and NT-proBNP ≥900 pg/mL: HR 3.60, 95% CI 1.86–6.98, P&lt;0.001).

Conclusion
Elevation of hsTnI or NT-proBNP was associated with poor prognosis in the current relatively severely ill COVID-19 patients. Measuring hsTnI or NT-proBNP can be an attractive option for risk stratification and deciding appropriate management in patients with COVID-19.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Institutional Research Fund at Kobe City Medical Center General Hospital