Predictive Factor for COVID-19 Worsening: Insights for High-Sensitivity Troponin and D-Dimer and Correlation With Right Ventricular Afterload

Abstract

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission. Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO₂, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6-96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0-116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76-128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047). Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

Keywords: COVID-19; D-dimer (DD); echocardiograghy; right ventricle; thrombosis; troponin.

Figure 1

D-Dimer and high-sensitivity cardiac troponin (Hs-cTnI) involvement in intensive care unit (ICU) referral. We used different D-dimer level cutoffs (>1,000 ng/mL, >2,000 ng/mL, >3,000 ng/mL) as potential prognostic criteria for ICU referral. Receiver operating characteristics (ROC) curve analysis associating D-dimer above 1,000 ng/mL, gender and pneumonia at CT scan for ICU transfer (in yellow) increases area under the curve (AUC) in contrast to D-dimer ≥1,000 ng/mL alone (AUC, 79.1; 95% CI, 68–90, p = 0.04). Addition of Hs-cTnI to this model (in green) allowed reaching AUC of 84.9 (95% CI, 74–96, p = 0.03). Hs-cTnI alone was the best predictive ROC curve (in red) for ICU outcome with AUC of 86.4 (95% CI, 77–96).

Figure 2

Hypothesis of a potential pathophysiological mechanism explaining pulmonary and cardiac dysfunction in COVID-19 and resulting in troponin and D-dimer increase at admission to the hospital.