Elevated Cardiac Troponin I Is Associated with Poor Outcomes in COVID-19 Patients at an Academic Medical Center in Midwestern USA

Early reports from China suggest that cardiac troponin values >99th percentile upper reference limit (99th% URL) are powerful predictors of poor outcomes in patients with COVID-19 (1, 2,). Outcomes examined included intubation, ARDS, acute kidney injury (AKI), and death. In one report the univariate odds ratio for death was 80:1 when cardiac troponin I (cTnI) was above the 99th% URL (1). In fact, it was the strongest predictor of all biomarkers examined in 191 patients. In another study of 461 patients, cTnI values above the 99th% URL had an increased odds ratio for death of 10:1 (2). Furthermore, the odds ratios for intubation, ARDS, and AKI were 5:1, 4:1, and 10:1, respectively. A recent preprint from a large hospital system in New York City examined cTnI as a marker of mortality among 2736 admitted patients with COVID-19 (3). It showed that patients with modest elevations of cTnI (0.03–0.09 ng/mL) had an adjusted hazard ratio for mortality of 1.77 compared to those with undetectable cTnI while those with cTnI values >0.09 ng/mL had a hazard ratio of 3.23 for mortality. While the exact causes of increased cTn in patients with COVID-19 are unknown, these studies suggest it as a robust univariate marker for poor outcomes. With IRB approval we performed a retrospective observational study of 182 consecutive patients who were SARS-CoV-2 PCR+ admitted and discharged at Barnes Jewish Hospital/Washington University Medical Center to determine if elevated cTnI was associated with poor outcomes at our institution. cTnI testing was performed in the Barnes Jewish Hospital Laboratory using the contemporary cTnI assay on the Abbott Architect i2000. The 99th% URL for this method is 0.028 ng/mL and the limit of quantification is 0.03 ng/mL. The reference interval is <0.03 ng/mL. Outcomes were determined by review of the electronic health record (EPIC) and physician notes for: death, intubation, acute respiratory distress syndrome, or acute hypoxic respiratory failure (ARDS/AHRF) and AKI. AKI was defined using RIFLE criteria of 2-fold increase in creatinine and urine output less than 5 mL/kg/h. Both initial and peak cTnI values were examined as univariate markers at 3 concentration ranges; undetectable (<0.03 ng/mL), moderate (0.03–0.09 ng/mL), and elevated (>0.09 ng/mL). While we could not rule-in acute myocardial infarction, we also examined a subgroup of patients who exhibited a rise and/or fall of cTnI defined as a rise and/or fall of at least 0.2 ng/mL and a peak value >0.2 ng/mL. Of the 182 patients admitted with COVID-19, 103 (56.6%) were male and the median (range) age was 64 years (19–98). 143 patients had physician ordered cTnI, with an overall prevalence of cardiac injury in this subpopulation (at least one value ≥0.03) of 55.9%. Patients without physician ordered cTnI had improved ARDS/AHRF outcomes (OR = 0.30, 95% CI; 0.12–0.74) (Table 1) relative to those with cTnI ordered with all results being undetectable (<0.03 ng/mL) which was the reference population for calculating all odds ratios. Patients with at least one cTnI ≥0.1 ng/mL had an OR of 17.86 (95% CI; 5.62–50.94) for all-cause mortality. Among patients with a rise and/or fall in cTnI, the OR for mortality was 25.81 (95% CI; 6.61–80.74), of ARDS/ARF was 7.43 (1.96–25.12), of AKI was 15.83 (4.54–53.56), and of intubation was 30.94 (95% CI; 8.44–94.88). Outcomes among patients with COVID-19 infection. All cause mortality in patients with confirmed COVID-19 infections. Patients placed in hospices (n = 5) are included in this group. One patient was intubated unrelated to COVID-19 and was excluded from intubation calculations. Outcomes among patients with COVID-19 infection. All cause mortality in patients with confirmed COVID-19 infections. Patients placed in hospices (n = 5) are included in this group. One patient was intubated unrelated to COVID-19 and was excluded from intubation calculations. Our findings confirm that in a Midwestern USA institution elevated cTnI concentrations are a powerful univariate marker for poor outcomes as seen in early studies (1–3,). However, there are limitations to this retrospective observational study. Preexisting cardiovascular conditions are known to be a risk factor for poor outcomes in COVID-19 disease (4,) and we were not able to sufficiently determine the presence or absence of preexisting cardiovascular comorbidities. Yet, in the New York study, the presence of preexisting cardiovascular disease/risk factors did not affect the hazard ratios for mortality among patients with elevated cTnI values (3,). The finding that having no cTnI ordered resulted in a reduced OR of ARDS suggests selection bias in our study that we minimized by using those with cTnI ordered but undetectable results as the reference population. It is also important to note that we cannot diagnose AMI in these patients as cTnI is a marker of cardiac injury and not myocardial infarction. Without evidence of thrombotic events or ischemic signs and symptoms we can only state the prevalence of cardiac injury. Nonetheless, it is becoming clear that cardiac troponin can be an ally in managing patients with COVID-19 (5). Combining troponin with other biomarkers may result in even better prognosis and future studies will be important to determine this (5). All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. C.W. Farnsworth, statistical analysis. Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or conflicts of interest: Employment or Leadership: M.G. Scott, Clinical Chemistry, AACC. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: M.G. Scott, Abbott Laboratories, Siemens Healthcare. Expert Testimony: None declared. Patents: None declared.