Myocardial Injury in Patients Hospitalized With COVID-19
- Troponin elevation occurs frequently among patients hospitalized with COVID-19, especially those with a history of cardiovascular disease.
- Most patients have only slight evidence of myocardial injury.
- Troponin elevation is associated with higher risk of mortality.
What is the degree of myocardial injury, based on troponin elevation, in a large cohort of patients hospitalized with coronavirus disease 2019 (COVID-19), and what are the associated outcomes?
Data were obtained retrospectively from the electronic medical record (EMR) of patients admitted with COVID-19 to one of five Mount Sinai Health System hospitals in New York City between February and April 2020. Patients with a troponin I drawn within 24 hours of admission were included. These levels were stratified into normal (0.00-0.03 ng/ml), mildly elevated (>0.03-0.09 ng/ml), and elevated (>0.09 ng/ml). Variables collected included demographics, laboratory values, and comorbidities based on International Classification of Diseases, Tenth Revision (ICD-10) billing codes. A CURB-65 score was computed on admission to reflect illness severity, reported as an integer between 0-5. The primary outcome was mortality, with a composite secondary outcome of mortality or mechanical ventilation.
Of patients admitted with COVID-19, 2,736 (89.1%) of 3,069 had ≥1 troponin I measurement within 24 hours of admission. The median age was 66.4 years, 59.6% were male, and 40.7% of patients were ages >70 years; 27.6% of patients self-identified as African American, and 27.6% as Hispanic or Latino. Mean body mass index (BMI) was 29.8 ± 6 kg/m2. Cardiovascular disease (CVD), comprised of either coronary artery disease (CAD), atrial fibrillation (AF), or heart failure (HF) was present in 24% of patients. The risk factors of hypertension (HTN) and diabetes (DM) were present in another 25.8% of the cohort. Statins were used in 36% of patients and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) in 22%.
Regarding troponin levels, 1,751 (64%) patients had an initial troponin in the normal range, while 455 (17%) had mild elevation and 530 (19%) had an elevated troponin; 173 (6.3%) patients had a troponin elevation over 1 ng/ml at any point during their hospital stay. Patients with normal troponin levels had a mean CURB-65 score of 0.9 ± 0.95, while mildly elevated and elevated troponins had scores of 1.76 ± 1.02 and 2.01 ± 1.05 (p < 0.001), respectively. As troponin levels increased, the proportion of patients with CVD increased. Patients with normal troponins had rates of CAD, AF, and HF at 9.8%, 5.2%, and 4.3%, while those with elevated troponins had rates at 34.9%, 13%, and 25.3%, respectively.
Of the COVID-19 patients, 18.5% died, while 40.1% remained hospitalized at the end of the study period. Increased age, BMI, and CURB-65 were associated with increased risk of death, while sex, race/ethnicity, and CVD were not. Statin use was associated with improved survival (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47-0.69), while ACE inhibitor and ARB use were not. After adjusting for disease severity, troponin elevations between 0.03-0.09 were associated with greater incidence of death (HR, 1.75; 95% CI, 1.37-2.24; p < 0.001) and troponin elevations over 0.09 ng/dl were associated with more pronounced risk of death (HR, 3.03). This increase in risk was present in patients with or without CVD or CVD risk factors (HTN, DM). The composite outcome of mortality or mechanical ventilation had similar HRs (1.75 for mild elevation and 2.97 for elevation).
Due to the retrospective/EMR-based methodology, the study is unable to account for differences in the use of heparin and other anticoagulants, antiplatelet agents, and experimental COVID-19 therapies (e.g., antivirals and anti-inflammatories), which may have had a significant effect on outcomes. Statin use, for example, was found to have a marked protective effect (HR, 0.57), but the authors acknowledge their inability to account for the potential confounder of discontinuation in critically ill, intubated patients.
- While myocardial injury was present among 36% of admitted patients with COVID-19, almost half of these had only very slight elevations in troponin (0.03-0.09 ng/ml).
- Troponin elevation tracked with increasing CURB-65 score, but even after adjusting for disease severity and other clinically relevant covariates, remained independently associated with risk of death, with the greatest HR in the group with the most significant lab abnormality (troponin I > 0.09 ng/ml).
- A number of limitations related to the retrospective design, exclusive use of data extracted from the EMR, short study period, and use of troponin I limit the generalizability of this study to other sites or epochs of the pandemic.
This is one of the first large studies coming out of New York City, the first epicenter of the COVID-19 pandemic in the United States. Previous small case series out of Europe and China had shown similar findings (i.e., that troponin elevations were frequent, more common in patients with pre-existing cardiovascular conditions, and associated with adverse outcomes), so the significance of this study is primarily its confirmation of these findings in a much larger cohort.
Due to the methodology used and the rapidly changing nature of the pandemic, these findings will likely need additional confirmation in different sites and waves of coronavirus infection. Moreover, the study offers little information on key questions: 1) What causes troponin elevation in these patients (acute coronary syndrome, supply-and-demand mismatch, microvascular thrombosis, nonischemic myocardial injury, etc.)? 2) Are distinct treatment strategies indicated in COVID-19 patients with laboratory evidence of myocardial injury?
Keywords: Angiotensin-Converting Enzyme Inhibitors, Atrial Fibrillation, Body Mass Index, Coronary Artery Disease, Coronavirus, COVID-19, Critical Illness, Diabetes Mellitus, Heart Failure, Primary Prevention, Risk Factors, Troponin I, Ventilators, Mechanical
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