What Does Elevated Troponin Mean in COVID-19?

Cardiac injury was common among those hospitalized for COVID-19 and found to be associated with a several-fold increase in mortality risk, according to a hospital in Wuhan, China.

Abnormally high levels of high-sensitivity cardiac troponin I (above the 99th-percentile upper reference limit) were observed in 19.7% of consecutive patients with lab-confirmed COVID-19, reported Bo Yang, MD, PhD, of Renmin Hospital of Wuhan University, and colleagues in a paper published online in JAMA Cardiology.

COVID-19 was more severe when accompanied by cardiac injury, as these patients were:

• More likely to require noninvasive mechanical ventilation (46.3% vs 3.9%, P<0.001) or invasive mechanical ventilation (22.0% vs 4.2%, P<0.001) than those without cardiac injury
• More likely to have complications, including acute respiratory distress syndrome, acute kidney injury, electrolyte disturbances, hypoproteinemia, and coagulation disorders
• A higher mortality risk (51.2% vs 4.5%), whether considered by time from symptom onset (HR 4.26, 95% CI 1.92-9.49) or from admission to end of follow-up (HR 3.41, 95% CI 1.62-7.16)

The retrospective cohort study included 416 patients with sufficient medical records and lab results from Jan. 20 to Feb. 10 of this year, with last follow-up on Feb. 15.

COVID-19 patients who showed signs of cardiac injury tended to be older and have more comorbidities (such as a history of coronary heart disease and hypertension) compared with peers who didn't have cardiac injury.

Abnormal laboratory and chest radiographic findings were more common in this group at admission:

• Elevated leukocyte counts
• Higher levels of C-reactive protein, procalcitonin, creatinine kinase-myocardial band, myohemoglobin, N-terminal pro-B-type natriuretic peptide, aspartate aminotransferase, and creatinine
• More prevalent bilateral pneumonia
• Higher likelihood of multiple mottling and ground-glass opacity

"Based on these lines of evidence, we hypothesize that an intense inflammatory response superimposed on preexisting cardiovascular disease may precipitate cardiac injury observed in patients with COVID-19 infections," Yang's team said.

Not reported in this paper were D-dimer levels, which another Chinese group found to be generally elevated in severe cases of COVID-19 -- suggestive of abnormal clotting requiring anticoagulation therapy.

"This is one of many papers now flying out from China indicating that COVID-19 infection is associated with increases in cardiac troponin," commented Allan Jaffe, MD, of Mayo Clinic in Rochester, Minnesota, who was not involved with the study.

"Best guess is that most of this is myocardial injury due to critical illness," Jaffe told MedPage Today. "Thus, although an adverse sign, these increases should not in general cause clinicians to consider invasive evaluation and intervention for MI."

That last point was stressed by James Januzzi, MD, of Massachusetts General Hospital in Boston.

Caregivers should understand that the myocardial injury detected in patients with COVID-19 cannot be blamed on acute MI (type 1 or type 2) without other corroborative evidence such as ECG changes, symptoms suggesting myocardial ischemia, or other clinical evidence, he said.

"A mistaken diagnosis of MI has ramifications for patients, along with risk for exposure of staff related to further downstream testing that might not be needed in most cases," according to Januzzi.

"Some clinicians have said they measure troponin in their COVID-19 patients to provide guidance on therapy," he said. "My hope would be we might see some data emerge to suggest there's utility here, but until then clinicians should be cautious in how they interpret the result and how they respond to it."

People included in the study had a median age of 64 years, and 50.7% were women. They had spent a median 10 days from symptom onset to hospital admission.

The most common symptoms reported were fever (80.3%), cough (34.6%), and shortness of breath (28.1%).

Limited data had been collected from patients in isolation wards or the ICU, study authors acknowledged.

"The present study lacks evidence from MRI or echocardiography to determine the features of myocardial injury. On the basis of the present results of [high-sensitivity troponin I] and ECG findings in a subset of patients, we can only estimate the severity of cardiac injury," Yang's group said.

"Thus, because of the current limited evidence, the question of whether the SARS-CoV-2 virus can directly injure the heart requires further demonstration," according to them.

Yang and colleagues cited some evidence suggesting that COVID-19-induced cardiac injury might be mediated by angiotensin-converting enzyme 2 (ACE2), which is the receptor through which the SARS-CoV-2 virus that causes the disease enters human cells.

"Of note, several investigations have demonstrated that SARS-CoV-2 and SARS-CoV share the same host receptor [ACE2], which may have many protective effects on CVDs [cardiovascular diseases]," according to Chengzhi Yang, MD, PhD, and Zening Jin, MD, PhD, both of Beijing Tiantan Hospital and Capital Medical University, China.

"Therefore, ACE2 may play two contrary roles in patients with COVID-19, especially those with comorbid CVDs. On the one hand, ACE2 may provide protection against hypertension, myocardial fibrosis, myocardial hypertrophy, arrhythmia, atherosclerosis, and sodium-water retention. On the other hand, ACE2 acts as the gate for SARS-CoV-2 infection," they wrote in an accompanying opinion article.

ACE inhibitors and angiotensin receptor blockers (ARBs) upregulating ACE2 activity may therefore increase the risk of SARS-CoV-2 infection, according to Yang and Jin, who urged further study on the potential associations of these common medications with susceptibility and prognosis of COVID-19.

However, the Heart Failure Society of America, American College of Cardiology, and American Heart Association, among other professional organizations, have recommended against stopping renin-angiotensin-aldosterone system drugs over these concerns.

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