SARS-CoV-2 and Myocardial Injury: 3 Broad Causes and Their Implications

When it comes to myocardial injury and COVID-19, questions are many and answers remain few. But a new focused review of myocardial injury and SARS-CoV-2, the coronavirus that causes COVID-19, helpfully lays out three key relevant questions and identifies three broad causes of acute cardiac injury in this setting, along with general management considerations for each.

The short review, written by Paul C. Cremer, MD, of the Section of Cardiovascular Imaging in Cleveland Clinic’s Department of Cardiovascular Medicine, appears in Cleveland Clinic Journal of Medicine’s collection of COVID-19 Curbside Consults.

Three essential questions

After noting that acute cardiac injury (defined broadly as an elevated high-sensitivity troponin I or troponin T upon admission or during hospitalization) has been associated with a striking mortality rate of over 50% in initial reports of COVID-19 patients in China, Dr. Cremer identifies three questions as most pertinent to ultimately addressing this association:

• What is the mechanism of SARS-CoV-2–associated myocardial injury?
• To what extent are SARS-CoV-2 patients with myocardial injury a distinct population?
• What are possible treatment options for myocardial injury associated with SARS-CoV-2?

Regarding mechanism, Dr. Cremer writes that “the primary question is whether SARS-CoV-2 precipitates myocardial infarction with an oxygen supply-demand imbalance, either with or without acute coronary plaque pathology (type I and II myocardial infarction), or, conversely, causes myocardial injury mediated by viruses or cytokines.” He then reviews supportive and opposing evidence for each putative mechanism, noting that conclusions remain premature for now.

The second key question — whether SARS-CoV-2 patients with myocardial injury represent a distinct population — is tightly interlaced with the first, Dr. Cremer points out. Notably, COVID-19 patients with elevated troponins tend to be older and to have more cardiovascular comorbidities. “These findings support myocardial oxygen supply-demand mismatch with resultant ischemia in a vulnerable population,” he writes, but he also cites various observations suggesting that some COVID-19 patients may develop a hyperinflammatory state that perpetuates nonischemic myocardial injury.

While further data emerge to better clarify a potential profile of COVID-19 patients with myocardial injury, Dr. Cremer advises that troponin testing be considered upon admission with continued surveillance testing during the first days of hospitalization. He also recommends assessing whether the presentation is characterized by a modest troponin elevation in a patient with cardiac risk factors or a more substantial troponin elevation in a patient with hyperinflammation.

In patients with positive troponin findings, the third key question — treatment options — is informed by the suspected answers to the first two, Dr. Cremer notes. “Specifically,” he writes, “does the mechanism of injury seem more likely related to myocardial infarction with oxygen supply-demand mismatch or direct myocardial injury? And is this a patient with underlying cardiac conditions, hyperinflammation or both?”

Therapeutic options for type I myocardial infarction are well established, and treatment of type II myocardial infarction involves addressing the underlying cause and applying therapies to improve the myocardial oxygen supply-demand mismatch. Medications such as beta-blockers and vasodilators must be used judiciously to avoid precipitating decompensated heart failure or shock. Revascularization is rarely indicated in this context, and the effect of antiplatelet and anticoagulant therapy is uncertain.

In COVID-19 patients with hyperinflammation, immunosuppression may improve outcomes, Dr. Cremer notes. This raises the possibility of benefit from immune treatments for cardiac disease that target autoinflammation. These include colchicine, which inhibits tubulin polymerization and inflammasome activity, and anakinra and canakinumab, which inhibit interleukin-1. Notably, the latter is a cytokine central to the interleukin-6 signaling pathway, a target that shows promise in treating severe COVID-19 pneumonia. Clinical trials in patients with COVID-19 are currently underway with both colchicine (NCT04326790, NCT04322565, NCT04322682) and anakinra (NCT04324021).

For now, three broad causes of injury

It’s possible that myriad causes of acute cardiac injury in troponin-positive patients with COVID-19 will ultimately be identified, the review concludes. In the meantime, Dr. Cremer says clinicians can think in terms of three broad causative categories and manage patients accordingly:

• Ischemic ST elevation in a coronary artery distribution, in which case patients need emergency revascularization
• Lower levels of troponin elevation in the setting of myocardial oxygen supply-demand mismatch, in which case patients need supportive care
• Greater degrees of troponin elevation and hyperinflammation, in which case patients may need immunosuppressive therapy

“The incidence and overlap in each of these categories are unknown, but for patients in the third category, we may soon have effective therapies that target the inflammasome,” Dr. Cremer writes.

The full review (with references) is freely available here.