Myocardial Injury Seen in Over One-Third of Hospitalized COVID-19 Patients
The data confirm earlier reports and show that these patients are at an increased risk of dying in the hospital.
(UPDATE) Roughly one third of patients hospitalized with COVID-19 have some degree of myocardial injury and these patients are at an increased risk of death when compared with patients who lack elevations in cardiac troponin levels, according to a new analysis.
Even milder forms of myocardial injury—for example, individuals with cardiac troponin levels ranging from 0.03 to 0.09 ng/mL—were associated with an increased risk of death (adjusted HR 1.75; 95% CI 1.37-2.24). For patients with greater myocardial injury, who had cardiac troponin levels exceeding 0.09 ng/mL, the risk of death was more than threefold higher when compared with patients without cardiac damage (adjusted HR 3.03; 95% CI 2.42-3.80).
“This analysis started at the start of the pandemic,” lead investigator Anuradha Lala, MD (Icahn School of Medicine at Mount Sinai, New York, NY), told TCTMD. “The first case in New York was March 1st, and there were some early observations of patients having myocardial involvement. Those initially came from China and Italy, and then we started to see it on the wards. I was on COVID-19 service for 4 weeks and it was clear that—all these patients have a troponin assessment when they come to the emergency room, or within 24 hours of admission—we were seeing these low-level troponin elevations, but it was hard to make sense of what it meant in the setting of COVID-19. Everything was just so unknown.”
The new observational study, which was published online ahead of print in the Journal of the American College of Cardiology, included 3,069 patients with COVID-19 hospitalized at one of five New York City hospitals that are part of the Mount Sinai Health System. The goal of the analysis was to understand the prevalence of troponin elevations in COVID-19 patients, the range of troponin levels when elevated, and their prognostic implications, said Lala.
We were seeing these low-level troponin elevations, but it was hard to make sense of what it meant in the setting of COVID-19. Everything was just so unknown. Anuradha Lala
Nearly 90% of hospitalized patients had at least one troponin I measurement within 24 hours of admission. Of these, 1,751 had a normal cardiac troponin I (0-0.03 ng/mL), 455 had mildly elevated levels (0.03-0.09 ng/mL), and 530 had significantly elevated levels (> 0.09 ng/mL). More than one-third of patients with significant myocardial injury had preexisting CAD compared with 21.3% of patients with mildly elevated cardiac troponin I and 9.8% of those with normal levels. Atrial fibrillation and heart failure were also more prevalent in individuals with significantly increased troponin I.
Of the 2,736 patients included in the study, 18.2% died, 41.4% were discharged home, and 40.1% remained hospitalized at the time of the analysis. In a Cox proportional hazard regression model, older age, higher body mass index, and greater illness severity were associated with an increased risk of in-hospital mortality. After adjusting for clinically relevant covariates, both mild and significant forms of myocardial injury were associated with an increased risk of death. The risk was consistent in patients with and without CVD, as well as in those with and without cardiovascular risk factors.
To TCTMD, Lala said that while myocardial injury was evident in 36% of hospitalized COVID-19 patients, the increase in cardiac troponin I was often mild. “In this analysis of nearly 3,000 patients, troponin elevations were generally at low levels,” she said. “A majority of the patients had troponins less than 1 [ng/mL]. It’s an elevated troponin level, but it’s not dramatically elevated.” Nonetheless, they “observed a pretty strong association with the risk of death after adjusting for a number of clinically relevant factors,” including preexisting cardiovascular disease, said Lala.
Mohammad Madjid, MD (University of Texas Health Science Center, Houston), who has previously studied the impact of influenza on the heart. said the present study helps researchers better understand the cardiovascular burden of COVID-19, and he praised the group for conducting a large study across the five metropolitan hospitals.
“While previous studies suggested that elevated troponins might predict poor outcomes, this study shows that there is a dose-response relationship and higher troponin levels are associated with a much higher risk for mortality,” he said in an email. “It appears that few cases are due to acute MI and cardiac injury is the main culprit.”
He noted that the New York City cohort had a high mortality rate at 18.5%, so it’s unknown how generalizable the findings will be for lower-risk patients and for patients with COVID-19 who weren’t hospitalized.
Mechanisms Underlying Myocardial Injury
In their paper, the researchers state that very few patients met the strict criteria for acute MI according to the Fourth Universal Definition.
“Though some patients in this cohort certainly suffered ischemic myocardial damage from either type 1 or 2 myocardial infarction, it is possible that a majority of injury observed was mediated through a noncoronary mechanism,” they write in the paper. It is unknown if the injury was the direct effect of the virus on the heart or the cytokine storm that is a hallmark of severe COVID-19. It is also possible that myocardial injury could result from coronary ischemia brought on by increased thrombotic activity in this disease.
Nicholas Mills, MBChB, PhD (University of Edinburgh, Scotland), who wasn’t involved in the study, said the US data are consistent with many reports from the Hubei province in China as well as observations from Europe. The new report is very welcome, he said, and adds to the body of knowledge, but there are still many unknowns. “In this series cardiac troponin was measured on clinical indication, and therefore this cohort represents a selected group of higher-risk patients,” he wrote in an email. “The true prevalence of myocardial injury is likely to be substantially lower.”
In many COVID-19 cases, troponin elevation appears to represent acute myocardial injury but not an acute coronary syndrome. Gregg Fonarow
Like the researchers, Mills stressed that the underlying mechanism for the myocardial injury is not known. While it might reflect preexisting cardiovascular disease or nonischemic injury, as suggested by the researchers, Mills pointed out that two-thirds of the patients with more substantial elevations in cardiac troponin I did not have known cardiac disease. There were no other cardiac investigations performed in patients, such as 12-lead electrocardiogram, to shed light on the underlying etiology, he said.
Also commenting on the study for TCTMD, Gregg Fonarow, MD (University of California, Los Angeles), said that since the earliest publications of patients hospitalized with COVID-19, there has been a lot of debate as to whether the troponin elevations represent type 1 or type 2 MIs, nonischemic myocardial injury, acute myocarditis, or other mechanisms.
“As the evidence evolved, it has become more clear that the elevations in troponin are in concert with inflammatory and acute phase markers, and frequently don’t follow a pattern consistent with type 1 myocardial infarction,” he said. “In many COVID-19 cases, troponin elevation appears to represent acute myocardial injury but not an acute coronary syndrome.”
While the mechanisms might not be known, Lala said if she sees a recently hospitalized COVID-19 patient with elevated troponin levels, she will likely keep a closer eye on him or her. “I think it may—and this is a hypothesis—help us triage patients, or at least in our mind think about some patients a little bit differently,” she said.
Mills agreed that the information is clinically useful, as it can help physicians develop critical care pathways. “Whilst myocardial injury in many may simply reflect illness severity and the main implication will be to support the appropriate triage of patients to a higher-intensity location in the hospital, injury may also arise due to specific cardiac conditions such as myocardial infarction, myocarditis, and Takotsubo cardiomyopathy, and appropriate treatment for these conditions may improve our patients’ likelihood of survival,” he wrote.
Like Mills, Fonarow said cardiac troponin levels provide prognostic information that can facilitate risk stratification and patient triage. What’s not known and will require further study, however, is whether therapies targeted for prevention or the treatment of myocardial injury improve patient outcomes.
To TCTMD, Madjid said he doesn’t believe there is enough data yet to recommend widespread measurements of cardiac troponin levels in all patients with COVID-19. “But if we ever decide to do it, there should be clear- cut guidance on how to interpret it and essentially prevent inappropriate caths,” he said. “From this report, it appears that troponin measurement did not lead to increased unnecessary catheterization.”
Lala A, Johnson KW, Januzzi JL, et al. Prevalence and impact of myocardial injury in patients hospitalized with COVID-19 infection. J Am Coll Cardiol. 2020;Epub ahead of print.
- Lala reports honoraria from Zoll.
- Mills reports funding from the British Heart Foundation and receiving honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx.
- Fonarow and Madjit report no relevant conflicts of interest.