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Clinical Context

Multiorgan involvement in hospitalized patients with COVID-19 is common, particularly among persons with cardiovascular disease (CVD) or risk factors. Elevated cardiac troponin, reflecting acute myocardial injury (AMI), predicts worse prognosis.

Cardiac magnetic resonance (CMR) imaging is the reference standard for AMI, as it reveals structure, function, scar, and inflammation. Initial imaging studies of COVID-19 reported a myocarditis-like injury pattern, but these were small and had other limitations.

Study Synopsis and Perspective

Hospitalized patients with COVID-19 with high troponin levels are twice as likely to have cardiac abnormalities than patients with normal troponin, with or without COVID-19, a multicenter UK study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular (CV) outcomes at 12 months.

"We know that multiorgan involvement in hospitalized patients with COVID-19 is common... and may result in [AMI], detected by an increase in cardiac troponin concentrations," John P. Greenwood, PhD, of the University of Leeds in England, told theheart.org |Medscape Cardiology. "Elevated cardiac troponin is associated with a worse prognosis.

"Multiple mechanisms of myocardial injury have been proposed and... mitigation or prevention strategies likely depend on the underpinning mechanisms," he continued. "The sequelae of scar may predispose to late events."

The study, published January 27 in Circulation, also identified a new pattern of microinfarction on CMR imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Greenwood said.

A total of 342 patients with COVID-19 and elevated troponin levels (COVID-19+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an "urgent public health study" in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19, before vaccination, and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR imaging at a median of 21 days after discharge.

Researchers also recruited 2 prospective control groups: 64 patients with COVID-19 and normal troponin levels (COVID-19+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and CV comorbidities (COVID-19−/comorbidity+).

Overall, participants' median age was 61 years, and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality (eg, left or right ventricular impairment, scar, or pericardial disease) was twice as great (61%) in COVID-19+/troponin+ cases compared with control participants (36% for patients with COVID-19+/troponin− vs 31% for patients with COVID-19−/comorbidity+).

Specifically, more cases than control participants had ventricular impairment (17.2% vs 3.1% and 7.1%) or scar (42% vs 7% and 23%).

The myocardial injury pattern differed between cases and control participants, with cases more likely to have infarction (13% vs 2% and 7%) or microinfarction (9% vs 0 and 1%).

Still, there was no between-group difference in nonischemic scar (13% vs 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases compared with 1.7% in control participants without COVID-19: "much lower" than in previous studies, Greenwood noted.

During follow-up, 4 patients with COVID-19+/troponin+ (1.2%) died, and 34 (10.2%) experienced a subsequent major adverse cardiovascular event (MACE), which was similar to control participants (6.1%).

Myocardial scar, but not previous COVID-19 or troponin level, was an independent predictor of MACE (odds ratio [OR] 2.25 [95% CI: 1.12, 4.57).

"These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors," the authors concluded.

Greenwood added, "We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after [AMI] associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity."

Commenting on the study for theheart.org | Medscape Cardiology, James A. de Lemos, MD, co-chair of the American Heart Association's COVID-19 CVD Registry Steering Committee and a professor of medicine at The University of Texas Southwestern Medical Center in Dallas, Texas, said, "This is a tour de force collaboration -- obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury."

Overall, he said, the findings "do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities."

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne in Lausanne, Switzerland, noted in a related editorial,^[2] "We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of preexisting comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved.

"In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers," they concluded.

No commercial funding or relevant financial relationships were reported.

Clinical Implications

• Patients with COVID-19 and elevated cardiac troponin were twice as likely to have cardiac abnormalities as control participants.
• A newly described CMR imaging pattern of microinfarction highlights the prothrombotic nature of COVID-19.
• Implications for the Healthcare Team: The clinical severity of COVID-19 is most often dictated by the presence of preexisting comorbidity, with antecedent ischemic scar now included on the list of preexisting conditions that clinicians should take into account when making management decisions.

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