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Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.
Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).
That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.
The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could potentially be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculate.
The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.
One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published January 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin-Madison.
“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, told theheart.org | Medscape Cardiology.
Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”
The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”
The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.
Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published December 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tennessee.
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Reassurance and Concern
“The incidence is much lower than we feared, and so that’s reassuring,” Clark told theheart.org | Medscape Cardiology. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”
The study’s two non-COVID-19 control groups — elite athletes in one and nonathletes in the other — allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).
As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Clark said.
The LGE finding, write Clark and his Vanderbilt coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”
Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.
“And you get a little bit in the mid-septum, as well,” Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”
Conceivably, Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”
It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, observed for theheart.org | Medscape Cardiology.
“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Baggish, who directs the Cardiovascular Performance Program at his center and is unaffiliated with either study.
Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, cautions an accompanying editorial from Jonathan H. Kim, MD, MSc.
Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argues Kim, from Emory University School of Medicine, Atlanta.
There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”
Interestingly, the estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”
The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
Routine CMR for Positive Cases
The University of Wisconsin group looked at all of their institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.
The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.
All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group writes. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.
Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report notes.
The Vanderbilt analysis from Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.
They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.
The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reports.
The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group writes. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.
At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Baggish noted, so their clinical implications are unknown.
“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”
Starekova had no disclosures. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other couthors are in the report. Clark and his coauthors had no disclosures. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.
Circulation. Published online December 17, 2020. Full text