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Myocarditis is very uncommon in patients with SARS-CoV-2 infection and endomyocardial biopsy should not be routinely used in the setting of COVID-19, concludes a new report by a team of cardiologists and pathologists.
In a review of all published cases to date, Aloke V. Finn, MD, and colleagues from the CVPath Institute in Gaithersburg, Maryland, found histologically defined myocarditis in only 4.5% of highly selected COVID cases undergoing autopsy or endomyocardial biopsy.
"Using current histological criteria, myocarditis is actually very uncommon in the reported literature, such that we saw that from 201 highly selected cases — most of which were autopsy cases, but nine of them were biopsy cases — only nine cases of myocarditis were reported," Finn told theheart.org | Medscape Cardiology.
Finn is the medical director and chief scientific officer at CVPath and an interventional cardiologist at the University of Maryland School of Medicine in Baltimore, Maryland. Finn and his colleagues — including first author Rika Kawakami, MD, also from CVPath Institute — published their findings in the January 26 issue of the Journal of the American College of Cardiology.
In the nine biopsy cases reported in the literature, diagnostic criteria for myocarditis were met in only two cases, one of whom was in a 43-year-old woman who tested negative for the SARS-CoV-2 virus.
Among 192 published autopsy cases, myocarditis was seen in only seven individuals. Among the 15 published autopsy series included was the recent European Heart Journal study by Basso et al, covered by theheart.org | Medscape Cardiology when it published online in November.
In the Basso autopsy series, which examined hearts from 21 COVID-19 patients, three were fulfilled the criteria for myocarditis. This high rate (14.2%), said Finn, might in part be due to selection bias as the cases were referred from four separate institutions.
The cardiology community started worrying early about myocarditis after a case series from Wuhan, China suggested that fulminant myocarditis was involved in 7% of COVID-related deaths.
The current findings are consistent with another just-published literature review, which involved 277 autopsied hearts pooled from 22 publications and showed that although myocarditis was reported in 20 hearts (7.2%), closer examination showed that most cases were not functionally significant, and the "true prevalence" was much lower (<2%).
"We've all seen the case reports in the literature and the media of COVID-19-induced myocarditis and we wanted to clarify, in a systematic manner, how common it actually is, and the answer is 'not very'," said Finn.
Going a step further, Finn and colleagues also looked their own CVPath experience. CVPath, a nonprofit research institute that receives funding from a number of companies, has an ongoing collaboration with the Ospedale Papa Giovanni Hospital in Bergamo, Italy and received 15 hearts from people from that region who died in the hospital from COVID-19. To this they added one heart from a patient who died from COVID-19 in Baltimore.
None of the 16 hearts they examined met the criteria for myocarditis. Three had evidence of either microvascular or epicardial thrombosis in the setting of acute myocardial infarction, along with neutrophilic infiltration.
"This is just confirming that myocarditis is not a major issue for people with COVID-19 infection," said Finn. "Not only did we not see myocarditis in these hearts, but in the majority of cases, we weren't even able to find PCR evidence of virus in the heart. We found it in the lung, as you would expect, but not in the heart."
In two of 16 cases (13%), virus was detected in the heart by PCR. In 12 of 16 cases (75%), the pathologists found virus in the lungs. Finn noted, however, that because these tissues were fixed and shipped overseas, this finding should be viewed with caution.
Given their findings, Finn and colleagues suggest that endomyocardial biopsy, given its inherent risks, should not be routinely used to diagnose myocarditis in patients with COVID-19.
"We know that the diagnostic yield is going to be low, and even if you do find myocarditis, there are currently no data to guide us on how to treat it," said Finn.
"We do suggest it can still be considered for the worst cases, where the patient is essentially dying and you are desperate to understand what's happening and maybe you'll consider using a left ventricular assist device or something, but otherwise, it's not going to help," he added.
Finn and colleagues have another study in press that provides a systematic and quantitative analysis of the impact of COVID-19 on the heart.
"I think their conclusions are very reasonable," said Leslie T. Cooper, Jr, MD, Mayo Clinic, Jacksonville, Florida, in an interview. "I agree that the majority of cardiac injury in COVID-19 is not related to myocarditis as defined by the classic histological criteria."
Cooper's career has focused on the diagnosis and management of uncommon cardiomyopathies, especially autoimmune variants of myocarditis. He is the cofounder and medical director of the Myocarditis Foundation.
How to reconcile this very low rate of histologic myocarditis with studies that have shown MRI abnormalities in COVID-19 is still an issue, he added, given that no studies to date have done MRI imaging and simultaneous heart biopsy.
"The way I could reconcile this is to say that new MRI findings broadly reflect cardiac effects of systemic as well as local inflammation, which could be edema, other causes of increased extracellular volume, or scar. SARS-CoV2 does not usually cause classic myocarditis."
Finn and Cooper both stressed that this study is referring to adult cases and is not directly relevant to the multisystem inflammatory syndrome in children, or MIC-S, that has been described in pediatric COVID sufferers, or to the issues of myocarditis in young athletes and return to sport recommendations.
The CVPath Institute is a nonprofit research institute that receives funding from a number of companies. Finn and Copper reported no relevant conflicts of interest.
J Am Coll Cardiol. 2021;77:314-325. Full text
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Cite this: Limited Pathologic Evidence That SARS-CoV-2 Infection Causes Myocarditis - Medscape - Jan 21, 2021.