A careful look at the heart after death from COVID-19 suggested
cardiac damage was common, but more from clotting than inflammation,
researchers reported.
Autopsies on 40 people who died of COVID-19 showed that 14 had
cardiac injury as indicated by myocardial necrosis: an acute myocardial
infarction of at least 1 cm2 in three (7.5%) and smaller focal myocyte necrosis in 11 (27.5%).
Microthrombi were frequent, whereas none of those patients had
myocarditis, except sarcoid involvement in one case, reported Giulio
Guagliumi, MD, of Ospedale Papa Giovanni XXIII in Bergamo, Italy, and
colleagues at the virtual TCT Connect meeting.
Epicardial
coronary artery thrombosis was found in two of the myocardial necrosis
patients (14.2%) and microthrombi in nine (64.3%).
"We did not expect this," said study co-author Renu Virmani, MD, of
CVPath Institute in Gaithersburg, Maryland. The first case that prompted
this investigation was one that presented with more intramyocardial
capillary thrombi than she had ever seen.
"That alerted us so we made a concerted effort to look by multiple
sections. We took as much as 10 sections from the myocardium, from every
wall, from two levels so that we would not miss these things," she said
at the session. "That's what led us to discover that there's more than
just troponin I rise but really more to do with the fact that there is
true necrosis and not so much myocarditis."
Ischemic EKG changes had been present in more of the myocardial necrosis cases (43% vs 8% without necrosis, P=0.03)
and 44% of those with microthrombi. Notably, though, the virus was
detected in the heart for only nine patients (22.5%), with no difference
by myocardial necrosis or microthrombi presence.
"It
seems to be unlikely that the direct viral invasion of the heart is
playing a major role in making myocardial necrosis and microthrombi,"
Guagliumi told the virtual audience.
The microthrombi were rich in platelets, fibrin II, and complement activation terminal products.
"New targeted therapeutic approaches are needed for the prevention
and treatment of cardiac injury of the patients with COVID-19 disease,"
Guagliumi concluded.
Yet there are important implications for treatment now as well,
commented session co-chair Timothy Henry, MD, of The Christ Hospital in
Cincinnati.
"The prothrombotic aspect of acute coronary syndromes in patients who
are COVID-positive [is] becoming increasingly clear," he told MedPage Today.
"We know that in patients ST elevation- and COVID-positive there's a
higher percentage of people that have no clear culprit, so you go [to
angiography] and they have normal coronary arteries. A lot of people are
considering that myocarditis."
But
that now appears to be relatively rare, he said. "It's more likely to
be microthrombi. I think that's a really important point, because
influenza for example has more endocarditis. People need to be aware of
the importance of microthrombi."
For ST-elevation patients without obstructive disease, he said,
"typically we just stop, and we don't do anything else. Should we treat
them differently? And even if they do have epicardial disease, they
still [might] have microthrombi."
Session discussion panelist Valentin Fuster, MD, PhD, of Icahn School
of Medicine at Mount Sinai in New York City, noted that the pathology
findings help in answering the key question: "Is this predominantly
platelets or is this predominant of fibrin?"
Virmani noted that both were found, "but I was more impressed by the
fibrin." Transmission electron microscopy in a few cases showed fibrin
much more prominently, she said.
"I think this really makes us focus on anticoagulating these
patients," commented panelist Mamas Mamas, BMBCh, of Keele University in
Keele, England.(And if you do it as soon as diagnosed then you might not even see them as hospital patients or morgue candidates.)
Henry
also raised the question of intracoronary lysis for persistent ST
elevation and no epicardial disease. "I'm not sure what to do with
them," he said. "We know that they have higher mortality. It's clearly a
problem that needs to be solved."
Virmani suggested that troponin elevation beyond 1 ng/dL might help guide that decision.
Individualized decisions, taking into account complicating factors
like extracorporeal membrane oxygenation or intubation, will be
important, Henry agreed.
"In real time, having been on STEMI call here in New York during the
pandemic, it is difficult to use any kind of threshold of a biomarker
because it is such a dynamic process and resource allocation becomes a
really big part of our strategy for management," cautioned session
co-chair Sahil Parikh, MD, of NewYork-Presbyterian/Columbia University
Medical Center in New York City. "For patients with extensive LV
dysfunction, those are the ones I would target, and other patients I
would try to ride them out with anticoagulants."
Henry's North American COVID Myocardial Infarction Registry (NACMI)
will follow patients out 1 year to help determine true incidence of
lasting cardiac damage. "But part of the problem with myocardial damage
is I don't know [whether] you can distinguish from an MRI very easily an
infarction from widespread microthrombi versus myocarditis," Henry
said. "I think that might be difficult to tell the difference."
In the autopsy series, diffuse alveolar damage turned up in nearly
all of the lungs examined, with pulmonary artery thrombus in nearly half
and microthrombi in the alveolar septa in about a quarter.
Another presentation showed proof of concept that microvascular lung
thrombosis could be diagnosed with invasive optical coherence tomography
in COVID-19 patients with high D-dimer levels even CT scans were
negative for pulmonary embolism.
Parikh noted that such a strategy could be useful "perhaps as a
diagnostic test for some of these unexplained dyspneic patients who are
post-COVID-19 without any sort of either macro manifestations on imaging
or clinically that explain their dyspnea."
However, he cautioned that this approach could have practical
challenges and risk damage to vessels that are too small or too short.
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