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COVID Heart Autopsies Point More to Clot Damage Than Myocarditis

— Results bolster case for anticoagulation in hospitalized patients

Ƶ MedicalToday

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 .

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 Ƶ. "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.

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.

Disclosures

Guagliumi disclosed no relevant relationships with industry.