An autopsy study published in Circulation finds that 35% of patients dying with coronavirus disease 2019 (COVID-19) had evidence of cardiac injury identified by the presence of myocyte necrosis, while the most common pathologic cause of myocyte necrosis was microthrombi.
“Cardiac injury is common in hospitalised patients with COVID-19 and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain,” wrote Dario Pellegrini, MD, Ospedale Papa Giovanni XXIII, Bergamo, Italy, and colleagues. “Here we report the first systematic analysis of the causes of cardiac injury in subjects dying of COVID-19 infection.”
Researchers conducted a systematic pathologic analysis of 40 hearts from hospitalised patients dying of COVID-19 to determine the pathologic mechanisms of cardiac injury. Average age of the patients was 74 years with the majority of them (72.5%) being male. Most (90%) of the patients were admitted for severe respiratory failure (median PaO2/FiO2 ratio, 123), while 4 (10%) patients presented with a cardiovascular emergency (three ST-segment elevation myocardial infarction [STEMI], one stroke). Except for the patients admitted with STEMI, no other cases of clinical myocardial infarction were recorded during hospitalisation.
Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with patients without necrosis, patients with necrosis tended to be female, had a greater prevalence of chronic kidney disease, had a higher rate of STEMI at presentation, and shorter symptom onset to admission. Meanwhile, the incidence of severe coronary artery disease (ie, >75% cross sectional narrowing) was not significantly different between those with and without necrosis.
Of the 14 patients with myocyte necrosis, 3 (21.4%) showed evidence of acute myocardial infarction defined as ≥1 cm2 area of necrosis, while 11 (78.6%) showed evidence of focal (> 20 necrotic myocytes with an area of ≥ 0.05 mm2 but <1 cm2) myocyte necrosis. Additionally, cardiac thrombi were present in 11 (78.6%) of the 14 cases with necrosis, whereby 2 (14.2%) had epicardial coronary artery thrombi while 9 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries.
The researchers then compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19-negative cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from COVID-19-positive and COVID-19-negative patients presenting with STEMI. They found that microthrombi from COVID-19 patients had significantly greater fibrin and terminal complement C5b-9 immunostaining compared to intramyocardial thromboemboli from COVID-19-negative patients and to aspirates from STEMI patients (both non COVID-19 and COVID-19). There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and COVID-19-negative STEMI patients.
“Clinicians should be aware of the possibility of microthrombi which may not be detectable clinically as a cause of cardiac injury in subjects with COVID-19 infection,” the authors noted. “Cardiac microthrombi would not be detectable clinically as no laboratory test can specifically detect microthrombi but future studies should be directed towards developing methods and laboratory testing to diagnose this type of injury.”
“The use of tailored anti-thrombotic strategies to counteract the effects of microthrombi on the heart may be useful and should be examined,” the authors added.