tetano
Editor, Senior Moderator
Circulation
. 2021 Jan 22.
doi: 10.1161/CIRCULATIONAHA.120.051828. Online ahead of print.
Microthrombi As A Major Cause of Cardiac Injury in COVID-19: A Pathologic Study
Dario Pellegrini[SUP] 1 [/SUP], Rika Kawakami[SUP] 2 [/SUP], Giulio Guagliumi[SUP] 1 [/SUP], Atsushi Sakamoto[SUP] 2 [/SUP], Kenji Kawai[SUP] 2 [/SUP], Andrea Gianatti[SUP] 1 [/SUP], Ahmed Nasr[SUP] 1 [/SUP], Robert Kutys[SUP] 2 [/SUP], Liang Guo[SUP] 2 [/SUP], Anne Cornelissen[SUP] 2 [/SUP], Lara Faggi[SUP] 1 [/SUP], Masayuki Mori[SUP] 2 [/SUP], Yu Sato[SUP] 2 [/SUP], Irene Pescetelli[SUP] 1 [/SUP], Matteo Brivio[SUP] 1 [/SUP], Maria Romero[SUP] 2 [/SUP], Renu Virmani[SUP] 2 [/SUP], Aloke V Finn[SUP] 3 [/SUP]
Affiliations
Abstract
Background: Cardiac injury is common in hospitalized patients with COVID-19 and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with SARS-CoV-2 remain uncertain. Methods: We conducted a systematic pathologic analysis of 40 hearts from hospitalized patients dying of Coronavirus Disease 2019 (COVID-19) in Bergamo, Italy to determine the pathologic mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. As compared to subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and shorter symptom onset to admission. The incidence of severe coronary artery disease (i.e., >75% cross sectional narrowing) was not significantly different between those with and without necrosis. 3/14 (21 .4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction defined as ≥1 cm[SUP]2[/SUP] area of necrosis while 11/14 (78.6%) showed evidence of focal (> 20 necrotic myocytes with an area of ≥ 0.05 mm[SUP]2[/SUP] but <1 cm[SUP]2[/SUP]) myocyte necrosis. Cardiac thrombi were present in 11/14 (78.6%) cases with necrosis, with 2/14 (14.2%) having epicardial coronary artery thrombi while 9/14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19 positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19 infected patients presenting with ST-segment elevation myocardial infarction (STEMI). Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19 positive and negative STEMI patients. Conclusions: The most common pathologic cause of myocyte necrosis was microthrombi. Microthrombi were different in composition as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to coronary thrombi retrieved from COVID-19 positive and negative STEMI patients. Tailored anti-thrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.
Keywords: COVID-19; SARS-CoV-2; cardiovascular disease; heart.
. 2021 Jan 22.
doi: 10.1161/CIRCULATIONAHA.120.051828. Online ahead of print.
Microthrombi As A Major Cause of Cardiac Injury in COVID-19: A Pathologic Study
Dario Pellegrini[SUP] 1 [/SUP], Rika Kawakami[SUP] 2 [/SUP], Giulio Guagliumi[SUP] 1 [/SUP], Atsushi Sakamoto[SUP] 2 [/SUP], Kenji Kawai[SUP] 2 [/SUP], Andrea Gianatti[SUP] 1 [/SUP], Ahmed Nasr[SUP] 1 [/SUP], Robert Kutys[SUP] 2 [/SUP], Liang Guo[SUP] 2 [/SUP], Anne Cornelissen[SUP] 2 [/SUP], Lara Faggi[SUP] 1 [/SUP], Masayuki Mori[SUP] 2 [/SUP], Yu Sato[SUP] 2 [/SUP], Irene Pescetelli[SUP] 1 [/SUP], Matteo Brivio[SUP] 1 [/SUP], Maria Romero[SUP] 2 [/SUP], Renu Virmani[SUP] 2 [/SUP], Aloke V Finn[SUP] 3 [/SUP]
Affiliations
- PMID: 33480806
- DOI: 10.1161/CIRCULATIONAHA.120.051828
Abstract
Background: Cardiac injury is common in hospitalized patients with COVID-19 and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with SARS-CoV-2 remain uncertain. Methods: We conducted a systematic pathologic analysis of 40 hearts from hospitalized patients dying of Coronavirus Disease 2019 (COVID-19) in Bergamo, Italy to determine the pathologic mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. As compared to subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and shorter symptom onset to admission. The incidence of severe coronary artery disease (i.e., >75% cross sectional narrowing) was not significantly different between those with and without necrosis. 3/14 (21 .4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction defined as ≥1 cm[SUP]2[/SUP] area of necrosis while 11/14 (78.6%) showed evidence of focal (> 20 necrotic myocytes with an area of ≥ 0.05 mm[SUP]2[/SUP] but <1 cm[SUP]2[/SUP]) myocyte necrosis. Cardiac thrombi were present in 11/14 (78.6%) cases with necrosis, with 2/14 (14.2%) having epicardial coronary artery thrombi while 9/14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19 positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19 infected patients presenting with ST-segment elevation myocardial infarction (STEMI). Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19 positive and negative STEMI patients. Conclusions: The most common pathologic cause of myocyte necrosis was microthrombi. Microthrombi were different in composition as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to coronary thrombi retrieved from COVID-19 positive and negative STEMI patients. Tailored anti-thrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.
Keywords: COVID-19; SARS-CoV-2; cardiovascular disease; heart.