Myocardial Inflammation and Dysfunction in COVID-19–Associated Myocardial Injury

Abstract

Background: Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed. Methods: We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy. Results: Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%–60.5%) but moderately to severely reduced left ventricular global longitudinal strain of −11.2% (−7.6% to −15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (−11.2% [−9.2% to −14.7%] versus −15.6% [−12.5% to −19.6%] at follow-up; P =0.041). Conclusions: In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.

Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity

“…During acute COVID-19, patients with elevated cardiac troponin have been reported to have elevated T1, extracellular volume and LGE measurements, in addition to enhanced macrophage numbers in myocardial biopsies 6 . In our study, higher concentrations of cTnT and NT-proBNP on admission were associated with the presence of scar or reduced LVEF on CMR after 6 months, and the highest concentrations were seen in patients classified with major CMR pathology.…”

“…Myocardial injury, reflected by elevated concentrations of cardiac troponins, is frequent but the prevalence depends on the baseline risk of the population and clinical setting 5 . A large proportion of hospitalized COVID-19 patients with elevated cardiac troponins has been reported to have elevated cardiovascular magnetic imaging (CMR) measurements of T1, extracellular volume or late gadolinium enhancement (LGE) with a non-ischemic pattern in the acute phase 6 . Retrospective studies have suggested that cardiac troponin and natriuretic peptides are markers of risk in COVID-19 2 , 7 .…”

The Right Ventricle in COVID-19

“…In spite of this evidence, the actual incidence of typical myocarditis (as diagnosed by the presence of at least seven CD3-positive T-lymphocytes/mm 2 ) in COVID-19 is extremely uncommon, occurring in only 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy (EMB) [124]. In contrast to the paucity of data regarding lymphocytic myocarditis in COVID-19, there is a significant proportion of autopsy [127] and EMB [128] specimens displaying an increased interstitial macrophage infiltration of the myocardium. Such high levels of myocardial macrophages point to non-specific myocardial inflammation resulting from high systemic levels of cytokines instead of direct viral-mediated myocarditis [127,129], as reported in other forms of pneumonias, although the occurrence of myocardial injury appears significantly higher in COVID than non-COVID pneumonia [120].…”

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation

“…[ 122 ] A study of Post-acute COVID-19 syndrome in Bergamo, Italy, found hypercoagulation in 17% of patients with D-dimer values that increased more than two times above 500 ng/mL [ 123 ]. In addition, ischemic cardiovascular events are increasing in COVID-19 [ 124 ], myocardial injury and elevated troponin levels are also reported [ 125 ] Inflammation and vascular leakage Trypomastigotes boost their infectivity through activation of the mast cell/kallikrein-kinin system pathway, resulting in inflammatory oedema [ 126 ] At the site of infection by T cruzi , C5a, and bradykinin are released and modulate innate and adaptive immunity, inflammation, and plasma leakage [ 127 ] The severity of COVID-19 is related to increased inflammation markers such as C-reactive protein (CRP), interleukin-6, nuclear factor kappa B (NFκB), and tumour necrosis factor-alpha (TNFα) as well as multiorgan failure [ 128 ] Mid-Regional proAdrenomedullin (MR-proADM), a marker of endothelial integrity and vascular leakage, is also related to severity and mortality in COVID-19 [ 129 ] During COVID-19, inflammation, vasodilation, hypotension, and plasma leakage may be due to the bradykinin system, in particular des-Arg9-BK, which acts on Bradykinin 1 (B1) receptor [ 130 ] …”

“…A study of Post-acute COVID-19 syndrome in Bergamo, Italy, found hypercoagulation in 17% of patients with D-dimer values that increased more than two times above 500 ng/mL [ 123 ]. In addition, ischemic cardiovascular events are increasing in COVID-19 [ 124 ], myocardial injury and elevated troponin levels are also reported [ 125 ]…”