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. 2020 May 5;S1547-5271(20)30422-7.
doi: 10.1016/j.hrthm.2020.05.001. Online ahead of print.

Recognizing COVID-19-related Myocarditis: The Possible Pathophysiology and Proposed Guideline for Diagnosis and Management

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Free PMC article

Recognizing COVID-19-related Myocarditis: The Possible Pathophysiology and Proposed Guideline for Diagnosis and Management

Bhurint Siripanthong et al. Heart Rhythm. .
Free PMC article

Abstract

Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host's immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown.

Keywords: Arrhythmias; Coronavirus disease 2019; Endomyocardial biopsy; Fulminant myocarditis; Interleukin-6; SARS-CoV-2.

Figures

Figure 1
Figure 1
The proposed pathophysiology of SARS-CoV-2 myocarditis. SARS-CoV-2 utilizes the spike protein (primed by TMPRSS2) to bind ACE2 to allow cell entry. Intracellular SARS-CoV-2 might impair stress granule formation via its accessory protein. Without the stress granules, the virus is allowed to replicate and damage the cell. Naïve T-lymphocytes can be primed for the viral antigens via antigen-presenting cells and cardiotropism by the heart-produced hepatocyte growth factor (HGF). The HGF binds c-Met, a HGF receptor on the T-lymphocytes. The primed CD8+ T-lymphocytes migrate to the cardiomyocytes and cause myocardial inflammation through cell-mediated cytotoxicity. In the cytokine storm syndrome, where pro-inflammatory cytokines are released into the circulation, T-lymphocyte activation is augmented and releases more cytokines. This results in a positive-feedback loop of immune activation and myocardial damage. ACE2 = Angiotensin-converting enzyme 2; APC = Antigen-presenting cell; HGF = Hepatocyte growth factor; IL-6 = Interleukin-6; MHC = Major histocompatibility complex; TCR = T-cell receptor.
Figure 2
Figure 2
Arrhythmogenesis in SARS-CoV-2-related myocarditis. The possible mechanisms responsible for arrhythmias in SARS-CoV-2-related myocarditis. 1, 2 and 3 could occur in the acute setting while 4 and 5 occur in the chronic/healed myocarditis. Modified with permission from Peretto et al.33ACE2 = Angiotensin-converting enzyme 2; IL-6 = Interleukin-6.
Figure 3
Figure 3
Typical CMR and CT findings of myocarditis: Panels A and D. Cardiac edema (yellow arrows) in the T2-weighted mode. Panels B and C. LGE of the subepicardial region (yellow arrows) of the ventricles, a sign of myocardial fibrosis or scarring. Panel E. Mid-myocardial LGE (yellow arrows) is often present in the acute setting and resolved at follow-up. Panel F. LGE resolved in the chronic case; these areas may initially represent acute myocardial edema (yellow arrows) and resolve over time. Panels G and H. CMR imaging, the region of interest measurements obtained, G, before and, H, after gadolinium chelate administration. Panels I and J. Reformatted cardiac CT, the region of interest measurements obtained, I, before and, J, after administration of an iodinated contrast agent. For cardiac CT, the anterolateral myocardium was most reliably identified before administration of an iodinated contrast agent. There, a region of interest from the anterolateral myocardium was used for attenuation measurements. A focal myocardial scar was identified on delayed CMR images and was not included in the region of interest. Orange outline = myocardium, white circle = blood pool. A-F modified from Kociol et al. and G-J from Nacif et al. with permissions. LGE = Late Gadolinium Enhancement
Figure 4
Figure 4
Suggested diagnostic and management protocol for SARS-CoV-2-related myocarditis. ACS = acute coronary syndrome; CMR = cardiovascular magnetic resonance; CO = cardiac output; CRP = C-reactive protein; CT-CA = computerized tomography coronary angiogram; cTn = Cardiac troponin; DCCV = direct current cardioversion; ECG = electrocardiogram; ECMO = Extracorporeal membrane oxygenation; EMB = endomyocardial biopsy; ESR = Erythrocyte sedimentation rate; IABP = intra-aortic balloon pump; NSAID = Non-steroidal anti-inflammatory drug; NT-proBNP = N-terminal pro-B-type natriuretic peptide; TTE = transthoracic echocardiogram; VAD = ventricular assist device; ΔΔ = differential diagnoses

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