COVID-19 and myocarditis: a systematic review and overview of current challenges

Abstract

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Cardiac complications during the active phase of COVID-19: review of the current evidence

“…Comparing that with the reported cases of myocarditis in COVID-19 patients, most presented with fever (up to 58%), dyspnea (up to 74%), and chest pain (up to 25%) [41,42], which coincide with the previous diagnostic symptoms of myocarditis [40]. Moreover, utilized diagnostic methods included cardiac biomarkers levels, ECG, echocardiography, and CMR, showed a wide range of abnormalities reaching up to 90, 84, 79, and 76%, respectively [41,42], which could further support myocardial injury. CMR changes included late gadolinium enhancement (50%) and diffuse edema and myocardial inflammation (76%); alarmingly, the former could be associated with lifethreatening arrythmias and sudden cardiac death [43], and the latter with severe complications including heart failure [44].…”

“…In an early study from Wuhan, China, with 187 patients, mortality rate increased from 7.62 to 13.3% in those with CVD history, and to 37.5% with both CVD history and acutely increased troponin T [8]. These early observations were also supported by more recent systematic reviews of myocarditis cases, where mortality rates with myocarditis were higher than the reported overall COVID-19 mortality [11], and ranged from 13 to 26% [41,42,45]. In addition to increasing mortality, myocardial injury could worsen COVID-19 recovery course.…”

“…CMR changes included late gadolinium enhancement (50%) and diffuse edema and myocardial inflammation (76%); alarmingly, the former could be associated with lifethreatening arrythmias and sudden cardiac death [43], and the latter with severe complications including heart failure [44]. Histologic evidence is still limited, EMB, done in a minority of the patients, demonstrated myocardial inflammation with predominant macrophages, confirming myocardial inflammation (eight cases), and one case showed SARS-CoV-2 in cardiomyocytes [41], providing in-vivo proof of possible direct viral injury (Table 1).…”

“…The 2013 European Society of Cardiology position statement defines clinically suspected myocarditis in a patient having ≥ 1 clinical criterion such as chest pain or palpitations and ≥ 1 diagnostic criterion such as elevated troponin I or T, electrocardiography (ECG) or cardiac magnetic resonance (CMR) findings [40]. Comparing that with the reported cases of myocarditis in COVID-19 patients, most presented with fever (up to 58%), dyspnea (up to 74%), and chest pain (up to 25%) [41,42], which coincide with the previous diagnostic symptoms of myocarditis [40]. Moreover, utilized diagnostic methods included cardiac biomarkers levels, ECG, echocardiography, and CMR, showed a wide range of abnormalities reaching up to 90, 84, 79, and 76%, respectively [41,42], which could further support myocardial injury.…”

COVID-19 and Acute Myocardial Injury and Infarction: Related Mechanisms and Emerging Challenges

“…myocarditis caused by direct virus invasion of the myocardium has not convincingly been demonstrated as yet, 41 with possible rare exceptions, 42 as myocardial injury is more likely related to systemic consequences rather than direct damage by COVID-19. 43,44 Thus, due to the low frequency of COVID-19-induced myocarditis and unclear therapeutic implications, investigators have advised against the use of EMB to diagnose myocarditis in the setting of COVID-19. 45 Anyhow, CMR is suggested as the preferred imaging modality for non-invasive evaluation in acute myocarditis, enabling risk stratification and prognostication.…”