Fulminant Myocarditis and Cardiogenic Shock Following COVID-19 Infection Versus COVID-19 Vaccination: A Systematic Literature Review

Abstract

Background: Myocarditis, diagnosed by symptoms and troponin elevation, has been well-described with COVID-19 infection, as well as shortly after COVID-19 vaccination. The literature has characterized the outcomes of myocarditis following COVID-19 infection and vaccination, but clinicopathologic, hemodynamic, and pathologic features following fulminant myocarditis have not been well-characterized. We aimed to compare clinical and pathological features of fulminant myocarditis requiring hemodynamic support with vasopressors/inotropes and mechanical circulatory support (MCS), in these two conditions. Methods: We analyzed the literature on fulminant myocarditis and cardiogenic shock associated with COVID-19 and COVID-19 vaccination and systematically reviewed all cases and case series where individual patient data were presented. We searched PubMed, EMBASE, and Google Scholar for “COVID”, “COVID-19”, and “coronavirus” in combination with “vaccine”, “fulminant myocarditis”, “acute heart failure”, and “cardiogenic shock”. The Student’s t-test was used for continuous variables and the χ2 statistic was used for categorical variables. For non-normal data distributions, the Wilcoxon Rank Sum Test was used for statistical comparisons. Results: We identified 73 cases and 27 cases of fulminant myocarditis associated with COVID-19 infection (COVID-19 FM) and COVID-19 vaccination (COVID-19 vaccine FM), respectively. Fever, shortness of breath, and chest pain were common presentations, but shortness of breath and pulmonary infiltrates were more often present in COVID-19 FM. Tachycardia, hypotension, leukocytosis, and lactic acidosis were seen in both cohorts, but patients with COVID-19 FM were more tachycardic and hypotensive. Histologically, lymphocytic myocarditis dominated both subsets, with some cases of eosinophilic myocarditis in both cohorts. Cellular necrosis was seen in 44.0% and 47.8% of COVID-19 FM and COVID-19 vaccine FM, respectively. Vasopressors and inotropes were used in 69.9% of COVID-19 FM and in 63.0% of the COVID-19 vaccine FM. Cardiac arrest was observed more in COVID-19 FM (p = 0.008). Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock was also used more commonly in the COVID-19 fulminant myocarditis group (p = 0.0293). Reported mortality was similar (27.7%) and 27.8%, respectively) but was likely worse for COVID-19 FM as the outcome was still unknown in 11% of cases. Conclusions: In the first series to retrospectively assess fulminant myocarditis associated with COVID-19 infection versus COVID-19 vaccination, we found that both conditions had a similarly high mortality rate, while COVID-19 FM had a more malignant course with more symptoms on presentation, more profound hemodynamic decompensation (higher heart rate, lower blood pressure), more cardiac arrests, and higher temporary MCS requirements including VA-ECMO. In terms of pathology, there was no difference in most biopsies/autopsies that demonstrated lymphocytic infiltrates and some eosinophilic or mixed infiltrates. There was no predominance of young males in COVID-19 vaccine FM cases, with male patients representing only 40.9% of the cohort.

Natural Course of COVID-19 and Independent Predictors of Mortality

“…This is particularly relevant considering that a recent meta-analysis compared fulminant myocarditis associated with COVID-19 infection versus COVID-19 vaccination. While this study reported a similarly high mortality rate and no differences in most biopsies/autopsies between these conditions, COVID-19 fulminant myocarditis was associated with a more aggressive course with more severe hemodynamic decompensation and more cardiac arrests [ 24 ].…”

Mechanical Circulatory Support Systems in Fulminant Myocarditis: Recent Advances and Outlook

“…Both males and females were almost equally distributed, and the median age was reported to be 45 years. The authors describe a comparably high necessity of inotropes and MCS paired with a high mortality rate of 27.7% [ 33 ]. Treatment options for myocarditis vary depending on the severity of disease and the underlying cause of myocarditis.…”

“…Unlike other forms of FM that are primarily defined by their histological features, COVID-19-associated AM displays heterogeneous histological presentations [ 32 ]. In both COVID-19- and vaccination-associated forms, LM appears to be the most commonly reported pattern, followed by eosinophilic and mixed infiltrates [ 33 ]. Ammirati et al reported 10 fulminant cases that required temporary MCS systems with a median support time of 5 days.…”

“…Moreover, VA-ECMO was used more often in the COVID-19 group, possibly reflecting an increased oxygen demand. Despite these differences, overall mortality rates were comparably high in both groups [ 33 ]. As of yet, there are no clear treatment recommendations for COVID-19 and vaccination-related FM due to the novelty of the field.…”

“…When EMB was available, most reported cases were treated based on their histological presentation. Furthermore, many patients received Remdesivir or Hydroxy-chloroquine [ 33 ]. Finally, Maunier et al emphasised the possible therapeutic value of Anakinra in 7 paediatric cases of COVID-19-associated FM [ 106 ].…”