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

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.

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

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.

Myocarditis following COVID-19 vaccination in adolescents and adults: a cumulative experience of 2021.

Clinical course and outcomes of myocarditis after COVID-19 vaccination remain variable. We retrospectively collected data on patients > 12 years old from 01/01/2021 to 12/30/2021 who received COVID-19 messenger RNA (mRNA) vaccination and were diagnosed with myocarditis within 60 days of vaccination. Myocarditis cases were based on case definitions by authors. We report on 238 patients of whom most were male (n = 208; 87.1%). The mean age was 27.4 ± 16 (range 12-80) years. Females presented at older ages (41.3 ± 21.5 years) than men 25.7 ± 14 years (p = 0.001). In patients > 20 years of age, the mean duration from vaccination to symptoms was 4.8 days ± 5.5 days, but in < 20, it was 3.0 ± 3.3 days (p = 0.04). Myocarditis occurred most commonly after the Pfizer-BioNTech mRNA vaccine (n = 183; 76.45) and after the second dose (n = 182; 80%). Symptoms started 3.95 ± 4.5 days after vaccination. The commonest symptom was chest pain (n = 221; 93%). Patients were treated with non-steroidal anti-inflammatory drugs (n = 105; 58.3%), colchicine (n = 38; 21.1%), or glucocorticoids (n = 23; 12.7%). About 30% of the patients had left ventricular ejection fraction but more than half recovered the on repeat imaging. Abnormal cardiac MRIs were common; 168 patients (96% of 175 patients that had MRI) had late gadolinium enhancement, while 120 patients (68.5%) had myocardial edema. Heart failure guideline-directed medical therapy use was common (n = 27; 15%). Eleven patients had cardiogenic shock; and 4 patients required mechanical circulatory support. Five patients (1.7%) died; of these, 3 patients had endomyocardial biopsy/autopsy-confirmed myocarditis. Most cases of COVID-19 vaccine myocarditis are mild. Females presented at older ages than men and duration from vaccination to symptoms was longer in patients > 20 years. Cardiogenic shock requiring mechanical circulatory support was seen and mortality was low. Future studies are needed to better evaluate risk factors, and long-term outcomes of COVID-19 mRNA vaccine myocarditis.

SARS-CoV-2 infection in heart transplant recipients: a systematic literature review of clinical outcomes and immunosuppression strategies.

The impact of SARS-CoV-2 infection on heart transplant recipients is unknown. Literature is limited to case reports and series. The purpose of this study is to identify the clinical features, outcomes, and immunosuppression strategies of heart transplant recipients with COVID-19 infection. A systematic review was conducted using the search term "Coronavirus" or COVID," "SARS-CoV-2," "cardiac transplantation," and "heart transplant." Case reports and retrospective studies were gathered by searching Medline/PubMed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science. Thirty-three articles were selected for review. We identified 74 cases of SARS-CoV-2 infection in heart transplant and heart-kidney transplant recipients. The mean age was 60.5 ± 15.8 years, and 82.4% were males with median time from transplant of 6.5 years. Commonest symptoms were fever, cough, and dyspnea, but new left ventricular (LV) dysfunction was rare. Leukocytosis, lymphopenia, elevated inflammatory markers, and bilateral ground-glass opacities were common. Mortality was high, with particularly poor survival in patients who required intensive care unit (ICU) admission and older patients. Immunosuppression involved discontinuation of antimetabolites and steroids. COVID-19 infection in heart transplant (HT) recipients presents similarly to the general population, but new onset of LV dysfunction is uncommon. Immunosuppression strategies include increase in corticosteroids and discontinuation of antimetabolites.

Calcineurin-Inhibitor Induced Pain Syndrome in a Heart Transplant Patient.

Calcineurin-inhibitor induced pain syndrome (CIPS) also called the "symmetrical bone syndrome" is a condition describing reversible lower extremity pain in patients after organ transplantation who are receiving calcineurin inhibitors, especially tacrolimus. We present a case of CIPS after orthotopic heart transplant complicated with concurrent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We emphasize the presentation; diagnostic evaluation, and findings. We then discuss the proposed pathophysiologic mechanisms of CIPS and conclude with discussion of management strategies. Additionally, we present a table to guide clinicians in assessing posttransplant bone pain syndromes. To our knowledge, this is the first article to describe a case of CIPS with concurrent SARS-CoV-2 infection.

Clinical variants of myocardial involvement in COVID-19-positive patients: a cumulative experience of 2020.

Myocardial injury, diagnosed by troponin elevation, is common in COVID-19 patients, but cardiac involvement with clinical manifestations occurs less frequently. We analyzed the literature on COVID-19 (2020) and systematically reviewed the cases where individual patient data were presented. We searched PubMed and Google Scholar for "COVID," "COVID-19," and "coronavirus" in combination with "myocarditis," "heart failure," "takotsubo," "cardiomyopathy," and "cardiogenic shock." We identified 90 cases of COVID-19 with myocardial involvement, mean age 52.9 ± 18.3 years, 54.5% males. Of them, 55 survived (61.1%), 20 died (22.2%), and in 15 (16.7%) the outcome was unknown at the time of publication. Among patients with known outcome, mortality was 26%. The nadir LVEF was 31.7 ± 13.1% and recovered to 50.1 ± 16.0%. Pericardial effusion was a common finding, reported in 21 (23.3%) of patients, including moderate size effusion in 8.9% and large in 7.8%. The effusion caused tamponade in 11 (12.2%) of patients. Out of 83 patients who experienced a decrease in LVEF, 30 could be classified as takotsubo syndrome. The takotsubo patients were older than those with myocarditis, and with relatively high proportion of males. About one third of the cases was complicated by cardiogenic shock. Myocardial involvement in COVID-19 patients most often presents as a new, rapid decrease in LVEF, although normal LVEF or takotsubo-like wall motion pattern does not rule out myocarditis. Moderate and large pericardial effusion is common, and cardiac tamponade occurs in 12.2% of patients. Cardiogenic shock develops in one third of the patients. Mortality appears to be high at 26%.

Acute Biventricular Heart Failure After COVID-19 Infection in an Orthotropic Heart Transplant Patient: A Case Report.

The cardiac effects of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include myocarditis, takotsubo cardiomyopathy, pericardial effusion, and cardioembolic events in the general population. The effects of SARS-CoV-2 in heart transplant patients are unclear. We describe a case of myocarditis in the transplanted heart that responded to methylprednisolone.

Fulminant myocarditis: COVID or not COVID? Reinfection or co-infection?

We describe a unique case of fulminant myocarditis in a patient with presumed SARS-CoV-2 reinfection. Patient had initial infection 4 months backand had COVID-19 antibody at the time of presentation. Endomyocardial biopsy showed lymphocytic myocarditis, that is usually seen in viral myocarditis. The molecular diagnostic testing of the endomyocardial biopsy for cardiotropic viruses was positive for Parvovirus and negative for SARS-CoV-2. Authors highly suspect co-infection of SARS-CoV-2 and Parvovirus, that possibly triggered the immune cascade resulting in fulminant myocarditis. Patient was hemodynamically unstable with ventricular tachycardia and was supported on VA ECMO and Impella CP. There was impressive recovery of left ventricular function within 48 h, leading to decannulation of VA ECMO in 72 h. This unique case was written by the survivor herself.

Cardiogenic shock following cardiac tamponade and Takotsubo in COVID-19.

Introduction: Takotsubo is often described as stress-induced cardiomyopathy and is a known cause of heart failure. Objective: Review the clinical course of a young coronavirus disease 2019 (COVID-19) patient who developed Takotsubo following cardiac tamponade. Case presentation: A 42-year-old woman presented to the emergency department with fever, altered mental status and hypoxia. She was ultimately found to be in cardiac tamponade and within 2 hours of a pericardiocentesis she developed Takotsubo and was in cardiogenic shock. Her family decided to place her on comfort measures and she died the same day. Discussion: This case illustrates the increasing number of cardiovascular complications being reported in COVID-19 and highlights the importance of clinicians to be aware of these challenges. Conclusion: Here, we report a distinct presentation of cardiogenic shock in a young COVID-19 patient. The rapid onset of her suspected Takotsubo and the severity of her disease were striking features in this case.