Fulminant Giant Cell Myocarditis vs. Lymphocytic Myocarditis: A Comparison of Their Clinical Characteristics, Treatments, and Outcomes

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM).Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0–10.2) mg/L vs. 13.6 (12.6–14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0–3.2) ng/ml vs. 14.6 (3.0–64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0–61.5) IU/L vs. 997.0 (50.0–3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761–0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213–0.9964).Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

Multimodality imaging and histopathology in a young man presenting with fulminant lymphocytic myocarditis and cardiogenic shock after mRNA-1273 vaccination

A 38-year-old man presented with several days of chest pain and shortness of breath 8 days after receiving the first dose of an mRNA-1273 vaccine. The patient was found to have new left ventricular ejection fraction of 10% in the setting of hypotension and cardiogenic shock requiring mechanical support with an axial flow catheter pump. The presentation was concerning for acute fulminant myocarditis secondary to an inflammatory response from the recent mRNA-1273 vaccine. The patient was treated with pulse dose steroids for 3 days, ultimately leading to haemodynamic recovery and removal of mechanical circulatory support. Endomyocardial biopsy was performed and showed focal lymphocytic interstitial infiltrate with myocyte damage consistent with lymphocytic myocarditis. The patient had improvement of cardiac function which was seen on serial imaging.

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections in Kurdistan Province, Iran: A Case Series

Background: Coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and is the cause of an ongoing pandemic, with increasing deaths worldwide. Here in we present the results of the histopathological study of the main organs of 25 patients who died due to confirmed COVID-19.Methods: In this case series, patients base on needle necropsy of multiple organs of dead patients with a positive antemortem SARS-CoV-2 (COVID-19) real time PCR. Needle necropsy of corpses of 25 patients enrolling the study were performed until 3 hours after death in the negative-pressure isolation morgue who hospitalized at Kurdistan University of medical sciences Tohid and Kowsar hospitals with proved COVID-19 infection and were died due to severe disease manifestations.Results: The mean age of the participants in this study was 74.68 ± 9.41 (52–91) years old. The participants included 19 men (76%) and 6 women (24%). In myocardial necropsy, twelve patients were reported to be lymphocytic myocarditis, three of them were reported to have pericarditis as well, and in one case focal visual fibrosis was reported. Histopathological examinations of liver revealed that among twenty-two samples, five cases had acute hepatitis that four of them were mild in type. Steatohepatitis was reported in six cases and two of them were macrovesicular in type. Macrovesicular Steatosis was reported along with steatohepatitis and stage 4 fibrosis through trichrome staining. Muscles necropsy revealed viral myositis for three patients.Conclusions: Our study shows extra-pulmonary multi organ involvement through COVID-19 disease. 77% of patients representing acute or chronic hepatitis and 48% of them revealed lymphocytic myocarditis accompanied with pericarditis in 12% of cases and 12% of patient’s show myositis. It looks diffuse inflammatory disease which attacks to some organs like myocardium, liver and muscles. Broad extra pulmonary pathology and laboratory findings are occurred that all suggestive of multi organ involvement directly or through systemic viremia and immune system response.

Comparative efficacy and safety of mycophenolate mofetil and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis

Purpose To compare of the efficacy and safety of mycophenolate mofetil (MM) and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis. Methods The study included 45 patients with lymphocytic myocarditis, 34 male, the average age 48.1±11.2 years. The diagnosis of myocarditis is verified by endomyocardial biopsy. In ten patients of both groups, the parvovirus B19 DNA was detected in the myocardium. All patients had heart failure 3 [3; 3] NYHA class. High immune activity was indicated by the presence of anti-heart antibodies in all patients. Group 1 included twenty-six patients who received MM 2 g per day. Twenty of them were naive; six patients received MM instead of azathioprine, which was canceled due to cytopenia and/or insufficient effect. Group 2 included nineteen patients who received azathioprine at an average dose of 100 [75; 150] mg per day. Patients of both groups also received methylprednisolone in an average starting dose 24 [24; 32] mg per day and standard therapy for heart failure. Initial group distribution was random. Patients in both groups did not differ significantly in baseline parameters. The mean follow-up period was 23 [8; 57] months (12 and 34 months in the groups). The study is approved by the university ethics committee. Results The level of anti-heart antibodies significantly decreased in both groups. In both groups there was a significant improvement in the structural and functional parameters of the heart: NYHA class decreased from 3 [2.75; 3] to 2 [1; 2] (group 1, p<0.001) and from 3 [3; 3] to 2 [1; 2] (group 2, p<0.001), LV EF increased initially from 30.6±7.8 to 40.1±7.5% (group 1, p<0.001) and from 27.9±8.1 to 37.1±7.6% (group 2, p<0.01), by the end of follow-up to 45.9±9.0% (group 1, p<0.001) and to 42.4±13.7% (group 2, p<0.01). LV EDD significantly decreased from 6.4±0.6 to 6.1±0.8 cm (p<0.01), left atria size from 4.9±0.7 to 4.3±0.6 cm (p<0.05) and pulmonary arteria systolic pressure from 37.8±12.3 to 29.3±7.6 (p<0.05) only in the group 1. No direct side effects of MM were noted. Cytopenia due to treatment of azathioprine developed in 3 patients and required its replacement. There were no significant differences between groups 1 and 2 in overall mortality (7.7 vs 15.8%) and the transplant + death rate (7.7 vs 21.1%). The better survival in the MM group may be due to a shorter follow-up period. Conclusion In patients with lymphocytic myocarditis, a combination of moderate doses of corticosteroids with MM is at least no less effective and safe than steroids with azathioprine. With a shorter follow-up period, the tendency to lower mortality and a more pronounced improvement in structural parameters with better tolerance was noted in the MM group. MM should be considered as an alternative option in the treatment of isolated lymphocytic myocarditis. FUNDunding Acknowledgement Type of funding sources: None.

Features of the expression of fibroblast growth factor in patients with idiopathic atrial fibrillation and verified myocarditis

Introduction Myocarditis and inflammatory changes in the myocardium can be one of the causes of the development and progression of atrial fibrillation (AF). The biomarker FGFβ is involved in the processes of angiogenesis, repair of heart tissues and stimulates fibroblasts. Purpose To assess the dynamics and to identify the relationship of fibroblast growth factor (FGFβ) expression and myocardial inflammatory diseases revealed by the results of histological examination of endomyocardial biopsy in patients with various forms of idiopathic AF. Methods Subjects were 40 patients (41.0±9.2 y.o.) with idiopathic AF, the arrhythmic history constituted 4.9±3.9 years. The patients were divided into 3 groups: 1–with paroxysmal AF (n=15), 2–persistent (n=12), 3–long-term persistent (n=13) depending on the form of AF. All patients underwent radiofrequency ablation (RFA) of the pulmonary veins and endomyocardial byopsy with histologic and immunohistochemical studies. In 1st group active lymphocytic myocarditis (ALM) were found in 40% patients (n=6); in 2d and 3d groups – 66.7% (n=8 in each gr.). All other patients showed signs of lymphocytic infiltration (LI). The serum levels of FGFβ determined all patients in prior to intervention (T1) and in 6 months after RFA (T2). Results Comparative analysis showed, in patients with morphologically verified ALM, the FGFb levels in 6 months after RFA in 1st gr. was significantly higher than in 3d gr. (p=0.036). In patients gr.1 with ALM the levels of FGFb was higher (at stages T1 and T2) than in patients with LI (p=0.055 and p=0.06, respectively). In 1st gr., a positive association between the levels of FGFb (T1) and the degree of activity of inflammatory processes caused in 6 months after RFA (R=0.95 p=0.005) were identified. In 1st gr., the relationship between the degree of activity of inflammatory processes and fibrotic changes (R=−0.77 p=0.009) and an association of FGFb with the value of cardiac ejection fraction was obtained (R=0.90 p=0.037). In 2d gr., strong correlations of FGFb with the degree of activity of inflammatory processes (R=0.79 p=0.019) and ejection fraction (RT1=0.73 p=0.039, RT2=0.96 p=0.0002) were revealed. In 3d gr., the FGFb levels was significantly higher in patients with LI than with ALM (14.74 [13.28; 14.80] and 6.92 [5.65; 9.90] pg/ml, respectively; p=0.048). In 3d gr., the severity of fibrotic changes was associated with FGFb expression (RT1=−0.73 p=0.041, RT2=−0.85 p=0.008). Conclusion The relationships of FGFb with the degree of activity of inflammatory processes in groups with paroxysmal and persistent AF were revealed. In patients with active lymphocytic myocarditis, the FGFb level was significantly higher in paroxysmal AF than in long-term persistent AF. Our study showed, increased expression of FGFb is associated with inflammatory processes of active lymphocytic myocarditis, and may be due to intense proliferation and differentiation of fibroblasts in paroxysmal AF. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Cardiology Research Institute, Tomsk NRMC

Effectiveness of immunosuppressive therapy for lymphocytic myocarditis according: data from actual clinical practice

Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility.

Myocarditis and Inflammatory Cardiomyopathy

Activation of the inflammatory system occurs in most patients with advanced heart failure, regardless of etiology, and contributes to the pathophysiological milieu and the progression of the disease. The term inflammatory cardiomyopathy (ICM) refers to a group of disorders for which an acute or chronic myocardial inflammation is the central cause of abnormal cardiac structure or impaired cardiac function. The most common cause of inflammatory cardiomyopathy is lymphocytic myocarditis, which is most usually triggered by a viral infection, and occasionally by other infectious agents. Rare causes of specific inflammatory cardiomyopathies include cardiac sarcoidosis, giant cell myocarditis and eosinophilic myocarditis. Inflammatory cardiomyopathy can also occur in connection with autoimmune inflammatory diseases. Typical manifestations of inflammatory cardiomyopathy include chest pain, heart failure, and arrhythmias, but these symptoms and signs are unspecific. Although non-invasive diagnostic methods are emerging, the gold standard of diagnosis is the histological examination of an endomyocardial biopsy. Owing to the invasive nature of this technique and a modest diagnostic sensitivity, its use is limited. Therefore, the identification of inflammatory cardiomyopathy is elusive and the true incidence of the condition remains unknown. In most cases of lymphocytic myocarditis, recovery occurs within a few weeks following supportive treatment. In patients with cardiac sarcoidosis, giant cell myocarditis or eosinophilic myocarditis the use of immunosuppressive treatment is recommended, as is the case in myocarditis associated with autoimmune disorders. Such interventions may also have beneficial effects in chronic viral myocarditis once the virus has been cleared. In severe cases, treatment with mechanical circulatory support and/or heart transplantation may be required. Randomized intervention trials including antiviral, immunomodulating, or immunosuppressive agents are lacking. Similarly, new molecular-based methods and therapies tailored to specific pathogeneses have a potential to improve diagnosis and outcomes in patients with inflammatory cardiomyopathy. Still, such techniques and interventions are to be evaluated in adequate randomized controlled studies.