Treatment Of Myocarditis Research Articles

Combination of chronic myocarditis and progressive coronary artery disease: differential diagnosis and stepwise treatment

Aim. To assess the differential diagnosis in a patient with a combination of coronary artery disease and myocarditis and the results of stepwise treatment (including immunosuppressive therapy (IST), and coronary stenting).Material and methods. A 56-year-old female patient with hypertension, obesity (body mass index, 31,6 kg/m2), diabetes and psoriasis developed shortness of breath after a respiratory viral infection. Primary echocardiography revealed left heart dilatation, ejection fraction (EF) of 21%. Coronary angiography revealed anterior descending artery stenosis of 75%, circumflex artery — 80%, right coronary artery (RCA) — 70%. RCA stenting was performed and cardiovascular and diuretic therapy was started. However, shortness of breath and low exercise tolerance persisted.Results. In the blood test, anti-endothelial cell antibodies were 1:320, anticardiomyocyte and anti-smooth muscle antibodies — 1:80, anti-cardiac conduction system fibers — 1:320 (N≤1:40). During myocardial perfusion scintigraphy with computed tomography, an uneven distribution of the indicator was noted. Signs of myocardial scarring and indications for further revascularization were not revealed. Cardiac magnetic resonance imaging confirmed a decrease in left ventricular (LV) contractility (LVEF 37%) and moderate dilatation. Biopsy was not performed due to dual antiplatelet therapy. The condition is regarded as infectious-immune myocarditis. IST was started with azathioprine 150 mg/day. We noted dyspnea relief and a stable increase in LVEF to 50-52%. The clinical course was complicated by sick sinus syndrome with pauses up to 6 seconds and presyncope; a pacemaker was implanted. After 5 years from the onset of IST, dyspnea episodes reappeared without exacerbation of myocarditis. As their cause, ischemia was diagnosed due to the progression of coronary atherosclerosis. Symptoms regressed after repeated coronary stenting.Conclusion. The presence of moderate coronary atherosclerosis without signs of ischemia and myocardial infarction should not be considered as the only cause of severe systolic myocardial dysfunction. Diagnosis and treatment of myocarditis in combination with coronary artery disease is carried out according to the standard principles and can improve LV systolic function and control the heart failure symptoms.

Immune checkpoint inhibitor myocarditis: a systematic case study

Myocarditis is a life-threatening complication of immune checkpoint inhibitor therapy. Over the past ten years, drugs in this group have been used in the treatment of a wide range of hematological diseases and solid tumors. With steadily growing life expectancy of cancer patients, problems associated with treatment complications are increasingly coming to the fore. Since 2016, publications have appeared on cases of autoimmune myocarditis during checkpoint inhibitor therapy (CIT), among which there are quite a few single-center retrospective and observational studies. At the same time, the problem of diagnosis and treatment of immune checkpoint inhibitor myocarditis remains unresolved.This paper presents a review on the problem of immune checkpoint inhibitor myocarditis, as well as the results of a systematic analysis of PubMed database publications.

Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: A Systematic Review.

Treatment of giant cell myocarditis (GCM) can require bridging to orthotopic heart transplantation (OHT) or recovery with mechanical circulatory support (MCS). Since the roles of MCS and immunotherapy are not well-defined in GCM, we sought to analyze outcomes of patients with GCM who required MCS. A systematic search was performed in June 2019 to identify all studies of biopsy-proven GCM requiring MCS after 2009. We identified 27 studies with 43 patients. Patient-level data were extracted for analysis. Median patient age was 45 (interquartile range (IQR): 32–57) years. 42.1% (16/38) were female. 34.9% (15/43) presented in acute heart failure. 20.9% (9/43) presented in cardiogenic shock. Biventricular (BiVAD) MCS was required in 76.7% (33/43) of cases. Of the 62.8% (27/43) of patients who received immunotherapy, 81.5% (22/27) used steroids combined with at least one other immunosuppressant. Cyclosporine was the most common non-steroidal agent, used in 40.7% (11/27) of regimens. Immunosuppression was initiated before MCS in 59.3% (16/27) of cases, after MCS in 29.6% (8/27), and not specified in 11.1% (3/27). Immunosuppression started prior to MCS was associated with significantly better survival than MCS alone (p = 0.006); 60.5% (26/43) of patients received bridge-to-transplant MCS; 39.5% (17/43) received bridge-to-recovery MCS; 58.5% (24/41) underwent OHT a median of 104 (58–255) days from diagnosis. GCM recurrence after OHT was reported in 8.3% (2/24) of transplanted cases. BiVAD predominates in mechanically supported patients with GCM. Survival and bridge to recovery appear better in patients on immunosuppression, especially if initiated before MCS.

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice.

Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti‐inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE−/−) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non‐induced by human oxidized low‐density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE−/− mice were fed either a Western diet or a chow diet. Acacetin pro‐drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 μmol/L. Moreover, 3 μmol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet‐fed apoE−/− mice. Our findings demonstrate the anti‐oxidative and anti‐atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic‐related cardiovascular diseases (CVD).

Cardiotoxicity Related to Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICI) have modified the management of patients with cancer. Their administration is associated with an increased risk of toxicities that can affect every organ. Cardiovascular toxicities, particularly myocarditis, can occur with a low incidence (< 1%) in patients treated with ICI, but with a high fatality rate (30–50%). In this review, we discuss the mechanisms, diagnostic work-up, and management of cardiovascular toxicities associated with ICI. The main mechanisms of ICI-related myocarditis were first described in 2016 and are due to an infiltrate comprised T cells positive for CD3+, CD4+, and CD8+ and macrophages positive for CD68. The diagnosis of ICI-associated myocarditis remains challenging and is made on the combination of a clinical syndrome, an electrocardiogram (ECG), biomarker data, and imaging criteria. In most clinical scenarios, endomyocardial biopsy now plays a pivotal role, and the limitation of CMR in this context should be recognized. Glucocorticoids (oral or intravenous) are the first-line treatment for myocarditis confirmed by CMR and/or endomyocardial biopsy. The management of steroid-refractory myocarditis relies on the initiation of immunosuppressive therapies (ATG, infliximab, mycophenolate mofetil, and/or abatacept). However, the potential role of these drugs should be confirmed in well-designed prospective trials, as none of these strategies has been thoroughly evaluated prospectively. ICI-related myocarditis is an emerging toxicity in patients treated with immunotherapy. The diagnosis should be made promptly since it is associated with a high fatality rate. Corticosteroids are considered as the first-line treatment.

Zapalenie mięśnia sercowego u dzieci i młodzieży — przegląd piśmiennictwa

Myocarditis is defined by the World Health Organization as an inflammatory disease involving cardiomyocytes, interstitial tissue, vessels and occasionally the pericardium. In this article, literature from the past 5 years regarding epidemiology, diagnostic tests, treatment and prognosis in myocarditis in young children and adolescents was analyzed. For this purpose the Pubmed database was screened using the key words “myocarditis” and “children”, yielding 117 articles. This list of was narrowed down to those in which the study group consisted of at least 5 people and included information about: symptoms and signs, abnormalities in additional tests, etiology, treatment, length of hospitalization and mortality. Finally, the review included 17 studies, describing 1891 children with a diagnosis of myocarditis. The analysis shows that myocarditis is a rare disease. Two peaks of the disease are observed: the first in newborns and infants, the second one in adolescents. Age less than 2 years is a predictor of severe prognosis. In reported cases the most common symptoms were: fatigue, chest pain, palpitations or irregular heart rhythm. Tachycardia, tachypnoe, hypotension and hepatomegaly dominated among findings in physical examination. The interview, the result of physical examination and additional tests (troponin levels, electrocardiogram, echocardiogram) are helpful in making a diagnosis. Cardiac magnetic resonance imaging is used to confirm the diagnosis. In the analyzed group, 65–90% of children were treated in the Intensive Care Unit. Extracorporeal membrane oxygenation was used in 168 cases, a ventricular assist device was implanted in 35 children and 38 children underwent heart transplantation. The mortality rate in myocarditis remains high (25–35% in analyzed studies). Up to 25% of children may develop chronic heart failure. Due to the unpredictable course of this disease, patients in the acute period of the disease should be hospitalized, and after being discharge from the hospital undergo further cardiological check-up.

Abstract 13538: Trends in Utilization and Outcomes of Mechanical Circulatory Support for Patients With Myocarditis

Introduction: Outcomes of mechanical circulatory support (MCS) to treat myocarditis are not well described. Hypothesis: We hypothesize that MCS is increasingly utilized for the treatment of myocarditis and is associated with high morbidity and mortality. Methods: This study utilized admissions from the National Inpatient Sample (NIS) from 2012-2016. Patient-encounters with myocarditis were identified using ICD-9/10 codes. Weighted population estimate outcomes comparing encounters with MCS or without MCS were calculated. Mode of MCS was examined and trends in MCS treatment, mortality and morbidity were assessed using logistic regression models. Results: Of the 48,965 encounters for myocarditis between 2012 and 2016, 1,910 patients died (3.9%) and 255 (0.5%) underwent transplant. MCS was used in 2,215 patients (4.5%): extra corporeal membrane oxygenation (ECMO) in 590, durable ventricular assist device (VAD) in 150, temporary VAD (tVAD) in 320, and intra-aortic balloon pump (BP) in 770. Over 5 years there was no change in the frequency of MCS and mortality in MCS patients remained stable (p for trends &gt;0.3 ). However, the use of ECMO increased from 23.2% in 2012 to 38.5% in 2016 while BP use decreased from 60.9% to 26.4% (p trend for both &lt;0.05). Mortality (25.5% vs 2.9%), infection (32.7% vs 11.7%), stroke (10.2% vs 2.2%), bleeding events (16.0% vs 2.2%) and arrhythmia (58.9% vs 29.0%), were higher in MCS (p for all &lt;0.0001). Incidence of mortality, stroke, and bleeding differed by mode of MCS support {ECMO (31.2%, 15.3%, 23.7%), BP (18.2%, 4.6%, 7.8%), tVAD (26.6%, 4.7%, 7.8%) and VAD (6.7%, 6.7%, 16.7%) (p for all &lt;0.05)} with ECMO having the highest number of complications. Conclusion: MCS is utilized in 5% of patients with myocarditis. ECMO has become the most common support modality, but its use is associated with significant morbidity and mortality. Further evaluation of how patient characteristics influence the MCS type utilized and their impact on outcomes is needed.

Management and Treatment of Myocarditis in Athletes.

Purpose of reviewMyocarditis is an inflammation of the myocardium that can often be associated with cardiac dysfunction and arrhythmias, and is even one of the leading causes for sudden cardiac death (SCD) in athletes. This review aims to summarize the current evidence and treatment guidelines for the management of myocarditis in the active population.Recent findingsPhysical exertion is likely a trigger for dangerous arrythmias and further propagates myocardial damage in athletes with myocarditis. For this reason, abstinence from sports is a critical facet of management in the initial inflammatory period. The use of cardiac magnetic resonance imaging, specifically late gadolinium enhancement, to guide return to play decisions is becoming more common in clinical practice.SummaryEstablishing a stepwise approach for proper diagnosis and risk stratification, with an emphasis on contemporary cardiac magnetic resonance (CMR) imaging techniques, in myocarditis is critical. After a diagnosis of myocarditis is made, it is imperative for any athlete or highly active individual to refrain from physical exercise. Additionally, therapy for heart failure should be applied in cases of myocarditis with cardiac dysfunction. Undoubtedly, COVID 19, and its potential to cause myocarditis, is sure to change the landscape of management of this disease.

Treatment of virus negative chronic myocarditis: long term follow-up of TIMIC trial

Abstract Background The TIMIC trial demonstrated the short term efficacy of immunosuppression (IMS) in virus-negative inflammatory cardiomyopathy. However long term outcome of patients responsive to this treatment is still unclear. Purpose To assess the long term outcome of patients enrolled in the TIMIC trial. Methods The 85 (51 M, 34 F, 42.7±14.7 years) patients with endomyocardial biopsy proven virus-negative chronic inflammatory cardiomyopathy, enrolled in the TIMIC trial and treated either with prednisone and azathioprine (prednisone 1mg kg–1 day–1 for 4 weeks followed by 0.33 mg kg–1 day–1 for 5 months and azathioprine 2 mg kg–1 day–1 for 6 months) or placebo for 6 months, were evaluated in a long-term follow-up of up to 18 years (mean 15.2±2.0 SD, range 12–18 ys). Patients treated with placebo at the end of the 6-month enrollment because of the lack of improvement received IMS for further 6 months. Results At 6 months' follow-up 89% patients showed a significant improvement of left ventricular ejection fraction compared to baseline (LVEF rising from 27.0±5.7 to 46.2±6.4, % p&amp;lt;0.001). This improvement was maintained in the long term follow-up (LVEF 51.1±6.4%, p&amp;lt;0.001). Importantly, the 42 patients initially on placebo showed an improvement comparable to the branch on IMS either on short (EF from 27.7% to 46.8±6.2%) and on long term follow up (LVEF from 27.7% to 50.6±5.6%, p&amp;lt;0.001). Nine patients (11%) did not show a significant improvement of LVEF either at short and long term follow-up and among them 4 died and 2 had a cardiac transplantation. Five patients (5.8%) had a relapse of the cardiac inflammatory process that promptly responded to a new TIMIC dose treatment. Four of them (4F, 41.2±9.4 ys age) had concomitant autoimmune diseases and the relapse was within the first 2 years after IMS discontinuation. One patient (M, 56 ys) had a relapse after 10 years following a flu-like syndrome. Conclusion Immunosuppressive therapy of virus negative inflammatory cardiomyopathy warrants in susceptible patients a long term recovery of heart function with very low incidence of recurrences, that respond to a new TIMIC protocol dose treatment. Long term efficacy of TIMIC-IMS therapy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIFA

Osteoglycin silencing exerts inhibitory effects on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation in a mouse model of myocarditis.

Osteoglycin (Ogn), a class III SLRP member with multiple glycosylation sites, has been proposed to be engaged in cardiac dysfunction and adverse remodeling in human heart failure following myocardial infarction. However, the underlying mechanism remains to be elucidated. Thus, we sought to define the role of Ogn in regulation of the Wnt pathway on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation (EMT/EndMT) in mice with myocarditis. The pathological changes are observed, while hematoxylin-eosin staining and picric acid Sirius red staining were conducted in successfully constructed myocarditis mouse models. Immunohistochemistry and enzyme-linked immunosorbent assay were adopted to determine Ogn and β-catenin levels and serum procollagen propeptide concentrations in the mouse myocardial tissues, respectively. Expression of Ogn and Wnt signaling pathway-related factors were measured by reverse transcription quantitative polymerase chain reaction and western blot assay, cell viability by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle distribution and apoptosis by flow cytometry. We saw indicative pathological changes accompanied by many Ogn and β-catenin positive cells and increased serum procollagen propeptide, in the mouse myocardial tissues. Loss function assays showed reduced levels of Ogn, β-catenin, LRP6, TGF-β1, Twist, FSP-1, α-SMA and higher levels of E-cadherin and VE-cadherin, together with decreased proliferation rate, as well as increased apoptosis rate, indicating that the Wnt signaling pathway, proliferation were inhibited while apoptosis was enhanced with upon gene silencing. Coherently, depletion of Ogn inhibits myocardial fibroblasts proliferation and EMT/EndMT while facilitating myocardial fibroblasts apoptosis in myocarditis through the Wnt signaling pathway, thus serving as an intervention target for the molecular treatment of myocarditis.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

ACHY BREAKY HEART

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Acute pericarditis accounts for about 5% of presentations of acute chest pain. Of those cases of pericarditis an etiology is found in about 22% of cases. Etiologies commonly include neoplasms, tuberculosis, infections, collagen diseases and thyroid disorders. CASE PRESENTATION: Our patient is a 16 year old healthy female that presented to the hospital with six days of fever, sore throat, cough, pleuritic chest pain and progressive dyspnea. She was sent to the emergency department (ED) by her pediatrician due hypotension. Upon arrival her blood pressure (BP) while supine was 70/40 and 50/30 with standing, with a heart rate (HR) of 121 bpm. In the ED she received 3 liters of normal saline. On admission BP was 107/63, HR 90, respiratory rate 33 and oxygen saturation was 80% on room air. The patient appeared drowsy. Her hands were cold and her lower extremities were warm; capillary refill was 4 seconds. Cardiovascular exam was normal with no pericardial friction rub. Lung exam was significant for diffuse inspiratory and expiratory crackles and decreased breath sounds at the left lung base. Initial laboratory work was significant for hemoglobin 10.5 g/dl, Sodium 128 mEq/L, creatinine 1.3 mg/dl, AST 129 U/L, ALT 72 U/L and Albumin 2.7 gm/dl. Troponin peaked at 0.682 ng/ml. BNP 141 pg/ml. Electrocardiogram showed nonspecific T wave abnormalities. Respiratory viral panel and rapid strep were negative. Chest radiograph showed patchy left lower lobe airspace disease that progressed bilaterally within 24 hours. Initial echo showed normal biventricular function with trivial pericardial effusion. She was diagnosed with acute perimyocarditis and treated with Ketorolac and IV Furosemide. Over her hospital course her respiratory distress worsened and she developed a moderate to large pericardial effusion 2 days after her initial echo. Work up included positive ANA (1:5120, speckled pattern), positive lupus anticoagulant, smith antibody and RNP antibody. Our patient was diagnosed with lupus (SLE) pericarditis and she was treated with high dose Methylprednisolone and Hydroxychloroquine which improved her pericardial effusion. DISCUSSION: This is a case of a female diagnosed with SLE perimyocarditis with pericardial effusion. This patient did not initially meet criteria for lupus, but by the end of her hospital course she met 4/11 criteria. Cardiac disease is rarely a presenting manifestation of SLE and only 1% of cases of SLE, in children and adults, present with pericarditis. While it is rare to present with cardiac symptoms, most patient with SLE develop cardiovascular manifestations at some point. Asymptomatic pericarditis is found in >50% of patients with SLE. Myocarditis, endocarditis and CAD are rare manifestations. CONCLUSIONS: This case highlights the importance of having a high index of suspicion for lupus in a patient that is not responding to initial treatment for viral myocarditis. Reference #1: Ansari, A., Larson, P. H., & Bates, H. D. (1985). Cardiovascular manifestations of systemic lupus erythematosus: Current perspective. Progress in Cardiovascular Diseases, 27(6), 421–434. doi: 10.1016/0033-0620(85)90003-9 Reference #2: Zayas, R., Anguita, M., Torres, F., Gime´nez, D., Bergillos, F., Ruiz, M., … Valle´s, F. (1995). Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. The American Journal of Cardiology, 75(5), 378–382. doi: 10.1016/s0002-9149(99)80558-x Reference #3: Durrance, R. J., Movahedian, M., Haile, W., Teller, K., & Pinsker, R. (2019). Systemic Lupus Erythematosus Presenting as Myopericarditis with Acute Heart Failure: A Case Report and Literature Review. Case Reports in Rheumatology, 2019, 1–7. doi: 10.1155/2019/6173276 DISCLOSURES: No relevant relationships by Alejandra Grana, source=Web Response

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES‐HF Registry

AimsDespite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry.Methods and resultsWe analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter‐quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50–60%) on admission vs. 60% (IQR: 55–60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta‐blockers (71.9%) and angiotensin‐converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both.ConclusionsThis preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow‐up data.

Clinical characteristics and outcome of 64 patients with severe COVID-19

Objective: To investigate the causes of death in patients with severe COVID-19. Methods: A retrospective analysis was performed on 64 patients with severe COVID-19 admitted to Wuhan Pulmonary Hospital from January 12, 2020 to February 28, 2020. There were 36 males and 28 females, aging from 44 to 85 years[median 68 (62, 72)]. Fifty-two patients (81%) had underlying comorbidities. The patients were divided into the death group (n=40) and the survival group (n=24) according to the treatment outcomes. In the death group, 24 were male, and 16 were female, aging from 49 to 85 years [median 69 (62, 72)], with 31 cases (78%) complicated with underlying diseases. In the survival group, there were 12 males and 12 females, aging from 44 to 82 years[median 66 (61,73)], with 21 cases (88%) with comorbidities. Clinical data of the two groups were collected and compared, including general information, laboratory examinations, imaging features and treatments. For normally distributed data, independent group t test was used; otherwise, Mann Whitney test was used to compare the variables. χ(2) test and Fisher exact test was used when analyzing categorical variables. Results: The median of creatine kinase isozyme (CK-MB) in the death group was 19.0 (17.0,23.0) U/L, which was higher than that in the survival group 16.5 (13.5,19.6) U/L. The median level of cTnI in the death group was 0.03 (0.03, 0.07) μg/L, which was significantly higher than that in the survival group (0.02, 0.03) μg/L, with a statistically significant difference between the two groups (P=0.007). The concentration of myoglobin in the death group was 79.5 (28.7, 189.0) μg/L, which was higher than 33.1 (25.7, 54.5) μg/L in the survival group. The level of D-dimer in the death group was 2.0 (0.6, 5.2) mg/L, which was higher than 0.7 (0.4, 2.0) mg/L in the survival group. The LDH level of the death group was 465.0 (337.5,606.5) U/L, which was higher than that of the survibal group, 341.0 (284.0,430.0) U/L, the difference being statistically significant (P=0.006). The concentration of alanine aminotransferase in the death group was 40.0 (30.0, 48.0) U/L, which was higher than 32.5 (24.0, 40.8) U/L in the survival group, and the difference was statistically significant (P=0.047).Abnormal ECG was found in 16 cases (62%) in the death group, which was significantly higher than that in the survival group (29%), the difference being statistically significant (P=0.024) .The main causes of death were severe pneumonia with acute respiratory distress syndrome (ARDS, n=20), acute heart failure(n=9), atrial fibrillation(n=3) and multiple organ dysfunction syndrome (MODS, n=3). Conclusions: ARDS caused by severe pneumonia and acute heart failure and atrial fibrillation caused by acute viral myocarditis were the main causes of death in severe COVID-19 patients. Early prevention of myocardial injury and treatment of acute viral myocarditis complicated with disease progression may provide insights into treatment and reduction of mortality in patients with severe COVID-19.

Tofacitinib for treatment in immune-mediated myocarditis: The first reported cases.

Immune checkpoint inhibitors (ICI) has demonstrated significant clinical benefit in advanced cancer. Despite favorable benefits, the use of ICI is accompanied by various side effects, which are inflammatory side effects potentially affecting any organ. Among which myocarditis is the most severe and has a relatively high mortality. However, there is no effective treatments, and many patients respond poorly to glucocorticoids and immunosuppressants. Therefore, it is urgent to explore effective treatments. Here we describe two patients with metastatic cancer who developed immune-mediated myocarditis after receiving anti-programmed cell death protein (PD)-1 antibody. The main clinical manifestations are dyspnea. All patients had an elevation of cardiac enzyme, a variety of atypical electrocardiographic (ECG) abnormalities and preserved left ventricular ejection fraction (LVEF). All our patients underwent cardiac MRI (CMRI) and suggested typical features of myocarditis, including myocardial oedema and delayed enhancement.Management and outcome: All patients were treated promptly with glucocorticoids, followed by other immunosuppressive treatments include plasma exchange and intravenous immunoglobulin (IVIG). However, no significant improvement was observed and we then administered tofacitinib 5 mg twice daily to treat the refractory myocarditis and the elevated levels of pro-inflammatory cytokines. All patients recovered and were discharged. No major adverse reaction was reported during tofacitinib therapy. To our knowledge, this is the first report in the world of patients with ICI-associated myocarditis treated with oral tofacitinib. Our results can at least provide a new option for clinical treatment of refractory myocarditis or other immune-related adverse events.

Acute myocarditis in a patient with parainfluenza infection, seven years after bone marrow transplantation

Myocarditis is an inflammatory disease of the myocardium, with heterogeneous etiology. Although rare, myocarditis can be a complication of the influenza infection. In the majority of cases, viral myocarditis is a self-limiting infection passing without permanent changes in the myocardium. We present a clinical case of a 30-year-old woman with acute heart failure in the course of respiratory infection accompanied by severe systolic dysfunction (left ventricular (LV) ejection fraction (EF) 16%). The patient was treated according to the current guideline recommendations for the treatment of acute and chronic heart failure with the conjunction of immunomodulating and metabolic therapy. During hospitalization from microbial and viral testing, acute-phase antibodies to parainfluenza virus were identified. Following the treatment, a complete resolution of heart failure symptoms and restoration of LVEF to baseline (40%) was observed. Timely initiation of treatment in myocarditis, followed by good clinical course and regression of LV systolic dysfunction, in some cases may cancel invasive procedures such as endomyocardial biopsy.

Myocarditis in Children: Clinical Overview, Diagnosis and Treatment

The lecture presents modern views on the problem of myocarditis in pediatrics. Current ideas about the definition, prevalence, etiology and pathogenesis of inflammatory myocardial lesions in children are presented. Features of clinical manifestations of the disease in patients of different age groups, difficulties of diagnosis and treatment of myocarditis and its complications are disclosed in accordance with federal clinical recommendations. Special attention is paid to diagnostic approaches adjusted with the European society of cardiologists, including first and second level techniques, determination of indications for their implementation and diagnostic capabilities, as well as differential diagnosis of myocarditis with other cardiological diseases. Issues of heart failure treatment in myocarditis and indications for heart transplantation for patients under 18 years of age were also discussed. The lecture has illustrated clinical examples that clearly demonstrate the diversity of the clinical picture and the ambiguity of myocarditis prognosis in children and teenagers.

The Effects of Sodium Phosphocreatine on ECG Abnormalities and Cardiac Markers of Neonatal Asphyxia Based on Big Data Statistics

Myocardial damage after neonatal asphyxia is one of the common diseases of newborn, its harm is great, can affect the prognosis of newborn asphyxia. Serum creatine kinase isoenzyme (ck-mb), troponin (cTnI), creating kinase (CK), lactate dehydrogenase (LDH), poly hydroxybutyrate dehydrogenase (HBDH) and myoglobin (MB) are commonly used markers of serum myocardial injury. The determination of these indicators is of certain value for the diagnosis, treatment and efficacy evaluation of myocardial injury after suffocation. CP has been widely used in adult angina pectoris, myocardial infarction, various causes of cardiac dysfunction and other diseases, used to protect the myocardial function, has achieved good efficacy. In pediatric clinical work, CP has been used in the treatment of viral myocarditis, pediatric pneumonia or viral infection with heart damage, but few studies have been conducted on the myocardial damage in neonatal asphyxia.

Immunoglobulin free light chains as an inflammatory biomarker of heart failure with myocarditis

BackgroundIn this study, we measured immunoglobulin free light chains (FLC), a biomarker of inflammation in the sera of patients with heart failure due to myocarditis. MethodsFLC kappa and FLC lambda were assayed in stored serum samples from patients with heart failure with myocarditis from the US myocarditis treatment trial by a competitive-inhibition multiplex Luminex® assay. ResultsThe median concentration of circulating FLC kappa/lambda ratio was significantly lower in the sera from patients with heart failure with myocarditis than in healthy controls, and FLC kappa/lambda ratio had good diagnostic ability for identification of heart failure with myocarditis. Further, FLC kappa/lambda ratio was an independent prognostic factor for overall survival, and allowed creation of three prognostic groups by combining with N-terminal pro-B-type natriuretic peptide. ConclusionsThis study suggests that FLC kappa/lambda ratio is a promising biomarker of heart failure with myocarditis.

Could phenothiazine-benznidazole combined chemotherapy be effective in controlling heart parasitism and acute infectious myocarditis?

Phenothiazines inhibit major antioxidant defense mechanisms in trypanosomatids and exhibit potent cytotoxic effects in vitro. However, the relevance of these drugs in the treatment of Trypanosoma cruzi-induced acute myocarditis is poorly explored, especially in combination with reference trypanocidal drugs. Thus, we compared the antiparasitic and cardioprotective potential of thioridazine (TDZ) and benznidazole (Bz) administered in monotherapy and combined in a murine model of T. cruzi-induced acute myocarditis. Female mice were randomized into six groups: (i) uninfected untreated, (ii) infected untreated, or infected treated with (iii) Bz (100 mg/kg), (iv) TDZ (80 mg/kg), (v) Bz (100 mg/kg) + TDZ (80 mg/kg), or (vi) Bz (50 mg/kg) + TDZ (80 mg/kg). Infected animals were inoculated with 2000 T. cruzi trypomastigotes and treated by gavage for 20 days. Animals that received TDZ alone presented the highest levels of parasitemia, parasitic load and anti-T. cruzi immunoglobulin G titers; cardiac upregulation of N-acetyl-β-D-glucosaminidase activity, nitric oxide, malondialdehyde and cytokines (IFN-γ, TNF-α, IL-10 and IL-17); as well as microstructural damage compared to the other groups (p < 0.05). These parameters were reduced in groups receiving Bz monotherapy compared to the other groups (p < 0.05). The combination of TDZ and Bz attenuated the response to treatment, worsening parasitological control, oxidative heart damage and myocarditis compared to the group treated with Bz alone (p < 0.05). Our results indicate that when administered alone, TDZ potentiated the pathological outcomes in animals infected with T. cruzi. Moreover, TDZ attenuated the antiparasitic effect of Bz when administered together, impairing parasitological control, potentiating inflammation, molecular oxidation and pathological microstructural remodeling of the heart. Thus, our findings indicate that TDZ acts as a pharmacological risk factor and Bz-based monotherapy remains a better cardioprotective drug against Trypanosoma cruzi-induced acute myocarditis.