Myocarditis Research Articles

Analysis of Cytokine Profiles in Pediatric Myocarditis Multicenter Study.

Acute myocarditis (AM) is an inflammatory disease of the heart muscle that can progress to fulminant myocarditis (FM), a severe and life-threatening condition. The cytokine profile of myocarditis in children, especially in relation to fulminant myocarditis, is not well understood. This study aims to evaluate the cytokine profiles of acute and fulminant myocarditis in children. Pediatric patients diagnosed with myocarditis were included in the study. Cytokine levels were measured using a multiplexed fluorescent bead-based immunoassay. Statistical analysis was performed to compare patient characteristics and cytokine levels between FM, AM, and healthy control (HC) groups. Principal component analysis (PCA) was applied to cytokine groups that were independent among the FM, AM, and HC groups. The study included 22 patients with FM and 14 with AM patients. We identified four cytokines that were significantly higher in the FM group compared to the AM group: IL1-RA (p = 0.002), IL-8 (p = 0.005), IL-10 (p = 0.011), and IL-15 (p = 0.005). IL-4 was significantly higher in the AM group compared to FM and HC groups (p = 0.006 and 0.0015). PDGF-AA, and VEGF-A were significantly lower in the FM group than in the AM group (p = 0.013 and <0.001). Similar results were obtained in PCA. Cytokine profiles might be used to differentiate pediatric FM from AM, stratify severity, and predict prognosis. The targeted therapy that works individual cytokines might provide a potential treatment for reducing the onset of the FM and calming the condition, and further studies are needed.

Yohimbine Treatment Alleviates Cardiac Inflammation/Injury and Improves Cardiac Hemodynamics by Modulating Pro-Inflammatory and Oxidative Stress Indicators.

Acute myocarditis, also known as myocardial inflammation, is a self-limited condition caused by systemic infection with cardiotropic pathogens, primarily viruses, bacteria, or fungi. Despite significant research, inflammatory cardiomyopathy exacerbated by heart failure, arrhythmia, or left ventricular dysfunction and ithas a dismal prognosis. In this study, we aimed to evaluate the therapeutic effect of yohimbine against lipopolysaccharide (LPS) induced myocarditis in rat model. The anti-inflammatory activity of yohimbine was assessed in in-vitro using RAW 264.7 and H9C2 cells. Myocarditis was induced in rats by injecting LPS (10mg/kg), following the rats were treated with dexamethasone (2mg/kg) or yohimbine (2.5, 5, and 10mg/kg) for 12h and their therapeutic activity was examined using various techniques. Yohimbine treatment significantly attenuated the LPS-mediated inflammatory markers expression in the in-vitro model. In-vivo studies proved that yohimbine treatment significantly reduced the LPS-induced increase of cardiac-specific markers, inflammatory cell counts, and pro-inflammatory markers expression comparedto LPS-control samples. LPS administration considerably affected the ECG, RR, PR, QRS, QT, ST intervals, and hemodynamic parameters, and caused abnormal pathological parameters, in contrast, yohimbine treatment substantially improved the cardiac parameters, mitigated the apoptosis in myocardial cells and ameliorated the histopathological abnormalities that resulted in an improved survival rate. LPS-induced elevation of cardiac troponin-I, myeloperoxidase, CD-68, and neutrophil elastase levels were significantly attenuated upon yohimbine treatment. Further investigation showed that yohimbine exerts an anti-inflammatory effect partly by modulating the MAPK pathway. This study emphasizes yohimbine's therapeutic benefit against LPS-inducedmyocarditis and associated inflammatory markers responseby regulating the MAPK pathway.

Janssen COVID-19 vaccine-related acute myocarditis

Janssen COVID-19 vaccine-related acute myocarditis

Acute myocarditis: an overview of pathogenesis, diagnosis and management.

Acute myocarditis encompasses a diverse presentation of inflammatory cardiomyopathies with infectious and non-infectious triggers. The clinical presentation is heterogeneous, from subtle symptoms like mild chest pain to life-threatening fulminant heart failure requiring urgent advanced hemodynamic support. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, diagnostic approach, management strategies, and directions for future research in acute myocarditis. The pathogenesis of myocarditis involves interplay between the inciting factors and the subsequent host immune response. Infectious causes, especially cardiotropic viruses, are the most frequently identified precipitants. However, autoimmune processes independent of microbial triggers, as well as toxic myocardial injury from drugs, chemicals or metabolic derangements also contribute to the development of myocarditis through diverse mechanisms. Furthermore, medications like immune checkpoint inhibitor therapies are increasingly recognized as causes of myocarditis. Elucidating the nuances of viral, autoimmune, hypersensitivity, and toxic subtypes of myocarditis is key to guiding appropriate therapy. The heterogeneous clinical presentation coupled with non-specific symptoms creates diagnostic challenges. A multifaceted approach is required, incorporating clinical evaluation, electrocardiography, biomarkers, imaging studies, and endomyocardial biopsy. Cardiovascular magnetic resonance imaging has become pivotal for non-invasive assessment of myocardial inflammation and fibrosis. However, biopsy remains the gold standard for histological classification and definitively establishing the underlying etiology. Management relies on supportive care, while disease-specific therapies are limited. Although some patients recover well with conservative measures, severe or fulminant myocarditis necessitates aggressive interventions such as mechanical circulatory support devices and transplantation. While immunosuppression is beneficial in certain histological subtypes, clear evidence supporting antiviral or immunomodulatory therapies for the majority of acute viral myocarditis cases remains insufficient. Substantial knowledge gaps persist regarding validated diagnostic biomarkers, optimal imaging surveillance strategies, evidence-based medical therapies, and risk stratification schema. A deeper understanding of the immunopathological mechanisms, rigorous clinical trials of targeted therapies, and longitudinal outcome studies are imperative to advance management and improve the prognosis across the myocarditis spectrum.

Biomedical Applications of Wavelet Transform Algorithm on Deep Learning Ultrasonic Image Optimization as a Prognosis Model for Acute Myocarditis

We aimed to investigate the biomedical methods of wavelet transform algorithm on ultrasonic image denoising algorithm and the risk factors for the adverse prognostic events of patients with myocarditis and analyse its correlation with free triiodothyronine (FT3) level. A retrospective study was performed to include 68 patients diagnosed with acute myocarditis (AM). The included patients were enrolled into adverse event (AE) group (n = 7) and non-adverse event (NAE) group (n = 61). The clinical data, laboratory examination indicators, echocardiographic parameters, and thyroid functions between the patients in the two groups at admission were compared. Besides, wavelet transform (WT) algorithm was employed to process ultrasonic images containing noises. Univariate and multivariate analysis were performed using Logistic regression model. It was demonstrated that peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) (35.279, 0.847) of wavelet transform algorithm were higher than those of denoising convolutional neural network (DnCNN) algorithm (30.673, 0.582) and Red-Net algorithm (28.489, 0.638). In the AE group, the QRS interval was longer ([102 (93, 135) ms] versus [86 (79, 102) ms]), the proportion of prolonged QRS period was higher (28.57%, 9.83%), and the creatine kinase isoenzyme, a marker of myocardial injury, was higher [32.87 (13.64, 78.62) U/L] versus 12.02 (9.89, 27.65) U/L], and the level of FT3 was lower [1.87 (1.23, 2.36) pg/mL versus 2.83 (1.83, 3.45) pg/mL] compared to the NAE group. The left ventricular ejection fraction (LVEF) in the adverse event group was lower than that in the non-adverse event group [45.78 (36.18, 54.32) % versus 63.72 (54.82, 64.68)]. Multivariate Logistic regression analysis showed that the risk factors for adverse events in patients with acute myocarditis included QRS interval &gt; 120 ms (OR = 1.021), creatine kinase isoenzyme &gt; 24 U/L (OR = 1.024), FT3 (OR = 0.067), and LVEF &lt; 50% (OR = 0.973). This work confirmed that the wavelet transform algorithm can optimize the image quality of echocardiography, improve the clarity, and provide a feasible idea for improving the prognosis of patients with acute myocarditis.

Factors Associated With an Electronic Health Record-Based Definition of Postacute Sequelae of COVID-19 in Patients With Systemic Autoimmune Rheumatic Disease.

Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

Auguste François Chomel (1788-1858) and his Work on Rheumatism: Introducing Rheumatic Heart.

In the early 19th century, Auguste François Chomel gathered the knowledge on rheumatism, systematised it, and published it in his majestic work Pathologie Générale. In his treatise, for the first time, rheumatic heart was discussed. Taking into account the opinions of the ancient Greek physicians, he had described the disease as an acute or chronic manifestation of the inflammation of the heart due to rheumatism. His publication rendered rheumatic heart an issue in vogue for his era, a disease being mentioned in all textbooks of the internal pathology.

Endomyocardial biopsy in clinical practice: the diagnostic yield and insights from a 5-year single-center experience

ObjectivesEndomyocardial biopsy (EMB) is a diagnostic tool for evaluating various cardiac conditions, such as myocarditis and myocardial infiltrative diseases. It is also the gold standard screening technique for detecting allograft rejection after heart transplantation. Despite advances in noninvasive imaging modalities for myocardial tissue characterization, EMB is still necessary for making a definitive diagnosis and determining treatment for certain conditions. Herein, we report our recent experience using EMB and its diagnostic yield. Methods and ResultsWe retrospectively reviewed EMBs performed at our institution from March 2018 through March 2023. Clinical data, including patient characteristics, indication and diagnostic yield of EMB, and procedure-related complications, were collected. Histopathological findings of the biopsies were recorded and classified based on the degree to which they matched the clinical diagnosis and cardiac magnetic resonance imaging (CMR) findings. A total of 212 EMBs obtained in 178 consecutive patients were retrospectively analyzed, with 42 biopsies performed for allograft rejection surveillance (10 patients) and the remaining performed for presumptive diagnosis of acute myocarditis or unexplained cardiomyopathy. Among the non-heart transplant cases, 54.7% of EMBs provided a clear diagnosis. The most common diagnosis was myocarditis (69%), followed by cardiac amyloidosis (CA) (26%). EMB was also helpful in detecting several rare cardiac conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), Fabry disease, and cardiac sarcoidosis. In a cohort of 101 patients who underwent both CMR and EMB, the results were concordant in 66% of cases. However, in 24.7% of patients, EMB was able to identify pathological conditions where CMR results were inconclusive, highlighting its complementary role in determining an accurate diagnosis. No complications were reported in any of the 212 EMBs performed. ConclusionsWith advances in cardiac imaging modalities, EMB is not routinely indicated for the diagnosis of cardiomyopathy. However, EMB is still an important tool for diagnosing specific cardiac diseases and could be crucial for confirming the diagnosis. EMB is generally safe if performed at experienced centers.

Expanded application of wearable cardioverter defibrillators beyond current guidelines: proposal for a European register explained through single clinical scenarios

The wearable cardioverter defibrillator (WCD) is becoming a more and more widely used instrument for the prevention of sudden cardiac death of patients either with a secondary prevention implantable cardioverter...

Dengue Myocarditis with Gitelman Syndrome Presenting as Arrhythmic Syncope: A Case Report of Acute Fulminant Dengue Myocarditis Resulting to Acquired Long QT Syndrome

Dengue Myocarditis with Gitelman Syndrome Presenting as Arrhythmic Syncope: A Case Report of Acute Fulminant Dengue Myocarditis Resulting to Acquired Long QT Syndrome

Apoptosis, a useful marker in the management of hot-phase cardiomyopathy?

'Hot phases', characterized by chest pain and troponin release, may represent the first clinical presentation of arrhythmogenic cardiomyopathies. Differential diagnosis with acute myocarditis is an unmet challenge for the clinicians. We sought to investigate histological and genetic features in patients with cardiomyopathy presenting with hot phases. We evaluated a case series of consecutive patients hospitalized for suspected 'hot-phase cardiomyopathy' in two Italian centres from June 2017 to March 2022 (median follow-up 18 months) that underwent both endomyocardial biopsy (EMB) and genetic testing. Apoptosis was confirmed with TUNEL assay. Among the 17 enrolled patients (mean age 34 ± 15 years, 76% male), only six patients (35%) presented standard histological and immunohistochemical markers for significant cardiac inflammation at EMB. Conversely, apoptosis was found in 13 patients (77%). Genetic testing was positive for a pathogenic/likely pathogenic (P/LP) variant in genes involved in cardiomyopathies (most frequently in DSP) in eight patients (48%), rising to 62% among patients with apoptosis on EMB. Notably, all patients without apoptosis tested negative for P/LP disease-related variants. Left ventricular ejection fraction was lower in patients showing apoptosis at EMB compared to those without (p = 0.003). Apoptosis, rather than significant inflammation, was mostly prevalent in this case series of patients with 'hot-phase' presentation, especially in carriers of variants in cardiomyopathy-related genes. Detecting apoptosis on EMB might guide clinicians in performing genetic testing and in more tailored therapeutic choices in 'hot-phase cardiomyopathy'.

The inflammatory spectrum of cardiomyopathies.

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.

Acute myocardial infarction-like event in a young patient with biventricular arrhythmogenic cardiomyopathy

The article describes a clinical case of biventricular arrhythmogenic cardiomyopathy (ACM) presented with myocardial infarction (MI) — like event in a young patient. The patient was hospitalized with suspected acute coronary syndrome and an episode of ventricular tachycardia (VT). Based on increased cardiac troponin, left ventricular systolic dysfunction with wall motion abnormalities, and nonobstructive coronary arteries the initial diagnosis of type 2 MI was made. To verify the etiology behind VT and ventricular structural abnormalities cardiac magnetic resonance imaging (MRI) was performed. Abnormalities of both right and left ventricles demonstrated by MRI and supported by the genetic testing established the diagnosis of biventricular ACM. Since the diagnosis was made, initially diagnosed MI was reassessed in favor of acute myocardial injury as a characteristic of ACM course. ACM should be included into differential diagnosis with MI and acute myocarditis in patients with elevated troponin and nonobstructive coronary arteries.

Sex and Age Characteristics in Acute or Chronic Myocarditis: A Descriptive, Multicenter Cohort Study

BackgroundUnderstanding the clinical features of myocarditis in various age groups is required to identify age-specific disease patterns. ObjectivesThe objective of this study was to examine differences in sex distribution and clinical outcomes in patients with myocarditis of various ages. MethodsPatients with acute or chronic myocarditis in 3 centers in Berlin, Germany from 2005 to 2021 and in the United States (National Inpatient Sample) from 2010 to 2019 were included. Age groups examined included “prepubescent” (below 11 years for females and below 13 years for males), adolescents (11 [female] or 13 [male] to 18 years), young adults (18-35 years), “middle-aged adults” (35-54 years), and older adults (age >54 years). In patients admitted to the hospital, hospital mortality, length of stay, and medical complication rates were examined. ResultsOverall, 6,023 cases in Berlin and 9,079 cases in the U.S. cohort were included. In both cohorts, there were differences in sex distribution among the 5 age categories, and differences in the distribution were most notable in adolescents (69.3% males vs 30.7% females) and in young adults (73.8% males vs 26.3% females). Prepubescent and older adults had the highest rates of in-hospital mortality, hospital length of stay, and medical complications. In the Berlin cohort, prepubescent patients had higher levels of leukocytes (P < 0.001), antistreptolysin antibody (P < 0.001), and NT-proBNP (P < 0.001) when compared to young adults. ConclusionsIn this study, we found that sex differences in myocarditis and clinical features of myocarditis were age-dependent.

Characterisation and management of expected and unexpected urgent findings from positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in cardiovascular disease

BackgroundCardiac 18F-fluorodeoxyglucose (FDG)-PET-CT plays an important role in the assessment of cardiovascular diseases. Effective management of urgent scan findings facilitates optimal patient care. MethodsWe characterised the management of urgent, expected and unexpected findings in patients referred for cardiac [18F]fluorodeoxyglucose integrated with computed tomography (FDG-PET-CT) at the Royal Brompton Hospital (United Kingdom). Urgent findings are escalated by the reporting physicians/radiologists raising RadAlert notifications to the referring clinician. We characterised the indications and time to management (TTM) between the RadAlert and the resulting management. As controls, we characterised the TTM of 33 urgent findings identified before the RadAlert system was implemented. ResultsOf the 1497 consecutive FDG-PET-CT scans screened (April 2021 to February 2023), 93 RadAlerts were suitable for analysis (TTM 7 days [interquartile range: 2–14]). Expected urgent findings included active cardiac sarcoidosis (56%; TTM 8 days [5–18]), heart transplant rejection (12%; 6 ± 4 days), infective endocarditis (9%; 2 days [1–12]), cardiac device infections (5%; 1 day [0–2]), acute myocarditis (2%; 5 and 14 days) and epicardial mass (1%; 1 day). TTM did not differ significantly between indications (P = 0.06). RadAlert cases had significantly shorter TTM than controls without RadAlert, P = 0.001. After the RadAlerts, 81% of patients had clinical reviews, and 55% had escalation of medical/surgical therapies. Unexpected findings (total N = 45; median TTM 6 days [1–10]) included malignancies (N = 3), infections (N = 2), pneumothorax (N = 1), benign diagnosis (N = 30), unclear diagnosis (N = 5) and 4 findings disappeared on repeat imaging. ConclusionsCardiac FDG-PET-CT identifies expected and unexpected findings in a range of cardiovascular diseases. Serious, unexpected findings are rare and can be effectively escalated by the RadAlert system.

Rate of cardiovascular events up to 8 years after uncomplicated myocarditis: a nationwide cohort study.

While prognosis of acute myocarditis with uncomplicated presentation is perceived as benign, data on long-term outcomes are scarce. We evaluated rates of myocarditis-associated cardiovascular events after a first-time hospitalization with uncomplicated acute myocarditis in patients without known heart disease. In this retrospective nationwide population-based cohort study from 2013 to 2020, hospitalized patients with uncomplicated acute myocarditis but without known heart disease were 1:1 propensity score-matched with surgical controls hospitalized for laparoscopic appendectomy. As assessed in time-to-event analyses, the primary outcome was a composite of rehospitalization for myocarditis, pericardial disease, heart failure and its complications, arrhythmias, implantation of cardiac devices, and heart transplant. After matching, we identified 1439 patients with uncomplicated acute myocarditis (median age of 35 years, 74.0% male) and 1439 surgical controls (median age of 36 years, 74.4% male). Over a median follow-up of 39 months, compared with surgical controls, the hazard ratio for the primary composite outcome was 42.3 [95% confidence interval (CI) 17.4-102.8], corresponding to an incidence rate of 43.7 vs. 0.9 per 1000 patient-years (py) and an incidence rate difference of 42.7 (95% CI 36.7-48.8) per 1000 py. Patients hospitalized with uncomplicated acute myocarditis and no known prior heart disease were associated with substantial risk for cardiovascular events over a follow-up of up to 8 years. This calls for a more efficient therapeutic management of this population of patients.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Systematic Aetiological Assessment of Myocarditis: A Prospective Cohort Study.

Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids exist for aetiological assessments. From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of myocarditis. Of the 84 patients (median age 34 years, range 22-41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still's disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

Current Treatment and Immunomodulation Strategies in Acute Myocarditis.

Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.

Red Flags in Acute Myocarditis.

Acute myocarditis is an inflammatory disease of the heart that may occur in the setting of infection, immune system activation or exposure to certain drugs. Often, it is caused by viruses, whereby the clinical course is usually benign; however, it may also present with rapidly progressive fulminant myocarditis, which is associated with high morbidity and mortality. This review highlights the critical red flags - from the clinical, biochemical, imaging and histopathological perspectives - that should raise the index of suspicion of acute myocarditis. We also present an illustrative case of a young female patient with rapidly progressive cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation as a bridge to orthotopic heart transplantation. The patient showed no clinical or echocardiographic recovery signs and eventually underwent orthotopic heart transplantation. Furthermore, we elaborate on the classifications of acute myocarditis based on clinical presentation and histopathology classifications, focusing on identifying key red flags that will inform early diagnosis and appropriate management in such challenging cases.