Diagnosis and management of cancer therapy-related myocarditis in a young female: A case report and review of literature.

BACKGROUND: The treatment of choice for Extra-osseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET), a rare neoplasm, is the VAC/IE regimen. This regimen includes Doxorubicin, Vincristine, Cyclophosphamide, Ifosfamide, and Etoposide, all of which have cardiotoxic effects. Myocarditis, a potentially threatening side effect following cancer therapy, can be accurately managed and diagnosed. CASE PRESENTATION: In the current study, we report the case of a 19-year-old female with a mass on the abdominal wall, diagnosed with ES/PNET. She was treated with the VAC/IE regimen. A month after the last session of chemotherapy, she experienced dyspnea. Upon evaluation, a high level of troponin and a low left ventricular ejection fraction (LVEF) were detected via transthoracic echocardiography. She was treated with anti-heart failure drugs, but the response was unsatisfactory. The possibility of Cancer therapy-related myocarditis was suspected, and cardiac magnetic resonance imaging (CMR) confirmed acute myocarditis. This patient exhibited a significant response to intravenous immunoglobulin (IVIG), with her LVEF improving from 30-35% to 50% within three months. CONCLUSION: In this case, based on negative tests and the absence of viral signs and symptoms, Cancer therapy-related myocarditis is highly suspected as the cause of myocarditis. This case underscores the importance of accurately utilizing CMR as a non-invasive method for diagnosing myocarditis. It effectively highlights the identification of reversible myocarditis with appropriate treatment and the notable response to IVIG, suggesting its potential as a favorable treatment for myocarditis in younger patients.

Rationale and design of the French cohort of acute myocarditis diagnosed by cardiac magnetic resonance imaging (MyocarditIRM).

BACKGROUND: Acute myocarditis usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favourable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders, and is considered the leading cause of sudden cardiac death in young, apparently healthy, adults. There are no specific recommendations for acute myocarditis diagnosis and management, only expert consensus, given the lack of large databases. AIM: The main objective is to describe the contemporary presentation of acute myocarditis, its management and in-hospital outcomes. Secondary objectives are to investigate survival and event-free survival for up to 10years of follow-up, the determinants of prognosis, the modalities of treatment and follow-up and the gaps between expert consensus and real-life management. METHODS: MyocarditIRM is a prospective multicentre cohort that enrolled 803 consecutive patients with acute myocarditis in 49 participating centres in France between 01 May 2016 and 28 February 2019. The diagnosis of acute myocarditis was acknowledged by cardiac magnetic resonance, using the Lake Louise Criteria. Exclusion criteria were age<18years, lack of health coverage, contraindication to cardiac magnetic resonance and refusal to participate. Detailed information was collected prospectively, starting at admission. Cardiac magnetic resonance imaging (diagnosis and follow-up) is analysed centrally by the certified core laboratory IHU ICAN. Ten years of follow-up for each patient is ensured by linking with the French National Health Database, and includes information on death, hospital admissions, major clinical events and drug consumption. CONCLUSION: This prospective cohort with long-term follow-up represents the largest database on acute myocarditis worldwide, and will improve knowledge about its presentation, management and outcomes.

ACUTE MYOCARDITIS IN YOUNG AGE MIMICKING AS ST-ELEVATION MYOCARDIAL INFARCTION: CASE REPORT.

Acute myocarditis remains a diagnostic issue with a wide spectrum of clinical manifestations that could mimic ST-elevation myocardial infarction (STEMI). We present a case of a 26-year-old male with left-sided intense squeezing chest pain associated with elevated troponin, ST-segment elevations, and reduced ejection fraction. The patient was initially suspected of having a STEMI with non-obstructed coronary arteries (MINOCA). However, due to positive pair troponin tests, increased inflammatory markers there was suspected myocarditis and cardiac MRI confirmed this diagnosis. This case highlights the clinical significance of assessment of laboratory markers and cardiac MRI in diagnostics of myocarditis.

ELRL-MD: a deep learning approach for myocarditis diagnosis using cardiac magnetic resonance images with ensemble and reinforcement learning integration.

Objective.Myocarditis poses a significant health risk, often precipitated by viral infections like coronavirus disease, and can lead to fatal cardiac complications. As a less invasive alternative to the standard diagnostic practice of endomyocardial biopsy, which is highly invasive and thus limited to severe cases, cardiac magnetic resonance (CMR) imaging offers a promising solution for detecting myocardial abnormalities.Approach.This study introduces a deep model called ELRL-MD that combines ensemble learning and reinforcement learning (RL) for effective myocarditis diagnosis from CMR images. The model begins with pre-training via the artificial bee colony (ABC) algorithm to enhance the starting point for learning. An array of convolutional neural networks (CNNs) then works in concert to extract and integrate features from CMR images for accurate diagnosis. Leveraging the Z-Alizadeh Sani myocarditis CMR dataset, the model employs RL to navigate the dataset's imbalance by conceptualizing diagnosis as a decision-making process.Main results.ELRL-DM demonstrates remarkable efficacy, surpassing other deep learning, conventional machine learning, and transfer learning models, achieving an F-measure of 88.2% and a geometric mean of 90.6%. Extensive experimentation helped pinpoint the optimal reward function settings and the perfect count of CNNs.Significance.The study addresses the primary technical challenge of inherent data imbalance in CMR imaging datasets and the risk of models converging on local optima due to suboptimal initial weight settings. Further analysis, leaving out ABC and RL components, confirmed their contributions to the model's overall performance, underscoring the effectiveness of addressing these critical technical challenges.

STING-Targeted PET Imaging for Specific Detection and Therapeutic Monitoring of Myocarditis.

Imaging strategies for the specific detection and therapeutic monitoring of myocarditis are still lacking. Stimulator of interferon genes (STING) is a signal transduction molecule involved in an innate immune response. Here, we evaluated the feasibility of the recently developed STING-targeted radiotracer [18F]FBTA for positron emission tomography (PET) imaging to detect myocardial inflammation and monitor treatment in myocarditis mice. [18F]FBTA-PET imaging was performed in myocarditis mice and normal mice to verify the specificity of [18F]FBTA for the diagnosis of myocarditis. We also performed PET imaging in mice with myocarditis treated to verify the ability of [18F]FBTA in therapeutic monitoring. The expression of STING and inflammatory cell types was confirmed by flow cytometry and immunohistochemistry. [18F]FDG-PET imaging of myocarditis was used as a contrast. [18F]FBTA-PET imaging showed that the average radioactive uptake was significantly higher in the hearts of the myocarditis group than in the control group. STING was highly overexpressed in cardiac inflammatory cells, including macrophages, dendritic cells (DCs), and T cells. However, there was no significant difference in cardiac radiotracer uptake of [18F]FDG between the myocarditis group and the control group. Moreover, cardiac uptake of [18F]FBTA was significantly reduced in cyclosporin A-treated myocarditis mice and myocardial STING expression was also significantly reduced after the treatment. Overall, we showed that a STING-targeted PET tracer [18F]FBTA can be used to monitor changes in the inflammatory microenvironment in myocarditis. Besides, [18F]FBTA-PET is also suitable for real-time monitoring of myocarditis treatment, representing a promising diagnostic and therapeutic monitoring approach for myocarditis.

Chlamydia psittaci-related pleuro-myocarditis.

Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.

Cardiovascular magnetic resonance imaging and clinical follow-up in patients with clinically suspected myocarditis after COVID-19 vaccination.

BACKGROUND: The purpose of this study was to evaluate cardiovascular magnetic resonance (CMR) findings and their relationship to longer-term clinical outcomes in patients with suspected myocarditis following coronavirus disease 2019 (COVID-19) vaccination. METHODS: Consecutive adult patients who underwent clinically indicated CMR for evaluation of suspected myocarditis following messenger ribonucleic acid (mRNA)-based COVID-19 vaccination at a single center between 2021 and 2022 were retrospectively evaluated. Patients were classified based on the revised Lake Louise criteria for T1-based abnormalities (late gadolinium enhancement [LGE] or high T1 values) and T2-based abnormalities (regional T2-hyperintensity or high T2 values). RESULTS: Eighty-nine patients were included (64% [57/89] male, mean age 34 ± 13 years, 38% [32/89] mRNA-1273, and 62% [52/89] BNT162b2). On baseline CMR, 42 (47%) had at least one abnormality; 25 (28%) met both T1- and T2-criteria; 17 (19%) met T1-criteria but not T2-criteria; and 47 (53%) did not meet either. The interval between vaccination and CMR was shorter in those who met T1- and T2-criteria (28 days, IQR 8-69) compared to those who met T1-criteria only (110 days, IQR 66-255, p < 0.001) and those who did not meet either (120 days, interquartile range (IQR) 80-252, p < 0.001). In the subset of 21 patients who met both T1- and T2-criteria at baseline and had follow-up CMR, myocardial edema had resolved and left ventricular ejection fraction had normalized in all at median imaging follow-up of 214 days (IQR 132-304). However, minimal LGE persisted in 10 (48%). At median clinical follow-up of 232 days (IQR 156-405, n = 60), there were no adverse cardiac events. However, mild cardiac symptoms persisted in 7 (12%). CONCLUSION: In a cohort of patients who underwent clinically indicated CMR for suspected myocarditis following COVID-19 vaccination, 47% had at least one abnormality at baseline CMR. Detection of myocardial edema was associated with the timing of CMR after vaccination. There were no adverse cardiac events. However, minimal LGE persisted in 48% at follow-up.

Macrophage membrane-modified targeted phase-change nanoparticles for multimodal imaging of experimental autoimmune myocarditis.

Myocarditis is an important public health issue due to the high prevalence of sudden death in adolescents and young adults. Nevertheless, the early identification of myocarditis remains a serious problem for clinicians. There is no single non-invasive method to diagnose myocarditis in the currently available clinical guidelines and consensus. Molecular imaging is an effective approach for accurate diagnosis. Poly(lactic acid-glycolic acid) (PLGA) is considered to be the preferred carrier for molecular imaging because of its biosafety and modifiability. Macrophage membrane-modified biomimetic nanoprobes (MM-NPs) possess low immunogenicity and inflammation-directed chemotaxis capabilities and are repeatedly chosen as materials for targeted diagnosis and treatment of inflammatory diseases. In this study, experimental autoimmune myocarditis (EAM) was used as an animal model of inflammation. Previous studies have confirmed that this model is similar to pathological injury caused by acute myocarditis in humans. In multimodal imaging (US/PA/MRI), a phase-change material (PFH) and superparamagnetic iron oxide (SPIO) are used as imaging substances. Early identification of myocardial inflammatory sites was achieved by the tail vein injection of MM/NPs loaded with PFH and SPIO. This probe is expected to be a powerful tool for clinicians to diagnose myocarditis.

Prognostic value of visual and quantitative CMR regional myocardial function in patients with suspected myocarditis.

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HRadjusted = 1.132, 95% CI 1.020-1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification.

Immune checkpoint inhibitor-induced myopericarditis.

A woman in her 30s with a medical history of metastatic rectal adenocarcinoma, currently on pembrolizumab, which started a few weeks ago, was admitted for abdominal pain. During the hospital stay, she experienced sharp chest pain. Troponin was 1885 ng/mL which peaked at 7338 ng/mL. ECG was unremarkable. The echocardiogram showed an Ejection fraction (EF) of 55%-60% and basal-inferior wall hypokinesis. Left heart catheterisation showed no coronary abnormalities. Cardiac MRI showed a non-coronary area of focal T1 and T2 hyperintense signal and transmural delayed gadolinium enhancement in the mid-basal inferior/inferoseptal wall consistent with myocardial damage. Pericardium showed increased thickness and adhesions at the right ventricular outflow tract consistent with pericarditis. Steroid therapy was initiated, and a marked clinical response was achieved. Immune checkpoint inhibitor-induced myocarditis and pericarditis is a rare complication associated with a high mortality rate, if untreated. Diagnosis requires a multidisciplinary approach, and early detection is critical to preventing a fatal outcome.

Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

BACKGROUND: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS: Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS: What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Cardiac Magnetic Resonance Imaging Findings and Clinical Features of COVID-19 Vaccine-Associated Myocarditis, Compared With Those of Other Types of Myocarditis.

BACKGROUND: To compare the clinical and cardiac magnetic resonance (CMR) imaging findings of coronavirus disease 2019 (COVID-19) vaccine-associated myocarditis (VAM) with those of other types of myocarditis. METHODS: From January 2020 to March 2022, a total of 39 patients diagnosed with myocarditis via CMR according to the Modified Lake Louise criteria were included in the present study. The patients were classified into two groups based on their vaccination status: COVID-19 VAM and other types of myocarditis not associated with COVID-19 vaccination. Clinical outcomes, including the development of clinically significant arrhythmias, sudden cardiac arrest, and death, and CMR imaging features were compared between COVID-19 VAM and other types of myocarditis. RESULTS: Of the 39 included patients (mean age, 39 years ± 16.4 [standard deviation]; 23 men), 23 (59%) had COVID-19 VAM and 16 (41%) had other types of myocarditis. The occurrence of clinical adverse events did not differ significantly between the two groups. As per the CMR imaging findings, the presence and dominant pattern of late gadolinium enhancement did not differ significantly between the two groups. The presence of high native T1 or T2 values was not significantly different between the two groups. Although the native T1 and T2 values tended to be lower in COVID-19 VAM than in other types of myocarditis, there were no statistically significant differences between the native T1 and T2 values in the two groups. CONCLUSION: The present study demonstrated that the CMR imaging findings and clinical outcomes of COVID-19 VAM did not differ significantly from those of other types of myocarditis during hospitalization.

High risk and low prevalence diseases: Myocarditis.

INTRODUCTION: Myocarditis is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of myocarditis, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Myocarditis is an inflammatory syndrome of myocardium, most often resulting from a viral infection, that can cause life-threatening cardiovascular collapse. It has a highly variable presentation and no widely available specific diagnostic test, making it a challenging diagnosis. Emergency clinicians should obtain an electrocardiogram and perform bedside ultrasound to assess cardiac function. Treatment in the ED is largely supportive, focusing on resuscitation, cardiovascular support, cardiology specialist consultation, and appropriate disposition. CONCLUSIONS: An understanding of myocarditis can assist emergency clinicians in diagnosing and managing this potentially deadly disease.