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.

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.

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.

Echocardiographic predictors of positive left ventricular remodeling in patients with a history of active myocarditis.

INTRODUCTION: Myocarditis may be difficult to diagnose because of the variety of its clinical manifestations, and the clinical course of the disease can be unpredictable. Nevertheless, some patients may exhibit partial or full contractile recovery following myocarditis. Standard and speckle-tracking echocardiography may serve as tools to follow this recovery. OBJECTIVES: We aimed to evaluate predictors of positive left ventricular (LV) remodeling after active myocarditis (AM). PATIENTS AND METHODS: A database of a high­volume, tertiary cardiology center was searched for patients with AM hospitalized between 2016 and 2019. They were included in the analysis based on clinical manifestations and presence of at least 1 of the following diagnostic criteria: positive findings on electrocardiography / Holter monitoring, echocardiography, elevated troponin T/I levels, functional or structural abnormalities on cardiac imaging, or tissue characterization by cardiac magnetic resonance. LV global longitudinal strain and mechanical dispersion (MD; defined as SD of the time to peak longitudinal strain derived from all LV segments in 3 apical views) were determined. Echocardiographic response (positive LV remodeling measured by transthoracic echocardiography) was defined as end­systolic volume (ESV) reduction by 15% or greater or end-diastolic volume (EDV) reduction by 15% or greater from the baseline values. RESULTS: A total of 61 consecutive patients were recruited. The median follow­up was 1.4 years (range, 0.3-4). The mortality rate was 1.6%. Echocardiographic response was noted in 24 patients (39.4%). A multivariable Cox regression model including significant baseline differences as covariates showed that QRS duration (hazard ratio [HR], 1.31; 95% CI, 1.17-1.57; P = 0.049), MD (HR, 1.03; 95% CI, 1.01-1.07; P = 0.04), and mineralocorticoid receptor antagonist [MRA] use (HR, 8.60; 95% CI, 1.50-46.49; P = 0.01) were independently associated with positive LV remodeling with ESV reduction. MD (HR, 1.04; 95% CI, 1.02-1.06; P = 0.04) was also independently associated with positive LV remodeling with EDV reduction. CONCLUSIONS: Mechanical dispersion, QRS duration, and MRA use are independent predictors of positive LV remodeling in individuals with a history of AM.

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.

Protective effect of low-intensity pulsed ultrasound on immune checkpoint inhibitor-related myocarditis via fine-tuning CD4+ T-cell differentiation.

PURPOSE: Immune checkpoint inhibitors (ICIs) have transformed traditional cancer treatments. Specifically, ICI-related myocarditis is an immune-related adverse event (irAE) with high mortality. ICIs activate CD4+ T-lymphocyte reprogramming, causing an imbalance between Th17 and Treg cell differentiation, ultimately leading to myocardial inflammatory damage. Low-intensity pulsed ultrasound (LIPUS) can limit inflammatory responses, with positive therapeutic effects across various cardiovascular inflammatory diseases; however, its role in the pathogenesis of ICI-related myocarditis and CD4+ T-cell dysfunction remains unclear. Accordingly, this study investigated whether LIPUS can alleviate ICI-related myocarditis inflammatory damage and, if so, aimed to elucidate the beneficial effects of LIPUS and its underlying molecular mechanisms. METHODS: An in vivo model of ICI-related myocarditis was obtained by intraperitonially injecting male A/J mice with an InVivoPlus anti-mouse PD-1 inhibitor. LIPUS treatment was performed via an ultrasound-guided application to the heart via the chest wall. The echocardiographic parameters were observed and cardiac function was assessed using an in vivo imaging system. The expression of core components of the HIPPO pathway was analyzed via western blotting. RESULTS: LIPUS treatment reduced cardiac immune responses and inflammatory cardiac injury. Further, LIPUS treatment alleviated the inflammatory response in mice with ICI-related myocarditis. Mechanistically, in the HIPPO pathway, the activation of Mst1-TAZ axis improved autoimmune inflammation by altering the interaction between the transcription factors FOXP3 and RORγt and regulating the differentiation of Treg and Th17 cells. CONCLUSION: LIPUS therapy was shown to reduce ICI-related myocarditis inflammatory damage and improve cardiac function, representing an exciting finding for irAEs treatment.

Paclitaxel-induced myocarditis presenting as new-onset heart failure.

Myocarditis with systolic dysfunction is not typically associated with paclitaxel use. Here, we present a case of paclitaxel-induced myocarditis with systolic dysfunction developing after two cycles of carboplatin/paclitaxel in a woman with uterine papillary serous carcinoma and no cardiac risk factors. Myocarditis was diagnosed by cardiac MRI. The management of paclitaxel-induced myocarditis includes intravenous diuresis and initiation of heart failure with reduced ejection fraction guideline-directed medical therapy. Cessation of paclitaxel is also recommended in these patients.

Paucisymptomatic post COVID-19 myocarditis in a young athlete during return to play workflow: possible usefulness of global longitudinal strain analysis.

A young competitive athlete undergoes the diagnostic investigations protocol before returning to competitive practice (return to play protocol) after COVID-19 infection. Despite the paucisymptomatic presentation of COVID-19 infection and the absence of relevant anomalies in standard first-level diagnostic investigations, echocardiographic examination findings especially speckle tracking analysis (global longitudinal strain) along with some clinical aspects suggested further second-level investigations eventually allowing the identification of inflammatory myocardial damage.

Echocardiographic function evaluation in adolescents following BNT162b2 Pfizer-BioNTech mRNA vaccination: A preliminary prospective study.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) is crucial for preventing and minimizing illness. Myocarditis and pericarditis after messenger RNA (mRNA) COVID-19 vaccination in adolescents and young adult males have been reported. Most of the studies in this area rely on retrospective symptom reporting, especially for adolescents experiencing myocarditis as a potential side effect. However, prospective postvaccination echocardiographic evaluation is rare. METHODS: The study enrolled adolescents aged 12 to 15 years who received the second dose of the BNT162b2 Pfizer-BioNTech mRNA (BNT) vaccine. Serial echocardiographic examinations were conducted at baseline before vaccination, followed by subsequent assessments on days 2, 7, 14, and 28 to identify any notable differences or abnormal changes in cardiac function. Clinical symptom assessments were also recorded during each follow-up. RESULTS: The study included 25 adolescents, comprising 14 males and 11 females, who completed the four follow-ups. Their mean age was 14 ± 1 years. The average interval between the first and second BNT vaccine doses was 90 ± 7 days. Ejection fraction values were 73.8% ± 5.2% at baseline, followed by 75.7% ± 5.3%, 75.5% ± 4.6%, 75.7% ± 4.5%, and 77.8% ± 5.8% at day 2, 7, 14, and 28, respectively. The cardiac function remained stable across all time points, with no significant differences observed between male and female participants. Within postvaccination 48 hours, 18 (72%) of the enrolled adolescents experienced temporary discomfort symptoms, which completely resolved by the final follow-up on the 28th day after vaccination. CONCLUSION: Although adolescents vaccinated with the second dose of BNT vaccine commonly experienced transient postvaccination discomfort, the serial echocardiographic examinations did not reveal any significant deterioration of cardiac function within 28 days. Further studies are required to investigate the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination-associated myocarditis in adolescents and the related mechanisms.

The application of cardiac magnetic resonance imaging (CMR) in myocarditis after COVID-19 vaccines : Case series from single medical center in Taiwan.

During the coronavirus disease 2019 (COVID-19) pandemic, reports of vaccine-induced myocarditis, particularly messenger ribonucleic acid (mRNA)-based myocarditis, were widely spread. This case series describes various cases of COVID-19 vaccine-induced myocarditis confirmed by cardiac magnetic resonance imaging (MRI), including those who were administered rare protein-based vaccines. Eleven patients comprising eight males and three females with suspected myocarditis underwent cardiac MRI at Taichung Veterans General Hospital between October 2021 and May 2022. The median age of the patients was 33.5 years old (range: 22-57 years). The onset of myocarditis was mainly observed following mRNA vaccine inoculation. One patient received the MVC-COV1901 vaccine, a unique protein-based COVID-19 vaccine in Taiwan, and met the 2018 Lake Louise Criteria for the diagnosis of myocarditis, confirmed by cardiac MRI. Most patients reported chest discomfort after receiving various vaccine types. Among four patients with reduced left ventricular ejection fraction (LVEF), two showed LVEF restoration during the follow-up period, and the other two were lost to follow-up. Cardiac MRI characterizes myocardial features such as edema, inflammation, and fibrosis, and has been proven to diagnose myocarditis accurately with a sensitivity of 87.5% and a specificity of 96.2% according to the 2018 Lake Louise criteria. This diagnosis was achieved without invasive procedures such as endomyocardial biopsy or coronary angiography.

Post-COVID-19 vaccination myocarditis: a prospective cohort study pre and post vaccination using cardiovascular magnetic resonance.

BACKGROUND: Concerns about COVID-19 vaccination induced myocarditis or subclinical myocarditis persists in some populations. Cardiac magnetic resonance imaging (CMR) has been used to detect signs of COVID-19 vaccination induced myocarditis. This study aims to: (i) characterise myocardial tissue, function, size before and after COVID-19 vaccination, (ii) determine if there is imaging evidence of subclinical myocardial inflammation or injury after vaccination using CMR. METHODS: Subjects aged ≥ 12yrs old without prior COVID-19 or COVID-19 vaccination underwent two CMR examinations: first, ≤ 14 days before the first COVID-19 vaccination and a second time ≤ 14 days after the second COVID-19 vaccination. Biventricular indices, ejection fraction (EF), global longitudinal strain (GLS), late gadolinium enhancement (LGE), left ventricular (LV) myocardial native T1, T2, extracellular volume (ECV) quantification, lactate dehydrogenase (LDH), white cell count (WCC), C-reactive protein (CRP), NT-proBNP, troponin-T, electrocardiogram (ECG), and 6-min walk test were assessed in a blinded fashion. RESULTS: 67 subjects were included. First and second CMR examinations were performed a median of 4 days before the first vaccination (interquartile range 1-8 days) and 5 days (interquartile range 3-6 days) after the second vaccination respectively. No significant change in global native T1, T2, ECV, LV EF, right ventricular EF, LV GLS, LGE, ECG, LDH, troponin-T and 6-min walk test was demonstrated after COVID-19 vaccination. There was a significant WCC decrease (6.51 ± 1.49 vs 5.98 ± 1.65, p = 0.003) and CRP increase (0.40 ± 0.22 vs 0.50 ± 0.29, p = 0.004). CONCLUSION: This study found no imaging, biochemical or ECG evidence of myocardial injury or inflammation post COVID-19 vaccination, thus providing some reassurance that COVID-19 vaccinations do not typically cause subclinical myocarditis.

Cardiac magnetic resonance in histologically proven eosinophilic myocarditis.

BACKGROUND: Eosinophilic myocarditis (EM) is a life-threatening acute heart disease. Cardiac magnetic resonance (CMR) excels in the assessment of myocardial diseases but CMR studies of EM are limited. We aimed to describe CMR findings in histologically proven EM. METHODS: Patients with histologically proven EM seen at an academic center from 2000 through 2020 were identified. Of the 28 patients ascertained, 15 had undergone CMR for diagnosis and constitute our study cohort. RESULTS: The patients, aged 51 ± 17 years, presented with fever (53%), dyspnea (47%), chest pain (53%), heart block (20%), and blood eosinophilia (60%). On CMR, all 15 patients had myocardial edema with 10 of them (67%) having abnormally high left ventricular (LV) mass as well. LV ejection fraction measured < 50% in 11 patients (73%) and < 30% in 2 (13%), but only 6 (40%) had dilated LV size. Eight patients (53%) had pericardial effusion. LV late gadolinium enhancement (LGE) was found in all but one patient (13/14; 93%). LGE was always multifocal and subendocardial but could involve any myocardial layer. Patients with necrotizing EM by histopathology (n = 6) had higher LGE mass (32.1 ± 16.6% vs 14.5 ± 7.7%, p = 0.050) and more LV segments with LGE (15 ± 2 vs 9 ± 3 out of 17, p = 0.003) than patients (n = 9) without myocyte necrosis. Two patients had LV thrombosis accompanying widespread subendocardial LGE. CONCLUSIONS: In EM, CMR shows myocardial edema and LGE that is typically subendocardial but can involve any myocardial layer. The left ventricle is often non-dilated with moderate-to-severe systolic dysfunction. Pericardial effusion is common. Necrotizing EM presents with extensive myocardial LGE on CMR.