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Cardiac toxicity is an adverse event of several classes of anti-cancer drugs. Herein, we present the case of a 52-year-old woman with metastatic renal cell carcinoma (RCC), previously treated with debulking surgery, pembrolizumab (immune checkpoint inhibitor) in combination with axitinib (tyrosine kinase inhibitor (TKI)), followed by lenvatinib (TKI) and belzutifan (HIF-2α inhibitor), who developed myocarditis proven by cardiac magnetic resonance and endomyocardial biopsy. The case was notable for reporting a not-yet described adverse event during treatment with belzutifan plus lenvatinib, the etiology of which was of unobvious determination given the pre-exposure to pembrolizumab, a known cause of drug-related myocarditis. We surmise that myocarditis was a delayed adverse event related to pembrolizumab (8 months after treatment interruption), although we emphasize that only attentive monitoring of cardiac adverse events of patients exposed to belzutifan and lenvatinib in the context of large clinical trials may rule out any causal implication of these drugs. [ABSTRACT FROM AUTHOR]

Myocarditis, marked by heart muscle inflammation, poses significant clinical challenges. This study, guided by PRISMA guidelines, explores the expanding role of artificial intelligence (AI) in myocarditis, aiming to consolidate current knowledge and guide future research. Following PRISMA guidelines, a systematic review was conducted across PubMed, Cochrane Reviews, Scopus, Embase, and Web of Science databases. MeSH terms including artificial intelligence, deep learning, machine learning, myocarditis, and inflammatory cardiomyopathy were used. Inclusion criteria involved original articles utilizing AI for myocarditis, while exclusion criteria eliminated reviews, editorials, and non-AI-focused studies. The search yielded 616 articles, with 42 meeting inclusion criteria after screening. The identified articles, spanning diagnostic, survival prediction, and molecular analysis aspects, were analyzed in each subsection. Diagnostic studies showcased the versatility of AI algorithms, achieving high accuracies in myocarditis detection. Survival prediction models exhibited robust discriminatory power, particularly in emergency settings and pediatric populations. Molecular analyses demonstrated AI's potential in deciphering complex immune interactions. This systematic review provides a comprehensive overview of AI applications in myocarditis, highlighting transformative potential in diagnostics, survival prediction, and molecular understanding. Collaborative efforts are crucial for overcoming limitations and realizing AI's full potential in improving myocarditis care. [ABSTRACT FROM AUTHOR]

Immunotherapy is increasingly used in advanced non-small-cell lung cancer (NSCLC), offering a significant anti-tumor response, as well as causing rising immune-related adverse effects. The incidence of immune checkpoint inhibitorinduced myocarditis-myositis-myasthenia gravis is increasing and particularly concerning due to its high mortality rate. Prompt recognition, diagnosis, and management are crucial. A 40-year-old patient, diagnosed with stage IV nononcogene addicted lung adenocarcinoma, with nivolumab-ipilimumab-chemotherapy as first-line treatment, developed a rare myocarditis-myositis-myasthenia gravis overlap syndrome. Following the treatment, the patient presented with flu-like symptoms and chest pain and subsequently transferred to the cardiac intensive care unit. The physical examination revealed a visual acuity deficit, diplopia, ophthalmoparesis, ptosis, mydriasis, dysphagia, dyspnea, headache, nausea, dry mouth, asthenia, myalgia, and muscle weakness. Imaging and laboratory tests confirmed the triad, showing an elevation of hs-cTnI and CK and positive results for anti-SAE1 and anti-PL-7 Abs. ECG revealed ST segment elevation and RBBB. The echo showed hyperechogenicity of the inferolateral wall, pericardial detachment, and thickening. The cardiac MRI demonstrated hypokinesia, edema, subepicardial LGE, and pericardial effusion. Muscle biopsy revealed muscle fiber necrosis and regeneration with B and T lymphocytic endomysial inflammatory infiltrate and expression of MHC-I. Treatment with oral prednisone, pyridostigmine, and IV Igs was started due to poor clinical response followed by methylprednisolone. Despite stopping immunotherapy, the patient continued to benefit from it, as highlighted on subsequent reevaluation CT scans by partial disease response, and as the patient was in complete remission, we decided to resume chemotherapy by omitting immunotherapy. At the radiological control following the four cycles of double CHT and during CHT maintenance, there was a further reduction of the disease. This report aims to raise awareness among physicians about these serious side effects. A multidisciplinary approach led to clinical improvement and early intervention, optimizing patient outcomes. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusions and Implications Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM.FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single‐cell RNA sequencing (scRNA‐seq) was performed to evaluate CD45+ cells in the heart.Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA‐seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8+ monocytes and S100a8+ neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti‐viral effects. Subsequently, Bst2-ILT7 ligand‐receptor‐mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo.Immunoglobin treatment significantly attenuated FM‐induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion To estimate the global burden of myocarditis in the general population from 1990 to 2021.Data on myocarditis were retrieved from the Global Burden of Disease Study 2021. Incidence, deaths, and disability‐adjusted life years (DALYs), along with their age‐standardized rates (ASRs) per 100 000 population, were used to measure the burden of myocarditis. Global, regional, and national analyses were performed for the period between 1990 and 2021. Further sub‐analyses were conducted based on age group, sex, and sociodemographic index (SDI). In 2021, there were 1.3 million (95% uncertainty interval [UI]: 1.1 to 1.6) incident cases, 31.7 thousand (95% UI: 25.5 to 37.1) deaths, and 96.3 thousand (95% UI: 79.6 to 114.8) DALY cases globally. The ASRs of incidence, death, and DALYs significantly decreased from 1990 to 2021, with percentage changes of −3.9% (95% UI: −4.7% to −2.9%), −28.2% (95% UI: −42.2% to −12.5%), and −37.8% (95% UI: −50.5% to −24.3%), respectively. The global burden of myocarditis was higher in males, children, and the elderly. Additionally, the burden of myocarditis varied widely across different SDI regions, with high SDI regions having the highest ASR of incidence, and high‐middle SDI regions having the highest ASRs of deaths and DALYs.Although the ASRs of incidence, deaths, and DALYs significantly decreased from 1990 to 2021, the global number of incidences, deaths, and DALYs increased substantially. Certain populations, including males, children, the elderly, and regions with advanced sociodemographic levels, experienced a heavier burden of myocarditis. [ABSTRACT FROM AUTHOR]

Introcudtion Myocarditis is one of the leading causes of sudden cardiac deaths among athletes. One of the factors increasing the risk of this disease is engaging in sports training during an infection. Many athletes, regardless of their level of advancement, are not aware of the risks associated with training during an infection, and those who are aware often ignore them and continue training. Purpose Assessment of behaviors and awareness among runners in Poland regarding the risk of developing myocarditis as a result of training during respiratory tract infections. Material and method In December 2023, a voluntary and anonymous online survey was conducted among a group of 399 adult runners from Poland. The survey included 13 questions, consisting of 11 singlechoice questions and 2 multiple-choice questions. Results The percentage of individuals who do not associate training during an infection with an increased risk of myocarditis amounts to as much as 44.4% (n=177), while a staggering 86.7% (n=346) of respondents declare that they undertake training during respiratory infections. Conslusion After analyzing the survey, it's evident that while the Polish running community recognizes the risks of training during infections, many still exercise despite symptoms. Although most understand that intense training and early return to sports can harm health, awareness of myocarditis risks from exertion during infection is lacking. Despite protocols for post-illness return to sports, there's a need for campaigns to educate the running community on infectionrelated training risks. [ABSTRACT FROM AUTHOR]

Although COVID-19 is a disease consisting of mostly upper and lower respiratory symptoms, a subset of patients develop cardiac sequelae including myocarditis and pericarditis. For these patients, a standardized set of diagnostic imaging techniques and treatments has not been established. While there have been numerous case reports on this topic, there are few reviews that evaluate the effectiveness of different treatment modalities with a significant number of cases. We reviewed 146 cases of patients (ages ranging from 2 months old to mid 80 s) obtained from searches on PubMed, Google Scholar, and several case report journals. ECG abnormalities, elevated inflammatory markers, and reduced left ventricular ejection fraction were most associated with COVID-19 myocarditis. While classic symptoms of COVID-19 include upper respiratory symptoms, a subset of patients diagnosed with COVID-19 displayed no signs of respiratory disease at all. In 22% of cases, cardiac sequelae was not present until after the patient recovered from COVID-19. Steroids were given in 57.5% of cases. Cardiac MRI was used in 40.4% of cases for diagnosis of myocarditis. Of all the patients who were treated with ECMO, 82.1% of these patients were able to fully recover. The use of cardiac MRI and transthoracic echocardiogram for diagnosis of COVID-19 myocarditis should be heavily considered in any patient with COVID-19 infection. ECMO, IVIG, steroids, and anticoagulants should also be heavily considered. A randomized controlled trial should be conducted to better associate treatments with outcomes. [ABSTRACT FROM AUTHOR]

Background: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT. Results: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15–20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1–5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875). Conclusions: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB. [ABSTRACT FROM AUTHOR]

The European Society of Cardiology (ESC), the American College of Cardiology, the American Heart Association, and expert consensus documents provide different diagnostic criteria for myocarditis. Their overlap and prognostic value have never been compared. This study aims to assess and compare the predictive value of ESC criteria for clinically suspected myocarditis, updated Lake-Louise criteria (LLC), American Heart Association criteria for probable acute myocarditis (pAM), and expert consensus criteria for acute myocarditis (AM) and complicated myocarditis (CM). Patients with a clinical suspicion of myocarditis referred for cardiac magnetic resonance were enrolled at 2 centers. Those with any prior cardiomyopathy were excluded. The association of composite outcome events (heart failure hospitalization, recurrent myocarditis, sustained ventricular tachycardia, or death) with ESC diagnostic criteria, LLC, pAM, AM, and CM were compared. Among 1,557 consecutive patients referred for cardiac magnetic resonance with possible myocarditis, 1,050 (62.6% male; 48.9 ± 16.8 years of age) were without an alternative diagnosis. Of those, 938 (89.3%) met ESC criteria for clinically suspected myocarditis, 299 (28.5%) LLC, and 356 (33.9%), 216 (20.6%), and 77 (7.3%) pAM, AM, and CM, respectively. Adverse events occurred in 161 patients (15.3%) during a median follow-up of 3.4 years. The highest annualized event rates (6.6%) were observed in patients meeting LLC, whereas negative ESC criteria indicated excellent prognosis (0.7% annualized event rate). Among all myocarditis definitions, ESC criteria and LLC were the strongest multivariable outcome predictors and had independent and incremental prognostic value (HR adjusted : 3.87; 95% CI: 1.22-12.2; P = 0.021, and HR adjusted : 2.53; 95% CI: 1.83-3.49; P < 0.001, respectively) when adjusted for clinical characteristics. In a real-world cohort of patients with possible myocarditis, diagnosis was reached in most patients using ESC criteria whereas only approximately one-quarter of patients reached a diagnosis with LLC. The independent prognostic value of ESC-criteria and LLC highlights the complementary role of clinical and CMR-based findings in the diagnosis and risk stratification of myocarditis. [ABSTRACT FROM AUTHOR]

Background: Chlamydia pneumoniae and human herpesvirus 6 (HHV-6) are uncommon aetiological agents in respiratory tract infections and are rarely associated with cardiogenic shock. This case report presents a rare instance of severe cardiomyopathy linked to these infections in a 19-year-old Asian female. The case highlights the importance of considering a broad differential diagnosis in acute heart failure, especially in young adults. Case report: The patient was admitted with chest pain and diagnosed with ST-elevation myocardial infarction (STEMI) based on electrocardiography. She subsequently developed heart failure, with a marked reduction in myocardial contractility and a left ventricular ejection fraction (LVEF) of 20%. Treatment included broad-spectrum antibiotics and inotropic support guided by hemodynamic monitoring, leading to clinical improvement. The patient was discharged in a significantly improved condition following a stay in the intensive care unit (ICU). Conclusions: This case emphasizes the importance of considering Takotsubo syndrome in differential diagnoses, especially in ICU patients presenting with cardiogenic shock, to improve outcomes and reduce mortality through timely and appropriate management. Inotropic support, often used in the ICU to treat hypoperfusion, may worsen outcomes in patients with Takotsubo syndrome by exacerbating basal hypercontractility and prolonging the acute phase through catecholamine receptor activation. [ABSTRACT FROM AUTHOR]

Background/Objectives: In cases of myocarditis, electrocardiograms (ECGs) may suggest a pattern of ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). NSTEMI patterns are less frequent in myocarditis cases, but it remains unclear if the presence of ST-segment elevation in myocarditis cases is related to a more severe condition and more damage in the myocardium. Methods: This is a retrospective study involving 38 patients admitted to hospital with myocarditis. Patients were divided into two groups: patients with ST-segment elevation (STE) patterns in the ECG (25), and patients without ST-segment elevation (non-STE) patterns (13). The data compared included results from epidemiological, laboratory, and instrumental tests. Data were analysed using IBM SPSS Statistics v26.0. A p value of <0.05 was established as the threshold for statistical significance. Results: C-reactive protein (CRP) levels were higher in the STE group (103.40 ± 82.04 mg/L vs. 43.54 ± 61.93 mg/L, p = 0.017). The left ventricle ejection fraction (LVEF) was significantly higher in the non-STE pattern group (49.71 ± 4.14 vs. 56.58 ± 3.99, p < 0.001). A lower LVEF correlates with higher TnI levels (r= −0.353, p = 0.032) and higher CRP levels (r = −0.554, p < 0.001). Lower left ventricle (LV) strain correlates with higher levels of Troponin I (TnI) (r = −0.641, p = 0.013). Conclusions: LVEFs in the STE group were lower compared to those in the non-STE pattern group. STE pattern was associated with higher CRP levels. Higher TnI levels in cases of myocarditis were associated with lower LV strain and lower LVEF; higher CRP levels also correlated with lower LVEF. Based on a 6-month echocardiographic follow-up, the prognosis of myocarditis was favourable. [ABSTRACT FROM AUTHOR]

Background: Pertussis is a highly contagious, vaccine-preventable acute respiratory infection caused by Bordetella pertussis (B. Pertussis) and affects all age groups. Since 1947, the Global Expanded Program on Immunization (EPI) was executed, and its incidence has been effectively curtailed. The reasons for the resurgence are multifactorial including the waning of vaccine acquired immunity, the difference in vaccination strategies, the adaptation of B. Pertussis strains, and an increase in disease awareness due to the strengthening of diagnostic sensitivity and surveillance sensitivity. Notably, Hewlett and Edwards proposed that the shift in pertussis transmission patterns plays an important role in pertussis resurgence. Diphtheria is an acute infectious disease of upper respiratory tract caused by toxigenic strains of Corynebacterium Diphtheriae (CD) and Corynebacterium other than diphtheriae (COD). The organism is locally invasive and causes exotoxin - mediated illness and can lead to complications like stridor, respiratory obstruction, myocarditis, nerve palsy, renal insufficiency and death in severe cases. The objective of the present study is to isolate and identify the etiological agents in clinically suspected cases of Diphtheria and Pertussis. Materials & Methods: This Prospective study has been conducted in the department of Microbiology from Feb 2022 to Aug 2024. Samples with high clinical suspicion were received and processed. Two Throat swabs were collected in patients with clinical suspicion of Diphtheria. They were inoculated on Blood agar, Potassium Tellurite agar, Tinsdale agar. Gram staining and Albert staining were done. Molecular testing also performed for C. diphtheriae. Two nasopharyngeal swabs were collected in patients with clinical suspicion of Pertussis. They were inoculated on Bordet Gengou medium, Charcoal Agar with Cephalexin and Blood Agar and Mac Conkey agar. Gram Staining was performed and Biochemical testing was carried out. Molecular testing was carried out for B. Pertussis and B. parapertussis. Results: Out of 53 samples with clinical suspicion of Diphtheriae, 6 were positive for Corynebacterium diphtheria by culture. Molecular testing was also done for testing of rpo B gene and Tox A gene. 6 samples came to be positive for C. diphtheria rpo B gene where as one was positive for tox gene production. Out of 20 cases with strong suspicion of Pertussis, culture was positive for Bordetella pertussis in 2 samples. Molecular testing came out to be positive for one sample. Testing for the antibodies by ELISA two patients were serologically positive for Pertussis. Both Culture and molecular testing was positive in one sample. Both culture and serology was positive in one sample. Only serology was positive in one sample. Conclusion: A constant surveillance is needed for vaccine preventable diseases to predict the outbreak or resurgence of cases. [ABSTRACT FROM AUTHOR]

Myocarditis is a condition marked by inflammation of the heart muscle, which can lead to serious outcomes such as sudden cardiac death (SCD) and life-threatening arrhythmias. While myocarditis can affect any population, athletes, especially those engaged in high-intensity training, are at increased risk due to factors such as reduced immunity and increased exposure to pathogens. This review examines the clinical presentation, current guidelines, diagnostic challenges, and the significance of cardiac magnetic resonance imaging (CMR) in detecting myocardial inflammation and scarring. Current guidelines recommend a period of exercise restriction followed by thorough reassessment before athletes can return-to-play (RTP). However, there are several knowledge gaps, including the implications of persistent late gadolinium enhancement (LGE) on CMR and the optimal duration of exercise restriction. Additionally, the psychological impact of myocarditis on athletes highlights the importance of incorporating mental health support in the recovery process. A shared decision-making approach should be encouraged in RTP, considering the athlete's overall health, personal preferences, and the potential risks of resuming competitive sports. We have proposed an algorithm for RTP in athletes following myocarditis, incorporating CMR. Future research is warranted to refine RTP protocols and improve risk stratification, particularly through longitudinal studies that examine recovery and outcomes in athletes. [ABSTRACT FROM AUTHOR]

The management of resistant tuberculosis (tb) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensively drug-resistant (XDR) tb who received a treatment regimen including pretomanid, bedaquiline, linezolid, cycloserine, and amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG), and laboratory examinations, were typical for acute myocarditis; however, the patient was considered unstable, and further investigations, including magnetic resonance imaging (MRI), pericardiocentesis, and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which raised a high suspicion of drug induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant tb should be aware of this newly reported, potentially lethal, adverse event. [ABSTRACT FROM AUTHOR]

Background: Multiple reports have described myopericarditis following mRNA COVID-19 vaccination. However, data on the persistence of subclinical myocardial injury assessed by left ventricular (LV) longitudinal strain (LVLS) is limited. Objectives: Our aim was to assess LV function longitudinally in our cohort of COVID-19 vaccine-related myopericarditis using ejection fraction (EF), fractional shortening (FS), LVLS, and diastolic parameters. Methods: Retrospective, single-center review of demographic, laboratory, and management data was performed on 20 patients meeting diagnostic criteria for myopericarditis after mRNA COVID-19 vaccination. Echocardiographic images were obtained on initial presentation (time 0), at a median of 12 days (7.5, 18.5; time 1), and at a median of 44 days (29.5, 83.5; time 2). FS was calculated by M-mode, EF by 5/6 area-length methods, LVLS by utilization of TOMTEC software, and diastolic function by tissue Doppler. All parameters were compared across pairs of these time points using Wilcoxon signed-rank test. Results: Our cohort consisted predominantly of adolescent males (85%) with mild presentation of myopericarditis. The median EF was 61.6% (54.6, 68.0), 63.8% (60.7, 68.3), 61.4% (60.1, 64.6) at times 0, 1, and 2, respectively. Upon initial presentation, 47% of our cohort had LVLS < -18%. The median LVLS was -18.6% (-16.9, -21.0) at time 0, -21.2% at time 1 (-19.4, -23.5) (p = 0.004) and -20.8% (-18.7, -21.7) at time 2 (p = 0.004, as compared to time 0). Conclusions: Though many of our patients had abnormal strain during acute illness, LVLS improved longitudinally, indicating myocardial recovery. LVLS can be used as marker of subclinical myocardial injury and risk stratification in this population. [ABSTRACT FROM AUTHOR]

Detecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis. This study sought to assess the performance of cardiac magnetic resonance (CMR) for the detection of ongoing inflammation and the discrimination of chronic myocarditis from healed myocarditis. Consecutive patients with persistent symptoms (>30 days) suggestive of myocarditis were prospectively enrolled from a single tertiary center. All patients underwent a multiparametric 1.5-T CMR protocol including biventricular strain, T 1 /T 2 mapping, and late gadolinium enhancement (LGE). Endomyocardial biopsy was chosen for the reference standard diagnosis. Among 452 consecutive patients, 103 (median age: 50 years; 66 men) had evaluable CMR and cardiopathologic reference diagnosis: 53 (51%) with chronic lymphocytic myocarditis and 50 (49%) with healed myocarditis. T 2 mapping as a single parameter showed the best accuracy in detecting chronic myocarditis, if abnormal in ≥3 segments (92%; 95% CI: 85-97), and provided the best discrimination from healed myocarditis, as defined by the area under the receiver-operating characteristic curve (0.87 [95% CI: 0.79-0.93]; P < 0.001), followed by radial peak systolic strain rate of the left ventricle (0.86) and the right ventricle (0.84); T 1 mapping (0.64), extracellular volume fraction (0.62), and LGE (0.57). Specificity increased when T 2 mapping was combined with elevation of either troponin or C-reactive protein. A multiparametric CMR protocol allows detection of ongoing myocardial inflammation and discrimination of chronic myocarditis from healed myocarditis, with segmental T 2 mapping and biventricular strain analysis showing higher diagnostic accuracy compared with T 1 mapping, extracellular volume fraction, and LGE. The use of biomarkers (troponin or C-reactive protein) may improve specificity. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Long COVID is a condition where symptoms or complications persist beyond 3 months after COVID-19 infection. Although most athletes experience mild symptoms, those involved in sports with higher cardiovascular demands can develop long COVID, which can negatively impact sports performance. This narrative review aimed to analyze the long COVID in athletes, especially cardiovascular effects; to alert medical and sporting community for the clinical aftermaths of COVID-19, focusing on physical activity; and to discuss the potential return-to-play strategies for these athletes. Methods: An electronic search in PubMed database for articles published between January/2020 and February/2023 was performed including athletic populations with COVID-19, emphasizing long-term complications, especially the cardiovascular effects. Results and Conclusions: While severe cardiac complications are rare, athletes with long COVID often experience symptoms such as fatigue, dyspnea, palpitations, and exercise intolerance. To manage athletes with long COVID, individualized and structured return-to-play programs with the involvement of multidisciplinary teams are crucial. This underscores the importance of recognizing long COVID in athletes, raising awareness of its potential impacts, and implementing strategies to ensure a safe return to play. [ABSTRACT FROM AUTHOR]

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis. [ABSTRACT FROM AUTHOR]

Myocarditis after the COVID-19 vaccine is one of the important adverse events following immunization, observed mainly after mRNA-based vaccines. Importantly, post-vaccination myocarditis was less common than myocarditis after SARS-CoV-2 infection, as it was scored at 19.7 per 1,000,000 doses and 2.76 per 1000 infections. Predominantly, its course was benign and, compared with the myocarditis after COVID-19 infection, significantly fewer patients developed heart failure or died among patients with post-vaccination myocarditis. The group at highest risk of myocarditis related to COVID-19 vaccination were young males who received a second dose of an mRNA vaccine. It was observed that, among mRNA vaccines, specifically mRNA-1273 was associated with a higher risk of myocarditis. The mechanism underlying myocarditis after COVID-19 vaccination is still under investigation and certain processes are being considered. Currently, some follow-up assessments of patients who developed vaccine-induced myocarditis are available and suggest a favorable prognosis. The aim of this review is to discuss the most recent data on myocarditis after COVID-19 vaccination considering its epidemiology, clinical presentation, diagnosis, management, relative risk of myocarditis compared with SARS-CoV-2 infection, potential underlying mechanism, and follow-up data of patients who developed post-vaccination myocarditis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Methods: Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE". Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). Results: Echocardiograms from 175 patients (median age 15 years, IQR 7.9–16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (p < 0.001), with optimal cutoff values of −18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and –17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). Conclusions: In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF. [ABSTRACT FROM AUTHOR]

Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM experience recurrence with a life‐threatening fulminant form. Although combining steroids and immunosuppressants, such as azathioprine and mycophenolate mofetil, has demonstrated favourable outcomes in patients with LM, their efficacy is limited to the chronic phase. Indeed, various immunosuppressants have been used for LM with fulminant manifestation; however, their evidence remains lacking. In our case series, two patients with LM experienced fulminant relapses during steroid tapering, and another presented persistent cardiac enzymes elevation despite steroid therapies. Consequently, we initiated calcineurin inhibitors alongside steroids, resulting in well‐controlled clinical courses without further recurrence of LM and significant adverse effects. Our cases suggest calcineurin inhibitors as therapeutic options for managing steroid‐resistant LM with fulminant relapse. [ABSTRACT FROM AUTHOR]

Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results: We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions: The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimabassociated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICIinduced cardiotoxicity is methylprednisolone. However, the long-term or highdose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immunemediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use. [ABSTRACT FROM AUTHOR]

Histiocytoses are rare diseases characterised by infiltration of affected organs by myeloid cells with a monocyte or dendritic cell phenotype. Symptoms can range from self-resolving localised forms to multisystemic lesions requiring specific treatment. To demonstrate extremely rare cases of CD68-negative cardiac histiocytosis with expression of SARS-CoV-2 antigen in infiltrate cells. We demonstrated a case of Erdheim–Chester disease in a 67-year-old man with pericardial involvement and positive dynamics with vemurafenib treatment, an autopsy case of xanthogranulomatous myopericarditis in a 63-year-old man, surgical material of xanthogranulomatous constrictive pericarditis in a 57-year-old man, and an autopsy case of xanthogranulomatosis in a 1-month-old girl. In all cases, xanthogranuloma cells expressed CD163, many of them spike protein SARS-CoV-2, while CD68 expression was detected only in single cells. In this article, we demonstrated four cases of extremely rare CD68-negative cardiac xanthogranulomatosis in three adults and one child with expression of the spike protein SARS-CoV-2 in M2 macrophages. This potential indirect association between COVID-19 and the development of histiocytosis in these patients warrants further investigation. To substantiate this hypothesis, more extensive research is needed. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors can cause immune-related adverse events in various organ systems, with myocarditis being the most serious and life-threatening. This article reports three cases of immune myocarditis induced by camrelizumab, detailing the diagnostic and treatment process. Case Report: Three cases of immune-related myocarditis caused by the use of camrelizumab are reported. Three patients (case 1, male, 44 years old; case 2, male, 69 years old; and case 3, male, 53 years old) were treated with the immune checkpoint inhibitor, camrelizumab 200 mg, intravenously for nasopharyngeal and esophageal cancers. In case 1, 18 days after the 3rd cycle of immunotherapy, the patient’s troponin levels were elevated. In case 2, 1 day after the 1st cycle of treatment, troponin levels were elevated. The electrocardiogram showed right bundle branch block with left anterior branch block and abnormal ST-T segments in the lower wall, and the echocardiogram showed segmental ventricular dyskinesia and thickening of the myocardium of the left and right ventricles. In case 3, 12 days after the 3rd cycle of treatment, the patient developed chest tightness and breathlessness, and cardiac biomarkers were elevated. The electrocardiogram showed borderline QT interval prolongation and extensive ST-T segment changes, and cardiac ultrasound showed thinning of the myocardium in the middle and lower left ventricular anterior and lower posterior walls and loss of motility. All 3 patients were diagnosed with immune-associated cardiomyositis induced by camrelizumab, and camrelizumab was discontinued. In case 1, methylprednisolone succinate was administered as an intravenous infusion of 500 mg once a day for 4 days, and the patient’s troponin levels gradually decreased. In case 2, following the administration of intravenous methylprednisolone succinate sodium (500 mg) once daily for 5 consecutive days, the patient experienced gastrointestinal bleeding. The hormone dose was then reduced, and intravenous immune globulin (IVIG) 10 g/day was added. Treatment continued for 3 days after the patient’s death due to immune myocarditis and heart failure combined with gastrointestinal bleeding. Case 3 underwent a tracheotomy and received methylprednisolone sodium succinate (240 mg) intravenous drip daily for 7 days. Camrelizumab was discontinued. Although troponin and NT-proBNP levels remained elevated with an upward trend 7 days after starting treatment, they decreased after adding IVIG 20 g/day for 3 days. Treatment continued for another 3 days after improvement in cardiac biomarkers. After gradually reducing the hormone dose over 5 days following the stabilization of the patient’s condition, he was discharged from the hospital. The patient’s follow-up status is good. Conclusion: Emphasizing the importance of baseline assessment, early detection and timely intervention, standardized use of glucocorticosteroids, and the addition of immunosuppressants where necessary, these measures can be effective in reducing mortality and ultimately improving prognosis. [ABSTRACT FROM AUTHOR]

The risk for suffering immune checkpoint inhibitors (ICIs)‐associated myocarditis increases in patients with pre‐existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single‐cell RNA sequencing, and flow cytometry are used to decipher how anti‐cytotoxic T lymphocyte antigen‐4 m2a antibody (anti‐CTLA‐4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti‐CTLA‐4 m2a antibody increases cardiac fibroblast‐derived C‐X‐C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1‐Cxcr2 chemotaxis. It is identified that the C–C motif chemokine ligand 5 (Ccl5)‐neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF‐κB signaling, and cellular response to interferon‐gamma and that the Ccl5‐neutrophil subpopulation and its‐associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti‐CTLA‐4 m2a antibody‐induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5‐neutrophil subpopulation plays a critical role in aggravating anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs‐associated myocarditis. [ABSTRACT FROM AUTHOR]

Background: The intricate relationship among gut microbiota, serum metabolites, and immunophenotypes may significantly impact myocarditis. However, direct causal links between these domains and myocarditis are not well understood. Methods: The study performed Mendelian randomization (MR) analysis using genetic data from public sources. Exposure data included 211 gut microbiota, 486 serum metabolites, and 731 immunophenotypes from Mibiogen, the Metabolomics GWAS server, and GWAS catalog databases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on established criteria. Myocarditis data from GWAS (427,911 participants, 24, 180, 570 SNPs) were used as the outcome variable. MR analysis was conducted using Inverse Variance Weighting (IVW), with Cochran's Q test for heterogeneity and Egger's intercept to assess horizontal pleiotropy. Results: 9 gut microbiota, 10 serum metabolites, and 2 immunophenotypes were negatively associated with myocarditis risk. In contrast, 5 gut microbiota, 12 serum metabolites, and 7 immunophenotypes were positively associated with myocarditis risk (all, P < 0.05). Sensitivity analyses confirmed the stability of these results. Conclusion: This MR study suggests that gut microbiota, serum metabolites, and immunophenotypes may causally influence myocarditis risk. These findings provide genetic evidence for myocarditis etiology and could inform future precision prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Myocarditis is the most salient serious adverse event following messenger RNA-based Covid-19 vaccines. The highest risk is observed after the second dose compared to the first, whereas the level of risk associated with more distant booster doses seems to lie in between. We aimed to assess the relation between dosing interval and the risk of myocarditis, for both the two-dose primary series and the third dose (first booster). This matched case-control study included 7911 cases of myocarditis aged 12 or more in a period where approximately 130 million vaccine doses were administered. Here we show that longer intervals between each consecutive dose, including booster, may decrease the occurrence of vaccine-associated myocarditis by up to a factor of 4, especially under age 50. These results suggest that a minimum 6-month interval might be required when scheduling additional booster vaccination. Dosing interval has been suggested as a modifier in the risk of myocarditis associated with Covid-19 mRNA vaccination. Here, the authors show that longer intervals between each consecutive dose, including booster, may decrease the occurrence of myocarditis, especially under age 50. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific cause remains unidentified. Recent research has highlighted the potential role of genetic susceptibility in the development of myocarditis (and in some cases the development of inflammatory dilated cardiomyopathy, i.e., the condition in which there is chronic inflammation (>3 months) and left ventricular dysfunction\dilatation), with several studies indicating a correlation between myocarditis and genetic backgrounds. Notably, pathogenic genetic variants linked to dilated or arrhythmic cardiomyopathy are found in 8–16% of myocarditis patients. Genetic predispositions can lead to recurrent myocarditis and a higher incidence of ventricular arrhythmias and heart failure. Moreover, the presence of DSP mutations has been associated with distinct pathological patterns and clinical outcomes in arrhythmogenic cardiomyopathy (hot phases). The interplay between genetic factors and environmental triggers, such as viral infections and physical stress, is crucial in understanding the pathogenesis of myocarditis. Identifying these genetic markers can improve the diagnosis, risk stratification, and management of patients with myocarditis, potentially guiding tailored therapeutic interventions. This review aims to synthesize current knowledge on the genetic underpinnings of myocarditis, with an emphasis on desmoplakin-related arrhythmogenic cardiomyopathy, to enhance clinical understanding and inform future research directions. [ABSTRACT FROM AUTHOR]

Cardiovascular manifestations of coronavirus disease 2019 (COVID-19) include myocardial injury, heart failure, and myocarditis and are associated with long-term disability and mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antigens are found in the myocardium of COVID-19 patients, and human cardiomyocytes are susceptible to infection in cell or organoid cultures. While these observations raise the possibility that cardiomyocyte infection may contribute to the cardiac sequelae of COVID-19, a causal relationship between cardiomyocyte infection and myocardial dysfunction and pathology has not been established. Here, we generated a mouse model of cardiomyocyte-restricted infection by selectively expressing human angiotensin-converting enzyme 2 (hACE2), the SARS-CoV-2 receptor, in cardiomyocytes. Inoculation of Myh6-Cre Rosa26loxP-STOP-loxP-hACE2 mice with an ancestral, non-mouse-adapted strain of SARS-CoV-2 resulted in viral replication within the heart, accumulation of macrophages, and moderate left ventricular (LV) systolic dysfunction. Cardiac pathology in this model was transient and resolved with viral clearance. Blockade of monocyte trafficking reduced macrophage accumulation, suppressed the development of LV systolic dysfunction, and promoted viral clearance in the heart. These findings establish a mouse model of SARS-CoV-2 cardiomyocyte infection that recapitulates features of cardiac dysfunctions of COVID-19 and suggests that both viral replication and resultant innate immune responses contribute to cardiac pathology. IMPORTANCE Heart involvement after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurs in multiple ways and is associated with worse outcomes in coronavirus disease 2019 (COVID-19) patients. It remains unclear if cardiac disease is driven by primary infection of the heart or immune response to the virus. SARS-CoV-2 is capable of entering contractile cells of the heart in a culture dish. However, it remains unclear how such infection affects the function of the heart in the body. Here, we designed a mouse in which only heart muscle cells can be infected with a SARS-CoV-2 strain to study cardiac infection in isolation from other organ systems. In our model, infected mice show viral infection, worse function, and accumulation of immune cells in the heart. A subset of immune cells facilitates such worsening heart function. As this model shows features similar to those observed in patients, it may be useful for understanding the heart disease that occurs as a part of COVID-19. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease that may lead to dilated cardiomyopathy. Viral infection of the myocardium triggers immune responses, which involve, among others, macrophage infiltration, oxidative stress, expression of pro-inflammatory cytokines, and microRNAs (miRNAs). The cardioprotective role of estrogen in myocarditis is well documented; however, sex differences in the miRNA expression in chronic myocarditis are still poorly understood, and studying them further was the aim of the present study. Male and female ABY/SnJ mice were infected with CVB3. Twenty-eight days later, cardiac tissue from both infected and control mice was used for real-time PCR and Western blot analysis. NFκB, IL-6, iNOS, TNF-α, IL-1β, MCP-1, c-fos, and osteopontin (OPN) were used to examine the inflammatory state in the heart. Furthermore, the expression of several inflammation- and remodeling-related miRNAs was analyzed. NFκB, IL-6, TNF-α, IL-1β, iNOS, and MCP-1 were significantly upregulated in male mice with CVB3-induced chronic myocarditis, whereas OPN mRNA expression was increased only in females. Further analysis revealed downregulation of some anti-inflammatory miRNA in male hearts (let7a), with upregulation in female hearts (let7b). In addition, dysregulation of remodeling-related miRNAs (miR27b and mir199a) in a sex-dependent manner was observed. Taken together, the results of the present study suggest a sex-specific expression of pro-inflammatory markers as well as inflammation- and remodeling-related miRNAs, with a higher pro-inflammatory response in male CVB3 myocarditis mice. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n = 83,264, Crohn's disease [CD, n = 24,738], ulcerative colitis [UC, n = 46,409], and IBD-unclassified [IBD-U, n = 12,117]), general population reference individuals (n = 391,344), and IBD-free full siblings (n = 96,149) and followed until 2019. Primary outcome was incident myocarditis, and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHRs) and cumulative incidence of outcomes, along with 95% confidence intervals. RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in patients with IBD (incidence rate [IR] = 22.6/100,000 person-years) and 710 in reference individuals (IR = 12.9), with an aHR of 1.55 (95% confidence interval 1.33-1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to 1 extra myocarditis case in 735 patients with IBD until then. This increased risk was observed in CD (aHR = 1.48 [1.11-1.97]) and UC (aHR = 1.58 [1.30-1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs 3.5; aHR = 2.44 [1.89-3.15]), irrespective of IBD subtypes (CD: aHR = 2.39 [1.43-4.01], UC: aHR = 2.82 [1.99-4.00], and IBD-U: aHR = 3.14 [1.55-6.33]). Sibling comparison analyses yielded similar results. DISCUSSION: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low. [ABSTRACT FROM AUTHOR]

In suspected non–ST-segment elevation myocardial infarction (NSTEMI), this presumed diagnosis may not hold true in all cases, particularly in patients with nonobstructive coronary arteries (NOCA). Additionally, in multivessel coronary artery disease, the presumed infarct-related artery may be incorrect. This study sought to assess the diagnostic utility of cardiac magnetic resonance (CMR) before invasive coronary angiogram (ICA) in suspected NSTEMI. A total of 100 consecutive stable patients with suspected acute NSTEMI (70% male, age 62 ± 11 years) prospectively underwent CMR pre-ICA to assess cardiac function (cine), edema (T 2 -weighted imaging, T 1 mapping), and necrosis/scar (late gadolinium enhancement). CMR images were interpreted blinded to ICA findings. The clinical care and ICA teams were blinded to CMR findings until post-ICA. Early CMR (median 33 hours postadmission and 4 hours pre-ICA) confirmed only 52% (52 of 100) of patients had subendocardial infarction, 15% transmural infarction, 18% nonischemic pathologies (myocarditis, takotsubo, and other forms of cardiomyopathies), and 11% normal CMR; 4% were nondiagnostic. Subanalyses according to ICA findings showed that, in patients with obstructive coronary artery disease (73 of 100), CMR confirmed only 84% (61 of 73) had MI, 10% (7 of 73) nonischemic pathologies, and 5% (4 of 73) normal. In patients with NOCA (27 of 100), CMR found MI in only 22% (6 of 27 true MI with NOCA), and reclassified the presumed diagnosis of NSTEMI in 67% (18 of 27: 11 nonischemic pathologies, 7 normal). In patients with CMR-MI and obstructive coronary artery disease (61 of 100), CMR identified a different infarct-related artery in 11% (7 of 61). In patients presenting with suspected NSTEMI, a CMR-first strategy identified MI in 67%, nonischemic pathologies in 18%, and normal findings in 11%. Accordingly, CMR has the potential to affect at least 50% of all patients by reclassifying their diagnosis or altering their potential management. [Display omitted] [ABSTRACT FROM AUTHOR]

Historically, patients with myocarditis were considered for implantable cardioverter defibrillator (ICD) utilization only in the chronic phase of the disease following the development of persistent cardiomyopathy refractory to medical therapy or occurrence of a major ventricular arrhythmic event. However, recent literature has indicated that ventricular arrhythmias are frequently reported even in the acute phase of the disease, challenging the long-standing perception that this disease process was largely reversible. Given this changing environment of information, the latest US and European guidelines were recently updated in 2022 to now consider ICD implantation during the acute phase which has significantly increased the number of individuals eligible for these devices. Additionally, several studies with small subgroups of patients have demonstrated a possible benefit of wearable cardioverter defibrillators (WCDs) in this patient demographic. Assuming that larger studies confirm their utility, it is possible that WCDs can assist in detection of ventricular arrhythmias and selection of high-risk candidates for ICD implantation, while providing temporary protection for a small percentage of patients before the development of a major arrhythmic event. This review ultimately serves as a comprehensive review of the most recent guidelines for defibrillator use in acute and chronic myocarditis. The latest US and European guidelines support ICD use for myocarditis patients following the development of persistent cardiomyopathy refractory to medical therapy or occurrence of a major ventricular arrhythmic event. Previously, patients in the acute phase were excluded from ICD utilization even after experiencing malignant ventricular tachycardia or ventricular fibrillation due to the long-standing perception that this disease process was largely reversible. However, recent literature has indicated that ventricular arrhythmias are frequently reported even in the acute phase of the disease. Additionally, we found that the myocardial damage that is inflicted persists many years after the initial episode. Given this changing environment of information, guidelines were recently updated in 2022 to now consider ICD implantation during the acute phase which has significantly increased the number of individuals eligible for these devices. We support possible ICD utilization for secondary prevention during the acute phase of myocarditis given the elevated risk of arrhythmia recurrence and the fact that any ventricular arrhythmia can induce sudden cardiac death. Future prospective studies are needed to assess which patients may benefit most from early ICD implantation. WCDs have improved survival in patient populations at high-risk for sudden cardiac death who are not candidates for ICD implantation. After analyzing several recent studies with small subgroups of patients, WCDs appear to demonstrate similar efficacy for myocarditis patients as well. Assuming that larger studies confirm their utility, we believe that WCDs can assist in detection of ventricular arrhythmias and selection of high-risk candidates for ICD implantation. Furthermore, WCDs have the additional benefit of acting as primary prevention by providing temporary protection for a small percentage of myocarditis patients before they develop a major arrhythmic event. [Display omitted] • Myocarditis can lead to ventricular arrhythmias including sudden cardiac death. • Currently, implantable cardioverter defibrillators (ICDs) are indicated for primary prevention in select myocarditis patients. • ICD indications expanded as secondary prevention in acute and chronic myocarditis. • Wearable cardioverter defibrillators can bridge patients to an ICD to protect against life-threatening arrhythmias. [ABSTRACT FROM AUTHOR]

Myocarditis, a significant public health issue, can lead to heart failure and death. While endomyocardial biopsy (EMB) provides accurate diagnoses, its invasiveness limits its use in severe cases. Alternatively, cardiac magnetic resonance (CMR) offers a non-invasive method to detect and monitor myocarditis, displaying myocardial involvement with high signal contrast. Traditional studies on myocarditis often rely on supervised learning, which faces challenges such as the need for large, well-labeled datasets. A diagnostic model for myocarditis is introduced in this paper, utilizing CMR images and employing a semi-supervised generative adversarial network (SS-GAN) to enhance classifier performance, complemented by differential evolution (DE) for hyperparameter optimization. The semi-supervised nature of SS-GAN is pivotal in scenarios where labeled data is scarce or imbalanced. A regularization strategy is included to address missing modes and stabilize SS-GAN training. Feature vectors extracted by the discriminator are utilized to guide the generator in producing accurate outputs. Additionally, a reconstruction loss is incorporated into the loss function of SS-GAN, compelling the generator to reconstruct outputs based on the discriminator's features, thereby aligning outputs closer to actual data configurations. This enhancement not only improves SS-GAN performance but also ensures high-quality outputs. To minimize reliance on hyperparameters, the Random Key method is employed, optimized using the DE algorithm. The efficacy of the model is demonstrated on the Z-Alizadeh Sani myocarditis dataset, with further validation achieved through experiments on the EMIDEC dataset, assessing transfer learning (TL) effects. F-measures of 91.124% and 89.511% are achieved on the Z-Alizadeh Sani myocarditis and EMIDEC datasets, respectively, indicating superior performance over existing techniques. [ABSTRACT FROM AUTHOR]

Myocarditis poses a significant health threat, often leading to severe outcomes such as heart failure or death. While endomyocardial biopsy (EMB) is a reliable diagnostic method, its invasive nature limits its use to severe cases. Cardiac magnetic resonance (CMR) offers a less invasive alternative by utilizing enhanced signal contrast to detect and monitor myocarditis, effectively highlighting affected myocardial areas. This study introduces an advanced model designed to overcome challenges like initial weight sensitivity and class imbalance, which are often overlooked in existing research. The model employs multiple convolutional neural networks (CNNs) to extract feature vectors from images for classification. To address class imbalance, a proximal policy optimization (PPO)-based algorithm is utilized, significantly improving the training process by preventing abrupt policy shifts and stabilizing them. This mechanism rewards precise classification of underrepresented classes more heavily than overrepresented ones, promoting balanced learning. Additionally, the model incorporates a novel pre-training method, the mutual learning-artificial Bee Colony (ML-ABC) technique, which dynamically adjusts initial weight settings through mutual learning components. This approach enhances the model's initial ability to recognize complex patterns in myocardial images, improving classification accuracy. The model's efficacy was validated using the Z-Alizadeh Sani myocarditis dataset, achieving an impressive F-measure of 83%. These results highlight the model's superiority over existing methods and confirm its potential for clinical use, marking a significant advancement in the early detection and treatment of myocarditis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have transformed the treatment for multiple cancers and are increasingly used in recent years, but they can cause potentially life-threatening cardiac toxicity. We report a case of a 64-year-old gentleman who presented to the Emergency Department with symptoms of fatigue and breathlessness whilst receiving treatment with an immune checkpoint inhibitor, pembrolizumab, for cholangiocarcinoma. He was found to be in cardiogenic shock with an abnormal electrocardiogram and elevated cardiac troponin at presentation. Echocardiogram demonstrated severely impaired right and left ventricular function. Computed tomography pulmonary angiography and invasive coronary angiography excluded pulmonary embolism and acute myocardial infarction, respectively, and he was diagnosed with immune checkpoint inhibitor associated myocarditis. He was treated with high-dose methylprednisolone and a dobutamine infusion. Within days, his troponin and C-reactive protein levels decreased, and his left ventricular function improved. He was established on heart failure therapies and discharged from hospital 12 days later. [ABSTRACT FROM AUTHOR]

Background Mesalazine is an established first-line therapy for inflammatory bowel disease (IBD) and remains the mainstay of treatment for mild to moderate ulcerative colitis (UC). Both mesalazine and UC are rare but recognized causes of myopericarditis. Cardiac magnetic resonance (CMR) is a non-invasive method of assessing for myopericarditis. This case reports highlights the importance of early CMR in diagnosis, and management of myocarditis in a patient with IBD. Case summary A 28-year-old male was admitted with a 2-day history of chest pain. Three weeks prior to this presentation, the patient was initiated on mesalazine for UC. Serum troponin T and C-reactive protein were elevated. An echocardiogram showed borderline low left ventricular systolic function (LVEF = 50–55%). A CMR showed extensive patchy late gadolinium enhancement (LGE) in the mid to epicardial basal and mid lateral wall. The findings were consistent with acute myocarditis, and a working diagnosis of mesalazine-induced myocarditis was made. Mesalazine was stopped and guideline-directed anti-inflammatories initiated. Oral prednisolone was also introduced for IBD control. Follow-up CMR at four months showed near complete resolution of LGE. Discussion Myocarditis in the context of IBD may be infective, immune-mediated or due to mesalazine hypersensitivity. Histological conformation was not available in this case. This case report highlights the importance of access to early CMR in order establish the diagnosis and withdrawal of the culprit medication. In the majority of cases, CMR will replace the need for endomyocardial biopsy; however, this may still be required in the most severe cases. [ABSTRACT FROM AUTHOR]

Background ICI-associated myocarditis is a rare but severe and potentially life-threatening complication that typically manifests shortly after treatment initiation. It may present in many different ways, ranging from fulminant to non-fulminant, even including clinical and electrocardiographic findings mimicking ST-elevation Myocardial Infarction (STEMI). Case summary A 72-year-old woman with a history of non-small cell lung carcinoma presented at the emergency department with symptoms of general asthenia and chest pain, following recent ICI-therapy initiation. Electrocardiogram showed ST elevation in the lateral leads and led to prompt admission for urgent invasive coronary angiography, which ruled out significant coronary artery disease. Urgent cardiac magnetic resonance had to be aborted due to claustrophobia. Endomyocardial biopsy—performed the day after urgent hospital admission and before starting high-dose corticosteroids—confirmed acute ICI-associated myocarditis. On the sixth day of hospitalization, the patient developed transient complete heart block and non-sustained ventricular tachycardia, necessitating temporary transjugular pacemaker insertion. Cellcept (mycophenolate mofetil) was associated due to rising troponin levels. Following a three-week hospital stay, the patient was discharged with a regimen of gradually tapering steroids and continued Cellcept therapy. Two months post-discharge, the patient was readmitted due to severe pneumonia, ultimately resulting in the patient's demise. Discussion We present the case of a fulminant ICI-associated myocarditis. The case illustrates the diagnostic workup and treatment strategies of an (in the end) fatal adverse event from the use of immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Myocarditis is a rare cardiomyocyte inflammatory process, typically caused by viruses, with potentially devastating cardiac sequalae in both competitive athletes and in the general population. Investigation into myocarditis prevalence in the Coronavirus disease 2019 (COVID-19) era suggests that infection with Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an independent risk factor for myocarditis, which is confirmed mainly through cardiovascular magnetic resonance imaging. Recent studies indicated that athletes have a decreased risk of myocarditis after recent COVID-19 infection compared to the general population. However, given the unique nature of competitive athletics with their frequent participation in high-intensity exercise, athletes possess distinct factors of susceptibility for the development of myocarditis and its subsequent severe cardiac complications (e.g., sudden cardiac death, fulminant heart failure, etc.). Under this context, this review focuses on comparing myocarditis in athletes versus non-athletes, owing special attention to the distinct clinical presentations and outcomes of myocarditis caused by different viral pathogens such as cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, human immunodeficiency virus, and Parvovirus B19, both before and after the COVID-19 pandemic, as compared with SARS-CoV-2. By illustrating distinct clinical presentations and outcomes of myocarditis in athletes versus non-athletes, we also highlight the critical importance of early detection, vigilant monitoring, and effective management of viral and non-viral myocarditis in athletes and the necessity for further optimization of the return-to-play guidelines for athletes in the COVID-19 era, in order to minimize the risks for the rare but devastating cardiac fatality. [ABSTRACT FROM AUTHOR]

The mechanism underlying myopericarditis associated with mRNA COVID-19 vaccination, including increased susceptibility in young males, remains poorly understood. This study aims to explore the hypothesis that engaging in physical exercise at the time of mRNA COVID-19 vaccination may promote a cardiac inflammatory response, leading to the development of myopericarditis. Male BALB/c mice underwent treadmill running or remained sedentary for five weeks. Subsequently, two doses of the Pfizer/BioNTech vaccine or vehicle were administered with a 14-day interval, while the exercise regimen continued. The animals were euthanized days after the second vaccination. Vaccination was followed by body weight loss, increased hepatic inflammation, and an antigen-specific T cell response. Small foci of fibrovascular inflammation and focal cell loss were observed in the right ventricle, irrespective of vaccination and/or exercise. Vaccination did not elevate cardiac troponin levels. Cardiac tissue from the vaccinated mice showed upregulated mRNA expression of the genes IFNγ and IL-1β, but not IL-6 or TNFα. This pro-inflammatory signature in the heart was not exacerbated by endurance exercise. Ex vivo vascular reactivity remained unaffected by vaccination. Our data provide evidence for the cardiac safety of mRNA COVID-19 vaccination. The role of exercise in the development of pro-inflammatory cardiac changes post mRNA vaccination could not be established. [ABSTRACT FROM AUTHOR]

Advances in the etiological classification of myocarditis and inflammatory cardiomyopathy (ICM) have reached a consensus. However, the mechanism of myocarditis/ICM remains unclear, which affects the development of treatment and the improvement of outcome. Cellular transcription and metabolic reprogramming, and the interactions between cardiomyocytes and non-cardiomyocytes, such as the immune cells, contribute to the process of myocarditis/ICM. Recent efforts have been made by multi-omics techniques, particularly in single-cell RNA sequencing, to gain a better understanding of the cellular landscape alteration occurring in disease during the progression. This article aims to provide a comprehensive overview of the latest studies in myocarditis/ICM, particularly as revealed by single-cell sequencing. [ABSTRACT FROM AUTHOR]

Anti-mitochondrial antibody (AMA)-positive myopathy, a recently identified condition with significant cardiac involvement, poses a serious challenge in treatment consensus due to its extreme rarity. While several studies demonstrate the efficacy of high-dose prednisolone in managing this disease, the current literature lacks substantial evidence regarding the effectiveness of biologic therapy or low-dose prednisolone for remission induction. Here, we present a case of AMA-positive myocarditis that emerged during rheumatoid arthritis treatment with tocilizumab (TCZ) and low-dose prednisolone (PSL). Successfully, intensive immunosuppressive therapy with high-dose PSL proved effective in stabilizing this condition. Our case highlights the necessity of a robust immunosuppressive approach, favoring high-dose PSL over the combination of low-dose PSL and TCZ in this disease. [ABSTRACT FROM AUTHOR]

Abstract Myocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant blood metabolites and the risk of myocarditis has not been well-established. To identify potential biometabolic markers associated with myocarditis, we conducted a two-sample Mendelian randomization (MR) study. We performed preliminary MR analysis using the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods to adjust for false discovery rate (FDR). Confounders were screened using the GWAS Catalog website. Sensitivity analyses included Cochrane Q-test, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), scatterplots, funnel plots, and forest plots. For genetic and directional analysis, we employed co-localization analysis and the Steiger test. MR analysis was performed using the FinnGen database and meta-analysis was performed using the IEU database. MR analysis identified significant correlations for five metabolic biomarkers after FDR correction. These included four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, and 5-acetylamino-6-formylamino-3-methyluracil, as well as one unknown metabolite, X-25,422. Among these, kynurenine (OR = 1.441, 95%CI = 1.089–1.906, p-value = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029–1.550, p-value = 0.029) were identified as risk factors for myocarditis, while deoxycarnitine (OR = 0.813, 95%CI = 0.676–0.979, p-value = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95% CI = 0.775–0.962, p-value = 0.018), and X-25,422 (OR = 0.721, 95%CI = 0.587–0.886, p-value = 0.009) were found to be protective factors. No evidence of heterogeneity, horizontal pleiotropy, or sensitivity issues was observed, and no shared genetic factors between exposure and outcome were detected. The causality was in the correct direction. Meta-analysis further confirmed the causal relationship between the five metabolites and myocarditis. This study identifies a causal relationship between five circulating metabolites and myocarditis. Kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, X-25,422, and 5-acetylamino-6-formylamino-3-methyluracil may serve as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of the condition.

Purpose: Here, we describe cardiac magnetic resonance imaging (CMR) findings in patients with proven COVID-19 infection and presenting with cardiac problems both at presentation and in convalescence from a tertiary care center, in North India. A pertinent review of the literature is also discussed. Materials and Methods: Retrospective analysis of patients with real-time reverse transcriptase-polymerase chain reaction proven COVID-19 infection either at presentation or convalescence referred for CMR at our facility from January 2021 to December 2023 was done. CMR was performed on a 3T system (Ingenia, Philips Healthcare, Best, The Netherlands) and examinations were customized according to the clinical indications. Results: Retrospective analysis yielded 14 patients (4 at presentation; 10 in convalescence). Patients at presentation 4/14 had clinically presented with chest pain with raised troponins and electrographic abnormalities, while 10/14 patients had presented with clinical features of heart failure with two-dimensional transthoracic echocardiography demonstrating systolic dysfunction with reduced left ventricular ejection fraction. Out of 14, 4 patients at presentation, CMR showed features of acute myocarditis in three patients, while one had inferior wall myocardial infarction (MI) (this patient on catheter angiogram had aneurysmally dilated coronary arteries with thrombus and stenosis in the mid right coronary artery which was successfully stented). Out of 14, 10 patients on CMR had features of dilated cardiomyopathy (DCMP). Conclusion: Cardiac involvement in COVID-19 can have vivid clinicoradiological presentations with features of myocarditis and MI at presentation or DCMP in convalescence. CMR in such cases is a problem-solving tool where myocarditis is candidly differentiated from MI. Moreover, follow-up CMR demonstrates temporal changes in COVID-19-associated myocarditis and evaluation of cardiac structure and function in patients presenting with DCMP.

This article discusses the problem of underuse, low availability of modern imaging techniques such as magnetic resonance imaging of the heart (MRI). This technique is characterized by high accuracy and uniqueness in the diagnosis of myocardial lesions of various genesis. The widespread introduction of this technique in emergency cardiology departments can improve the accuracy of diagnosis and the effectiveness of patient therapy. Despite the high costs of implementation and current use, modern diagnostic methods can save healthcare resources by reducing hospital stays and improving treatment outcomes.

Abstract Although COVID-19 is a disease consisting of mostly upper and lower respiratory symptoms, a subset of patients develop cardiac sequelae including myocarditis and pericarditis. For these patients, a standardized set of diagnostic imaging techniques and treatments has not been established. While there have been numerous case reports on this topic, there are few reviews that evaluate the effectiveness of different treatment modalities with a significant number of cases. We reviewed 146 cases of patients (ages ranging from 2 months old to mid 80 s) obtained from searches on PubMed, Google Scholar, and several case report journals. ECG abnormalities, elevated inflammatory markers, and reduced left ventricular ejection fraction were most associated with COVID-19 myocarditis. While classic symptoms of COVID-19 include upper respiratory symptoms, a subset of patients diagnosed with COVID-19 displayed no signs of respiratory disease at all. In 22% of cases, cardiac sequelae was not present until after the patient recovered from COVID-19. Steroids were given in 57.5% of cases. Cardiac MRI was used in 40.4% of cases for diagnosis of myocarditis. Of all the patients who were treated with ECMO, 82.1% of these patients were able to fully recover. The use of cardiac MRI and transthoracic echocardiogram for diagnosis of COVID-19 myocarditis should be heavily considered in any patient with COVID-19 infection. ECMO, IVIG, steroids, and anticoagulants should also be heavily considered. A randomized controlled trial should be conducted to better associate treatments with outcomes.

Abstract Objectives To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis. Methods In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge. Results In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p

Abstract Aims Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.

Background: Chlamydia pneumoniae and human herpesvirus 6 (HHV-6) are uncommon aetiological agents in respiratory tract infections and are rarely associated with cardiogenic shock. This case report presents a rare instance of severe cardiomyopathy linked to these infections in a 19-year-old Asian female. The case highlights the importance of considering a broad differential diagnosis in acute heart failure, especially in young adults. Case report: The patient was admitted with chest pain and diagnosed with ST-elevation myocardial infarction (STEMI) based on electrocardiography. She subsequently developed heart failure, with a marked reduction in myocardial contractility and a left ventricular ejection fraction (LVEF) of 20%. Treatment included broad-spectrum antibiotics and inotropic support guided by hemodynamic monitoring, leading to clinical improvement. The patient was discharged in a significantly improved condition following a stay in the intensive care unit (ICU). Conclusions: This case emphasizes the importance of considering Takotsubo syndrome in differential diagnoses, especially in ICU patients presenting with cardiogenic shock, to improve outcomes and reduce mortality through timely and appropriate management. Inotropic support, often used in the ICU to treat hypoperfusion, may worsen outcomes in patients with Takotsubo syndrome by exacerbating basal hypercontractility and prolonging the acute phase through catecholamine receptor activation.