Temporary mechanical circulatory support as a bridge to durable left ventricular assist device as destination therapy in fulminant giant cell myocarditis：A case report.

Fulminant giant cell myocarditis is a fatal form of acute myocarditis leading to a rapid-onset clinical presentation with lethal arrhythmias, acute heart failure, or cardiogenic shock requiring mechanical circulatory support. We report the case of a 52-year-old female diagnosed with fulminant myocarditis requiring veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump(IABP) support. Due to hemodynamic instability, she was transferred to our hospital by helicopter on day 4. On arrival at our hospital, she underwent percutaneous balloon atrial septostomy to decompress the left ventricle. Although the left ventricular distension and pulmonary edema improved after atrial septostomy, no signs of biventricular function recovery were identified on day 14. On day 23, V-A ECMO and IABP were switched to a durable left ventricular assist device(LVAD) system and a right ventricular assist device(RVAD) with ECMO (RVAD-ECMO) under median sternotomy. On day 37, RVAD-ECMO was eventually removed and rehabilitation was started with the remaining LVAD support as destination therapy. On day 78, the patient was finally discharged with LVAD support to follow-up as an outpatient. This case underscores the importance of a multidisciplinary approach and rigorous monitoring to optimize outcomes in the treatment of fulminant giant cell myocarditis.

A Diagnostic Dilemma: A Case of Complicated Pneumonia With Pyelonephritis and Subclinical Myocarditis.

A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.

Cardiovascular adverse events associated with immune checkpoint inhibitors: a meta-analysis.

Objective: To evaluate the cardiovascular safety of anticancer drug immune checkpoint inhibitors (ICIs) used in patients with malignant tumors. Methods: Four clinical research databases that have been completed since their establishment were searched, and the odds ratios and 95% confidence intervals of each indicator were statistically calculated. Results: 62 randomized controlled trial and controlled trials were included. In single drug treatment ICIs group, the overall risk of cardio cerebral Vascular disease at all levels was higher than that in the placebo/chemotherapy group. Especially in all grades of Myocarditis and above grade 3 compared with normal controls, except for pericardial lesions, other indicators have no obvious side effects. Conclusion: Single drug use of an anti-tumor ICIs may increase cardiovascular side effects risk in cancer patients, so we need to strengthen monitoring, identification and management, and timely intervention to manage ICI induced adverse events.

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis. Methods: PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Results: Five cohort studies were included (average age 65-68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72-10.19, p = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43-50.89, p < 0.001) and lower LVEF (WMD = - 8.00%, 95% CI: -13.60 to -2.40, p = 0.005). Notably, T2 value (WMD = -0.23 ms, 95% CI: -1.86 to -1.39, p = 0.779) was not associated with MACE in patients with ICI-related myocarditis. Conclusions: LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.

Global burden of myocarditis in youth and middle age (1990-2019): A systematic analysis of the disease burden and thirty-year forecast.

BACKGROUND: Myocarditis is increasingly recognized as a critical health issue, particularly among youth and middle-aged populations. This study aims to analyze the global burden and trends of myocarditis in these age groups to emphasize the need for region-specific prevention and treatment strategies. METHODS: Using data from the Global Burden of Disease (GBD) study (1990-2019), we evaluated the age-standardized rates (ASR) of myocarditis in individuals aged 10 to 54 years. We calculated average annual percentage changes (AAPC) and estimated annual percentage changes (EAPC). Additionally, we examined the correlation between myocarditis incidence and the Human Development Index (HDI) and Socio-demographic Index (SDI). Age and sex trends in myocarditis were analyzed, and Bayesian age-period-cohort (BAPC) models were used to forecast prevalence trends up to 2050. RESULTS: The High-income Asia Pacific region had the highest ASR of myocarditis, while North Africa and the Middle East had the lowest. North Africa and the Middle East also experienced the fastest average annual growth in ASR, whereas High-income North America saw the most significant decline. Correlational analysis showed that countries with a high SDI exhibited higher myocarditis ASR. The burden of myocarditis was greater among males than females, with this disparity increasing with age. Projections indicate a stable trend in the incidence of myocarditis among the youth and middle-aged population up to 2050, although the total number of cases is expected to rise. CONCLUSION: Our study reveals a significant upward trend in myocarditis among youth and middle-aged populations, highlighting the urgency for early monitoring and preventative strategies.

Cryptic late-onset myocarditis after coronavirus vaccination.

As we enter a new era of mRNA-based therapeutics, evidence on genetic or environmental factors that might predispose to unknown off-target side effects, gains in importance. Among these factors, exercise appears likely to have influenced otherwise cryptic cases of early-onset postvaccination myocarditis. And the existence of a distinct late-onset myocarditis is now being recognized. Here, three case-history reports suggest crypticity (the author's own case), unless provoked by a preexisting cardiac morbidity (one case), or by immune checkpoint blockade to enhance anticancer autoimmunity (several cases). These reports are supported by noninvasive fluorodeoxyglucose-based cardiac scan comparisons of multiple vaccinated and unvaccinated subjects. In pre-pandemic decades, applications for funds by the leading innovator in mRNA-based therapeutics seldom gained peer-review approval. Thus, at the start of the pandemic, the meager data on such side effects could justify only emergency approval. We must do better.

Clinical Characteristics and Mechanisms of Acute Myocarditis.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05335928.

Hypereosinophilia and Left Ventricular Thrombus: A Case Report and Literature Review.

Left ventricular thrombus (LVT) has historically been reported as a complication of acute left ventricular (LV) myocardial infarction. It is most commonly observed in cases of LV systolic dysfunction attributed to ischemic or nonischemic etiologies. Conversely, the occurrence of LVT in normal LV systolic function is an exceptionally rare presentation and is predominantly associated with conditions such as hypereosinophilic syndrome (HES), cardiac amyloidosis, left ventricular noncompaction, hypertrophic cardiomyopathy (HCM), hypercoagulability states, immune-mediated disorders, and malignancies. Notably, hypereosinophilia (HE) has been linked with thrombotic events. Intracardiac thrombus is a well-known complication of eosinophilic myocarditis (EM) or Loeffler endomyocarditis, both of which are considered clinical manifestations of HES. We present a case of a 63-year-old male with normal LV systolic function, HE, and noncontributory hypercoagulability workup, who presented with thromboembolic complications arising from LVT. Interestingly, the diagnostic evaluation for EM and Loeffler endocarditis was nonconfirmatory. Additionally, we performed a literature review to delineate all similar cases. This article also outlines the pathophysiology, diagnosis, and treatment approaches for hypereosinophilic cardiac involvement with a specific focus on LVT.

An autopsy case of lung adenocarcinoma with immune checkpoint inhibitor-induced pneumonia and fulminant myocarditis following pembrolizumab administration: a case report.

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

Cardiac magnetic resonance in a rare case of recurrent mesalazine-induced myocarditis.

Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis.

This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case.

Functions and Clinical Significance of Myocardial Cell-Derived Immunoglobulins.

Immunoglobulins (Igs) have been widely accepted to be exclusively expressed by B cells. Nonetheless, this theory is challenged by mounting evidence which suggests that Igs can also be generated by non B cells (non B-Ig), including cardiomyocytes (CM). Non B-Ig exhibits unique physical and chemical characteristics, unique variable region sequences and functions, which diverge from those of B-Ig. For instance, non B-Ig demonstrates hydrophobicity, limited diversity in the variable region, and extracellular matrix protein activity. Likewise, cardiomyocytes can express different classes of Igs, including IgM, IgG, and free Igκ light chains (cardiomyocyte derived-Igs, CM-Igs). In particular, CM-Igs can be secreted into the extracellular space in various cardiovascular diseases, such as myocardial ischaemia and myocardial fibrosis where they might be involved in complement activation and direct damage to cardiomyocytes. Nevertheless, the precise pathological activity of CM-Igs remains unclear. Recently, Zhu et al. focused on studying the sequence characteristics and functions of CM-Igκ; they discovered that the CM-Igκ exhibits a unique VJ recombination pattern, high hydrophobicity, and is principally located on the intercalated discs and cross striations of the cardiomyocytes. Interestingly, loss of Igκ in cardiomyocytes results in structural disorders in intercalated discs and dysfunction in myocardial contraction and conduction. Mechanically, Igκ promotes the stabilisation of plectin, a cytoskeleton cross-linker protein that connects desmin to desomsome, to maintain the normal structure of the intercalated disc. This finding indicates that CM-Igκ plays an integral role in maintaining cytoskeleton structure. Consequently, it is imperative to reveal the physiological functions and mechanisms of pathological injury associated with CM-Igs.

Implantation and removal of central temporary paracorporeal biventricular support for COVID-19-associated myocarditis.

This case report illustrates how to implant a central paracorporeal temporary biventricular assist device in a 17-year-old patient with acute heart failure due to a fulminant form of coronavirus disease 2019 myocarditis. The procedure was carried out after prior veno-arterial extracorporeal membrane oxygenation support. Myocardial biopsies and biventricular assist device explants are also included in the report. The patient was weaned on postoperative day 6 and discharged without any significant complications. One year after the event, the patient remains asymptomatic with normal biventricular function and a normal lifestyle.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

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.

Cardiovascular Magnetic Resonance Before Invasive Coronary Angiography in Suspected Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: 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. OBJECTIVES: This study sought to assess the diagnostic utility of cardiac magnetic resonance (CMR) before invasive coronary angiogram (ICA) in suspected NSTEMI. METHODS: 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 (T2-weighted imaging, T1 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. RESULTS: 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). CONCLUSIONS: 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.

Investigating TIP30-Mediated regulation of mTORC1 signaling as a therapeutic strategy for coxsackievirus B3-Induced viral myocarditis.

This study aims to elucidate the role of TIP30 (30 KDa HIV-1 TAT-Interacting Protein) in the progression of coxsackievirus B3 (CVB3)-induced viral myocarditis. TIP30 knockout and wildtype mice were intraperitoneally infected with CVB3 and evaluated at day 7 post-infection. HeLa cells were transfected with TIP30 lentiviral particles and subsequently infected with CVB3 to evaluate viral replication, cellular pathogenesis, and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Deletion of the TIP30 gene heightened heart virus titers and mortality rates in mice with CVB3-induced myocarditis, exacerbating cardiac damage and fibrosis, and elevating pro-inflammatory factors level. In vitro experiments demonstrated the modulation of mTORC1 signaling by TIP30 during CVB3 infection in HeLa cells. TIP30 overexpression mitigated CVB3-induced cellular pathogenesis and VP1 expression, with rapamycin, an mTOR1 inhibitor, reversing these effects. These findings suggest TIP30 plays a critical protective role against CVB3-induced myocarditis by regulating mTORC1 signaling.

Sex based differences in clinical characteristics of patients with acute myocarditis: A cohort study.

BACKGROUND: This study investigated sex differences in acute myocarditis patients during index hospitalization. METHODS: We included 365 patients with acute myocarditis, hospitalized with continuous monitoring at the Intensive care unit (ICU), from 2000-2023 into the Basel Myocarditis Cohort study. We compared sex differences in clinical presentation, the presenting ECG prior medical history, inflammatory and cardiac biomarkers, cardiac imaging, arrhythmia occurrence and short to midterm outcomes. RESULTS: Mean age was 41.3 years and 26.3% were female. Compared to men, women were older (median 49.7 vs 38.3 years, p<0.001) at the time of diagnosis and presented more frequently with dyspnea (41 vs 26%, p=0.013) and a higher Killip class (p=0.011). In the presenting ECG, men had a higher occurrence of diffuse ST-elevation (38 vs 9%, p<0.001) and PQ-depression (31 vs 20%, p=0.042), compared to women. Women had higher NT-proBNP levels (1180 vs 387 ng/l, p=0.015), lower cardiac troponin T levels (389 vs 726 ng/l, p=0.006), less segments with non-ischemic LGE on CMR (1 vs 3, p=0.005) but similar LVEF (55 vs 55%, p=0.629), compared to men. Overall, hospital stay was longer in women compared to men (7 vs 5 days, p=0.018) with a similar length of ICU stay (2.6 vs 2.7 days, p=0.922). Women developed more often severe arrhythmia (8.3 vs 2.2%, p=0.015) and heart failure during the hospitalization (31.3 vs 16.4%, p=0.003). CONCLUSION: Compared to men, women with acute myocarditis were older at the time of diagnosis, presented more often with heart failure and had an increased frequency of severe arrhythmia.

Acute lymphocytic myocarditis characterized by cardiogenic shock and conduction system abnormalities in patients with Hashimoto's thyroiditis: a case report and review of literature.

Background: Acute myocarditis (AM) is an inflammatory heart disease that may occur as a consequence of autoimmune disorders. Although the correlation between myocarditis and hyperthyroidism has been reported in the literature, the association with hypothyroidism is less frequent. Case summary: We describe a characteristic case of lymphocytic acute myocarditis deteriorated into cardiogenic shock due to Hashimoto's thyroiditis treated with vasopressor and inotropic drugs in combination with corticosteroid. On admission, electrocardiography revealed a sinus tachycardia with 1st degree atrioventricular (AV) block, right bundle branch block (RBBB), and left anterior fascicular block. Laboratory tests demonstrated a severe hypothyroidism and high-titre serum of antibodies against thyroglobulin. She presented a favourable clinical course, restoring haemodynamic stability. A resolution of hypothyroidism and a progressive reduction of the value of antibodies against thyroglobulin occurred. On Day 35, the patient was discharged showing on electrocardiogram the occurrence of left posterior fascicular block, disappearance of 1st degree AV block and partial improvement of RBBB along with the normalization of the left ventricular contractility abnormalities on echocardiography. Discussion: Autoimmune features, mostly Hashimoto's thyroiditis, are associated in lymphocytic acute myocarditis to a worse prognosis and an increased risk of recurrence. More studies are needed to elucidate the underlying mechanism.

New insights gained from cellular landscape changes in myocarditis and inflammatory cardiomyopathy.

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.