High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.

Pitavastatin ameliorates myocardial injury by inhibiting myocardial inflammation and oxidative stress by modulating the microRNA-106B-5p/mitogen-activated protein kinase kinase kinase 2 axis.

Myocarditis (MC) is a myocardial inflammatory disease that threats human life. Pitavastatin (Pit) is a unique lipophilic statin with potent effects on lowering plasma total cholesterol and triacylglycerols. It has been reported to have pleiotropic effects, such as reducing inflammation and oxidative stress. However, the regulatory mechanism of Pit in MC remains a mystery. Two MC models were established in vitro (lipopolysaccharides-(LPS)-stimulated H9c2 cells) and in vivo (intraperitoneal injection of LPS in mice). The levels of microRNA-106b-5p (miR-106b-5p) and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) were detected. ELISA was used to analyze in vivo cell inflammatory factors and myocardial injury markers, kits were used to detect the expression of antioxidant enzymes, cell counting kit-8 (CCK-8) was used to detect cell proliferation, and flow cytometry was used to detect apoptosis. Hematoxylin and eosin (HE) staining was used to detect the pathological changes of myocardial tissue in mice, and TUNEL staining was used to detect in vivo tissue cell apoptosis. The regulatory mechanism of Pit on miR-106b-5p/MAP3K2 was verified by a series of functional rescue experiments. The results demonstrated that in LPS-induced H9c2 cells, antioxidant enzymes decreased and pro-inflammatory factors and cardiac injury markers increased (p<0.05). However, these phenomenons were attenuated by Pit pretreatment. LPS decreased miR-106b-5p and elevated MAP3K2 in H9c2 cells, while Pit could recover their expression patterns (p<0.05). MAP3K2 was confirmed as a target gene of miR-106b-5p. Upregulating miR-106b-5p or downregulating MAP3K2 could further promote the protective effect of Pit, and vice versa (p<0.05). In addition, in the LPS-induced MC mouse model, histological examination showed that Pit significantly improved the myocardial tissue damage in MC mice, while downregulating miR-106b-5p or upregulating MAP3K2 could suppress the ameliorative effect of Pit (p<0.05). In conclusion, our study demonstrated that Pit ameliorates myocardial injury by suppressing myocardial inflammation and oxidative stress by modulating the miR-106b-5p/MAP3K2 axis.

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.

Clinical Characteristics and Mechanisms of Acute Myocarditis.

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

Diagnostic Value of Cardiovascular Magnetic Resonance T1 and T2 Mapping in Acute Myocarditis: A Systematic Literature Review.

Background and Objectives: Over the past decade, there has been increasing attention paid to advanced and innovative cardiovascular magnetic resonance (CMR) modalities, such as T1 and T2 mapping, which play a major role in diagnosing diffuse myocardial disease. There is little data summarizing the current evidence regarding the diagnostic accuracy of T1 and T2 mapping, and extracellular volume (ECV) in acute myocarditis. The aim of our study was to select, analyze, and systematically review the recent scientific literature on the diagnostic value of CMR T1 and T2 parametric mapping in clinically suspected acute myocarditis. Materials and Methods: The literature search was performed in the PubMed database. Articles published in the years 2014-2024 were included in the analysis. At the initial stage, 458 articles were reviewed, and 13 exploratory research studies were further analyzed and presented in this systematic literature review. Results: The analysis included 686 patients with clinically suspected myocarditis and 372 subjects in the control group. The average age of patients with suspected myocarditis was 40.25 years; 26% of them were women. Prolonged native myocardial T1 relaxation time provides diagnostic accuracy in the setting of suspected acute myocarditis ranging from 69 to 99%, with sensitivity from 64 to 98% and specificity from 87 to 100%. Diagnostic accuracy of prolonged T2 relaxation time ranges from 47 to 87%, with sensitivity being from 48% to 94% and specificity from 60% to 92%. ECV alone showed moderate diagnostic performance, with diagnostic accuracy ranging from 62% to 76%, sensitivity from 47% to 73%, and specificity from 76% to 90%. T1 and T2 mapping and ECV, combined with the late gadolinium enhancement (LGE) technique, increases the probability of detecting myocardial inflammatory changes at various stages of the disease, improving the diagnostic accuracy to 96%. Conclusions: New quantitative CMR techniques, i.e., T1 and T2 mapping, have an advantage over conventional CMR sequences in detecting inflammatory myocardial structural changes and play an important role in diagnosing acute myocarditis. Incorporating these sequences in daily clinical practice increases the diagnostic value of CMR in acute myocarditis and becomes an alternative to endomyocardial biopsy, which has been considered the gold standard until now.

DNA Virome in Cardiac Tissue from Green Sea Turtles (Chelonia mydas) with Myocarditis.

As part of a sea turtle health monitoring program on the central east coast of Queensland, Australia, stranded and sick green sea turtles (Chelonia mydas) were subjected to necropsy and histopathology. A subset of these turtles had myocarditis of varying severity, which could not be attributed to parasitism by spirorchid flukes or bacterial infections. We, therefore, undertook an investigation to determine whether virus infections might be part of the pathogenesis. Deep sequencing revealed abundant DNA virus contigs in the heart tissue, of which CRESS and circoviruses appeared to be the most consistently present. Further analysis revealed the homology of some of the circoviruses to the beak and feather disease virus. While a causative link to myocarditis could not be established, the presence of these viruses may play a contributing role by affecting the immune system and overall health of animals exposed to pollutants, higher water temperatures, and decreasing nutrition.

Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart.

Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication. ICI-mediated myocarditis (ICI-myocarditis) is a growing clinical entity given the widespread use of ICIs, its increased clinical recognition and growing use of combination ICI treatment, a well-documented risk factor for ICI-myocarditis. In this Review, we approach ICI-myocarditis from a basic and mechanistic perspective, synthesizing the recent data from both preclinical models and patient samples. We posit that mechanistic understanding of the fundamental biology of immune-checkpoint molecules may yield new insights into disease processes, which will enable improvement in diagnostic and therapeutic approaches. The syndrome of ICI-myocarditis is novel, and our understanding of immune checkpoints in the heart is in its nascency. Yet, investigations into the pathophysiology will inform better patient risk stratification, improved diagnostics and precision-based therapies for patients.

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.

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.

Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis, particularly severe ICI-associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis. METHODS: Clinical and electrocardiographic data of 73 cancer patients with ICI-associated myocarditis were retrospectively collected. The severity of ICI-associated myocarditis was graded using the NCCN guidelines for managing immunotherapy-related toxicities. Myocarditis grades 1-2 and grades 3-4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis. RESULTS: Among the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT-proBNP level was associated with severe myocarditis. CONCLUSIONS: ECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI-associated myocarditis.

Effect and mechanism of T lymphocytes on human induced pluripotent stem cell-derived cardiomyocytes via Proteomics.

BACKGROUND: Abnormalities in T cell activation play an important role in the pathogenesis of myocarditis, and persistent T cell responses can lead to autoimmunity and chronic cardiac inflammation, as well as even dilated cardiomyopathy. Although previous work has examined the role of T cells in myocarditis in animal models, the specific mechanism for human cardiomyocytes has not been investigated. METHODS: In this study, we constructed the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and established the T cell-mediated cardiac injury model by co-culturing with activated CD4 + T or CD8 + T cells that were isolated from peripheral mononuclear blood to elucidate the pathogenesis of myocardial cell injury caused by inflammation. RESULTS: By combination of quantitative proteomics with tissue and cell immunofluorescence examination, we established a proteome profile of inflammatory myocardia from hiPSC-CMs with obvious cardiomyocyte injury and increased levels of lactate dehydrogenase content, creatine kinase isoenzyme MB and cardiac troponin. A series of molecular dysfunctions of hiPSC-CMs was observed and indicated that CD4 + cells could produce direct cardiomyocyte injury by activating the NOD-like receptor signals pathway. CONCLUSIONS: The data presented in our study established a proteome map of inflammatory myocardial based on hiPSC-CMs injury model. These results can provide guidance in the discovery of improved clinical treatments for myocarditis.

Unveiling Cellular Identities and Gene Expression Pathways in Overlapping Myocarditis and Myositis.

Immune checkpoint therapies can drive antitumor responses and benefit patients but can also induce life-threatening immune-related adverse events such as myocarditis and myositis. These immune-related adverse events are rare but carry substantial morbidity and mortality. In this issue, Siddiqui and colleagues use single-cell RNA and T-cell receptor sequencing to identify novel cellular subsets and propose various mechanisms that could contribute to the pathogenesis of immune checkpoint inhibitor-associated myocarditis and myositis. These new insights should help move the field toward the development of improved treatment and prevention options, ultimately improving patient outcomes. See related article by Siddiqui et al., p. 964 (1).

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.

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.

Coronavirus disease 2019-related myocarditis genes contribute to ECMO prognosis.

BACKGROUND: Acute myocardial injury, cytokine storms, hypoxemia and pathogen-mediated damage were the major causes responsible for mortality induced by coronavirus disease 2019 (COVID-19)-related myocarditis. These need ECMO treatment. We investigated differentially expressed genes (DEGs) in patients with COVID-19-related myocarditis and ECMO prognosis. METHODS: GSE150392 and GSE93101 were analyzed to identify DEGs. A Venn diagram was used to obtain the same transcripts between myocarditis-related and ECMO-related DEGs. Enrichment pathway analysis was performed and hub genes were identified. Pivotal miRNAs, transcription factors, and chemicals with the screened gene interactions were identified. The GSE167028 dataset and single-cell sequencing data were used to validate the screened genes. RESULTS: Using a Venn diagram, 229 overlapping DEGs were identified between myocarditis-related and ECMO-related DEGs, which were mainly involved in T cell activation, contractile actin filament bundle, actomyosin, cyclic nucleotide phosphodiesterase activity, and cytokine-cytokine receptor interaction. 15 hub genes and 15 neighboring DEGs were screened, which were mainly involved in the positive regulation of T cell activation, integrin complex, integrin binding, the PI3K-Akt signaling pathway, and the TNF signaling pathway. Data in GSE167028 and single-cell sequencing data were used to validate the screened genes, and this demonstrated that the screened genes CCL2, APOE, ITGB8, LAMC2, COL6A3 and TNC were mainly expressed in fibroblast cells; IL6, ITGA1, PTK2, ITGB5, IL15, LAMA4, CAV1, SNCA, BDNF, ACTA2, CD70, MYL9, DPP4, ENO2 and VEGFC were expressed in cardiomyocytes; IL6, PTK2, ITGB5, IL15, APOE, JUN, SNCA, CD83, DPP4 and ENO2 were expressed in macrophages; and IL6, ITGA1, PTK2, ITGB5, IL15, VCAM1, LAMA4, CAV1, ACTA2, MYL9, CD83, DPP4, ENO2, VEGFC and IL32 were expressed in vascular endothelial cells. CONCLUSION: The screened hub genes, IL6, ITGA1, PTK2, ITGB3, ITGB5, CCL2, IL15, VCAM1, GZMB, APOE, ITGB8, LAMA4, LAMC2, COL6A3 and TNFRSF9, were validated using GEO dataset and single-cell sequencing data, which may be therapeutic targets patients with myocarditis to prevent MI progression and adverse cardiovascular events.

Case report: Potential role of immunotherapy in thymic malignancies: a unique case of a durable and complete response upon an immune checkpoint inhibitor.

Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders. In this case report, we present the 21-year history of a patient diagnosed with advanced B2/B3 thymoma and Good's syndrome. The patient achieved a complete and durable response after receiving only two cycles of the immune checkpoint inhibitor Nivolumab. However, this positive outcome was accompanied by the development of severe immune-related myocarditis complicated by reactivation of cytomegalovirus. Moreover, the patient developed a highly uncommon subdiaphragmatic pararectal dissemination of the thymic tumor, which is a condition rarely described in the literature. Despite the success in achieving complete and durable response with immune checkpoint inhibitors, the emergence of immune-related adverse events highlights the potential challenges associated with these treatments, emphasizing the need for careful monitoring and a comprehensive understanding of the intricate interplay between cancer, immune system dysregulations and immunotherapy.

Case Report: Non-ischemic Papillary Muscle Rupture due to MRSA Myocarditis with Concurrent Thromboembolic Myocardial Infarction Secondary to Infective Endocarditis.

Non-ischemic papillary muscle rupture (PMR) is rare. PMR caused by myocarditis in the presence of concurrent infective endocarditis (IE) and myocardial infarction (MI) has not been described. We report a 46-year-old male with recurrent MRSA bacteremia who presented in septic shock and suffered cardiac arrest. Echocardiography revealed acute mitral valve regurgitation resulting from posteromedial PMR. An intra-aortic balloon pump was implanted. Angiography revealed thrombotic occlusion of a small distal left circumflex artery. Emergent mitral valve replacement surgery was performed. MRSA myocarditis and IE were diagnosed by tissue cultures. Coexistence of myocarditis, IE, and MI poses a challenge in determining etiology.

Long-term cardiovascular inflammation and fibrosis in a murine model of vasculitis induced by Lactobacillus casei cell wall extract.

Background: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. Methods: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. Results: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Conclusion: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.

Levosimendan: efficacy and safety in pediatric heart failure treatment.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of levosimendan as an alternative treatment for pediatric patients with decompensated heart failure unresponsive to conventional inotropes and to emphasize its role in enhancing cardiovascular stability. METHODS: A total of 15 pediatric patients with decompensated heart failure, stemming from acute fulminant myocarditis (53.3%) and post-congenital heart disease surgery complications (46.7%), received levosimendan. The evaluation focused on adverse effects, respiratory support requirements, and concurrent inotropic medication use during levosimendan treatment. Key cardiovascular parameters were assessed at 0, 6, 12, and 24 h post-levosimendan infusion. RESULTS: Levosimendan administration significantly improved key cardiovascular metrics. Left ventricular ejection fraction increased notably from 45±14.8% to 58±15.6% at 24 h (p<0.001). Systolic and diastolic blood pressures rose significantly, with systolic increasing from 79 (68-90) to 98 (89-109) mmHg and diastolic from 47 (40-57) to 66 (54-76) mmHg by 24 h (p<0.001). Heart rate decreased from 162 (111-175) to 132 (99-148) bpm (p=0.02), and lactate levels significantly decreased from 4.15 (2.3-6.5) to 1.85 (0.8-2.6) mmol/L within 6 h (p<0.001). CONCLUSION: Levosimendan demonstrates its significance in managing pediatric heart failure, indicating its safety and potential to enhance cardiac outcomes by reducing reliance on traditional inotropes.