Dilated cardiomyopathy is a rare but severe myocardial disease in the paediatric population, often leading to heart failure, heart transplantation, or sudden cardiac death. Genetic factors are a major contributor to childhood dilated cardiomyopathy. Recently, biallelic variants in the PPP1R13L gene have been implicated in a novel syndromic form of early-onset dilated cardiomyopathy, characterised by cardiac dysfunction alongside variable ectodermal features. We report a 4-year-old boy who presented with decompensated heart failure and echocardiographic findings consistent with dilated cardiomyopathy. Syndromic features included sparse, dry hair, high anterior hairline, broad nasal bridge, and pointed teeth. Genetic analysis revealed a novel homozygous frameshift variant in the PPP1R13L gene (c.2368_2375dup; p. Pro793Glyfs*32), classified as pathogenic. The clinical course was complicated by recurrent ventricular arrhythmias and ultimately sudden cardiac death. PPP1R13L-related cardiomyopathy should be considered in children with early-onset dilated cardiomyopathy and syndromic features. Early diagnosis is critical for clinical management, arrhythmia surveillance, and appropriate family counselling.

Uraemic cardiomyopathy is a term widely used to describe the severe myocardial disease characterized by left ventricular hypertrophy and diffuse interstitial fibrosis that occurs in kidney failure. The causative factors are multiple and include many of the haemodynamic and metabolic abnormalities that are present in patients with chronic kidney disease (CKD). These abnormalities start to cause left ventricular damage and dysfunction in the early stages of CKD, probably from an estimated glomerular filtration rate of approximately 60 ml/min/1.73 m2. The term 'uraemic cardiomyopathy' is therefore misleading and inaccurate, and we suggest instead using the term 'CKD-associated cardiomyopathy'. In this Review, we describe the clinical manifestations and myocardial abnormalities seen on imaging in both CKD and kidney failure, discuss the multiple and interacting causative factors, and consider both established and prospective treatment options. A better understanding of the pathogenesis of CKD-associated cardiomyopathy is likely to lead to the introduction of effective preventive therapies, with success measured as a reduction in the proportion of patients reaching kidney failure with severe cardiomyopathy and ultimately in a reduction in the mortality from this condition.

Introduction: Fulminant myocarditis (FM) is a severe inflammatory myocardial disease that progresses rapidly and is often fatal. Diagnosing and predicting FM is challenging due to its acute nature and poor prognosis. Understanding the proteomic profiles of FM patients could shed light on underlying pathological mechanisms, unveil novel biomarkers for early detection, and guide the development of targeted therapeutic interventions. Research Questions: What are the proteomic signatures associated with cardiac dysfunction and disease severity in FM patients? Can S100A8/S100A9 be validated as biomarkers for the diagnosis and severity assessment of FM? How does the inhibition of the S100A8/A9 affect the progression of FM? Methods: A comprehensive proteomic analysis was conducted using plasma samples collected from FM patients across three clinical cohorts. The findings were validated in an independent patient cohort to ensure reliability. Additionally, a CVB3-induced FM mouse model was used to further explore the role of these biomarkers in myocardial tissues and to assess the effects of targeted therapeutic interventions. Specifically, the study evaluated the impact of ABR-238901, an inhibitor targeting the S100A8/A9, on the progression of FM mouse model. Results: Proteomic analysis revealed a marked activation of innate immune responses and significant metabolic disturbances in FM patients. Notably, the proteins S100A8 and S100A9 were identified as key biomarkers, with their elevated plasma levels strongly correlating with increased cardiac dysfunction and disease severity. Elevated levels of the S100A8/A9 heterodimer were associated with more serious FM. In the CVB3-induced FM mouse models, an increase in S100A8/S100A9 levels in myocardial tissues was observed. Treatment with ABR-238901 significantly reduced mortality by mitigating acute inflammation and improving cardiac function. Conclusion: S100A8/A9 emerged as an essential biomarker and a promising therapeutic target for FM. These findings offer new insights into FM diagnosis and suggest potential intervention strategies. These results pave the way for further research to validate the clinical application of S100A8/A9-targeted therapies, potentially improving outcomes for patients suffering from this severe cardiac condition.

Dilated cardiomyopathy (DCM) is considered a severe non-ischemic myocardial disease, and there is currently no effective method for the early detection of DCM. Therefore, we aimed to use machine learning algorithms to discover more accurate factors to guide clinical drug development and precision medicine diagnosis. Two datasets containing patients with DCM and healthy controls were downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed genes (DEGs) between the DCM patients and normal samples were identified using the limma package. In addition, to screen for DEGs closely associated with immune inflammation, we collected immune-related genes and defined overlapping genes as differential immune genes (Immune-DEGs). Protein-protein interaction (PPI) network construction and functional enrichment analysis were then functionally validated for the differential immune genes. Subsequently, we further screened the immune-DEGs using the least absolute shrinkage and selection operator (LASSO) technique and support vector machine algorithm (SVM), resulting in the screening of five potential modulators closely associated with DCM. Finally, the diagnostic efficacy of the modifiers was assessed using subject operating characteristic curves based on independent external data, and the intrinsic pathological mechanisms of different differential immune genes were explored by immune infiltration analysis. A consensus of 184 differential immune genes were identified, and the functional enrichment results of their PPI network modules suggested that inflammation, immune disorders, and viral infections play an essential role in the pathogenesis of DCM. Five signature genes were then further screened using LASSO and SVM algorithms: KLRC4, CCL4, IGHV3-33, ITGAL, and inducible T-cell kinase. This study constructed a gene set of potential DCM regulators with five immune-related genes, which could provide a new strategy for the diagnosis and treatment of DCM.

Dilated cardiomyopathy (DCM) in children is a severe myocardial disease characterized by enlargement of the left ventricle or both ventricles with impaired contractile function. DCM can cause adverse consequences such as heart failure, sudden death, thromboembolism, and arrhythmias. This article reviews the latest advances in genotype and phenotype research in pediatric DCM. With the development of gene sequencing technologies, considerable progress has been made in genetic research on DCM. Research has shown that DCM exhibits notable genetic heterogeneity, with over 100 DCM-related genes identified to date, primarily involving functions such as calcium handling, the cytoskeleton, and ion channels. As human genomic variations are linked to phenotypes, DCM phenotypes are influenced by numerous genetic variations across the entire genome. Children with DCM display high genetic heterogeneity and are characterized by early onset, rapid disease progression, and poor prognosis. The genetic architecture of pediatric DCM markedly differs from that of adult DCM, necessitating analyses through clinical phenotyping, familial cosegregation studies, and functional validation. Clarifying the genotype-phenotype relationship can improve diagnostic accuracy, enhance prognosis, and guide follow-up treatment for genotype-positive and phenotype-negative patients identified through genetic testing, providing new insights for precision medicine. Future research should further explore novel pathogenic genes and mutations and strengthen genotype-phenotype correlation analyses to facilitate precise diagnosis and treatment of DCM in children.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation.

Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach

Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

Currently, surgery is the most popular treatment method for esophageal cancer. Radiation is not main treatment but only a supporting one. This situation is now changing because of chemoradiotherapy (CRT). In the 1980s, although most patients treated with radiotherapy were inoperable for extremely advanced or some medical reasons, treatment outcome of surgery was undoubtedly superior to that of radiotherapy. Low-dose rate radiotherapy has many biological benefits. We tried low-dose rate telecobalt therapy (LDRT) as a boost to improve the outcome of radiotherapy for esophageal cancer. However, the LDRT did not improve survival. Since 1990s, studies have demonstrated the effectiveness of CRT using cisplatin and 5-fluorouracil. We made a prospective comparison of surgery and CRT with salvage surgery after recurrence for operable esophageal cancer. Five-year survival rates of 75 CRT patients and 76 surgery ones were 67.5 and 57.7 %, respectively. Twenty-eight patients in the CRT group underwent salvage surgery and 14 survived. Thirty-nine patients in the CRT group (52 %) survived, preserving their esophagus and their QOL was excellent. CRT with salvage surgery should be offered to all operable patients. After CRT, some patients complained severe radiation pneumonitis and myocardial disease. Radiation field should be as small as possible, including the low-dose area. Dose distribution of proton and heavy particle therapies is superior to ordinary radiotherapy. In future, particle beam therapy alone or in combination with photon beam therapy will become widespread as a radiotherapy method during CRT for esophageal cancer.

We read with great interest the letter by Mr Ze-Zhou Song. Mr Song raises important issues on the impact of how deformation parameters such as strain and strain rate are influenced by several conditions and diseases other than myocardial infarction. This has previously been shown in hypertensive and diabetic patients without recognized ischaemic events as well as in other conditions. This aspect will have to be considered when interpreting our results, as well as in the clinical context. In our present study [1], we intentionally did not exclude patients with co-morbidities. We agree with Dr Hoffmann in his reply to a similar request from Mr Song in the European Heart Journal that an exclusion of patients with other conditions would reduce the applicability of the study in clinical practice [2]. The statistical power of our present study [1] was not designed for subgroup analysis, and skewness of other conditions between the groups might therefore have an influence on our results. We have therefore included information on patients' co-morbidity in our paper, and there was no co-morbidity within the reference population. When excluding severe myocardial disease, the impact of other conditions on left ventricular function is limited when compared with the impact of a transmural myocardial infarct [1]. In a clinical context, assessment of regional myocardial function would have to be performed and compared with global left ventricular function in order to distinguish regional disease (such as myocardial ischaemia) from systemic diseases affecting the global left ventricular function in a more homogeneous pattern. We agree with Mr Song that the clinician should consider other conditions resulting in impaired deformation when applying deformation imaging for the assessment of myocardial viability.The main purpose of our present study [1] was to assess the ability of longitudinal speckle tracking strain measurements to distinguish between different levels of myocardial infarct transmurality and to explore the relationship between strain measurements and infarct mass at the territorial and global levels in a chronic ischaemic population [2]. As Mr Song correctly mentions, myocardial motion is complex. The myocardial fibre orientation gradually shifts from a counter-clockwise oblique longitudinal direction in the endocardial layer to near circumferential in the mid-myocardial layer and clockwise oblique longitudinal in the subepicardial layer [3]. This results in three main deformation patterns: longitudinal shortening, circumferential shortening and rotation. Radial thickening is due to a combination of myocyte thickening and shearing of the oblique fibre layers in the subendocardium [4,5]. Assessment of circumferential shortening and radial thickening strains in an infarct population was performed on parasternal short-axis views by Becker et al. [6]. Our present study was not designed for multiple parasternal short-axes imaging, and assessment of short-axis deformation was therefore not feasible. We do agree that a direct comparison of all deformation patterns needs further echocardiographic studies, as present knowledge in this field is limited to MRI (magnetic resonance imaging) studies.

A patient with severe myocardial disease and acute-on-chronic renal failure was undergoing a brachial plexus block for formation of an arteriovenous fistula when accidental intravascular injection of ropivacaine resulted in ventricular fibrillation. Cardiopulmonary resuscitation was instituted immediately and the advanced life support algorithm was followed until the return of sinus rhythm. Although, in comparison with bupivacaine, ropivacaine appears to be a safer local anaesthetic agent in the setting of intravenous injection, the emphasis on safety should remain a priority. Awareness of the risk of central nervous system and cardiovascular toxicity and preparation for immediate commencement of resuscitation in the event of toxicity remain of paramount importance.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial beta-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

Antithrombotic Therapy in Atrial Fibrillation-To the Editor

Clinical profile of patients with Chagas' disease before and during sustained ventricular tachycardia

Severe degenerative myocardial disease occurred in female C3H/OUJ mice fed purified diets for 36 weeks; the diet contained 5% or 20% fat as non-hydrogenated soybean oil. Deaths of lactating females of this group (17/35 high fat diet and 7/35 low fat diet animals) were due to sudden cardiovascular collapse. Cardiomegaly with marked atrial and ventricular myocardial mineralization was seen at necropsy. Histologically, the random, myopathic foci were characterized by severe myocardial degeneration, mineralization, and fibrosis. Mural thrombosis, pulmonary arteriosclerosis, and mild myocardial inflammatory cell infiltrates were also present. Pathological changes were similar to those of dystrophic cardiac calcinosis, an incidental necropsy finding in certain mouse strains.

Long-standing bidirectional tachycardia in a patient with hypokalemic periodic paralysis

Percutaneous catheter valvuloplasty was performed in 37 patients between 60-88 years of age (mean age 74.5 years): 16 of these patients were in functional class IV, with pulmonary oedema at the time of the procedure. A good haemodynamic result was obtained in 32 patients, but 3 of them had to be operated upon subsequently, because of persistence of their symptoms. Two successfully dilated patients died in the hospital, one of cardiac failure following myocardial dysfunction caused by multiple infarcts which had no relation to the aortic dilatation, the other of neurological complications after dilatation. Thus, the primary success rate was 27/37 (73%). The first 10 patients with good initial results have been followed up for more than 6 months. The functional result has been maintained in 8 cases with moderate myocardial dysfunction (left ventricular ejection fraction 0.41 to 0.7), one with restenosis at Doppler assessment. Two patients with severe myocardial dysfunction (left ventricular ejection fraction 0.22 and 0.25) had recurrent cardiac failure, with valvular restenosis in one case. One of them died at home. Percutaneous aortic valvuloplasty is therefore an effective means of treating calcified aortic stenosis in elderly patients. The benefits of this procedure have been maintained for as long as 6 months provided myocardial dysfunction was moderate. At its present stage of development, the technique allows only partial reduction of the aortic stenosis, which may explain the absence of long-term improvement in patients with severe myocardial disease.

Left bundle branch block with right axis deviation: A marker of congestive cardiomyopathy

Clinical recognition of giant left ventricular aneurysm

Spectrum of congestive heart failure late after aortic valve or mitral replacement: Differentiation of valvular versus myocardial cause by radionuclide ventriculogram-ejection fraction