Treatment Of Dilated Cardiomyopathy Research Articles

Advances in dilated cardiomyopathy evaluation via cardiac MRI diagnosis and prognosis: a literature review

With a variety of aetiologies and clinical presentations, Dilated Cardiomyopathy (DCM) presents considerable hurdles for both diagnosis and treatment. Cardiac magnetic resonance imaging (CMR) has become a useful diagnostic technique for DCM, providing information on the anatomy, physiology, and tissue properties of the heart. Using both well-established and recently developed CMR techniques, this review investigates the function of CMR in the diagnosis and treatment of idiopathic DCM. Using reliable databases, a thorough search of the literature was carried out with an emphasis on papers released between 2014 and 2024. English-language literature examining the clinical uses of CMR in idiopathic DCM were included in the inclusion criteria. A vital component of the assessment of dilated cardiomyopathy (DCM) is cardiac magnetic resonance imaging (CMR), which provides thorough insights into the anatomy and function of the heart. Precise evaluation of tissue properties, ventricular function, and cardiac shape is made possible by CMR, which helps DCM patients get an accurate diagnosis and risk assessment. The use of advanced CMR methods, such as T1 mapping and late gadolinium enhancement (LGE) imaging, yields significant insights into the underlying aetiologies and myocardial fibrosis. Furthermore, customized prognostic evaluations are provided by CMR-based risk stratification algorithms that include many factors, improving clinical decision-making in DCM treatment. Continuous developments are expected to improve prognostic utility and accuracy, which will need efforts to lower prices and increase accessibility in order to achieve better patient outcomes and wider clinical usage

Screening for immune-related biomarkers associated with myasthenia gravis and dilated cardiomyopathy based on bioinformatics analysis and machine learning

BackgroundWe aim to investigate genes associated with myasthenia gravis (MG), specifically those potentially implicated in the pathogenesis of dilated cardiomyopathy (DCM). Additionally, we seek to identify potential biomarkers for diagnosing myasthenia gravis co-occurring with DCM. MethodsWe obtained two expression profiling datasets related to DCM and MG from the Gene Expression Omnibus (GEO). Subsequently, we conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on these datasets. The genes exhibiting differential expression common to both DCM and MG were employed for protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, machine learning techniques were employed to identify potential biomarkers and develop a diagnostic nomogram for predicting MG-associated DCM. Subsequently, the machine learning results underwent validation using an external dataset. Finally, gene set enrichment analysis (GSEA) and machine algorithm analysis were conducted on pivotal model genes to further elucidate their potential mechanisms in MG-associated DCM. ResultsIn our analysis of both DCM and MG datasets, we identified 2641 critical module genes and 11 differentially expressed genes shared between the two conditions. Enrichment analysis disclosed that these 11 genes primarily pertain to inflammation and immune regulation. Connectivity map (CMAP) analysis pinpointed SB-216763 as a potential drug for DCM treatment. The results from machine learning indicated the substantial diagnostic value of midline 1 interacting protein1 (MID1IP1) and PI3K-interacting protein 1 (PIK3IP1) in MG-associated DCM. These two hub genes were chosen as candidate biomarkers and employed to formulate a diagnostic nomogram with optimal diagnostic performance through machine learning. Simultaneously, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in both DCM and MG, with MID1IP1 and PIK3IP1 showing significant associations with invasive immune cells. ConclusionWe have elucidated the inflammatory and immune pathways associated with MG-related DCM and formulated a diagnostic nomogram for DCM utilizing MID1IP1/PIK3IP1. This contribution offers novel insights for prospective diagnostic approaches and therapeutic interventions in the context of MG coexisting with DCM.

Imagenetics for Precision Medicine in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common heart muscle disorder of nonischemic etiology associated with heart failure development and the risk of malignant ventricular arrhythmias and sudden cardiac death. A tailored approach to risk stratification and prevention of sudden cardiac death is required in genetic DCM given its variable presentation and phenotypic severity. Currently, advances in cardiogenetics have shed light on disease mechanisms, the complex genetic architecture of DCM, polygenic contributors to disease susceptibility and the role of environmental triggers. Parallel advances in imaging have also enhanced disease recognition and the identification of the wide spectrum of phenotypes falling under the DCM umbrella. Genotype-phenotype associations have been also established for specific subtypes of DCM, such as DSP (desmoplakin) or FLNC (filamin-C) cardiomyopathy but overall, they remain elusive and not readily identifiable. Also, despite the accumulated knowledge on disease mechanisms, certain aspects remain still unclear, such as which patients with DCM are at risk for disease progression or remission after treatment. Imagenetics, that is, the combination of imaging and genetics, is expected to further advance research in the field and contribute to precision medicine in DCM management and treatment. In the present article, we review the existing literature in the field, summarize the established knowledge and emerging data on the value of genetics and imaging in establishing genotype-phenotype associations in DCM and in clinical decision making for DCM patients.

Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial.

Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients' quality of life. This trial aims to further evaluate KXF's safety and efficacy in managing DCM-related heart failure. This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee's heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded. This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients. China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.

Cypher/ZASP drives cardiomyocyte maturation via actin-mediated MRTFA-SRF signalling.

Rationale: Cardiomyocytes (CMs) undergo dramatic structural and functional changes in postnatal maturation; however, the regulatory mechanisms remain greatly unclear. Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is an essential sarcomere component maintaining Z-disc stability. Deletion of mouse Cypher and mutation in human ZASP result in dilated cardiomyopathy (DCM). Whether Cypher/ZASP participates in CM maturation and thereby affects cardiac function has not been answered. Methods: Immunofluorescence, transmission electron microscopy, real-time quantitative PCR, and Western blot were utilized to identify the role of Cypher in CM maturation. Subsequently, RNA sequencing and bioinformatics analysis predicted serum response factor (SRF) as the key regulator. Rescue experiments were conducted using adenovirus or adeno-associated viruses encoding SRF, both in vitro and in vivo. The molecular mechanisms were elucidated through G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly assays, and co-sedimentation assays. Results: Cypher deletion led to impaired sarcomere isoform switch and morphological abnormalities in mitochondria, transverse-tubules, and intercalated discs. RNA-sequencing analysis revealed significant dysregulation of crucial genes related to sarcomere assembly, mitochondrial metabolism, and electrophysiology in the absence of Cypher. Furthermore, SRF was predicted as key transcription factor mediating the transcriptional differences. Subsequent rescue experiments showed that SRF re-expression during the critical postnatal period effectively rectified CM maturation defects and notably improved cardiac function in Cypher-depleted mice. Mechanistically, Cypher deficiency resulted in the destabilization of F-actin and a notable increase in G-actin levels, thereby impeding the nuclear localisation of myocardin-related transcription factor A (MRTFA) and subsequently initiating SRF transcription. Conclusion: Cypher/ZASP plays a crucial role in CM maturation through actin-mediated MRTFA-SRF signalling. The linkage between CM maturation abnormalities and the late-onset of DCM is suggested, providing further insights into the pathogenesis of DCM and potential treatment strategies.

Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

Protective Effect of Beta-CasomorPhin-7 on Oxidative Stress and Inflammatory Response in Adriamycin Cardiomyopathy

Adriamycin (ADR) is an anthracycline antibiotic with the advantages of wide anti-tumor spectrum and strong anti-tumor activity. It is one of the most effective anti-tumor drugs at present, and is widely used in the treatment of leukemia and various entities. Tumor. However, cardiotoxicity of doxorubicin can lead to irreversible myocardial damage, ultimately leading to dilated cardiomyopathy (DCM) or congestive heart failure (CHF). Therefore, to explore the mechanism of ADR-induced myocardial injury, and to find effective and effective protective drugs for the clinical expansion of doxorubicin application range is of great significance. We simulated the ADR myocardial injury model by in vivo and in vitro, and the degree of damage of cardiomyocytes by ADR was observed by detecting the corresponding biochemical indicators and tissue staining. And the expression levels of oxidative stress and inflammatory factors were detected by Western blotting and others methods. Beta-casomorPhin-7 can alleviate myocardial damage caused by ADR, inhibit the expression of oxidative stress and inflammation-related factors, and activate TLR4-MyD88-NF-κB signaling pathway. β-CM-7 inhibits ADR-induced cardiomyocyte oxidative stress and inflammatory responses by activating the TLR4-MyD88-NF-κB signaling pathway. This will provide a new intervention target for the treatment of DCM.

The effect of ivabradine therapy on dilated cardiomyopathy patients with congestive heart failure: a systematic review and meta-analysis.

Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and meta-analysis to study the efficacy and potential mechanisms of ivabradine's effect on cardiac function and prognosis in patients with DCM. We searched PubMed, Cochrane Library, Embase, Web of Science, and four registers through September 28, 2022. All controlled trials of ivabradine for the treatment of DCM with congestive heart failure were included. Articles were limited to English, with the full text and necessary data available. We performed random- or fixed effects meta-analyses for all included outcome measures and compared the effect sizes for outcomes in patients treated with and without ivabradine. The quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2.0). Five trials with 357 participants were included. The pooled risk ratio was 0.48 [95% confidence interval (CI) (0.18, 1.25)] for all-cause mortality and 0.38 [95% CI (0.12, 1.23)] for cardiac mortality. The pooled mean difference was -15.95 [95% CI (-19.97, -11.92)] for resting heart rate, 3.96 [95% CI (0.99, 6.93)] for systolic blood pressure, 2.93 [95% CI (2.09, 3.77)] for left ventricular ejection fraction, -5.90 [95% CI (-9.36, -2.44)] for left ventricular end-systolic diameter, -3.41 [95% CI (-5.24, -1.58)] for left ventricular end-diastolic diameter, -0.81 [95% CI (-1.00, -0.62)] for left ventricular end-systolic volume, -0.67 [95% CI (-0.86, -0.48)] for left ventricular end-diastolic volume, -11.01 [95% CI (-19.66, -2.35)] for Minnesota Living with Heart Failure score, and -0.52 [95% CI (-0.73, -0.31)] for New York Heart Association class. Ivabradine reduces heart rate and ventricular volume, and improves cardiac function in patients with DCM, but showed no significant effect on the prognosis of patients.

The Molecular Role of Immune Cells in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a rare and severe condition characterized by chamber dilation and impaired contraction of the left ventricle. It constitutes a fundamental etiology for profound heart failure and abrupt cardiac demise, rendering it a prominent clinical indication for heart transplantation (HTx) among both adult and pediatric populations. DCM arises from various etiologies, including genetic variants, epigenetic disorders, infectious insults, autoimmune diseases, and cardiac conduction abnormalities. The maintenance of cardiac function involves two distinct types of immune cells: resident immune cells and recruited immune cells. Resident immune cells play a crucial role in establishing a harmonious microenvironment within the cardiac tissue. Nevertheless, in response to injury, cardiomyocytes initiate a cytokine cascade that attracts peripheral immune cells, thus perturbing this intricate equilibrium and actively participating in the initiation and pathological remodeling of dilated cardiomyopathy (DCM), particularly during the progression of myocardial fibrosis. Additionally, immune cells assume a pivotal role in orchestrating the inflammatory processes, which are intimately linked to the prognosis of DCM. Consequently, understanding the molecular role of various immune cells and their regulation mechanisms would provide an emerging era for managing DCM. In this review, we provide a summary of the most recent advancements in our understanding of the molecular mechanisms of immune cells in DCM. Additionally, we evaluate the effectiveness and limitations of immunotherapy approaches for the treatment of DCM, with the aim of optimizing future immunotherapeutic strategies for this condition.

Analysis of the role of glucose metabolism-related genes in dilated cardiomyopathy based on bioinformatics.

Dilated cardiomyopathy (DCM) is a prevalent condition with diverse etiologies, including viral infection, autoimmune response, and genetic factors. Despite the crucial role of energy metabolism in cardiac function, therapeutic targets for key genes in DCM's energy metabolism remain scarce. Our study employed the GSE79962 and GSE42955 datasets from the Gene Expression Omnibus (GEO) database for myocardial tissue sample collection and target gene identification via differential gene expression screening. Using various R packages, GSEA software, and the STRING database, we conducted data analysis, gene set enrichment, and protein-protein interaction predictions. The least absolute shrinkage and selection operator (LASSO) and Support Vector Machine (SVM) algorithms aided in feature gene selection, while the predictive model's efficiency was evaluated via the receiver operating characteristic (ROC) curve analysis. We used the non-negative matrix factorization (NMF) method for molecular typing and the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm for predicting immune cell infiltration. The DLAT and LDHA genes may regulate the immune microenvironment of DCM by influencing activated dendritic cells, activated mast cells, and M0 macrophages, respectively. The BPGM, DLAT, PGM2, ADH1A, ADH1C, LDHA, and PFKM genes may regulate m6A methylation in DCM by affecting the ZC3H13, ALKBH5, RBMX, HNRNPC, METTL3, and YTHDC1 genes. Further regulatory mechanism analysis suggested that PFKM, DLAT, PKLR, PGM2, LDHA, BPGM, ADH1A, and ADH1C could be involved in the development of cardiomyopathy by regulating the Toll-like receptor signaling pathway. PFKM, DLAT, PKLR, PGM2, LDHA, BPGM, ADH1A, and ADH1C may serve as potential targets for guiding the diagnosis, treatment, and follow-up of DCM.

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure, and males are more likely to suffer from DCM than females. This research aimed at exploring possible DCM-associated genes and their latent regulatory effects in female and male patients. WGCNA analysis found that in the yellow module, 341 and 367 key DEGs were identified in females and males, respectively. A total of 22 hub genes in females and 17 hub genes in males were identified from the PPI networks of the key DEGs based on Metascape database. And twelve and eight potential TFs of the key DEGs were also identified in females and males, respectively. Eight miRNAs of 15 key DEGs were screened in both females and males, which may be differentially expressed in females and males. Dual-luciferase reporter assay demonstrated that miR-21-5P could directly target the key gene MATN2. Furthermore, Sex differences in KEGG pathways were identified. Both KOBAS and GSEA analysis identified 19 significantly enriched pathways related to immune response in both females and males, and the TGF-β signaling pathway was exclusively identified in males. Network pharmacology analysis revealed that seven key DEGs were potential targets for the treatment of DCM, of which the OLR1 gene was only identified in males, the expression levels of the seven genes were verified by RT-PCR. The above results could offer a novel understanding of sex differences in key genes and pathways in DCM progression.

Mechanism of angiotensin-converting enzyme inhibitors in the treatment of dilated cardiomyopathy based on a protein interaction network and molecular docking.

Dilated cardiomyopathy (DCM) is a severe manifestation or intermediate stage of cardiovascular disease progression with a significantly poor prognosis. Based on a protein interaction network and molecular docking, the present study determined the genes and mechanism of action of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of DCM, providing a direction for future studies on ACEI drugs for DCM. This is a retrospective study. DCM samples and healthy controls were downloaded from the GSE42955 dataset, and the targets of the potential active ingredients were obtained from PubChem. Hub genes in ACEIs were analyzed by constructing network models and a protein-protein interaction (PPI) network using the STRING database and Cytoscape software. Molecular docking was performed using Autodock vina software. Twelve DCM samples and five control samples were finally included. A total of 62 intersected genes were obtained by intersecting the differentially expressed genes with six ACEI target genes. PPI analysis identified 15 intersecting hub genes from these 62 genes. Enrichment analysis showed that the hub genes were associated with T helper type 17 (Th17) cell differentiation as well as the nuclear factor kappa-B (NF-kappa B), interleukin 17 (IL-17), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt), and Toll-like receptor signaling pathways. Molecular docking indicated that the compound Benazepril to produce favorable interactions with TNF proteins with a relatively higher score (-8.3). This study primarily revealed that the preventive and curative effects of ACEI treatment on DCM could be realized through multiple targets and pathways, and its mechanism of action is related to genes such as TNF, vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), Cyclin D1 (CCND1), and AKT serine/threonine kinase 1 (AKT1), with immune- and inflammation-related signaling pathways involvement.

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity.

This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM. GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart. A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts. Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.

TEAD1 trapping by the Q353R-Lamin A/C causes dilated cardiomyopathy.

Mutations in the LMNA gene encoding Lamin A and C (Lamin A/C), major components of the nuclear lamina, cause laminopathies including dilated cardiomyopathy (DCM), but the underlying molecular mechanisms have not been fully elucidated. Here, by leveraging single-cell RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), protein array, and electron microscopy analysis, we show that insufficient structural maturation of cardiomyocytes owing to trapping of transcription factor TEA domain transcription factor 1 (TEAD1) by mutant Lamin A/C at the nuclear membrane underlies the pathogenesis of Q353R-LMNA-related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in LMNA mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the LMNA mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of LMNA-related DCM.

Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan - A Report From Clinical Personal Records.

Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of β-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with β-blocker prescription. Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in Cardiovascular Disease: A Comprehensive Clinical Review on Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the most important causes of heart failure in developed and developing countries. Currently, most medical interventions in the treatment of DCM are mainly focused on mitigating the progression of the disease and controlling the symptoms. The vast majority of patients who survive till the late stages of the disease require cardiac transplantation; this is exactly why we need novel therapeutic interventions and hopefully treatments that can reverse the clinical cardiac deterioration in patients with DCM. Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a novel therapeutic intervention with such capacity; it can help us edit the genome of patients with genetic etiology for DCM and potentially cure them permanently. Thisreview provides an overview of studies investigating CRISPR-based gene editing in DCM, including the use of CRISPR in DCM disease models, phenotypic screening, and genotype-specific precision therapies. The review discusses the outcomes of these studies and highlights the potential benefits of CRISPR in developing novel genotype-agnostic therapeutic strategies for the genetic causes of DCM. The databases we used to extract relevant literature include PubMed,Google Scholar, and Cochrane Central. We used the Medical Subject Heading (MeSH) strategy for our literature search in PubMed and relevant search keywords for other databases.We screened all the relevant articles from inception till February 22, 2023. We retained 74 research articles after carefully reviewing each of them. We concluded thatCRISPR gene editing has shown promise in developing precise and genotype-specific therapeutic strategies for DCM, but there are challenges and limitations, such as delivering CRISPR-Cas9 to human cardiomyocytes and the potential for unintended gene targeting. This study represents a turning point in our understanding of the mechanisms underlying DCM and paves the way for further investigation into the application of genomic editing for identifying novel therapeutic targets. This study can also act as a potential framework for novel therapeutic interventions in other genetic cardiovascular diseases.

Identification of shared fatty acid metabolism related signatures in dilated cardiomyopathy and myocardial infarction.

It is to be elucidated the risk-predictive role of differentially expressed fatty acid metabolismrelated genes (DE-FRGs) in dilated cardiomyopathy (DCM) and myocardial infarction. Four gene enrichment analyses defined DE-FRGs'biological functions and pathways. Three strategies were applied to identify risk biomarkers and construct a nomogram. The 4-DE-FRG correlation with immune cell infiltration, drugs, and ceRNA was explored. DE-FRGs were enriched in lipid metabolism. A risk nomogram was established by ACSL1, ALDH2, CYP27A1and PPARA, demonstrating a good ability for DCM and myocardial infarction prediction. PPARA was positively correlated with adaptive immunocytes. Thirty-five drugs are candidate therapeutic targets. A nomogram and new biological targets for early diagnosis and treatment of DCM and myocardial infarction were provided.

Recent studies on dilated cardiomyopathy caused by TTN mutations in children

The mutations of TTN gene that encodes titin are the most common mutation type among the genetic causes of dilated cardiomyopathy (DCM). This article reviews the worldwide studies on potential molecular pathogenesis (transcription, post-translational modification, etc.), clinical phenotypes, and gene therapies of pediatric DCM caused by TTN mutations, with the hope of providing a reference for the precision treatment of pediatric DCM caused by TTN mutations.

Лікування пацієнта з дилатаційною кардіоміопатією із застосуванням мезенхімальних стовбурових клітин

Наведено 3-річне спостереження за пацієнтом з дилатаційною кардіоміопатією, для лікування якого були застосовані мезенхімальні стовбурові клітини пуповинної крові. У пацієнта після тяжкого перебігу хронічного міокардиту розвинулася дилатаційна кардіоміопатія. Лікування позитивно вплинуло на динаміку клінічного стану, поліпшення показників скорочувальної функції лівого шлуночка, поліпшення якості життя. Пацієнт був знятий з листа очікування трансплантації серця. Спостереження за хворим триває.

Efficacy and safety evaluation of Shenmai injections for dilated cardiomyopathy: A systematic review and meta-analysis of randomised controlled trials

BackgroundShenmai Injection (SMI), a Chinese herbal injection, is widely used in China for the adjuvant treatment of patients with dilated cardiomyopathy (DCM), yet its clinical efficacy and safety remain controversial. PurposeThe aim of this study was to systematically evaluate the efficacy and safety of SMI in the treatment of DCM. MethodsRandomised controlled trials (RCTs) of SMI in the treatment of DCM were searched for and collected from the PubMed, EMBASE, Cochrane Library, SinoMed, Wan Fang, CNKI, and VIP databases between the dates of establishment of each database and July 1, 2022. The methodological quality of the included studies was assessed, while the risk of bias was based on the Cochrane Collaboration tool. All data were analysed using the R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. ResultsIn total, 16 RCTs, including 1,455 participants, were examined in this study. Evidence showed that the combination of SMI treatment and conventional treatment appears to significantly increase the clinical efficacy rate (OR=3.65, 95%CI (2.52, 5.28), p < 0.01), improve cardiac function (e.g. increase left ventricular ejection fraction (LVEF) (MD=5.31, 95%CI (4.21, 6.40), p < 0.01), decrease left ventricular end-diastolic dimension (LVEDD) (MD=-4.57, 95% CI (-7.10, -2.04); p < 0.01) and left ventricular end-systolic diameter (LVESD) (MD=-2.46, 95% CI (-3.60, -1.33); p < 0.01), decrease brain natriuretic peptide (BNP) (MD=-215.85, 95% CI (-241.61, -190.10); p < 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (MD=-504.42, 95% CI (-687.73, -321.10); p < 0.01), and increase 6-min walk distance (6MWD) (MD=114.08, 95% CI (42.32, 185.85); p < 0.01).In addition, no serious adverse effects associated with SMI were observed during the study period, thus suggesting that SMI is safe. However, the quality of evidence for these results was rated as “very low” to “low”, mainly due to the poor methodological quality of the included RCTs, the small sample size, the high heterogeneity, and potential publication bias. ConclusionIn the present work, we provide evidence that combined SMI therapy is beneficial and safe for improving cardiac function in patients with DCM. However, due to limitations posed by the low methodological quality of the included trials, more rigorous and high-quality RCTs are needed to provide solid evidence.