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A 39-year-old woman with intermittent palpitations, psoriasis, and a family history of sudden death presented with dilated right heart chambers and an enlarged coronary sinus. Despite a normal bubble study, further evaluation with transesophageal echocardiography revealed an abnormal pulmonary venous return: the left pulmonary veins drained into the coronary sinus. Cardiac computed tomography confirmed this finding, suggesting a partial abnormal pulmonary venous return as the underlying issue. Cardiac catheterization indicated increased pulmonary artery flow with normal pulmonary vascular resistance. The patient was referred for surgery. In this pathway involving the differential diagnosis of right heart dilatation, despite a confusing history and conflicting findings, echocardiographic clues led to the diagnosis.
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Ecocardiografía Transesofágica , Humanos , Femenino , Adulto , Diagnóstico Diferencial , Ecocardiografía Transesofágica/métodos , Tomografía Computarizada por Rayos X/métodos , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/fisiopatología , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/etiología , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/anomalíasAsunto(s)
Cardiomiopatía Dilatada , Lamina Tipo A , Transducción de Señal , Vitamina D , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Humanos , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Transducción de Señal/genética , Vitamina D/metabolismo , Masculino , Femenino , Mutación , AdultoRESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation. Recently, some studies have reported that the autoimmune response in myocardial cells might be related to the pathogenesis of DCM. The CD247 gene has been previously found to be involved in autoimmune disease. Therefore, our study aimed to clarify the hypothesis that there is a certain linkage between polymorphisms of the CD247 gene and the triggering of DCM risk. METHODS: In the present study, two single nucleotide polymorphisms (SNPs) of the CD247 gene, rs12141731 and rs858543, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 355 DCM patients and 404 age- and sex-matched controls. RESULTS: Pearson's chi-squared test for the CD247 gene revealed that SNP rs858543 (p = 0.001, OR = 0.72, 95% CI = (0.588-0.882), but not SNP rs12141731, was associated with DCM in the Chinese Han population. Haplotype analysis revealed that the CC haplotype was associated with increased DCM susceptibility, while CT was a protective haplotype. Cox multivariate survival analysis indicated that the rs858543 TT genotype (HR: 0.608, 95% CI = 0.402-0.921, p = 0.019) was an independent multivariate predictor for longer overall survival in DCM patients. CD247 mRNA expression levels were significantly decreased in DCM patients (p = 0.02). CONCLUSIONS: Our study suggested that a polymorphism in the CD247 gene may be a risk factor for DCM in the Chinese Han population. TRIAL REGISTRATION: ChiCTR2000029701.
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Antígenos CD , Pueblo Asiatico , Cardiomiopatía Dilatada , Predisposición Genética a la Enfermedad , Haplotipos , Polimorfismo de Nucleótido Simple , Humanos , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/etnología , Cardiomiopatía Dilatada/mortalidad , Femenino , Masculino , Persona de Mediana Edad , China/epidemiología , Pueblo Asiatico/genética , Estudios de Casos y Controles , Factores de Riesgo , Antígenos CD/genética , Adulto , Estudios de Asociación Genética , Frecuencia de los Genes , Fenotipo , Anciano , Modelos de Riesgos Proporcionales , Pueblos del Este de Asia , Complejo CD3RESUMEN
High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart. The offspring of the asymptomatic parental lines are born healthy but manifest dilated cardiomyopathy and cardiac collapse during the first days of life. The pathogenesis, further enhanced by mtDNA mutagenesis, involves prenatal upregulation of mitochondrial integrated stress response and the ferroptosis-inducer MESH1, leading to cardiac fibrosis and cardiomyocyte death after birth. Our evidence indicates that the tight control of mtDNA replication is critical for early cardiac homeostasis. Importantly, ferroptosis sensitivity is a potential targetable mechanism for infantile-onset cardiomyopathy, a common manifestation of mitochondrial diseases.
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Replicación del ADN , ADN Mitocondrial , Miocitos Cardíacos , Animales , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Femenino , Masculino , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Ferroptosis/genética , Miocardio/metabolismo , Miocardio/patología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/genética , Ratones Endogámicos C57BL , Animales Recién Nacidos , Humanos , Corazón/fisiopatología , FibrosisRESUMEN
Heart failure (HF) is associated with global changes in gene expression. Alternative mRNA splicing (AS) is a key regulatory mechanism underlying these changes. However, the whole status of molecules involved in the splicing process in human HF is unknown. Therefore, we analysed the spliceosome transcriptome in cardiac tissue (n = 36) from control subjects and HF patients (with ischaemic (ICM) and dilated (DCM) cardiomyopathies) using RNA-seq. We found greater deregulation of spliceosome machinery in ICM. Specifically, we showed widespread upregulation of the E and C complex components, highlighting an increase in SNRPD2 (FC = 1.35, p < 0.05) and DHX35 (FC = 1.34, p < 0.001) mRNA levels. In contrast, we observed generalised downregulation of the A complex and cardiac-specific AS factors, such as the multifunctional protein PCBP2 (FC = -1.29, p < 0.001) and the RNA binding proteins QKI (FC = -1.35, p < 0.01). In addition, we found a relationship between SNPRD2 (an E complex component) and the left ventricular mass index in ICM patients (r = 0.779; p < 0.01). On the other hand, we observed the specific underexpression of DDX46 (FC = -1.29), RBM17 (FC = -1.33), SDE2 (FC = -1.35) and RBFOX1 (FC = -1.33), p < 0.05, in DCM patients. Therefore, these aetiology-related alterations may indicate the differential involvement of the splicing process in the development of ICM and DCM.
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Empalme Alternativo , Insuficiencia Cardíaca , Factores de Empalme de ARN , Empalmosomas , Transcriptoma , Humanos , Empalmosomas/metabolismo , Empalmosomas/genética , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Factores de Empalme de ARN/metabolismo , Factores de Empalme de ARN/genética , Anciano , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Miocardio/metabolismo , Miocardio/patología , Perfilación de la Expresión Génica , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
LMNA-related dilated cardiomyopathy (DCM) is an autosomal-dominant genetic condition with cardiomyocyte and conduction system dysfunction often resulting in heart failure or sudden death. The condition is caused by mutation in the Lamin A/C (LMNA) gene encoding Type-A nuclear lamin proteins involved in nuclear integrity, epigenetic regulation of gene expression, and differentiation. The molecular mechanisms of the disease are not completely understood, and there are no definitive treatments to reverse progression or prevent mortality. We investigated possible mechanisms of LMNA-related DCM using induced pluripotent stem cells derived from a family with a heterozygous LMNA c.357-2A>G splice-site mutation. We differentiated one LMNA-mutant iPSC line derived from an affected female (Patient) and two non-mutant iPSC lines derived from her unaffected sister (Control) and conducted single-cell RNA sequencing for 12 samples (four from Patients and eight from Controls) across seven time points: Day 0, 2, 4, 9, 16, 19, and 30. Our bioinformatics workflow identified 125,554 cells in raw data and 110,521 (88%) high-quality cells in sequentially processed data. Unsupervised clustering, cell annotation, and trajectory inference found complex heterogeneity: ten main cell types; many possible subtypes; and lineage bifurcation for cardiac progenitors to cardiomyocytes (CMs) and epicardium-derived cells (EPDCs). Data integration and comparative analyses of Patient and Control cells found cell type and lineage-specific differentially expressed genes (DEGs) with enrichment, supporting pathway dysregulation. Top DEGs and enriched pathways included 10 ZNF genes and RNA polymerase II transcription in pluripotent cells (PP); BMP4 and TGF Beta/BMP signaling, sarcomere gene subsets and cardiogenesis, CDH2 and EMT in CMs; LMNA and epigenetic regulation, as well as DDIT4 and mTORC1 signaling in EPDCs. Top DEGs also included XIST and other X-linked genes, six imprinted genes (SNRPN, PWAR6, NDN, PEG10, MEG3, MEG8), and enriched gene sets related to metabolism, proliferation, and homeostasis. We confirmed Lamin A/C haploinsufficiency by allelic expression and Western blot. Our complex Patient-derived iPSC model for Lamin A/C haploinsufficiency in PP, CM, and EPDC provided support for dysregulation of genes and pathways, many previously associated with Lamin A/C defects, such as epigenetic gene expression, signaling, and differentiation. Our findings support disruption of epigenomic developmental programs, as proposed in other LMNA disease models. We recognized other factors influencing epigenetics and differentiation; thus, our approach needs improvement to further investigate this mechanism in an iPSC-derived model.
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Cardiomiopatía Dilatada , Diferenciación Celular , Haploinsuficiencia , Células Madre Pluripotentes Inducidas , Lamina Tipo A , Miocitos Cardíacos , Transcriptoma , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Humanos , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Diferenciación Celular/genética , Haploinsuficiencia/genética , Femenino , Transcriptoma/genética , Pericardio/patología , Pericardio/metabolismo , Linaje de la Célula/genética , Análisis de la Célula Individual , Regulación de la Expresión Génica , Mutación/genética , AdultoRESUMEN
The synchronization of the electrical and mechanical coupling assures the physiological pump function of the heart, but life-threatening pathologies may jeopardize this equilibrium. Recently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a model for personalized investigation because they can recapitulate human diseased traits, such as compromised electrical capacity or mechanical circuit disruption. This research avails the model of hiPSC-CMs and showcases innovative techniques to study the electrical and mechanical properties as well as their modulation due to inherited cardiomyopathies. In this work, hiPSC-CMs carrying either Brugada syndrome (BRU) or dilated cardiomyopathy (DCM), were organized in a bilayer configuration to first validate the experimental methods and second mimic the physiological environment. High-density CMOS-based microelectrode arrays (HD-MEA) have been employed to study the electrical activity. Furthermore, mechanical function was investigated via quantitative video-based evaluation, upon stimulation with a ß-adrenergic agonist. This study introduces two experimental methods. First, high-throughput mechanical measurements in the hiPSC-CM layers (xy-inspection) are obtained using both a recently developed optical tracker (OPT) and confocal reference-free traction force microscopy (cTFM) aimed to quantify cardiac kinematics. Second, atomic force microscopy (AFM) with FluidFM probes, combined with the xy-inspection methods, supplemented a three-dimensional understanding of cell-cell mechanical coupling (xyz-inspection). This particular combination represents a multi-technique approach to detecting electrical and mechanical latency among the cell layers, examining differences and possible implications following inherited cardiomyopathies. It can not only detect disease characteristics in the proposed in vitro model but also quantitatively assess its response to drugs, thereby demonstrating its feasibility as a scalable tool for clinical and pharmacological studies.
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Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Microelectrodos , Síndrome de Brugada , Cardiomiopatía Dilatada/patología , Fenómenos Electrofisiológicos , Células CultivadasRESUMEN
Heart failure affects millions of people worldwide, with men exhibiting a higher incidence than women. Our previous work has shown that mosaic loss of the Y chromosome (LOY) in leukocytes is causally associated with an increased risk for heart failure. Here, we show that LOY macrophages from the failing hearts of humans with dilated cardiomyopathy exhibit widespread changes in gene expression that correlate with cardiac fibroblast activation. Moreover, we identify the ubiquitously transcribed t et ratricopeptide Y-linked (Uty) gene in leukocytes as a causal locus for an accelerated progression of heart failure in male mice with LOY. We demonstrate that Uty disruption leads to epigenetic alterations in both monocytes and macrophages, increasing the propensity of differentiation into profibrotic macrophages. Treatment with a transforming growth factor-ß-neutralizing antibody prevented the cardiac pathology associated with Uty deficiency in leukocytes. These findings shed light on the mechanisms that contribute to the higher incidence of heart failure in men.
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Cromosomas Humanos Y , Epigénesis Genética , Insuficiencia Cardíaca , Animales , Masculino , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Humanos , Cromosomas Humanos Y/genética , Fibrosis/genética , Fibrosis/patología , Macrófagos/metabolismo , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Modelos Animales de Enfermedad , Ratones , Femenino , Fenotipo , Ratones Endogámicos C57BL , Células Cultivadas , Ratones NoqueadosRESUMEN
BACKGROUND: This case report documents the first worldwide use of the Hybrid System from Spectrum Medical in a heart transplant procedure, focusing on its safety and efficacy. Traditional cardiopulmonary bypass systems often use an open reservoir, which increases the blood's exposure to air, thereby heightening the risk of an inflammatory response and gas embolism. In contrast, the Hybrid System is designed to improve surgical outcomes by significantly reducing the blood-air interface. This system utilizes a dual-chamber cardiotomy-venous reservoir with a collapsible soft bag, effectively minimizing blood contact with air and foreign materials. However, it is important to note that there is currently no evidence supporting the use of this methodology specifically in heart transplants. CASE PRESENTATION: A 41-year-old male managed with a left ventricular assist device because of dilated cardiomyopathy underwent a heart transplant using the Hybrid System. The perioperative and postoperative data provided evidence of the system's effectiveness. The selection of this patient was due to the absence of significant comorbidities unrelated to his primary cardiac condition, making him an ideal candidate to evaluate the system's performance. CONCLUSION: The Hybrid System is safe and efficient. The successful implementation in this case highlights its advantages over traditional cardiopulmonary bypass systems, suggesting a promising future in cardiac surgery. Further studies with routine cardiac surgery patients are required to validate these findings.
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Circulación Extracorporea , Trasplante de Corazón , Humanos , Masculino , Trasplante de Corazón/métodos , Adulto , Circulación Extracorporea/métodos , Corazón Auxiliar , Cardiomiopatía Dilatada/cirugíaRESUMEN
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.
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Actinas , Cardiomiopatía Dilatada , Miocitos Cardíacos , Factor de Respuesta Sérica , Transducción de Señal , Transactivadores , Animales , Miocitos Cardíacos/metabolismo , Factor de Respuesta Sérica/metabolismo , Factor de Respuesta Sérica/genética , Ratones , Actinas/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Sarcómeros/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Humanos , Ratones NoqueadosRESUMEN
Myocarditis (MC) is defined as an immunological inflammatory reaction with various etiologies, clinical presentations and prognoses within the myocardium. Currently, parvovirus B19 (PVB19) has become the main factor leading to this disease, replacing the previously dominant viruses A and B. In the case of chronic heart failure with subsequent dilated cardiomyopathy, approximately 67% have a viral etiology, and most of them are the result of PVB19 infection. However, the analysis showed a correlation between PVB19 infection and the risk of developing inflammatory dilated cardiomyopathy (DCMi). PVB19 is detected in 23% of patients with DCMi. Chronic infection may also contribute to progressive left ventricular failure in patients with a history of MC. The above effect suggests the active replication of PVB19 only in heart biopsies with inflammation due to MC or DCMi. Moreover, the supply of IFN-ß to suppress the active transcription of PVB19 accompanied by DCMi over a period of 6 months results in the normalization of NT-proBNP and an improvement in LVEF along with NYHA performance. The small number of reports on this topic and inaccuracies resulting from constantly conducted research and ongoing changes make it impossible to clearly answer the question of whether PVB19 is a factor inducing de novo MC and DCM or only accompanies the above conditions. However, large clinical cohort studies lead to the perception of PVB19 as a viral etiological agent capable of causing de novo MC together with DCMi.
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Insuficiencia Cardíaca , Miocarditis , Infecciones por Parvoviridae , Parvovirus B19 Humano , Humanos , Miocarditis/virología , Miocarditis/etiología , Parvovirus B19 Humano/patogenicidad , Insuficiencia Cardíaca/virología , Insuficiencia Cardíaca/etiología , Infecciones por Parvoviridae/complicaciones , Infecciones por Parvoviridae/virología , Cardiomiopatía Dilatada/virología , Cardiomiopatía Dilatada/patologíaRESUMEN
BACKGROUND: Chinese patent medicines (CPMs) are widely used in China as an adjuvant treatment in dilated cardiomyopathy with heart failure (DCM-HF). However, comprehensive and systematic evidence supporting the beneficial effects of CPMs combined with current complementary and alternative medicine (CAM) treatments against DCM-HF was limited. This network meta-analysis (NMA) aimed to assess and rank the relative efficacy of eight different CPMs for DCM-HF. METHODS: To retrieve randomized controlled trials (RCTs) focusing on the use of CPMs combined with CAM for DCM-HF, the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science Periodical Database (CSPD), Chinese Citation Database (CCD), Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov were comprehensively searched from their inception to 29 February 2024. The quality of the included RCTs was examined using the Cochrane Risk of Bias assessment tool, version 2.0 (RoB 2). Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the relative efficacy. Bayesian network meta-analysis was designed to assess the efficacy of different CPMs. RESULTS: After applying the inclusion and exclusion criteria, a total of 77 eligible RCTs involving 6980 patients were enrolled. The outcomes assessed included clinical effectiveness rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-min walk test (6MWT), brain natriuretic peptide (BNP), and cardiac output (CO). The results of the NMA indicated that Qili Qiangxin capsule (QLQX), Wenxin granule (WX), Tongxinluo capsule (TXL), Qishen Yiqi dropping pill (QSYQ), Shexiang Baoxin pill (SXBX), Yangxinshi tablet (YXST), Yixinshu capsule (YXSC), and Getong Tongluo capsule (GTTL) combined with CAM significantly improved performance compared with CAM alone in treating DCM-HF. YXST + CAM (MD = - 9.93, 95% CI - 12.83 to - 7.03) had the highest probability of being the best treatment on account of the enhancement of LVEF. WX + CAM had the highest likelihood of being the best treatment considering the improvement in LVEDD (MD = - 11.7, 95% CI - 15.70 to - 7.79) and 6MWT (MD = - 51.58, 95% CI - 73.40 to - 29.76). QLQX + CAM (MD = - 158.59, 95% CI - 267.70 to - 49.49) had the highest likelihood of being the best intervention for the reduction in BNP. TXL + CAM (MD = - 0.93, 95% CI - 1.46 to - 0.40) might be the optimal choice for increasing CO levels in DCM-HF patients. No serious treatment-emergent adverse events were observed. CONCLUSION: This NMA suggested that adding CPMs to the current CAM treatment exerted a more positive effect on DCM-HF. Thereinto, QLQX + CAM, TXL + CAM, WX + CAM, and YXST + CAM showed a preferable improvement in patients with DCM-HF when unified considering the clinical effectiveness rate and other outcomes. Furthermore, due to the lack of information on CPMs against DCM-HF and the uneven distribution of included studies among interventions, more high-quality studies are needed to provide more robust evidence to support our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42023482669).
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Teorema de Bayes , Cardiomiopatía Dilatada , Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Metaanálisis en Red , Humanos , Cardiomiopatía Dilatada/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Medicina Tradicional China/métodos , Medicamentos sin Prescripción/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Volumen Sistólico , Resultado del TratamientoRESUMEN
Dilated cardiomyopathy (DCM), known as myocardial metabolic dysfunction, is recognized as a clinical condition characterized by left ventricular dilation or improper contraction of cardiac muscles in the absence of coronary atherosclerosis and hypertension. It is an independent risk factor for cardiac function caused by a hyperglycemic condition in diabetic patients leading to heart failure (HF), which renders the early diagnosis of DCM highly challenging. Hence, detection of early diagnostic biomarkers in blood serum to identify DCM conditions is quite requisite. Brain natriuretic peptide (BNP) is a well-recognized biomarker for heart failure and reported as an early diagnostic biomarker for DCM. In this work, we developed a terbium citrate based MoS2 nanosheet (NS) coupled immunoprobe for the sensitive detection of BNP. The antibody conjugated Tb-citrate complex exhibits green fluorescence, which is quenched by the introduction of MoS2 NS. On subsequent addition of antigen BNP, the fluorescence is enhanced because of specific antigen-antibody interaction. The probe is selective and sensitive toward BNP in a linear range from 30.76 to 849.85 pg/mL with a low LOD of 3.87 pg/mL. The probe is validated in spiked human serum samples with good recovery percentage.
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Biomarcadores , Cardiomiopatía Dilatada , Disulfuros , Ensayo de Materiales , Molibdeno , Nanoestructuras , Péptido Natriurético Encefálico , Terbio , Péptido Natriurético Encefálico/sangre , Humanos , Terbio/química , Molibdeno/química , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/diagnóstico , Biomarcadores/sangre , Disulfuros/química , Nanoestructuras/química , Materiales Biocompatibles/química , Tamaño de la Partícula , Ácido Cítrico/química , LuminiscenciaAsunto(s)
Cardiomiopatía Dilatada , Corazón Auxiliar , Lamina Tipo A , Mutación , Humanos , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/terapia , Cardiomiopatía Dilatada/fisiopatología , Lamina Tipo A/genética , Masculino , Adulto , Persona de Mediana Edad , ElectrocardiografíaRESUMEN
In this study, we utilized the Olink Cardiovascular III panel to compare the expression levels of 92 cardiovascular-related proteins between patients with dilated cardiomyopathy combined with heart failure (DCM-HF) (n = 20) and healthy normal people (Normal) (n = 18). The top five most significant proteins, including SPP1, IGFBP7, F11R, CHI3L1, and Plaur, were selected by Olink proteomics. These proteins were further validated using ELISA in plasma samples collected from an additional cohort. ELISA validation confirmed significant increases in SPP1, IGFBP7, F11R, CHI3L1, and Plaur in DCM-HF patients compared to healthy controls. GO and KEGG analysis indicated that NT-pro BNP, SPP1, IGFBP7, F11R, CHI3L1, Plaur, BLM hydrolase, CSTB, Gal-4, CCL15, CDH5, SR-PSOX, and CCL2 were associated with DCM-HF. Correlation analysis revealed that these 13 differentially expressed proteins have strong correlations with clinical indicators such as LVEF and NT-pro BNP, etc. Additionally, in the GEO-DCM data sets, the combined diagnostic value of these five core proteins AUC values of 0.959, 0.773, and 0.803, respectively indicating the predictive value of the five core proteins for DCM-HF. Our findings suggest that these proteins may be useful biomarkers for the diagnosis and prediction of DCM-HF, and further research is prompted to explore their potential as therapeutic targets.
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Biomarcadores , Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Proteómica , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/diagnóstico , Humanos , Biomarcadores/sangre , Proteómica/métodos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Osteopontina/sangre , Péptido Natriurético Encefálico/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Fragmentos de Péptidos/sangre , Estudios de Casos y Controles , Adulto , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants. CASE PRESENTATION: We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579_1584delp. (Glu527_Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time. CONCLUSION: This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM.
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Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/diagnóstico , Masculino , Recién Nacido , Femenino , Secuenciación del Exoma , EmbarazoRESUMEN
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are extensively used in the management of heart failure because of their cardiovascular benefits. Adverse drug reactions associated with dapagliflozin include diabetic ketoacidosis, fungal infections, and increased blood glucose concentrations. However, abnormal uterine bleeding is not a known side effect of dapagliflozin. We report a 75-year-old Chinese woman with dilated cardiomyopathy and chronic heart failure who experienced abnormal uterine bleeding while taking dapagliflozin. Notably, cessation of dapagliflozin administration resulted in the disappearance of uterine bleeding. These findings suggest that dapagliflozin possesses additional potential mechanisms, but these mechanisms require further investigation. Furthermore, healthcare professionals should remain vigilant regarding the occurrence of uterine bleeding when prescribing dapagliflozin.
Asunto(s)
Compuestos de Bencidrilo , Cardiomiopatía Dilatada , Glucósidos , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Hemorragia Uterina , Humanos , Femenino , Anciano , Insuficiencia Cardíaca/inducido químicamente , Glucósidos/efectos adversos , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/uso terapéutico , Cardiomiopatía Dilatada/inducido químicamente , Hemorragia Uterina/inducido químicamente , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Enfermedad CrónicaRESUMEN
High-proportion spliced-in titin truncating variants (hiPSI TTNtvs) have been associated with an increased risk of atrial fibrillation, dilated cardiomyopathy (DCM) and heart failure in individuals of European ancestry1. However, similar data in individuals of African ancestry are lacking. Here we examined the association of hiPSI TTNtvs with atrial fibrillation, DCM and heart failure in individuals of African ancestry using data from the All of Us Research Program. Among 38,154 individuals of African ancestry, 169 (0.4%) individuals carried a hiPSI TTNtv. hiPSI TTNtv carriers were at a higher risk of developing atrial fibrillation (adjusted hazard ratio (HRadj) 2.42, 95% confidence interval (CI) 1.52-3.85), DCM (HRadj 2.82, 95% CI 1.81-4.39) and heart failure (HRadj 2.07, 95% CI 1.43-3.00) compared with noncarriers. The association of hiPSI TTNtvs with atrial fibrillation, DCM and heart failure was similar in individuals of African ancestry and those of European ancestry. Therefore, genetic testing for hiPSI TTNtvs may permit early identification of carriers and support preventive measures to reduce the likelihood of heart failure development both in individuals of European ancestry and in individuals of African ancestry.