Pubblicazioni recenti - dilated cardiomyopathy
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Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases-An Ultrastructural Pilot Study.
Int J Mol Sci2024 Jul;25(14):. doi: 7644.
Schönmehl Rebecca, Mendelsohn Daniel H, Winter Lina, Pabel Steffen, Niedermair Tanja, Evert Katja, Cheung Wing-Hoi, Wong Ronald Man Yeung, Schmitt Volker H, Keller Karsten, Barsch Friedrich, Dietl Alexander, Gummert Jan F, Schramm René, Sossalla Samuel, Brochhausen Christoph,
Abstract
BACKGROUND:
Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM).
METHODS:
Transmission electron microscopy was used to analyze mitochondria within 0-3.5 ?m and 3.5-7 ?m of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score.
RESULTS:
AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well.
CONCLUSION:
Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.
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Cardiomyopathy and Sudden Cardiac Death: Bridging Clinical Practice with Cutting-Edge Research.
Biomedicines2024 Jul;12(7):. doi: 1602.
Mistrulli Raffaella, Ferrera Armando, Salerno Luigi, Vannini Federico, Guida Leonardo, Corradetti Sara, Addeo Lucio, Valcher Stefano, Di Gioia Giuseppe, Spera Francesco Raffaele, Tocci Giuliano, Barbato Emanuele,
Abstract
Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies.
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Dilated cardiomyopathy due to a novel combination of TTN and BAG3 genetic variants: from acute heart failure to subclinical phenotypes.
Cardiovasc Pathol2024 Jul;():107675. doi: 10.1016/j.carpath.2024.107675.
Irene Bottillo, Carla Giordano, Pia Ciccone Maria, Gemma Pignataro Maria, Fiammetta Albi, Gabriella Parisi, Daniela Formicola, Simona Grotta, Federico Ranocchi, Giuli Maria Valeria, Checquolo Saula, Laura Masuelli, Federica Re, Silvia Majore, Giulia d'Amati, Paola Grammatico,
Abstract
Dilated cardiomyopathy (DCM) is defined as left ventricular enlargement accompanied by systolic dysfunction not explained by abnormal loading conditions or coronary heart disease. The DCM clinical spectrum is broad, ranging from subclinical to severe presentation with progression to end stage heart failure. To date, different genetic loci have been found to have moderate/definitive evidence for causality in DCM and pathogenic variants in the TTN gene represent the main genetic determinant. Here, we describe a family in which the co-occurrence of two genetic hits, one in the TTN and one in the BAG3 gene, was associated with heterogeneous clinical presentation ranging from subclinical phenotypes to acute cardiogenic shock mimicking fulminant myocarditis. We hypothesize that at least some specific BAG3 genotypes could be related to DCM presenting with acute heart failure and suggest that patients and relatives carrying BAG3 pathogenic variants should be addressed to a tertiary-level heart care center.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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Characterization and Long-Term Prognosis of Patients with Different Phenotypes of Dilated Cardiomyopathy.
J Cardiovasc Dev Dis2024 Jul;11(7):. doi: 220.
Zhang Shuyuan, Gao Shiqi, Tian Zhuang, Zhang Shuyang,
Abstract
BACKGROUND:
Long-term prognosis of dilated cardiomyopathy (DCM) in the Chinese population is lacking, and the left ventricular (LV) hypertrabeculation phenotype usually overlaps with DCM.
OBJECTIVES:
The study aims to investigate whether the presence of the LV hypertrabeculation phenotype confers additional adverse prognostic information for DCM patients.
METHODS:
We retrospectively reviewed all DCM patients (?18 years of age at diagnosis) hospitalized in the Peking Union Medical College Hospital between September 2002 and September 2022. The eligible patients were divided into two groups based on echocardiography at diagnosis: the isolated DCM ( = 353), and DCM with the LV hypertrabeculation phenotype ( = 97). The primary endpoint was major adverse cardiac events (MACEs), and multivariate Cox hazards regression models were used to compare the endpoints between the two groups.
RESULTS:
During a mean follow-up time of 4.6 years, there was no significant difference in the primary endpoint between the isolated DCM and DCM with the LV hypertrabeculation phenotype ( = 0.19). The risk of MACEs in the first 5 years was significantly higher in DCM with the LV hypertrabeculation phenotype than isolated DCM (adjusted HR [95%CI]: 1.83 [1.21-2.77]) and after 5 years the effect of the LV hypertrabeculation phenotype as a prognostic attenuated. Subgroup analysis found a significant interaction for the incidence of MACEs between sex and DCM subtypes ( for interaction = 0.01).
CONCLUSIONS:
DCM with LV hypertrabeculation phenotypes had a higher early (first 5 years) risk of MACEs. For males, the presence of LV hypertrabeculation phenotypes might be an important clue for identifying high-risk DCM patients.
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Arrhythmias and conduction disorders in patients with viral heart disease.
Minerva Cardiol Angiol2024 Jul;():. doi: 10.23736/S2724-5683.24.06506-2.
Osiecki Andrzej, Wiligórska Diana, Ko?os Ma?gorzata, Pawlak Agnieszka,
Abstract
Viral heart disease comprises of two cardiovascular entities being evoked by viral infection: acute viral myocarditis and viral cardiomyopathy. Viral myocarditis may completely resolve leaving no traceable sign or cause ongoing inflammation with subsequent development of hypokinetic dilated/non-dilated cardiomyopathy. The exact epidemiology of viral myocarditis remains unknown due to its sometimes asymptomatic course, but according to the Global Burden of Disease Study 2019, the prevalence of myocarditis in young adults is estimated to range between 6.1 per 100,000 in men and 4.4 per 100,000 in women, with the most common viral etiology. According to the literature viral genome can be found in considerable percentage (up to 67,4%) of endomyocardial biopsy specimens obtained from patients with idiopathic left ventricular dysfunction- suggesting viral etiology of the cardiomyopathy. In this review we would like to enlighten most common types of arrhythmias and conduction disorders as well as their prevalence in patients with viral heart disease. Moreover, our paper depicts probable pathological mechanisms in which viruses induce arrhythmias and cardiac conduction system disease in both, acute viral infection and chronic viral disease. We would also like to highlight unresolved problem of sudden death protection in the course of acute myocarditis.
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RNA Helicase DDX5 Maintains Cardiac Function by Regulating Alternative Splicing.
Circulation2024 Jul;():. doi: 10.1161/CIRCULATIONAHA.123.064774.
Jia Kangni, Cheng Haomai, Ma Wenqi, Zhuang Lingfang, Li Hao, Li Zhigang, Wang Ziyang, Sun Hang, Cui Yuke, Zhang Hang, Xie Hongyang, Yi Lei, Chen Zhiyong, Sano Motoaki, Fukuda Keiichi, Lu Lin, Pu Jun, Zhang Yan, Gao Ling, Zhang Ruiyan, Yan Xiaoxiang,
Abstract
BACKGROUND:
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear.
METHODS:
We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation-mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing.
RESULTS:
We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction-induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca/calmodulin-dependent protein kinase II? (), thus preventing the production of CaMKII?A, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca homeostasis. In line with this, we found increased intracellular Ca transients and increased sarcoplasmic reticulum Ca content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKII?A partially rescued the cardiac dysfunction and HF in knockout mice.
CONCLUSIONS:
These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF.
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Generation of human induced pluripotent stem cell (hiPSC) lines derived from three patients carrying the pathogenic CRYAB (A527G) mutation and one non-carrier family member.
Stem Cell Res2024 Jul;80():103497. doi: 10.1016/j.scr.2024.103497.
Kelters Ilse R, Verbueken Devin, Beekink Tess, Van Laake Linda W, Sluijter Joost P G, Maas Renee G C, Buikema Jan W,
Abstract
A newly identified pathogenic variant (A527G) in alpha B-crystallin (?B-crystallin) has been linked to congenital cataract and young-onset dilated cardiomyopathy (DCM) within a Dutch family, although the disease mechanism remains unclear. Four human induced pluripotent stem cell (hiPSC) clones were generated from three symptomatic patients carrying the A527G variant, and one healthy proband. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai viral pluripotency vectors. The established hiPSCs clones exhibited regular ESC-like morphology, expression of pluripotency markers, and normal karyotyping. These hiPSC lines can facilitate future studies to understand the chaperone function and its role in DCM disease progression.
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
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Comprehensive analysis of aberrantly methylated differentially expressed genes and validation of CDC6 in melanoma.
J Cancer Res Clin Oncol2024 Jul;150(7):362. doi: 10.1007/s00432-024-05851-x.
Liao Li, Han Wei, Shen Yue, Shen Guoliang,
Abstract
BACKGROUND:
Skin Cutaneous Melanoma (SKCM) is a highly aggressive malignant tumor with a significant increase in mortality upon metastasis. The molecular mechanisms driving melanoma progression remain largely unclear. Recent studies have highlighted the importance of epigenetic alterations, especially DNA methylation, in melanoma development. This study aims to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) in genome-wide profiles between primary and metastatic melanoma.
METHODS:
Gene expression profiling datasets GSE8401 and gene methylation profiling datasets GSE86355 were collected from the GEO database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were systematically identified. Integration of DEGs and DMGs yielded a set of MeDEGs, which subsequently underwent functional enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Survival analysis was used to select prognostic hub genes. In addition, 37 SKCM and 37 normal skin tissues from the First Affiliated Hospital of Soochow University (FAHSU) were collected for immunohistochemical (IHC) staining and evaluation. Furthermore, DNA methylation patterns of CDC6 were analyzed. To validate these findings, SKCM cell cultures were utilized to elucidate the expression and behavioral characteristics of CDC6. Additionally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted for CDC6.
RESULTS:
In our study, we discovered 120 hypomethylated-upregulated genes and 212 hypermethylated-downregulated genes. The hypomethylated-upregulated genes were notably associated with biological processes such as spindle assembly checkpoint signaling, mitotic spindle assembly, and negative regulation of mitotic metaphase/anaphase transition. Our pathway analysis revealed significant enrichment in pathways related to dilated cardiomyopathy, amino sugar metabolism, progesterone-mediated oocyte maturation, and chemical carcinogenesis. Conversely, hypermethylated-downregulated genes were found to be enriched in processes like epidermis development, keratinocyte differentiation, and skin development. Additionally, pathway analysis highlighted associations with estrogen signaling, Staphylococcus aureus infection, axon guidance, and arachidonic acid metabolism. Following the establishment of PPI networks and survival analysis, we identified 11 prognostic hub genes: CCNA2, CDC6, CDCA3, CKS2, DTL, HJURP, KRT5, KRT14, KRT15, KRT16, and NEK2. Notably, among the 11 hub genes, our findings indicate that CDC6 plays a pivotal role in enhancing the proliferation, migration, and invasion capabilities of melanoma cells in vitro.
CONCLUSIONS:
Our comprehensive genomic analyses reveal that genes with aberrant methylation exhibit differential expression during the transition from primary to metastatic melanoma. The identified genes, especially CDC6, which plays a crucial role in enhancing melanoma cell proliferation, migration, and invasion, provide valuable insights into potential methylation-based biomarkers. These findings could contribute significantly to advancing precision medicine in SKCM.
© 2024. The Author(s).
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Overcoming Double Jeopardy: Successful Orthotopic Heart Transplant in a Recipient With Bacterial and Fungal Infections.
Case Rep Cardiol2024 ;2024():4175313. doi: 4175313.
Munthananuchat Paopat, Naratreekoon Bundit, Kantathut Narongrit, Samankatiwat Piya, Trirattanapikul Akeatit, Yingchoncharoen Teerapat,
Abstract
Although active infection is generally a contraindication before an orthotopic heart transplant, a 16-year-old man diagnosed with dilated cardiomyopathy successfully underwent an orthotopic heart transplant despite having active probable invasive pulmonary aspergillosis and bacterial pneumonia in the presence of septic and cardiogenic shock.
Copyright © 2024 Paopat Munthananuchat et al.
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CRT for Dilated Cardiomyopathy: Time for a Personalized Approach.
JACC Clin Electrophysiol -
Genetic analysis and family screening for dilated cardiomyopathy: a retrospective analysis of the stepwise pedigree approach.
Scand Cardiovasc J2024 Dec;58(1):2379356. doi: 10.1080/14017431.2024.2379356.
Ylipää Josef, Andersson Therese,
Abstract
AIMS:
This study aimed to assess the practicality of using a stepwise pedigree-based approach to differentiate between familial and sporadic Dilated Cardiomyopathy (DCM), while also considering timing of the genetic analysis. The analysis includes an examination of the extent to which complete family investigations were conducted in real-world scenarios as well as the length of the investigation.
METHODS:
The stepwise pedigree approach involved conducting a comprehensive family history spanning 3 to 4 generations, reviewing medical records of relatives, and conducting clinical screening using echocardiography and electrocardiogram on first-degree relatives. Familial DCM was diagnosed when at least 2 family members were found to have DCM, and genetic analysis was considered as an option. This study involved a manual review of all DCM investigations conducted at the Centre of Cardiovascular Genetics at Umeå University Hospital, where the stepwise pedigree approach has been employed since 2007.
RESULTS:
The investigation process had a mean duration of 643 days (95% CI 560.5-724.9). Of the investigations preformed, 94 (68%) were complete, 12 (9%) were ongoing, and 33 (24%) were prematurely terminated and thus incomplete. At the conclusion of the investigations, 55 cases (43%) were classified as familial DCM, 50 (39%) as sporadic DCM, and 22 (18%) remained unassessed due to incomplete pedigrees. Among the familial cases, genetic verification was achieved in 40%.
CONCLUSION:
The stepwise pedigree approach is time consuming, and the investigations are often incomplete which may suggest that a more direct approach to genetic analysis, may be warranted.
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[Analysis of pediatric heart transplantation supported by extracorporeal membrane oxygenation].
Zhonghua Er Ke Za Zhi2024 Jul;62(8):770-774. doi: 10.3760/cma.j.cn112140-20240615-00401.
Zhao Z, Zhou C B, Liu A H, Lin Z L, Chen G Y, Wang Z, Li M, Wu M, Huang J S, Hong X Y,
Abstract
To summarize the clinical characteristics of patients with end-stage heart failure who receive heart transplant under extracorporeal membrane oxygenation (ECMO) support. The clinical data of 12 pediatric patients who received heart transplant with ECMO support in the Seventh Medical Center of Chinese People's Liberation Army General Hospital and Guangdong Provincial People's Hospital, from January 2019 to December 2023 was collected. The data included sex, age, weight, diagnosis, pre-ECMO lactate level, left ventricular ejection fraction (LVEF), vasoactive-inotropic score (VIS), and preoperative ECMO running time. Surgical data included cold ischemia time of the donor heart, cardiopulmonary bypass time, intraoperative use of immunosuppressant, postoperative use of ECMO, duration of postoperative ECMO, rate of successful weaning from ECMO, and survival discharge rate. The paired -test was performed to compare cardiac function indices before and after left ventricular decompression. The 12 patients ranged in age from 1.1 to 15.8 years, and weighted from 8 to 63 kg. Ten children were diagnosed with dilated cardiomyopathy, one with myocardial underdensification, and one with a novel heterozygous mutation of the SCN5A gene causing overlap syndrome complicated by fatal arrhythmia. Before ECMO, the lactate ranged from 0.6 to>15.0 mmol/L, the LVEF from 6.5% to 43%, and VIS from 3 to 108. Four patients underwent left ventricular decompression supported by preoperative ECMO, and their pulse pressure was significantly increased after decompression ((17.8±2.1) (9.8±1.5) mmHg, 1 mmHg=0.133 kPa, =11.31, =0.001), while there was no apparent change in LVEF ((26.8±4.4)% (24.9±4.9)%, =1.75, =0.178). A total of 7 children received a second run of ECMO after surgery and 3 of them successfully weaned off ECMO and survived to discharge. In the entire cohort, 10 were successfully weaned from ECMO and 8 survived to discharge. For children with end-stage heart failure supported by ECMO, left ventricular decompression can significantly improve pulse pressure. These patients will eventually require heart transplantation.
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An unusual cause of inappropriate shocks delivered by an implantable cardioverter defibrillator.
BMC Cardiovasc Disord2024 Jul;24(1):380. doi: 380.
Baldauf Benito, Lau Ernest W, Giaccardi Marzia, Bonnemeier Hendrik,
Abstract
INTRODUCTION:
Cardiac implantable electronic device (CIED) complications present significant challenges in clinical practice, especially in elderly patients with multiple comorbidities. Common adverse events include infection, lead malfunction, and device migration. Twiddler's Syndrome, a rare but serious CIED complication characterised by patient manipulation causing lead displacement and device malfunction, is often underreported. The literature consists mainly of case reports and small series, providing limited guidance on prevention and management. As CIEDs are critical for managing cardiac arrhythmias and heart failure, understanding and addressing Twiddler's Syndrome is essential. This case report aims to contribute to the literature by detailing a case of Twiddler's Syndrome, emphasising the importance of a multidisciplinary approach for optimal management.
CASE PRESENTATION:
A 59-year-old male presented with discomfort around his implantable cardioverter defibrillator (ICD) site and the sternal area over the past two days. He denied pain, dyspnoea, or dizziness. Clinical examination revealed a normal heart rhythm and no peripheral pulse deficit. Ultrasound revealed a reduced left ventricular ejection fraction. The atrial lead was not visible, and the shock coil was misplaced. ICD interrogation showed inappropriate shocks due to sensing artifacts and exit block in both leads, with no arrhythmias detected. An X-ray confirmed lead dislodgement and significant entanglement in the pocket. The patient was diagnosed with Twiddler's Syndrome and scheduled for surgical revision.
DISCUSSION/CONCLUSIONS:
Dilated cardiomyopathy (DCM), characterised by left ventricular dilatation and dysfunction, accounts for a significant proportion of systolic heart failure cases. Despite advancements in heart failure management, DCM patients remain at high risk for sudden cardiac death (SCD), making ICD implantation crucial. However, CIED placement carries risks of complications, including Twiddler's Syndrome. This condition can lead to lead dislodgement and device malfunction, resulting in inappropriate shocks and potential patient harm. In this case, a single-session extraction and re-implantation were successfully performed using a multidisciplinary approach, emphasising the importance of comprehensive management strategies to address such complications effectively. Regular follow-up showed no adverse events, highlighting the procedure's success and the potential benefits of using advanced antimicrobial adjuncts to prevent infections. This case underscores the need for awareness and standardised protocols for managing Twiddler's Syndrome to improve patient outcomes in the growing population of CIED recipients.
© 2024. The Author(s).
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Proteomic signatures improve risk prediction for common and rare diseases.
Nat Med2024 Jul;():. doi: 10.1038/s41591-024-03142-z.
Carrasco-Zanini Julia, Pietzner Maik, Davitte Jonathan, Surendran Praveen, Croteau-Chonka Damien C, Robins Chloe, Torralbo Ana, Tomlinson Christopher, Grünschläger Florian, Fitzpatrick Natalie, Ytsma Cai, Kanno Tokuwa, Gade Stephan, Freitag Daniel, Ziebell Frederik, Haas Simon, Denaxas Spiros, Betts Joanna C, Wareham Nicholas J, Hemingway Harry, Scott Robert A, Langenberg Claudia,
Abstract
For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, in 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements of ~3,000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81-6,038 cases). We then compared prediction models developed using proteomic data with models developed using either basic clinical information alone or clinical information combined with data from 37 clinical assays. The predictive performance of sparse models including as few as 5 to 20 proteins was superior to the performance of models developed using basic clinical information for 67 pathologically diverse diseases (median delta C-index?=?0.07; range?=?0.02-0.31). Sparse protein models further outperformed models developed using basic information combined with clinical assay data for 52 diseases, including multiple myeloma, non-Hodgkin lymphoma, motor neuron disease, pulmonary fibrosis and dilated cardiomyopathy. For multiple myeloma, single-cell RNA sequencing from bone marrow in newly diagnosed patients showed that four of the five predictor proteins were expressed specifically in plasma cells, consistent with the strong predictive power of these proteins. External replication of sparse protein models in the EPIC-Norfolk study showed good generalizability for prediction of the six diseases tested. These findings show that sparse plasma protein signatures, including both disease-specific proteins and protein predictors shared across several diseases, offer clinically useful prediction of common and rare diseases.
© 2024. The Author(s).
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Cardiac resynchronization therapy-defibrillator implantation with shock lead placement in the left bundle branch area: a case report.
Eur Heart J Case Rep2024 Jul;8(7):ytae323. doi: ytae323.
Yoshida Kenta, Yoshino Mitsuru, Kawabata Tokuma, Tasaka Hiroshi, Kadota Kazushige,
Abstract
BACKGROUND:
Cardiac resynchronization therapy (CRT) with biventricular pacing is a well-established therapy. Left bundle branch area pacing (LBBAP) is a safe technique providing physiological pacing, and LBBAP-optimized CRT (LOT-CRT) has been shown to provide better electrical resynchronization than traditional CRT. However, there are few reports on shock lead placement in the left bundle branch area (LBBA) during CRT-defibrillator (CRT-D) implantation.
CASE SUMMARY:
A 76-year-old woman with heart failure from dilated cardiomyopathy presented with left bundle branch block pattern (QRS duration, 160 ms). Left ventricular ejection fraction was 21%. Cardiac resynchronization therapy-defibrillator implantation was performed due to worsening symptoms. By reshaping the Agilis HisPro catheter and adding a septal curve, the shock lead was placed deep into the ventricular septum, narrowing QRS duration to 114 ms. Left ventricular activation time was 84 ms. A defibrillation threshold test confirmed successful treatment without adverse events. At 6-month follow-up, left ventricular ejection fraction improved from 21 to 63%, with the patient's condition improving from New York Heart Association class III to class I.
DISCUSSION:
It was reported that QRS narrowing in CRT was related to long-term mortality, and LOT-CRT further decreased QRS duration as compared with LBBP only or biventricular pacing and increased the response rate. Combining LBBAP with coronary sinus pacing can potentially achieve superior electrical resynchronization. Lack of a suitable tool for direct shock lead placement in LBBA necessitated additional LBBAP lead in conventional LOT-CRT. Our successful LOT-CRT-D procedure with minimal number of leads through Agilis HisPro catheter reshaping enabled direct LBBA shock lead placement.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Increased expression of human endogenous retrovirus K in endomyocardial biopsies from patients with cardiomyopathy - a transcriptomics meta-analysis.
BMC Genomics2024 Jul;25(1):707. doi: 707.
Heckmann Markus B, Finke Daniel, Sauerbrey Leander, Frey Norbert, Lehmann Lorenz H,
Abstract
Most studied, investigating transcriptional changes in myocardial biopsies focus on human genes. However, the presence and potential consequence of persistent expression of viral genes within the myocardium is unclear. The aim of the study was to analyze viral gene expression in RNAseq data from endomyocardial biopsies. The NCBI Bioproject library was screened for published projects that included bulk RNA sequencing data from endomyocardial biopsies from both healthy and diseased patients with a sample size greater than 20. Diseased patients with hypertrophic, dilated, and ischemic cardiomyopathies were included. A total of 507 patients with 507 samples from 6 bioprojects were included and mapped to the human genome (hg38). Unmappable sequences were extracted and mapped to an artificial 'super-virus' genome comprising 12,182 curated viral reference genomes. Subsequently, the sequences were reiteratively permutated and mapped again to account for randomness. In total, sequences from 68 distinct viruses were found, all of which were potentially human pathogenic. No increase in cardiotropic viruses was found in patients with dilated cardiomyopathy. However, the expression levels of the particle forming human endogenous retrovirus K were significantly increased (q?0.0003, ANOVA). Higher expression levels were associated with increased expression in mitochondrial pathways such as oxidative phosphorylation (p?0.0001). In Conclusion, expression of human endogenous retrovirus K is significantly increased in patients with dilated cardiomyopathy, which in turn was associated with transcriptional alterations in major cellular pathways.
© 2024. The Author(s).
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Pulmonary artery banding for cardiomyopathy in young children: First trial in China.
ESC Heart Fail2024 Jul;():. doi: 10.1002/ehf2.14978.
Dou Zheng, He Qiyu, Ma Kai, Wang Xu, Zeng Min, Pang Kunjing, Zhang Benqing, Rui Lu, Mao Fengqun, Yuan Jianhui, Wu Dongdong, Liu Yuze, Schranz Dietmar, Li Shoujun,
Abstract
AIMS:
Heritable dilated cardiomyopathy (DCM) or DCM associated with congenital or acquired left ventricular diseases carries a significant mortality risk. Pulmonary artery banding (PAB) has been proposed as an alternative to heart transplantation. This study aimed to delineate the clinical development, ventricular reverse remodelling, and functional regeneration of the dilated left ventricle, presenting as a pioneering approach in China.
METHODS AND RESULTS:
This prospective study was initiated in November 2021, involving paediatric patients with a significant dilated left ventricle and preserved right ventricle who underwent surgical PAB. The baseline characteristics and clinical information during follow-up were collected. Seven patients (five boys) with a median age of 240 (148, 1028) days have been included thus far. No procedural or follow-up mortality was observed. The modified Ross functional class improved from treatment to follow-up of 348 (200, 629) days, and the median left ventricular ejection fraction increased from 27.0 (15.0, 34.0) % before surgery to 61.0 (52.0, 68.0) % (P
CONCLUSIONS:
The application of PAB should adhere to strict criteria. Initial results are promising for infants and even toddlers with a dilated left ventricle and limited probability of spontaneous recovery. PAB can be an alternative when there is a shortage of donor transplants and assist devices, especially for low- and middle-income countries.
© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Ventricular assist device support in paediatric patients with restrictive cardiomyopathy - Clinical outcomes and haemodynamics.
Eur J Cardiothorac Surg2024 Jul;():. doi: ezae277.
Rohde Sofie, Miera Oliver, Sandica Eugen, Adorisio Rachele, Salas-Mera Diana, Wiedemann Dominik, Sliwka Joanna, Amodeo Antonio, Gollmann-Tepeköylü Can, Napoleone Carlo Pace, Angeli Emanuela, Veen Kevin, de By Theo, Meyns Bart,
Abstract
OBJECTIVES:
Restrictive cardiomyopathy is rare and is generally associated with worse clinical outcomes compared to other cardiomyopathies. Ventricular assist device support for these children is seldom applied and often hampered by the surgical difficulties.
METHODS:
All paediatric (
RESULTS:
Forty-four paediatric ventricular assist device-supported patients diagnosed with restricted cardiomyopathy were included, with a median age at implantation of 5.0?years. Twenty-six of the 44 patient with a restricted cardiomyopathy survived to transplantation (59.1%), 16 died (36.4%) and 2 are still on ongoing VAD support (4.5%) after a median duration of support of 95.5?days (IQR 33.3-217.8). Transplantation probability after 1 and 2?years of ventricular assist device support in patients with a restricted cardiomyopathy were comparable to patients with a dilated cardiomyopathy (52.3% vs 51.4% and 59.5% vs 60.1%, p?=?0.868). However, mortality probability was higher in the restricted cardiomyopathy cohort (35.8% vs 17.0% and 35.8% vs 19.0%, p?=?0.005). Adverse event rates were high (CVA in 31.8%, pump thrombosis in 29.5%, major bleeding 25.0%, eventual biventricular support in 59.1%). In the atrially cannulated group, CVA and pump thrombosis occurred in twice as much patients (21.1% vs 40.0%, p?=?0.595 and 15.8% vs 40.0%, p?=?0.464; probably non-significant due to the small numbers). Pulmonary arterial pressures improved after implantation of a ventricular assist device, and six patients who were initially labelled as ineligible due to pulmonary hypertension could eventually be transplanted.
CONCLUSIONS:
Ventricular assist device support in children with a restricted cardiomyopathy is rarely performed. Mortality and adverse event rates are high. On the other hand, survival to cardiac transplantation was 59.1% with all patients surviving the first 30?days after cardiac transplantation. Pulmonary arterial pressures improved while on support, potentially making cardiac transplantation a viable option for previously ineligible children.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Identification of senescence related hub genes and potential therapeutic compounds for dilated cardiomyopathy via comprehensive transcriptome analysis.
Comput Biol Med2024 Jul;179():108901. doi: 10.1016/j.compbiomed.2024.108901.
Du Chong, Wang Sibo, Shi Xinying, Jing Peng, Wang Hao, Wang Liansheng,
Abstract
BACKGROUND:
Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, the role of cellular senescence in DCM has not been fully elucidated. Here, we aimed to investigate senescence in DCM, identify senescence related characteristic genes, and explore the potential small molecule compounds for DCM treatment.
METHODS:
DCM-associated datasets and senescence-related genes were respectively obtained from Gene Expression Omnibus (GEO) database and CellAge database. The characteristic genes were identified through methods including weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and random forest. The expression of characteristic genes was verified in the mouse DCM model. Moreover, the CIBERSORT algorithm was applied to analyze immune characteristics of DCM. Finally, several therapeutic compounds were predicted by CMap analysis, and the potential mechanism of chlorogenic acid (CGA) was investigated by molecular docking and molecular dynamics simulation.
RESULTS:
Three DCM- and senescence-related characteristic genes (MME, GNMT and PLA2G2A) were ultimately identified through comprehensive transcriptome analysis, and were experimentally verified in the doxorubicin induced mouse DCM. Meanwhile, the established diagnostic model, derived from dataset analysis, showed ideal diagnostic performance for DCM. Immune cell infiltration analysis suggested dysregulation of inflammation in DCM, and the characteristic genes were significantly associated with invasive immune cells. Finally, based on the specific gene expression profile of DCM, several potential therapeutic compounds were predicted through CMap analysis. In addition, molecular docking and molecular dynamics simulations suggested that CGA could bind to the active pocket of MME protein.
CONCLUSION:
Our study presents three characteristic genes (MME, PLA2G2A, and GNMT) and a novel senescence-based diagnostic nomogram, and discusses potential therapeutic compounds, providing new insights into the diagnosis and treatment of DCM.
Copyright © 2024 Elsevier Ltd. All rights reserved.
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Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A.
Virol Sin2024 Jul;():. doi: S1995-820X(24)00113-5.
Dong Yanyan, Enze Shao , Li Siwei, Wang Ruiqi, Wang Dan, Wang Lixin, Yang Hong, He Yingxia, Luan Tian, Chen Yang, Wang Yao, Lin Lexun, Wang Yan, Zhong Zhaohua, Zhao Wenran,
Abstract
Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated cardiomyopathy. Group B coxsackievirus (CVB) is one of the leading causative pathogens of viral myocarditis, which primarily affects children and young adults. Due to the lack of vaccines, the development of antiviral medicines is crucial to controlling CVB infection and the progression of myocarditis. In this study, we investigated the antiviral effect of baicalein, a flavonoid extracted from Scutellaria baicaleinsis. Our results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected cells. In addition, significant reductions in viral protein 3D, viral RNA, and viral particles were observed in CVB3-infected cells treated with baicalein. We found that baicalein exerted its inhibitory effect in the early stages of CVB3 infection. Baicalein also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 infection. Our study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease 2A. Taken together, our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.
Copyright © 2024 The Authors. Publishing services by Elsevier B.V. All rights reserved.
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