Cardiogenetics最新文献

{"title":"Pathogenesis, Diagnosis and Risk Stratification in Arrhythmogenic Cardiomyopathy","authors":"Maria Teresa Florio, Filomena Boccia, E. Vetrano, M. Borrelli, T. Gossios, G. Palmiero","doi":"10.3390/cardiogenetics11040025","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040025","url":null,"abstract":"Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial disease associated with sudden cardiac death (SCD). It is most frequently caused by mutations in genes encoding desmosomal proteins. However, there is growing evidence that ACM is not exclusively a desmosome disease but rather appears to be a disease of the connexoma. Fibroadipose replacement of the right ventricle (RV) had long been the hallmark of ACM, although biventricular involvement or predominant involvement of the left ventricle (LD-ACM) is increasingly found, raising the challenge of differential diagnosis with arrhythmogenic dilated cardiomyopathy (a-DCM). A-DCM, ACM, and LD-ACM are increasingly acknowledged as a single nosological entity, the hallmark of which is electrical instability. Our aim was to analyze the complex molecular mechanisms underlying arrhythmogenic cardiomyopathies, outlining the role of inflammation and autoimmunity in disease pathophysiology. Secondly, we present the clinical tools used in the clinical diagnosis of ACM. Focusing on the challenge of defining the risk of sudden death in this clinical setting, we present available risk stratification strategies. Lastly, we summarize the role of genetics and imaging in risk stratification, guiding through the appropriate patient selection for ICD implantation.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43179337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease","authors":"Federica Amodio, M. Caiazza, F. Fimiani, P. Calabrò, G. Limongelli","doi":"10.3390/cardiogenetics11040023","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040023","url":null,"abstract":"MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49129862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arrhythmogenic Cardiomyopathy—Further Insight into the Clinical Spectrum of Desmoplakin Disease","authors":"J. Simpson, J. Anusas, Denise Oxnard, S. Wright, R. McGowan, C. Coats","doi":"10.3390/cardiogenetics11040022","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040022","url":null,"abstract":"Arrhythmogenic cardiomyopathy is a familial heart muscle disease characterized by structural, electrical, and pathological abnormalities. Recognition of left ventricular (LV) involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC) has led to the newer term of arrhythmogenic cardiomyopathy (ACM). We report on a family with autosomal dominant desmoplakin (DSP) related ACM to illustrate the broad clinical spectrum of disease. The importance of evaluation of relatives with cardiac magnetic resonance imaging and consideration of genetic testing in the absence of Task Force diagnostic criteria is discussed. The practical and ethical issues of access to the Guthrie collection for deoxyribonucleic acid (DNA) testing are considered.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47859416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of ABC Transporter Gene Expression in Atherosclerosis","authors":"S. Kotlyarov, A. Kotlyarova","doi":"10.3390/cardiogenetics11040021","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040021","url":null,"abstract":"ABC transporters are a large family of membrane proteins that transport chemically diverse substrates across the cell membrane. Disruption of transport mechanisms mediated by ABC transporters causes the development of various diseases, including atherosclerosis. Methods: A bioinformatic analysis of a dataset from Gene Expression Omnibus (GEO) was performed. A GEO dataset containing data on gene expression levels in samples of atherosclerotic lesions and control arteries without atherosclerotic lesions from carotid, femoral, and infrapopliteal arteries was used for analysis. To evaluate differentially expressed genes, a bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2) and the GEO2R and Phantasus tools (v. 1.11.0). Results: The obtained data indicate the differential expression of many ABC transporters belonging to different subfamilies. The differential expressions of ABC transporter genes involved in lipid transport, mechanisms of multidrug resistance, and mechanisms of ion exchange are shown. Differences in the expression of transporters in tissue samples from different arteries are established. Conclusions: The expression of ABC transporter genes demonstrates differences in atherosclerotic samples and normal arteries, which may indicate the involvement of transporters in the pathogenesis of atherosclerosis.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48749170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azygos Vein ICD Lead Implantation Lowers Defibrillation Threshold in a Patient with Hypertrophic Cardiomyopathy","authors":"G. Quarta, P. Ferrari, A. Giammarresi, G. Malanchini, C. Leidi, M. Senni, P. De Filippo","doi":"10.3390/cardiogenetics11040019","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040019","url":null,"abstract":"A 14-year-old boy with hypertrophic cardiomyopathy (HCM) diagnosed at the age of 1 year and with massive left ventricular hypertrophy suffered an episode of ventricular fibrillation during mild effort. He underwent a dual-chamber implantable cardioverter defibrillator (ICD) implantation. The defibrillation threshold testing (DFT) was ineffective. Subcutaneous multi-coli arrays tunneled into the left postero-lateral position and connected to the superior vena cava (SVC) port of the dual-chamber ICD were added to increase the myocardial mass involved in the defibrillation shock pathway. A new DFT was unsuccessful. The patient was transferred to our hospital for myectomy. An epicardial defibrillation patch was placed on the left ventricular lateral wall, but again, DFT testing was ineffective using the right ventricular (RV) coil to lateral patch as shock pathway. Another epicardial defibrillation patch was then placed on the inferior wall. In this case, DFT testing was effective with a defibrillation pathway between the two patches and the can. In November 2015, a high shock impedance alarm was recorded through remote monitoring, thus compromising the safety of the ICD shock pathway. The patient underwent the implant of a new trans-venous defibrillation coil lead in the azygos vein. After few months, the patient developed symptomatic severe aortic regurgitation and underwent an aortic valve replacement. During the operation, DFT testing was performed and was successful. Our case illustrates that azygous vein ICD lead implantation is efficacious in HCM with massive hypertrophy and high DFT, and prompts further studies to systematically investigate its efficacy in this particular subgroup of the HCM population.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48326251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific Deletion of the FHA Domain Containing SLMAP3 Isoform in Postnatal Myocardium Has No Impact on Structure or Function","authors":"Taha Rehmani, Jana Mlynarova, J. Byers, M. Salih, B. Tuana","doi":"10.3390/cardiogenetics11040018","DOIUrl":"https://doi.org/10.3390/cardiogenetics11040018","url":null,"abstract":"Sarcolemmal membrane-associated proteins (SLMAPs) belong to the superfamily of tail-anchored membrane proteins known to regulate diverse biological processes, including protein trafficking and signal transduction. Mutations in SLMAP have been linked to Brugada and defective sodium channel Nav1.5 shuttling. The SLMAP gene is alternatively spliced to generate numerous isoforms, broadly defined as SLMAP1 (~35 kDa), SLMAP2 (~45 kDa) and SLMAP3 (~80–95 kDa), which are highly expressed in the myocardium. The SLMAP3 isoform exhibits ubiquitous expression carrying an FHA domain and is believed to negatively regulate Hippo signaling to dictate cell growth/death and differentiation. Using the αMHC-MerCreMer-flox system to target the SLMAP gene, we specifically deleted the SLMAP3 isoform in postnatal mouse hearts without any changes in the expression of SLMAP1/SLMAP2 isoforms. The in vivo analysis of mice with SLMAP3 cardiac deficiency revealed no significant changes to heart structure or function in young or aged mice without or with isoproterenol-induced stress. SLMAP3-deficient hearts revealed no obvious differences in cardiac size, function or hypertrophic response. Further, the molecular analysis indicated that SLMAP3 loss had a minor impact on sodium channel (Nav1.5) expression without affecting cardiac electrophysiology in postnatal myocardium. Surprisingly, the loss of SLMAP3 did not impact Hippo signaling in postnatal myocardium. We conclude that the FHA domain-containing SLMAP3 isoform has no impact on Hippo signaling or sodium channels in postnatal myocardium, which is able to function and respond normally to stress in its absence. Whether SLMAP1/SMAP2 isoforms can compensate for the loss of SLMAP3 in the affairs of the postnatal heart remains to be determined.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43571054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in MYBPC3 and MYH7 in Association with Brugada Type 1 ECG Pattern: Overlap between Brugada Syndrome and Hypertrophic Cardiomyopathy?","authors":"M. Farnè, C. Balla, A. Margutti, R. Selvatici, M. De Raffele, A. Di Domenico, P. Imbrici, E. De Maria, M. Biffi, M. Bertini, C. Rapezzi, A. Ferlini, F. Gualandi","doi":"10.3390/cardiogenetics11030016","DOIUrl":"https://doi.org/10.3390/cardiogenetics11030016","url":null,"abstract":"Brugada syndrome (BrS) is an inherited disorder with high allelic and genetic heterogeneity clinically characterized by typical coved-type ST segment elevation at the electrocardiogram (ECG), which may occur either spontaneously or after provocative drug testing. BrS is classically described as an arrhythmic condition occurring in a structurally normal heart and is associated with the risk of ventricular fibrillation and sudden cardiac death (SCD). We studied five patients with spontaneous or drug-induced type 1 ECG pattern, variably associated with symptoms and a positive family history through a Next Generation Sequencing panels approach, which includes genes of both channelopathies and cardiomyopathies. We identified variants in MYBPC3 and in MYH7, hypertrophic cardiomyopathy (HCM) genes (MYBPC3: p.Lys1065Glnfs*12 and c.1458-1G > A, MYH7: p.Arg783His, p.Val1213Met, p.Lys744Thr). Our data propose that Brugada type 1 ECG may be an early electrocardiographic marker of a concealed structural heart disease, possibly enlarging the genotypic overlap between Brugada syndrome and cardiomyopathies.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45992029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human <i>SMAD4</i> Genomic Variants Identified in Individuals with Heritable and Early-Onset Thoracic Aortic Disease.","authors":"Shreyas A Bhave, Dong-Chuan Guo, Stoyan Angelov, Michael J Bamshad, Deborah A Nickerson, Dianna Milewicz, Mary C Wallingford","doi":"10.3390/cardiogenetics11030015","DOIUrl":"10.3390/cardiogenetics11030015","url":null,"abstract":"<p><p>Thoracic aortic aneurysms (TAAs) that progress to acute thoracic aortic dissections (TADs) are life threatening vascular events that have been associated with altered transforming growth factor (TGF) β signaling. In addition to TAA, multiple genetic vascular disorders, including hereditary hemorrhagic telangiectasia (HHT), involve altered TGFβ signaling and vascular malformations. Due to the importance of TGFβ, genomic variant databases have been curated for activin receptor-like kinase 1 (<i>ALK1</i>) and endoglin (<i>ENG</i>). This case report details seven variants in <i>SMAD4</i> that are associated with either heritable or early onset aortic dissections and compares them to pathogenic exon variants in gnomAD v2.1.1. The TAA and TAD variants were identified through whole exome sequencing of 346 unrelated heritable thoracic aortic disease (HTAD) and 355 individuals of early onset (age ≤ 56 years old) of thoracic aortic dissection (ESTAD). An allele frequency filter of less than 0.05% was applied in the Genome Aggregation Database (gnomAD exome v2.1.1) with a combined annotation dependent depletion score (CADD) greater than 20. These seven variants also have a higher REVEL score (>0.2), indicating pathogenic potential. Further <i>in vivo</i> and <i>in vitro</i> analysis is needed to evaluate how these variants affect mRNA stability and SMAD4 protein activity in association with thoracic aortic disease.</p>","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"11 3","pages":"132-138"},"PeriodicalIF":0.6,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495981/pdf/nihms-1761633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33482499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biventricular Strain Imaging with Cardiac MRI in Genotyped and Histology Validated Amyloid Cardiomyopathy.","authors":"Abhinay Reddy,&nbsp;Vasvi Singh,&nbsp;Badri Karthikeyan,&nbsp;Leyi Jiang,&nbsp;Silva Kristo,&nbsp;Sharma Kattel,&nbsp;Ram Amuthan,&nbsp;Saraswati Pokharel,&nbsp;Umesh C Sharma","doi":"10.3390/cardiogenetics11030011","DOIUrl":"https://doi.org/10.3390/cardiogenetics11030011","url":null,"abstract":"<p><p>Cardiac amyloidosis (CA) is a common and potentially fatal infiltrative cardiomyopathy. Contrast-enhanced cardiac MRI (CMR) is used as a diagnostic tool. However, utility of CMR for the comprehensive analysis of biventricular strains and strain rates is not reported as extensively as echocardiography. In addition, RV strain analysis using CMR has not been described previously.</p><p><strong>Objectives: </strong>We sought to study the global and regional indices of biventricular strain and strain rates in endomyocardial biopsy (EMB)-proven, genotyped cases of CA.</p><p><strong>Methods: </strong>A database of 80 EMBs was curated from 2012 to 2019 based on histology. A total of 19 EMBs positive for CA were subjected to further tissue-characterization with histology, and compared with four normal biopsy specimens. Samples were genotyped for ATTR- or AL-subtypes. Five patients, with both echocardiography and contrast-enhanced CMR performed 72-h apart, were subjected to comprehensive analysis of biventricular strain and strain-rates.</p><p><strong>Results: </strong>Histology confirmed that the selected samples were indeed positive for cardiac amyloid. Echocardiography showed reduced global and regional left-ventricular (LV) longitudinal strain indices. CMR with tissue-characterization of LV showed global reductions in circumferential, radial and longitudinal strains and strain-rates, following a general trend with the echocardiographic findings. The basal right-ventricular (RV) segments had reduced circumferential strains with no changes in longitudinal strain.</p><p><strong>Conclusions: </strong>In addition to providing a clinical diagnosis of CA based on contrast clearance-dynamics, CMR can be a potent tool for accurate functional assessment of global and regional changes in strain and strain-rates involving both LV and RV. Further studies are warranted to validate and curate the strain imaging capacity of CMR in CA.</p>","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"11 3","pages":"98-110"},"PeriodicalIF":0.6,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39265587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Human Biospecimen Repository for Clinical and Molecular Investigation of Thoracic Aortopathy.","authors":"Courtney E Vujakovich,&nbsp;Benjamin J Landis","doi":"10.3390/cardiogenetics11030017","DOIUrl":"https://doi.org/10.3390/cardiogenetics11030017","url":null,"abstract":"<p><p>Thoracic aortic aneurysm (TAA) is a heritable aortopathy with significant morbidity and mortality, affecting children and adults. Genetic causes, pathobiological mechanisms, and prognostic markers are incompletely understood. In 2015, the Collaborative Human Aortopathy Repository (CHAR) was created to address these fundamental gaps. Patients with thoracic aortopathy, associated genetic diagnoses, or aortic valve disease are eligible for prospective enrollment. Family members and controls are also enrolled. Detailed clinical and family data are collected, and blood and aortic tissue biospecimens are processed for broad usage. A total of 1047 participants were enrolled. The mean age in 834 affected participants was 47 ± 22 (range <1 to 88) years and 580 were male (70%). A total of 156 (19%) were under the age of 21 years. Connective tissue diagnoses such as Marfan syndrome were present in 123 (15%). Unaffected participants included relatives (<i>N</i> = 176) and healthy aorta tissue controls (<i>N</i> = 37). Aortic or aortic valve biospecimens were acquired from over 290 and 110 participants, respectively. RNA and protein were extracted from cultured aortic smooth muscle cells (SMCs) for 90 participants. Over 1000 aliquots of aortic SMCs were cryopreserved. The CHAR's breadth, robust biospecimen processing, and phenotyping create a unique, multipronged resource to accelerate our understanding of human aortopathy.</p>","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"11 3","pages":"148-163"},"PeriodicalIF":0.6,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}