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According to 2008 ESC classification, the term cardiomyopathy includes the categories of dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), and restricted cardiomyopathy (RCM). Cardiomyopathies are classified as genetic and nongenetic subcategories. In many cases, a definite causative gene mutation or an acquired cause can be identified, respectively.
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Left ventricular enlargement and dysfunction are fundamental components of dilated cardiomyopathy. Dilated cardiomyopathy is a major cause of heart failure and cardiac transplantation. A wide variety of etiologies underlie acquired and familial DCM. Familial disease is reported in 20% to 35% of cases. A genetic substrate is recognized in at least 3...
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... of etiology in the categories of genetic, mixed, and acquired disease. At the second level, the hypertrophic, arrhythmogenic, LV noncompaction, dilated, and restrictive cardiomyopathy subgroups are recognized. 7 The European Society of Cardiology introduced a clinically oriented system focusing more on the morphological and functional features 1 (Fig. ...
Similar publications
Dilated cardiomyopathy (DCM) is considered a predominantly inherited disease in dogs. Recent reports suggest an increased incidence of DCM in atypical breeds eating grain-free and/or legume-rich diets. Emerging communications have noted that there is an apparent increase in the DCM incidence rate in the United States (US). However, little data rega...
Dilated cardiomyopathy (DCM) is a clinical syndrome
characterized by left ventricular dilatation and contractile
dysfunction. It is the most common cause of heart failure
in young adults. The advent of next-generation sequencing
has contributed to the discovery of a large amount of
genomic data related to DCM. Mutations involving genes
that encode...
Background
The EPIC study defines criteria, including echocardiographic assessments of left atrial to aortic ratio (LA: Ao) and left ventricular internal diameter in diastole normalized for body weight (LVIDdN), for dogs with preclinical myxomatous mitral valve disease (MMVD) likely to benefit from pimobendan therapy. Access to echocardiography by...
Background
The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise b...
Citations
... Moreover, adult males seem to be more frequently affected than adult females [2,3]. Approximately 20 to 35%, or potentially up to 50% of patient cases, could be attributed to the genetic basis [4]. More than 100 genes have been associated with dilated cardiomyopathies [5][6][7][8]. ...
Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy.
... The most common etiology of congestive heart failure is ischemic cardiomyopathy, which arises from the presence of "coronary artery disease (CAD)". Nevertheless, ischemic cardiomyopathy is categorized as an independent disease entity and is solely recognized as a potential cause of dilated cardiomyopathy (DCM) in cases where there is a hidden disease in people without established "coronary artery disease (CAD)" [6,7]. ...
... Based on whole exome sequencing on multiple familial cases of Chagas disease, we have previously identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct nuclear-encoded genes, from which 20 were mitochondrial or inflammation-relatedmost of the latter involved in proinflammatory cytokine production (42). So, mitochondrial 4 dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants which increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium. Mutations in the mitochondrial genome accumulate over time in organs suffering mitochondrial dysfunction, resulting in decreased energy production and reactive oxygen species (ROS) overproduction. ...
Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central, South America. Thirty percent of the cases evolve into chronic cardiomyopathy (CCC) with worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate and severe CCC patients. MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with Brazilian healthy individuals. The European lineage is associated to protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. By mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of Chronic Chagas disease Cardiomyopathy.
... Primary dilated cardiomyopathy (DCM) is the presence of left ventricular dilatation with severely reduced systolic function in the absence of a cause. The hallmark of the disease is the left ventricular (LV) dilatation with systolic dysfunction [1]. DCM is the most common cause of cardiomyopathy in children with considerable morbidity and mortality [2]. ...
We aimed to detect residual cardiac dysfunction-if any-in children with recovered primary dilated cardiomyopathy (DCM) by using the left ventricular (LV) layer-specific myocardial strains. Fifty children with recovered primary DCM both clinically and echocardiographically were included as the patient group. Fifty healthy children of matched age and sex served as the control group. Echocardiographic evaluation was performed for all included children in the form of conventional echocardiography, tissue Doppler imaging (TDI), two-dimensional speckle tracking echocardiography (2D-STE), and LV layer-specific myocardial strain. Both LV systolic and diastolic functions measured by conventional echocardiography were similar in children with recovered DCM and the control group. There was a significant reduction in LV systolic and dias-tolic functions measured by TDI in the patient group. Moreover, there was a significant reduction of LV global longitudinal systolic strain (GLSS) by 2D-STE in children with recovered DCM. Interestingly, there was a significant reduction of LV layer-specific myocardial strain from endocardium to epicardium in children with recovered DCM compared to the healthy control. There was a significant positive correlation between different layer-specific myocardial strains and LV GLSS, LV ejection fraction, and LV peak systolic velocity. Left ventricular layer-specific myocardial strain can be a promising tool for early identifications of LV dysfunction in children with DCM. Subtle cardiac dysfunction is present in patients with recovered DCM, so long-term follow-up is recommended in these patients.
... The aetiologies resulting in DCM are various, about 50% of them are considered idiopathic. Surprisingly, the most idiopathic causes are related to genetic factors, and research shows that even those individuals, affected by non-idiopathic causes, seem to be associated the influence of a genetic background [47][48][49] . ...
Dilated cardiomyopathy (DCM), one of the most common types of cardiomyopathies has a heterogeneous nature and can be seen in Mendelian forms. Next Generation Sequencing is a powerful tool for identifying novel variants in monogenic disorders. We used whole-exome sequencing (WES) and Sanger sequencing techniques to identify the causative mutation of DCM in an Iranian pedigree. We found a novel variant in the GATA6 gene, leading to substituting Histidine by Tyrosine at position 329, observed in all affected family members in the pedigree, whereas it was not established in any of the unaffected ones. We hypothesized that the H329Y mutation may be causative for the familial pattern of DCM in this family. The predicted models of GATA6 and H329Y showed the high quality according to PROCHECK and ERRAT. Nonetheless, simulation results revealed that the protein stability decreased after mutation, while the flexibility may have been increased. Hence, the mutation led to the increased compactness of GATA6 . Overall, these data indicated that the mutation could affect the protein structure, which may be related to the functional impairment of GATA6 upon H329Y mutation, likewise their involvement in pathologies. Further functional investigations would help elucidating the exact mechanism.
... With the development of genetics, the concept of directing the treatment according to the genotype seems promising [121]. Τhe understanding of gene-specific pathogenetic mechanisms and the unraveling of the functional effects of each variant should dictate different therapeutic strategies. ...
Dilated cardiomyopathy (DCM) is an umbrella term entailing a wide variety of genetic and non-genetic etiologies, leading to left ventricular systolic dysfunction and dilatation, not explained by abnormal loading conditions or coronary artery disease. The clinical presentation can vary from asymptomatic to heart failure symptoms or sudden cardiac death (SCD) even in previously asymptomatic individuals. In the last 2 decades, there has been striking progress in the understanding of the complex genetic basis of DCM, with the discovery of additional genes and genotype–phenotype correlation studies. Rigorous clinical work-up of DCM patients, meticulous family screening, and the implementation of advanced imaging techniques pave the way for a more efficient and earlier diagnosis as well as more precise indications for implantable cardioverter defibrillator implantation and prevention of SCD. In the era of precision medicine, genotype-directed therapies have started to emerge. In this review, we focus on updates of the genetic background of DCM, characteristic phenotypes caused by recently described pathogenic variants, specific indications for prevention of SCD in those individuals and genotype-directed treatments under development. Finally, the latest developments in distinguishing athletic heart syndrome from subclinical DCM are described.
... Like canine DCM, the clinical phenotype, even within familial DCM, is incredibly heterogeneous. In addition to the major disease-inducing genes, the variable penetrance and expression of the disorder, as well as different sex susceptibilities, suggest that modifier genes could affect the severity and onset of DCM [59]. ...
Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.
... Aging, in addition to anemia caused by HF, has been imposed on the patient, and this is probably why we are witnessing more disorders due to HF at older ages (42,43). Several studies have shown that HF can be a multifactorial and sometimes complex disorder (44,45), and the role of genetic and hereditary factors in the etiology of HF has been confirmed today (46), and as mentioned earlier, there are patients with HF, whose disorder can only be justified by genetic and congenital pattern and anemia cannot be considered a cause for their disorder (47,48). Also, in our study, it was found that increasing the severity of anemia is likely to worsen the HF in patients and improve their mortality rate (Table 3). ...
Background: Heart failure (HF) is recognized as a structural and functional heart complication. Many studies have revealed that anemia plays an ambiguous role in this complication and can be a significant prognostic parameter in HF. In our trial, for clarification of this issue, the relationship between HF and anemia was studied. Methods: In this case-control study, 273 patients admitted to the CCU and post-CCU wards of Dezful Hospital, who were selected by the available sampling method, were studied. In this investigation, among 273 patients with HF, hematological, biochemical, and heart functional parameters were assessed and compared with 89 healthy volunteers. Consequently, the correlation between hematological parameters and functional heart parameters in the patients was evaluated via Pearson’s correlation coefficient. Results: The study subjects were tried to have similar conditions regarding their demographic characteristics. The mean age of the included participants was 53.68 ± 2.17 years. Our data revealed that HF occurs mainly at the age of 50 to 70 years, and patients had an 8.7% mortality risk. Hematocrit (HCT) had a significant reduction in the HF group in comparison to the normal range (P-value < 0.05), and HCT level in healthy subjects (P-value 0.02). Further, anemia is positively correlated with HF mortality rate and severity of HF indices in patients (P-value = 0.01). Conclusions: The results of our study, consistent with other previous studies, showed that HF patients have a low HCT level, and this reduction is associated with a marked decline in health status indices in HF patients. Also, our results revealed that patients with the lowest level of HCT are at high risk for HF symptoms.
... With the development of genetics, the concept of genotypeguided therapy is promising. At present, different treatment strategies should be adopted for different genetic changes (19). Combined with relevant conclusions in this study, we are expected to carry out personalized management of precision medicine for each DCM patients. ...
Background
The etiology of dilated cardiomyopathy (DCM) is unclear. Bioinformatics algorithms may help to explore the underlying mechanisms. Therefore, we aimed to screen diagnostic biomarkers and identify the landscape of immune infiltration in DCM.
Methods
First, the CIBERSORT algorithm was used to excavate the proportion of immune-infiltration cells in DCM and normal myocardial tissues. Meanwhile, the Pearson analysis and principal component analysis (PCA) were used to identify immune heterogeneity in different tissues. The Wilcoxon test, LASSO regression, and machine learning method were conducted to identify the hub immune cells. In addition, the differentially expressed genes (DEGs) were screened by the limma package, and DEGs were analyzed for functional enrichment. In the protein–protein interaction (PPI) network, multiple algorithms were used to calculate the score of each DEG for screening the hub genes. Subsequently, external datasets were used to further validate the expression of hub genes, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Finally, we examined the expression of hub biomarkers in animal models.
Results
A total of 108 DEGs were screened, and these genes may be related to biological processes such as cytolysis, positive regulation of cytokine secretion, etc. Two types of hub immune cells [activated natural killer (NK) cells and eosinophils] and four hub genes ( ASPN, CD163, IL10 , and LUM ) were identified in DCM myocardial tissues. CD163 was verified to have the capability to diagnose DCM with the most excellent specificity and sensitivity. It is worth mentioning that the combined CD163 and eosinophils may have better diagnostic efficacy. Moreover, the correlation analysis showed CD163 was negatively correlated with activated NK cells. Finally, the results of the mice model also indicated that CD163 might be involved in the occurrence of DCM.
Conclusion
ASPN, CD163, IL10 , and LUM may have a potential predictive ability for DCM, and especially CD163 showed the most robust efficacy. Furthermore, activated NK cells and eosinophils may relate to the occurrence of DCM.
... Dilated cardiomyopathy has symptoms of heart failure in 80% of patients 6 . In achieving optimal treatment strategies and predicting prognosis in clinical practice, it is 8 . DCM is a single entity and a non-specific phenotype, the typical response of the myocardium to the insult of genetic and environment 9 . ...
... Cases of DCM occur in 21-36% of people who consume alcohol, primarily in highincome countries 6 . History of heavy alcohol consumption (>80-100 g/day for over five years), genetic, race, behavioral factors can influence the occurrence of clinical heart failure and alcohol intake 8,17 . Alcoholic DCM, as a result of heavy alcohol consumption, causes structural damage, mainly affecting cardiomyocytes to become apoptotic 11 . ...
... Echocardiography can show "red flags" associated with a specific etiology 8 . In DCM conventional two-dimensional (2D) transthoracic echocardiographic (TTE) findings are left spherical ventricular dilatation, average/reduced wall thickness, reduced systolic movement, and endocardium inside. ...
p> Pendahuluan : Kardiomiopati dilatasi merupakan salah satu penyebab gagal jantung, patogenesisnya sangat bervariasi, mulai dari genetik, infeksi, autoimun, dan kardiotoksin. Melakukan pemeriksaan diagnostik mengenai penyebab yang mendasari akan lebih memahami bagaimana kardiomiopati berkembang. Manajemen juga bervariasi secara signifikan sesuai dengan individu. Tujuan dari studi ini adalah untuk membahas strategi diagnosis dan manajemen penyebab yang mendasari dalam memperbaiki kardiomiopati dilatasi untuk mencapai hasil yang lebih baik dan pengobatan yang optimal.
Metode : Proses pencarian artikel diakses pada tiga database elektronik, PubMed, PLOS ONE, dan Google Scholar. Data pada artikel sebelumnya terkait dengan teori dasar diagnosis dan manajemen kardiomiopati dilatasi. Kata kunci yang digunakan dalam pencarian artikel jurnal adalah kardiomiopati dilatasi, gagal jantung, diagnosis, manajemen, dan genetik. Kriteria penulisan artikel ini adalah tahun publikasi dalam 2011 hingga 2021, dalam bahasa Inggris, artikel teks lengkap, dan membahas diagnosis dan manajemen kardiomiopati dilatasi.
Hasil : Diperoleh dua puluh tujuh artikel sesuai dengan kriteria inklusi dan dibahas lebih lanjut dalam diagnosis dan pengelolaan kardiomiopati dilatasi.
Kesimpulan : Kardiomiopati dilatasi merupakan penyakit progresif pada otot jantung, terutama pembesaran dan pelebaran ventrikel. Proses penyakit ini dominan dikarenakan faktor genetik. Diagnosis kardiomiopati dilatasi tidak hanya dapat dilihat dari manifestasinya, tetapi memerlukan pencitraan dalam ekokardiografi, elektrokardiogram, resonansi magnetik kardio, pengujian genetik, dan biopsi endomiokardial. Mencapai manajemen yang optimal diperlukan untuk mencegah penurunan tingkat fraksi ejeksi, mengurangi perawatan pada pasien gagal jantung, dan mengurangi risiko kematian kardiovaskular. </p
