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Journal of the American College of... Jun 2016Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude... (Review)
Review
Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude alternative causes of left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. A significant proportion of DCM cases have an underlying genetic or inflammatory basis. Measurement of LV size and ejection fraction remain central to diagnosis, risk stratification, and treatment, but other aspects of cardiac remodeling inform prognosis and carry therapeutic implications. Assessment of myocardial fibrosis predicts both risk of sudden cardiac death and likelihood of LV functional recovery, and has significant potential to guide patient selection for cardioverter-defibrillator implantation. Detailed mitral valve assessment is likely to assume increasing importance with the emergence of percutaneous interventions for functional mitral regurgitation. Detection of pre-clinical DCM could substantially reduce morbidity and mortality by allowing early instigation of cardioprotective therapy.
Topics: Cardiomyopathy, Dilated; Humans; Phenotype
PubMed: 27339497
DOI: 10.1016/j.jacc.2016.03.590 -
Circulation Research Sep 2017Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic... (Review)
Review
Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.
Topics: Animals; Biopsy; Cardiac Imaging Techniques; Cardiomyopathy, Dilated; DNA Mutational Analysis; Genetic Markers; Genetic Predisposition to Disease; Humans; Molecular Diagnostic Techniques; Mutation; Myocardium; Phenotype; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Ventricular Function
PubMed: 28912180
DOI: 10.1161/CIRCRESAHA.116.309396 -
Heart Failure Reviews Jul 2022Dilated cardiomyopathy (DCM) is an umbrella term entailing a wide variety of genetic and non-genetic etiologies, leading to left ventricular systolic dysfunction and... (Review)
Review
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.
Topics: Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Humans; Phenotype; Precision Medicine; Ventricular Dysfunction, Left
PubMed: 34263412
DOI: 10.1007/s10741-021-10139-0 -
European Journal of Heart Failure Feb 2018Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with... (Review)
Review
Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.
Topics: Cardiomyopathy, Dilated; Disease Management; Early Diagnosis; Heart Failure; Humans; Prognosis
PubMed: 29271570
DOI: 10.1002/ejhf.1103 -
Circulation Research May 2022There is increasing evidence regarding the prevalence of genetic cardiomyopathies, for which arrhythmias may be the first presentation. Ventricular and atrial... (Review)
Review
There is increasing evidence regarding the prevalence of genetic cardiomyopathies, for which arrhythmias may be the first presentation. Ventricular and atrial arrhythmias presenting in the absence of known myocardial disease are often labelled as idiopathic, or lone. While ventricular arrhythmias are well-recognized as presentation for arrhythmogenic cardiomyopathy in the right ventricle, the scope of arrhythmogenic cardiomyopathy has broadened to include those with dominant left ventricular involvement, usually with a phenotype of dilated cardiomyopathy. In addition, careful evaluation for genetic cardiomyopathy is also warranted for patients presenting with frequent premature ventricular contractions, conduction system disease, and early onset atrial fibrillation, in which most detected genes are in the cardiomyopathy panels. Sudden death can occur early in the course of these genetic cardiomyopathies, for which risk is not adequately tracked by left ventricular ejection fraction. Only a few of the cardiomyopathy genotypes implicated in early sudden death are recognized in current indications for implantable cardioverter defibrillators which otherwise rely upon a left ventricular ejection fraction ≤0.35 in dilated cardiomyopathy. The genetic diagnoses impact other aspects of clinical management such as exercise prescription and pharmacological therapy of arrhythmias, and new therapies are coming into clinical investigation for specific genetic cardiomyopathies. The expansion of available genetic information and implications raises new challenges for genetic counseling, particularly with the family member who has no evidence of a cardiomyopathy phenotype and may face a potentially negative impact of a genetic diagnosis. Discussions of risk for both probands and relatives need to be tailored to their numeric literacy during shared decision-making. For patients presenting with arrhythmias or cardiomyopathy, extension of genetic testing and its implications will enable cascade screening, intervention to change the trajectory for specific genotype-phenotype profiles, and enable further development and evaluation of emerging targeted therapies.
Topics: Atrial Fibrillation; Cardiomyopathies; Cardiomyopathy, Dilated; Death, Sudden; Death, Sudden, Cardiac; Humans; Stroke Volume; Ventricular Function, Left
PubMed: 35617362
DOI: 10.1161/CIRCRESAHA.122.319835 -
Journal of Internal Medicine Oct 2019Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and, consecutively, contractile dysfunction. The causes of DCM are heterogeneous. DCM often... (Review)
Review
Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and, consecutively, contractile dysfunction. The causes of DCM are heterogeneous. DCM often results from myocarditis, exposure to alcohol, drugs or other toxins and metabolic or endocrine disturbances. In about 35% of patients, genetic mutations can be identified that usually involve genes responsible for cytoskeletal, sarcomere and nuclear envelope proteins. Due to its heterogeneity, a detailed diagnostic work-up is necessary to identify the specific underlying cause and exclude other conditions with phenotype overlap. Patients with DCM show typical systolic heart failure symptoms, but, with progress of the disease, diastolic dysfunction is present as well. Depending on the underlying pathology, DCM patients also become apparent through arrhythmias, thromboembolic events or cardiogenic shock. Disease progression and prognosis are mostly driven by disease severity and reverse remodelling within the heart. The worst prognosis is seen in patients with lowest ejection fractions or severe diastolic dysfunction, leading to terminal heart failure with subsequent need for left ventricular assist device implantation or heart transplantation. Guideline-based heart failure medication and device therapy reduces the frequency of heart failure hospitalizations and improves survival.
Topics: Age of Onset; Cardiomyopathy, Dilated; Diagnosis, Differential; Disease Progression; Heart Function Tests; Humans; Incidence; Mutation; Phenotype; Prevalence; Prognosis; Risk Factors
PubMed: 31132311
DOI: 10.1111/joim.12944 -
Revista Portuguesa de Cardiologia :... Mar 2017Cardiomyopathies are rare diseases of the heart muscle, of multiple causes, that manifest with various structural and functional phenotypes but are invariably associated... (Review)
Review
Cardiomyopathies are rare diseases of the heart muscle, of multiple causes, that manifest with various structural and functional phenotypes but are invariably associated with cardiac dysfunction. Dilated cardiomyopathy is the commonest cardiomyopathy in children, and the majority present before one year of age. Its etiology may be acquired or genetic. Myocarditis is an important cause and is responsible for the majority of acquired cases. Inherited (familial) forms of dilated cardiomyopathy may occur in 25-50% of patients. Echocardiographic and tissue Doppler studies are the basis for diagnosis of dilated cardiomyopathy in most patients. Marked dilatation of the left ventricle with global hypokinesis is the hallmark of the disease. This review will cover the classification, epidemiology and management of newborns with dilated cardiomyopathy. In particular, a comprehensive and up-to-date review of the genetic study of dilated cardiomyopathy and of detailed echocardiographic assessment of these patients will be presented.
Topics: Cardiomyopathy, Dilated; Humans; Infant, Newborn
PubMed: 28256370
DOI: 10.1016/j.repc.2016.10.007 -
Circulation. Arrhythmia and... Feb 2013
Review
Topics: Animals; Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Genetic Predisposition to Disease; Genetic Testing; Heart Failure; Humans; Phenotype; Treatment Outcome
PubMed: 23022708
DOI: 10.1161/CIRCEP.111.962050 -
Annals of Nutrition & Metabolism 2022Dilated cardiomyopathy (DCM) is the most common form of heart muscle disease characterized by progressive dilatation and ventricular dysfunction. Metabolomics is an... (Review)
Review
BACKGROUND
Dilated cardiomyopathy (DCM) is the most common form of heart muscle disease characterized by progressive dilatation and ventricular dysfunction. Metabolomics is an emerging and powerful discipline that provides a global information on the phenotype of mammalian systems via the study of endogenous and exogenous metabolites in cells, tissues, and biofluids. These studies aid in the identification of biomarkers to prevent diseases in later life or help to early detect onset of diseases as well as aiding in the elucidation of disease mechanisms.
SUMMARY
Metabolomics provides a unique opportunity to discover novel biomarkers for DCM. This review demonstrates evidence of metabolite-based biomarkers useful for predicting, diagnosing, and monitoring therapeutic interventions of DCM. Key metabolites identified as potential biomarkers for diagnosing DCM include acylcarnitines, succinic acid, malate, methylhistidine, aspartate, methionine, and phenylalanine. In terms of differentiating DCM from ischemic cardiomyopathy, potential biomarkers including 1-pyrroline-2-carboxylate, norvaline, lysophosphatidylinositol (16:0/0:0), phosphatidylglycerol, fatty acid esters of hydroxy fatty acid, and phosphatidylcholine were identified. Acylcarnitines, isoleucine and linoleic acid, and tryptophan were the main biomarkers to monitor treatment response to DCM. Mapping metabolites to metabolic pathways revealed dysregulation of branch-chain amino acid, glycolysis, tricarboxylic acid cycle, and triacylglycerol and pentose phosphate metabolism, which have the therapeutic potential for DCM. This review shows several limitations including the use of small sample sizes, lack of interpretation of age and sex differences in most studies, and the fact that studies have so far been limited to case-control study designs.
KEY MESSAGES
Metabolites have close proximity to disease phenotype. With recent advances in metabolomics field, potential biomarkers for DCM have been identified based on studies using different biological and metabolomics technologies. However, multicenter studies with larger populations that will lead to validation of these identified biomarkers to enable their clinical translation and utilization are still needed.
Topics: Animals; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Female; Humans; Linoleic Acid; Male; Mammals; Metabolomics
PubMed: 35472668
DOI: 10.1159/000524722 -
International Heart Journal Dec 2016A rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a...
A rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a single chamber pacemaker specific for animals that had a high frequency. However, the pacemaker used in this model is commercially unavailable. We developed a "pacing bigeminal" method using a commercially available dual-chamber (DDD) pacemaker to achieve high-frequency pacing. Twenty beagles were assigned to group A (n = 10) (pacing bigeminal method) and group B (n = 10) (traditional method). Echocardiographic measurements and electrocardiograms were obtained at baseline, at two weeks of pacing, and at 4 weeks of end pacing. LV anterior wall cardiac samples were obtained at 2 weeks of pacing and 4 weeks of end pacing for myocardial microscopic evaluation. Clinical manifestation and exposure time were also observed. After pacing for 10.5 ± 2.3 (714) days, the beagles in group B experienced heart failure, whereas in group A, only 7.9 ± 2.5 (5-12) days (P < 0.05) were needed to reach heart failure. Both methods could induce wide QRS duration, heart rate elevation, and myocardial microscopic changes (P > 0.05). In conclusion, this pacing bigeminal-induced heart failure method is feasible and can induce heart failure faster than the traditional method, which makes it a promising alternative method.
Topics: Animals; Cardiac Pacing, Artificial; Cardiomyopathy, Dilated; Disease Models, Animal; Dogs; Electrocardiography; Female; Male; Pacemaker, Artificial
PubMed: 27818474
DOI: 10.1536/ihj.16-043