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Lancet (London, England) Sep 2023Dilated cardiomyopathy is conventionally defined as the presence of left ventricular or biventricular dilatation or systolic dysfunction in the absence of abnormal... (Review)
Review
Dilated cardiomyopathy is conventionally defined as the presence of left ventricular or biventricular dilatation or systolic dysfunction in the absence of abnormal loading conditions (eg, primary valve disease) or significant coronary artery disease sufficient to cause ventricular remodelling. This definition has been recognised as overly restrictive, as left ventricular hypokinesis without dilation could be the initial presentation of dilated cardiomyopathy. The causes of dilated cardiomyopathy comprise genetic (primary dilated cardiomyopathy) or acquired factors (secondary dilated cardiomyopathy). Acquired factors include infections, toxins, cancer treatment, endocrinopathies, pregnancy, tachyarrhythmias, and immune-mediated diseases. 5-15% of patients with acquired dilated cardiomyopathy harbour a likely pathogenic or pathogenic gene variant (ie, gene mutation). Therefore, the diagnostic tests and therapeutic approach should always consider both genetic and acquired factors. This Seminar will focus on the current multidimensional diagnostic and therapeutic approach and discuss the underlying pathophysiology that could drive future treatments aiming to repair or replace the existing gene mutation, or target the specific inflammatory, metabolic, or pro-fibrotic drivers of genetic or acquired dilated cardiomyopathy.
Topics: Female; Pregnancy; Humans; Cardiomyopathy, Dilated; Causality; Catheters; Coronary Artery Disease; Mutation
PubMed: 37716772
DOI: 10.1016/S0140-6736(23)01241-2 -
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 -
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 -
Heart, Lung & Circulation Apr 2020Advances in human genome sequencing have re-invigorated genetics studies of dilated cardiomyopathy (DCM), facilitating genetic testing and clinical applications. With a... (Review)
Review
Advances in human genome sequencing have re-invigorated genetics studies of dilated cardiomyopathy (DCM), facilitating genetic testing and clinical applications. With a range of genetic testing options now available, new challenges arise for data interpretation and identifying single pathogenic variants from the many thousands of rare variants present in every individual. There is accumulating evidence that genetic factors have an important role in the pathogenesis of DCM. However, although more than 100 genes have been implicated to date, the sensitivity of genetic testing, even in familial disease, is only ∼25-40%. As more patients are genotyped, nuanced information about disease phenotypes is emerging including variability in age of onset and penetrance of DCM, as well as additional cardiac and extra-cardiac features. Genotype-phenotype correlations have also identified a subset of genes that can be highly arrhythmogenic or show frequent progression to heart failure. Recognition of variants in these genes is important as this may impact on the timing of implantable cardioverter-defibrillators or heart transplantation. Finding a causative variant in a patient with DCM allows predictive testing of family members and provides an opportunity for preventative intervention. Diagnostic imaging modalities such as speckle-tracking echocardiography and cardiac magnetic resonance imaging are increasingly being used to detect and monitor pre-clinical ventricular dysfunction in asymptomatic variant carriers. Although there are several examples of successful genotype-based therapy, optimal strategies for implementation of precision medicine in familial DCM remain to be determined. Identification of modifiable co-morbidities and lifestyle factors that exacerbate or protect against DCM development in genetically-predisposed individuals remains a key component of family management.
Topics: Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Genetic Predisposition to Disease; Genetic Testing; Humans; Mutation
PubMed: 31974027
DOI: 10.1016/j.hlc.2019.11.018 -
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 -
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 -
Nature Reviews. Disease Primers May 2019
Topics: Autoimmune Diseases; Cardiomyopathy, Dilated; Humans; Quality of Life
PubMed: 31073134
DOI: 10.1038/s41572-019-0088-x -
Journal of Internal Medicine Jan 2023Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is... (Review)
Review
Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiology-specific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immune-mediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy.
Topics: Humans; Cardiomyopathy, Dilated; Myocarditis; Heart; Arrhythmias, Cardiac; Inflammation
PubMed: 36030368
DOI: 10.1111/joim.13556 -
European Heart Journal Jun 2016In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap... (Review)
Review
Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.
In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
Topics: Cardiomyopathies; Cardiomyopathy, Dilated; Diagnosis, Differential; Early Diagnosis; Humans; Multimodal Imaging; Myocarditis; Pedigree; Risk Factors
PubMed: 26792875
DOI: 10.1093/eurheartj/ehv727