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Nature Reviews. Disease Primers May 2019Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by... (Review)
Review
Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter-defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.
Topics: Autoimmunity; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Echocardiography; Electrocardiography; Heart Failure; Humans; Inflammation; Magnetic Resonance Imaging; Prognosis; Quality of Life; Sex Factors
PubMed: 31073128
DOI: 10.1038/s41572-019-0084-1 -
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 -
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 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 -
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 -
Circulation Research Sep 2017Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetrical with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients and can be provoked in another third. The histological features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis. The hypertrophy is also frequently associated with left ventricular diastolic dysfunction. In the majority of patients, HCM has a relatively benign course. However, HCM is also an important cause of sudden cardiac death, particularly in adolescents and young adults. Nonsustained ventricular tachycardia, syncope, a family history of sudden cardiac death, and severe cardiac hypertrophy are major risk factors for sudden cardiac death. This complication can usually be averted by implantation of a cardioverter-defibrillator in appropriate high-risk patients. Atrial fibrillation is also a common complication and is not well tolerated. Mutations in over a dozen genes encoding sarcomere-associated proteins cause HCM. and , encoding β-myosin heavy chain and myosin-binding protein C, respectively, are the 2 most common genes involved, together accounting for ≈50% of the HCM families. In ≈40% of HCM patients, the causal genes remain to be identified. Mutations in genes responsible for storage diseases also cause a phenotype resembling HCM (genocopy or phenocopy). The routine applications of genetic testing and preclinical identification of family members represents an important advance. The genetic discoveries have enhanced understanding of the molecular pathogenesis of HCM and have stimulated efforts designed to identify new therapeutic agents.
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, Left
PubMed: 28912181
DOI: 10.1161/CIRCRESAHA.117.311059 -
Journal of Animal Science Jun 2020Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is... (Review)
Review
Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is commonly associated with a genetic predisposition in certain dog breeds and can also occur secondary to other diseases and nutritional deficiencies. Recent communications in veterinary journals have discussed a potential relationship between grain-free and/or novel protein diets to DCM, citing a subjective increase in DCM in dog breeds that are not known to have a genetic predisposition for the disease. This literature review describes clinical presentations of DCM, common sequelae, treatment and preventative measures, histopathologic features, and a discussion of the varied etiological origins of the disease. In addition, current literature limitations are addressed, in order to ascertain multiple variables leading to the development of DCM. Future studies are needed to evaluate one variable at a time and to minimize confounding variables and speculation. Furthermore, to prevent sampling bias with the current FDA reports, the veterinary community should be asked to provide information for all cases of DCM in dogs. This should include cases during the same time period, regardless of the practitioner's proposed etiology, due to no definitive association between diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs. In summary, in order to determine if certain ingredients, categories of diets, or manufacturing processes are related to an increased risk of DCM, further studies investigating these variables are necessary.
Topics: Animals; Breeding; Cardiomyopathy, Dilated; Diet; Dog Diseases; Dogs; Edible Grain
PubMed: 32542359
DOI: 10.1093/jas/skaa155 -
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 -
Journal of the American College of... Sep 2017Heart rate reduction as a therapeutic target has been investigated in adults with heart failure (HF). Ivabradine has shown promising efficacy, but has not been evaluated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Heart rate reduction as a therapeutic target has been investigated in adults with heart failure (HF). Ivabradine has shown promising efficacy, but has not been evaluated in children. Currently, treatment recommendations for chronic pediatric HF are based mainly on chronic HF guidelines for adults.
OBJECTIVES
The authors explored the dose-response relationship of ivabradine in children with dilated cardiomyopathy and symptomatic chronic HF. The primary endpoint was ≥20% reduction in heart rate from baseline without inducing bradycardia or symptoms.
METHODS
This was a randomized, double-blind, placebo-controlled, phase II/III study with 12 months of follow-up. Children (n = 116) receiving stable HF therapy were randomized to either ivabradine or placebo. After an initial titration period, the dose was adjusted to attain the primary endpoint. Left ventricular function (echocardiography), clinical status (New York Heart Association functional class or Ross class), N-terminal pro-B-type natriuretic peptide, and quality of life (QOL) were assessed.
RESULTS
The primary endpoint was reached by 51 of 73 children taking ivabradine (70%) versus 5 of 41 taking placebo (12%) at varying doses (odds ratio: 17.24; p < 0.0001). Between baseline and 12 months, there was a greater increase in left ventricular ejection fraction in patients taking ivabradine than placebo (13.5% vs. 6.9%; p = 0.024). New York Heart Association functional class or Ross class improved more with ivabradine at 12 months than placebo (38% vs. 25%; p = 0.24). There was a trend toward improvement in QOL for ivabradine versus placebo (p = 0.053). N-terminal pro-B-type natriuretic peptide levels decreased similarly in both groups. Adverse events were reported at similar frequencies for ivabradine and placebo.
CONCLUSIONS
Ivabradine safely reduced the resting heart rate of children with chronic HF and dilated cardiomyopathy. Ivabradine's effect on heart rate was variable, highlighting the importance of dose titration. Ivabradine treatment improved left ventricular ejection fraction, and clinical status and QOL showed favorable trends. (Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure from ages 6 months to 18 years; ISRCTN60567801).
Topics: Adolescent; Benzazepines; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Ivabradine; Male; Quality of Life; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left
PubMed: 28859790
DOI: 10.1016/j.jacc.2017.07.725