الفهرس 
CARDIIOMYOPATHYOnly 14 pages are availabe for public view
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Abstract
Cardiomyopathy (CM) is a heterogeneous disease caused by a functional abnormality of the cardiac muscle. CM is of two major types, dilated and hypertrophic, and is further classified as either primary or secondary. Secondary CM is caused by extrinsic factors, including infection, ischemia, hypertension, and metabolic disorders. Primary CM is diagnosed when the extrinsic factors of secondary CM are absent.
It is a common cause of heart failure in children and the most common indication for heart transplantation in children older than one year.
Dilated CM (DCM) is the most common form of CM worldwide and has many causes. In 30% to 48% of patients, DCM is genetically inherited. Moreover, inflammatory disorders such as myocarditis, or toxic agents such as medications and alcohol can result in DCM. Of all the DCM cases, 20% to 48% have a family history of the disease.
Most CM patients have a family history of the disease; hence, CM is probably genetically transmitted. The genetic components are possibly mutations in the DNAspiral, the protein structure of many genes. Current research is being conducted to identify the specific genes that cause CM and to better understand how these genetic abnormalities contribute to the disease. However, CM is a complex disease, with multiple diverse genes producing extremely variable outcomes.
The symptoms of CM may differ in every child. Symptoms can be absent, mild, or severe. Heart murmurs are not always present in children with CM. Because CM is not easily detected on physical examination, it is often diagnosed in its later stages.
Infants and children with DCM generally present with signs of congestive heart failure. Tachypnea, labored breathing, poor appetite, and slow weight gain are common symptoms in infants. In older children, there may be signs of poor exercise tolerance and gastrointestinal distress. In more severe cases, patients may experience syncope, arrhythmias, or sudden cardiac death. Another sign of DCM is greater dilation and a more spherical appearance of the left ventricle than usual, with raised wall stress and depressed systolic function. In addition, mitral regurgitation and ventricular arrhythmias can also develop. In the most severe cases, affected individuals present with symptoms and signs of heart failure.
Echocardiography is the most informative noninvasive test for diagnosing and classifying CM, and determining the degree of dysfunction in the heart muscle. Echocardiographic findings include left ventricular dilation and systolic dysfunction, with or without mitral regurgitation. In addition, pericardial effusion, especially in myocarditis and heart rhythm irregularities, can be observed.
Approximately one third of patients with DCM die of the disease, one third continue to have chronic heart failure requiring therapy, and one third of patients experience improvement in their condition. Causes of death include heart failure, ventricular arrhythmias, and transplantation-related complications (less common).
Children with underlying muscle disorders with progressive dilatation of the heart and worsening heart failure have a worse prognosis compared with patients with idiopathic DCM. If a treatable cause is discovered, prognosis is better. A history of viral illness in the three months before onset may suggest a better prognosis. Prognosis is worst for cardiomyopathy secondary to storage diseases that do not have effective therapy.
Initial therapy in dilated cardiomyopathy (DCM) is largely directed at the symptoms of the underlying heart failure. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers are used.
Perform general supportive measures in patients with DCM during acute-stage management, including endotracheal intubation and mechanical ventilation, vasoactive infusions, and fluid/acid-base management. Treat chest infections appropriately. Treat anemia appropriately. Supplemental oxygen is of benefit only in patients with hypoxia (as with pneumonia or pulmonary edema).
Cardiac transplantation is currently the optimal treatment for DCM-induced resistant chronic heart failure in children. Limiting factors include availability of a suitable donor, complications of rejection, and lifelong immunosuppression.
Stem cells, particularly cardiac stem cells, and cardiac progenitor cells may represent promising types of cellular therapy to replace dead myocardial cells, but the technology is presently a research topic rather than a clinical option.
Admission is necessitated for patients with DCM who have exacerbations of heart failure; often these are precipitated by chest infection. Admission may also be necessary for reevaluation if first-line medications fail to provide significant relief of symptoms (ie, resistant heart failure). During terminal illness, patients and parents might opt to stay in the hospital.
Ensuring an appropriate and palatable diet is a challenge. Temporary nasogastric tube feedings may be required for sick and severely anorectic children. Infants might need intravenous alimentation for relief from feeding activity. Powerful diuretics have largely obviated stringent restrictions on salt and fluid intake.
Enforced bed rest is impractical and probably unnecessary. Often, restriction of physical activity is self-enforced. In patients with chronic illness, regular graded exercise has been shown to improve effort tolerance and quality of life. Activity to the limit of tolerance should be encouraged. Patients should avoid competitive sports.
Considerable advances in the field of molecular genetics have provided important tools to elucidate genetic substrates for many genetic disorders that follow Mendelian inheritance patterns. The genetic underpinnings of heritable and potentially lethal cardiomyopathies including dilated cardiomyopathy (DCM), are now better understood.
The spectrum of genes linked to DCM is broad. The large number of genes that can be mutated in DCM parallels the large number of genes implicated in mental retardation or cancer. In addition to the gene spectrum for DCM, each gene harbors a large number of “private” mutations (or alleles), where the mutation is unique to a family. Genetic variation includes those variants that are much more highly prevalent in a population and also includes rare genetic variants (present in less than 1-5% of a given population).
Genetic testing for cardiovascular disease is becoming common, with several fee-for-service laboratories off erring testing in the USA. For hypertrophic cardio myopathy, the diagnostic yield of testing is 60–70%; however, testing for dilated cardiomyopathy has a yield much lower than 60%. The most frequently identifi ed gene is lamin A/C, but only when the disease is associated with atrioventricular block (with or without skeletal myopathy). In pure dilated cardio myopathy, the yield screening for a large number of genes is about 20%.
Familial dilated cardiomyopathy has been reported most commonly (approximately 90%) with AD inheritance. The genetic and clinical heterogeneity suggests causation by a single gene, with multiple other genetic and environmental factors altering its expressivity.
One of the most challenging issues in the investigation of genetic causes of DCM is the establishment of causation from a mutation, which in the case of AD inheritance is usually a single base missense or nonsense mutation. The disease phenotype should segregate with the mutation in a large family containing members that have both normal and affected phenotypes.
In screening asymptomatic members of FDC families, clinical disease has been identified in small children and infants. Several of the benefits and limitations of screening adults extend to children, including the possi-bility for treatment and the unknown significance of some screening results. Guidelines for the age at which children of a parent with IDC or FDC should be screened have not been established. Parents should be alert for symptoms of cardiac disease in at-risk children and should have a low threshold for having them evaluated. More aggressive presymptomatic screening is appropriate with disease onset in childhood in other family members. Echocardiograms and ECGs on children should be evaluated by centers that can interpret pediatric studies.
Genetic counseling is a communication process that includes both educational and therapeutic elements targeted to patients and their families who face the risk of a genetic disorder.
A genetic counseling session for patients with or at risk for FDC typically includes
1) A review of the characteristics, genetics, and inheritance pattern(s) of FDC;
2) A thorough family history and pedigree analysis to ascertain the likely pattern of inheritance in the family and identify at-risk relatives;
3) An explanation of the benefits, risks, and limitations of clinical and/or genetic testing for affected individuals and their at-risk relatives; and
4) Assisting the family in making psychosocial adjustments to the recognition of a potentially heritable disorder in the family.
Family members of patients with FDC should be counseled about the potential positive and negative consequences of screening, including clinical and genetic testing, and the associated uncertainties.
Genetic testing is often used to facilitate the confirmation of a clinical diagnosis. Although the criteria to establish a diagnosis of IDC are straightforward, establishing a diagnosis of FDC is more difficult and in cases of negative or inconclusive family history, genetic testing may be the only way to confirm FDC.