Approach Considerations
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. Survival rates of as much as 92% at 5 years [29] and 53% at 15 years have been reported. [30] A variety of other surgical procedures have been studied.
A comparison of DCM patient cohorts of 1990 to 1999 and 2000 to 2009 in the Pediatric Cardiomyopathy Registry revealed increased survival rate in the recent years although the cardiac transplant rates were similar. [31] This would suggest that non-transplant-related advances in therapy may be responsible for the improvement.
Pharmacologic Therapy
Diuretics, ACE inhibitors, and beta-blockers form the pharmacologic regimen for heart failure in DCM. Diuretics may provide an improvement in symptoms, whereas ACE inhibitors appear to prolong survival.
Beta-blocker therapy in children with chronic heart failure due to DCM has been shown to improve symptoms and left ventricular ejection fraction. Carvedilol is a beta-adrenergic blocker with additional vasodilating action. Carvedilol, in addition to standard therapy for dilated cardiomyopathy in children, is believed to improve cardiac function and symptoms; it is well tolerated, with minimal adverse effects, but close monitoring is necessary because it might worsen congestive heart failure and precipitate asthma. Furthermore, randomized control studies have not yet documented the beneficial effects of carvedilol, although it is not clear whether these studies were large enough to bring out the differences. [32]
Anticoagulants and antiarrhythmic agents, particularly amiodarone, are often used in patients with low myocardial contractility and symptomatic arrhythmias, respectively. Results are encouraging. Presence of intracardiac thrombi, symptomatic or not, is another indication for anticoagulant therapy. [33]
Carnitine supplements (100 mg/kg IV infusion over 30 min, followed by 100 mg/kg/day as continuous infusion for 24-72 hours; 25-50 mg/kg/dose PO bid or tid, not to exceed 200 mg/kg/day) reverse the myocardial dysfunction in most patients affected by systemic carnitine deficiency.
Heart rate reduction by ivabradine in children with DCM was attempted which showed improvement of left ventricular function and quality of life parameters [34] and such therapy is worth investigating in future studies.
Investigational drug therapy
Coenzyme Q10 has also been used in children with DCM, with variable results. [35]
Decreased serum levels of growth hormone (GH), which acts on cardiac myocytes primarily through insulinlike growth factor (IGF)-1, are associated with impaired myocardial growth and function, which can be improved with the restoration of GH/IGF-1 homeostasis. Based on this hypothesis and on observation of benefits in animal models, GH therapy has been used in children with DCM, but the results have not been conclusive.
Palliative, Bridge, and Experimental Surgery
Palliative surgical measures are associated with significant mortality and morbidity rates despite advances. Resection of a large segment of the hypertrophied ventricular muscle (Batista procedure) and repair or replacement of mitral valve to minimize volume overload of left ventricle have been used as palliative measures. Cardiomyoplasty is the transposition of electrically transformed skeletal muscle to provide systolic and diastolic augmentation to the native heart.
Mitral valve repair and partial left ventriculectomy have been found to be feasible in selected patients and help reduce symptoms in most patients and help [36] reduce left ventricular dimensions in some patients; however, whether it can modify the natural history, especially the need for cardiac transplantation, is unclear. [37]
Implantable mechanical support devices, modified for use in infants and children, have been introduced to support the failing heart until a suitable donor is available for transplantation (bridge to transplant). The Berlin Heart EXOR pediatric has also been successfully used in several centers. [38] Major limitations include infection, thromboembolism, disturbance from noise, and the need to frequently recharge batteries.
Cardiac resynchronization therapy using a biventricular pacemaker has been shown to be effective in adults with DCM. In addition, these devices are available with defibrillator backup for patients at risk for ventricular arrhythmias. They are used in children with DCM with early favorable results. [39]
In adult studies, some patients receiving prolonged support of left ventricular function with these devices have shown restoration of native cardiac function. In a few cases, myocardial recovery has been sufficient to permit successful removal of the left ventricular assist system, even after a year of use. This suggests a possible role for mechanical intervention at an earlier stage in viral myocarditis and DCM. A lesser degree of fibrotic changes in the left ventricle could improve the chances of recovery.
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. [40, 41]
Plasma exchange by producing immunoabsorption in order to eliminate autoantibodies in children with DCM resulted in improvement in cardiac function, [42] similar to that reported in adult subjects and may considered as a bridge transplant or ventricular assist devices.
Hospital Admission
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.
In addition to taking aggressive steps to treat the precipitating factor (infection, anemia), compliance with therapy has to be evaluated when symptoms persist.
Diminished absorption and waning action of diuretics can be partially overcome by parenteral administration of furosemide or by sequential segmental nephron blockade achieved by combining metolazone, a thiazide diuretic, with furosemide.
Intravenous infusions of beta agonists, such as dopamine and dobutamine, temporarily improve myocardial function and partly reverse the abnormal neuro-endocrine profile of chronic congestive heart failure. However, in the long-term, they increase myocardial irritability, leading to arrhythmia.
Intra-aortic balloon pump support may be successfully and safely used in patients with acute decompensated DCM as an urgent measure of cardiac support to stabilize the patient and maintain organ perfusion until transplantation is possible, until a ventricular assist device is placed, or until the patient recovers sufficiently to be weaned from intra-aortic balloon pump. [43]
Cardiac resynchronization therapy with AV synchronous biventricular pacing has been successful in some children with DCM and left bundle branch block (LBBB). Optimization of resynchronization for children with DCM is still in the early stages.
Automatic implantable cardioverter-defibrillators (ICDs) reduce sudden death, and their efficacy has been clearly demonstrated in adults with chronic congestive heart failure. However, their use in children has been limited. Studies have reported on the efficacy of ICDs in children with DCM and other cardiomyopathies. [44]
Studies in adults who died of heart failure report significant fatigue, dyspnea, and pain in the days before death. Concluding that a similar pattern would occur in children is logical.
Diet
Dietary requirements are high in children with DCM because of their catabolic state, recurrent infections, increased muscle activity, and need for rapid growth. Dietary intake may be inadequate consequent to the anorexia, dietary restrictions, malabsorption, diarrhea, and frequent exacerbations of heart failure.
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.
Activity
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.
All feasible support should be provided for peer interaction and participation in normal life activities. Restricted life activities, frequent diagnostic and therapeutic interventions, and an uncertain prognosis make these children prone to psychological problems that may significantly influence prognosis and outcome. Among the described abnormalities are inhibition of emotions, marked anxiety, depressive reaction with loneliness, low self-esteem, feelings of inadequacy, emotional lability, impulsiveness, and weakness of self-identity.
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Chest radiograph of a child with idiopathic dilated cardiomyopathy.
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Echocardiogram obtained from apical 4-chamber view revealing a dilated left atrium and left ventricle in a child with idiopathic dilated cardiomyopathy.
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This is a color Doppler echocardiogram obtained from apical 4-chamber view revealing a dilated left atrium and left ventricle with the blue jet of mitral regurgitation in a child with idiopathic dilated cardiomyopathy. Mild tricuspid regurgitation is also shown.
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This is an echocardiogram obtained from parasternal long axis view revealing a dilated left atrium and left ventricle in a child with idiopathic dilated cardiomyopathy.
Tables
- Table 1. Factors Identified as Causes of Myocardial Damage
- Table 2. Summary of Genetic Loci and Disease Genes for Familial Dilated Cardiomyopathy
- Table 3. Diagnosis of Dilated Cardiomyopathy in Children - Step I: Diagnosis
- Table 4. Diagnosis of Dilated Cardiomyopathy in Children - Step II: Identification of Any Underlying Etiology
Category Of Factors |
Specific Factors |
Viral infections (myocarditis) |
Coxsackievirus B, human immunodeficiency virus, echovirus, rubella, varicella, mumps, Epstein-Barr virus, cytomegalovirus, measles, polio |
Bacterial infections |
Diphtheria, Mycoplasma, tuberculosis, Lyme disease, septicemia |
Rickettsia |
Psittacosis, Rocky Mountain spotted fever |
Parasites |
Toxoplasma, Toxocara, Cysticercus |
Fungi |
Histoplasma, coccidioidomycoses, Actinomyces |
Neuromuscular disorders |
Duchenne or Becker muscular dystrophies, Friedreich ataxia, Kearns-Sayre syndrome, other muscular dystrophies |
Nutritional factors |
Kwashiorkor, pellagra, thiamine deficiency, selenium deficiency |
Collagen vascular diseases |
Rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Kawasaki disease |
Hematological diseases |
Thalassemia, sickle cell disease, iron deficiency anemia |
Coronary artery diseases |
Anomalous left coronary artery from pulmonary artery, infarction |
Drugs |
Anthracycline, cyclophosphamide, chloroquine, iron overload |
Endocrine diseases |
Hypothyroidism, hyperthyroidism, hypoparathyroidism, pheochromocytoma, hypoglycemia |
Metabolic disorders |
Glycogen-storage diseases, carnitine deficiency, fatty acid oxidation defects, mucopolysaccharidoses |
Malformation syndromes |
Cri-du-chat (cat-cry) syndrome |
Clinical Pattern |
Identified Genetic Loci |
Identified Disease Genes |
Autosomal dominant (AD) |
10q21-10q23, 9q13-q22, 1q32, 15q14, 2q31, 1q11-21 |
Actin, desmin, lamin A/C |
AD with conduction defect |
1p1-1q1, 3p22-3p25 |
... |
X-linked (XL) |
Xp21 |
Dystrophin |
XL cardio-skeletal (Barth syndrome) |
Xq28 (gene G4.5) |
Tafazzin |
Approach |
Findings |
Conclusion |
Clinical suspicion |
Infants and young children: Shortness of breath, feeding difficulties, wheezing, failure to thrive, recurrent chest infections, hepatomegaly, cardiomegaly Older children: Dyspnea, dependent edema, elevated jugular venous pressure, cardiomegaly |
Probable heart disease with heart failure |
Chest radiography |
Cardiomegaly, pulmonary plethora, prominent upper lobe veins, pulmonary edema, pleural effusion, collapsed left lower lobe |
High probability of heart failure with or without chest infection |
Electrocardiography |
Low-voltage complexes |
Pericardial effusion |
Presence of Q waves and inversion of T waves in leads I, II, aVL, and V4 through V6 (anterolateral infarction pattern) |
Anomalous left coronary artery from pulmonary artery |
|
Significant arrhythmia |
Dilated cardiomyopathy secondary to arrhythmia |
|
Left ventricular or biventricular hypertrophy with or without left ventricular strain pattern |
Often unhelpful |
|
Doppler echocardiographic studies* |
Significant congenital heart disease |
Diagnose primary disease |
Significant pericardial effusion with satisfactory left ventricular ejection fraction |
Diagnose pericardial effusion |
|
Left ventricular posterior wall hypokinesia with hyperechoic papillary muscles, retrograde continuous flow into proximal pulmonary artery |
Diagnose anomalous left coronary artery from pulmonary artery |
|
Dilated left ventricle (>95th percentile) with global hypokinesia (fractional shortening < 25%, ejection fraction < 50%), and no demonstrable structural heart disease |
Diagnose dilated cardiomyopathy |
Approach |
Findings |
Conclusion |
Clinical features |
Positive family history |
Genetic cause for dilated cardiomyopathy |
Acute or chronic encephalopathy, muscle weakness, hypotonia, growth retardation, recurrent vomiting, lethargy |
Inborn error of metabolism involving energy production |
|
Coarse or dysmorphic features, organomegaly, skeletal abnormalities, short stature, chronic encephalopathy, cherry-red spot in eyes |
Storage diseases |
|
Skeletal muscle weakness without encephalopathy |
Neuromuscular disorders |
|
Blood investigations |
High blood urea nitrogen and creatinine levels, low calcium and magnesium levels, electrolyte disturbances |
Help in the initial management; occasionally point to a cause of dilated cardiomyopathy, especially in neonates |
Elevated acute-phase reactants and cardiac enzyme levels |
Myocarditis |
|
Positive viral titers |
Viral myocarditis |
|
Low serum carnitine levels |
Systemic carnitine deficiency |
|
Hypoglycemia with low or no acidosis (ketosis) 1. High insulin levels, low free fatty acid 2. Low insulin levels, high free fatty acid |
1. Infant of diabetic mother, nesidioblastosis 2. Defect in fatty acid oxidation or carnitine metabolism |
|
Hypoglycemia with moderate or high acidosis (ketosis) 1. Low or normal lactate and abnormal urine and serum organic acid levels 1. High lactate |
1. Organic (propionic, methylmalonic) acidemias, or ß-ketothiolase deficiency 2. Glycogen storage disease, Bath and Sengers syndromes, pyruvate dehydrogenase deficiency, mitochondrial enzyme deficiency |
|
Hyperammonemia with acidosis |
Organic acidemias (as above) |
|
Specific enzyme assay |
Confirms enzymatic defect |
|
Absence of above physical and biochemical abnormalities |
Post myocarditis or idiopathic dilated cardiomyopathy |
|
Cardiac catheterization |
Evaluate hemodynamics |
Useful to predict prognosis and evaluate for transplant |
Coronary angiography |
Abnormal origin of left coronary artery from pulmonary artery |
Anomalous left coronary artery from pulmonary artery |
Myocardial biopsy |
Myocyte hypertrophy and fibrosis without lymphocytic infiltrate |
Dilated cardiomyopathy |
Inflammatory cell infiltration, cell necrosis |
Myocarditis |
|
Special stains |
Mitochondrial or infiltrative diseases |
|
Molecular studies (on blood, fibroblasts, or myocardial cells) |
Nucleic acid hybridization studies Polymerase chain reaction studies |
Myocarditis |
DNA mutation analysis |
Identifies specific genetic defect |
