Pediatric Dilated Cardiomyopathy Medication
- Author: Poothirikovil Venugopalan, MBBS, MD, FRCP(Glasg), FRCPCH; more...
Medication Summary
Medical therapy in dilated cardiomyopathy (DCM) includes diuretics, angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers. Antibiotics for endocarditis prophylaxis are administered to patients with certain cardiac conditions, such as DCM, before performing procedures that may cause bacteremia. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.
Diuretics
Class Summary
These agents are used to eliminate retained fluid and preload reduction.
Furosemide (Lasix)
Furosemide is the drug of choice for diuresis in acute heart failure and in exacerbations of chronic heart failure. It is also used for long-term management of chronic heart failure.
Furosemide inhibits reabsorption of fluid from the ascending loop of Henle in the renal tubule. When administered intravenously, it produces venodilation and lowers preload even before diuresis sets in.
Spironolactone (Aldactone)
Spironolactone is a potassium-sparing diuretic that acts on the distal convoluted tubule of the kidney as an aldosterone antagonist. It exhibits synergistic action with furosemide.
Angiotensin-Converting Enzyme Inhibitors
Class Summary
These drugs reduce afterload and decrease myocardial remodeling that worsens chronic heart failure.
Captopril
Captopril is accepted as an essential part of any therapy against heart failure, providing symptomatic improvement and prolonged survival. Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Enalapril (Vasotec)
This agent is an ACE inhibitor with prolonged duration of action with oral administration. A competitive inhibitor of ACE, it reduces angiotensin II levels, decreasing aldosterone secretion.
Cardiac Glycosides
Class Summary
These drugs provide improvement of symptoms with chronic administration. The role of cardiac glycosides is less clear than in the past.
Digoxin (Lanoxin)
Digoxin improves myocardial contractility, reduces heart rate, and lowers sympathetic stimulation in chronic heart failure. It inhibits the Na+-K+ ATPase pump. Sodium preferentially exchanges with calcium, increasing the intracellular calcium and resulting in an increase in contractility.
Anticoagulants
Class Summary
These agents are administered to prevent recurrence of thromboembolic episodes of cardiac origin.
Warfarin (Coumadin, Jantoven)
Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It prevents thrombus formation within cardiac chambers and the venous circulation. Tailor the dose to maintain an International Normalized Ratio (INR) of 2-3.
Beta-Adrenergic Blocking Agents
Class Summary
These agents block the beta-adrenergic receptor and are modulators of the autonomic system.
Propranolol (Inderal LA, Inderal XL)
Propranolol is a nonselective beta-adrenergic antagonist (ie, it inhibits both beta1- and beta2-adrenergic receptors).
Carvedilol (Coreg)
Carvedilol is a nonselective beta-blocker with additional direct vasodilator action.
Metoprolol (Lopressor, Toprol XL)
Metoprolol is a selective beta-1 adrenergic receptor blocker that decreases automaticity of contractions.
Adrenergic Agonist Agents
Class Summary
These agents are used in resistant cases as intravenous infusions and stimulate beta1-adrenergic receptors in the myocardium. They are also useful for periodic home inotropic therapy in end-stage disease, in which cardiac transplant is not feasible, to improve the quality of life. However, studies have shown increased mortality related to arrhythmogenic potential.
Dobutamine
Dobutamine is a synthetic catecholamine with potent cardiac-stimulating properties; in addition, it has direct vasodilating action on peripheral blood vessels. Infusion with or without additional dopamine in renal dose would be appropriate therapy for cardiogenic shock secondary to dilated cardiomyopathy.
Phosphodiesterase Enzyme Inhibitors
Class Summary
These agents elicit positive inotropic and vasodilatory effects.
Milrinone
Milrinone is a bipyridine with positive inotrope and vasodilator activity. Little chronotropic activity is observed. This agent differs in its mode of action from both digitalis glycosides and catecholamines. It selectively inhibits phosphodiesterase type III (PDE III) in cardiac and smooth vascular muscle, resulting in reduced afterload, reduced preload, and increased inotropy.
Milrinone is not approved by the US Food and Drug Administration (FDA) for use in pediatric patients. Nevertheless, it is often considered the drug of choice in pediatric patients in the intensive care unit setting.
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- 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 |
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