Idiopathic Dilated Cardiomyopathy

Idiopathic Dilated Cardiomyopathy (IDC)

Source: McKesson Health Solutions LLCUpdated: November 2002

What is idiopathic dilated cardiomyopathy (IDC)?
Idiopathic dilated cardiomyopathy (IDC) is a disease of unknown cause that results in an enlarged heart that does not pump properly. It is the most common reason people get heart transplants. The fact that it occurs so often, the mystery of its cause, and the lack of a long-term effective treatment other than heart transplant make IDC a problem for both the people who have it and their health care providers.

Most people with IDC are between 20 and 50 years old when they first see a health care provider for their disease. Blacks and men have a higher risk of developing IDC than whites and women.

How does it occur?
The cause is not known. Because IDC tends to run in families, it may be inherited. Virus infections of the heart muscle or an allergic response to some irritant could be other causes.

What are the symptoms?
IDC causes the heart chambers to dilate (expand). The heart itself may become very large, and the heart muscle gets thinner. The pumping of the heart gets weaker, and the circulation slows.

IDC results in a heart that is too weak to circulate the blood properly. The most common problem is congestive heart failure. The symptoms are shortness of breath with physical activity, waking from sleep at night short of breath, and swelling of the legs or ankles due to retention of fluids.

With poor circulation, blood clots may form in the heart, break off, and float in the bloodstream. These clots can clog the flow of blood in an artery. The loss of blood can cause damage to a kidney, an arm or a leg, and even cause a stroke. People with IDC often have abnormal heart rhythms that may result in sudden death.

How is it treated?
Your health care provider will consider all of the other causes that act like IDC and will treat them, if possible. Drinking too much alcohol may cause a weakened heart muscle. Treatment may be as simple as for you to stop drinking alcohol. On the other hand, alcohol causes these symptoms only rarely.

Treatment is directed at controlling congestive heart failure. You may take medicines that make your heart muscle pump more effectively. You may also take diuretics (water pills) to help reduce swelling in your legs and arms. Your health care provider may suggest that you reduce your physical activity and the amount of salt you eat.

Drugs called beta blockers are frequently used to treat IDC. Over the course of several months, they may improve heart function. Your health care provider may prescribe a drug called a vasodilator. These drugs make the blood vessels open up. The increased size of the blood vessels allows more blood to flow through them. This lowers blood pressure slightly and lessens the workload of the heart. Vasodilators usually reduce symptoms and decrease the chances that you will need to be treated for congestive heart failure in a hospital.

Your health care provider may also prescribe a blood-thinner (anticoagulant). Anticoagulants help to keep the blood from clotting and prevent artery blockages and strokes.Treatment of heart rhythm problems in IDC may be important. Sometimes a device called an implantable cardioverter-defibrillator (ICD) is needed to treat abnormal heart rhythms.

What about cardiac transplantation for IDC?
The outlook for patients with IDC is improving. A few lucky people get better on their own. For the rest, the disease may progress fast or slowly, or may not change for a long period of time. Treatment with combinations of drugs helps to significantly improve the outlook. Cardiac transplantation is an option for those who have severe symptoms that are not responding to medicines.

When should I call the health care provider?
Your health care provider will want to see you often to make sure your medicines are working well. If you notice rapid weight gain (over 3 to 5 days) or swelling of your legs or ankles, or if you develop increasing shortness of breath with physical activity, call your health care provider immediately. If you are taking anticoagulants, notify your health care provider of any excessive skin bruising or frequent nosebleeds.

Cardiomyopathy, Dilated

http://www.emedicine.com/ped/topic2502.htm

Last Updated: January 1, 2002

Author: Poothirikovil Venugopalan, MBBS, MD, MRCP (UK), FRCPCH, Consulting Staff, Department of Child Health, Division of Cardiology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman

Editor(s): Jeffrey Towbin, MD, Associate Chair of Pediatric/Cardiology, Professor, Departments of Pediatrics, Molecular and Human Genetics, Cardiovascular, Baylor College of Medicine and Texas Children's Hospital; Robert Konop, PharmD, Clinical Assistant Professor, Department of Pharmacy, Section of Clinical Pharmacology, University of Minnesota; Ameeta Martin, MD, Associate Professor, Department of Pediatrics, Section of Pediatric Cardiology, University of Nebraska College of Medicine; Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; and Steven Neish, MD, Director of Pediatric Cardiac Catheterization Services, Head of Pediatric Cardiology Division, Associate Professor, Department of Pediatrics, University of Wisconsin and Children's Hospital

Background: Idiopathic dilated cardiomyopathy (DCM) refers to congestive cardiac failure secondary to dilatation and systolic (and/or diastolic) dysfunction of the ventricles (predominantly left) in the absence of congenital, valvular, or coronary artery disease or any systemic disease known to cause myocardial dysfunction. DCM is the most common type of heart muscle disease in children.

All four cardiac chambers are dilated and hypertrophied. Dilation is more pronounced than hypertrophy, and the left ventricle is affected more often than the right ventricle. The cardiac valves are intrinsically normal, although the mitral and tricuspid valve rings are dilated and the valve leaflets do not appose each other in systole, giving rise to varying degrees of mitral and/or tricuspid regurgitation. Persistent mitral regurgitation leads to thickening of the mitral valve leaflets, and, at times, it is difficult to distinguish this thickening from other causes of mitral regurgitation. Thrombus formation (secondary to the low-flow cardiac output state) is often seen in the left ventricular apex and, at times, in the atria. Occasionally, the right ventricle is preferentially involved in the cardiomyopathic process. When this is noted, it may have a familial basis.

Pathophysiology: Injury to the myocardial cell is the initiating factor that leads to cell death. When there is considerable cell loss, the myocardium fails to generate enough contractile force to produce adequate cardiac output. This results in the activation of compensatory mechanisms: renin-angiotensin-aldosterone system, sympathetic stimulation, antidiuretic hormone production, release of atrial natriuretic peptide, tumor necrosis factor (TNF)-a, and mechanical factors, such as increased end-diastolic stretch on the ventricle. These contributory mechanisms help to maintain cardiac output in the initial phase; however, as myocardial damage progresses, persistent and excessive activation of compensatory mechanisms proves to be detrimental to cardiac function, and features of overt congestive heart failure set in.

Over-stretching of the ventricles causes myocardial thinning, cavity dilation, secondary valvular regurgitation, and compromised myocardial perfusion. The resulting sub–endocardial ischemia perpetuates myocyte damage.

Myocardial remodeling is an important contributor to worsening heart failure. Lost myocyte cells are replaced with fibrous tissue, thereby decreasing the compliance of the ventricle(s) and adversely affecting its performance. Aldosterone, angiotensin II, catecholamines, endothelins, and mechanical factors, such as excessive myocardial stretch and ischemia, have been identified as mediators of remodeling.

Apoptosis is a process of programmed cell death without fibrosis and is now believed to play a role in the continuing loss of myocardial cells in chronic heart failure. Overloading of myocytes possibly triggers apoptosis.

Heightened peripheral vasoconstriction, abnormal and excessive remodeling of the peripheral vasculature, and abnormalities in endothelium-dependent vasodilation contribute to the progression of heart failure. Abnormal responses to muscarinic stimulation along with a defect in the endothelial nitric oxide pathway have been suggested as the potential underlying mechanisms.

Altered gene expressions resulting in calcium handling abnormalities, down regulation of myosin to the less active beta isoform, and abnormal beta-receptor signal transduction have all been identified at the molecular level in the chronically failing heart.

Frequency:

In the US: Estimated incidence is 36.5 per 100,000 children.

Internationally: Incidence in Finland is 2.6 per 100,000 children. No reliable figures are available for the rest of the world.

Genetic causes account for more than 30% of DCM.

Mortality/Morbidity:

Mortality and morbidity have decreased greatly with advances in medical management. Studies from 1975-1990 reported 70% survival at 2 years and 52% survival at 11.5 years of follow-up. Studies from 1992-1997 document 85% survival at 5 years. In general, approximately one third of patients die from the disease, one third of patients continue to have chronic heart failure requiring therapy, and one third of patients experience improvement in their condition.

Causes of death include worsening heart failure, malignant ventricular arrhythmias, and transplantation-related complications (less common).

Sex: No sex predilection exists.

Age: All age groups are affected. However, studies suggest that 50% of patients with new onset of disease are younger than 2 years. Neonates and fetuses also may be affected.

History:

Onset is usually insidious but may be acute in up to 25% of patients, especially with a complicating lower respiratory infection.

Cough, poor feeding, irritability, and shortness of breath are usually the initial presenting symptoms.

Pallor, sweating, easy fatigability, failure to gain weight, and decreased urine output may be present.

Wheezing may be an important manifestation in infants.

Chest pain, palpitations, orthopnea, hemoptysis, frothy sputum, sudden death, abdominal pain, syncope, and neurologic deficit are other modes of presentation (20%).

Cardiomegaly detected incidentally on a chest radiograph or an arrhythmia detected incidentally on an ECG may form the basis for initial cardiac referral.

Approximately 50% of patients have a history of preceding viral illness. A detailed family history for familial cardiomyopathy is revealing in 4-25% of cases.

Physical:

In a patient with established disease, features of congestive heart failure are dominant.

The infant or young child with the disease is often tachypneic, tachycardic with weak peripheral pulses, and has cool extremities and hepatomegaly. Blood pressure is low with a decreased pulse pressure. In extreme cases, patients may present in shock.

Older children may show dependent edema, elevated jugular venous pulses, and fine basal crepitations in the lungs.

Major cardiac findings include cardiomegaly, quiet precordium, tachycardia, gallop rhythm (S₃ and/or S₄), accentuated P-2, and murmurs of mitral and tricuspid regurgitation. Murmurs may be inconspicuous initially when presenting in acute heart failure.

Infants often present with predominantly respiratory signs and, in the absence of a precordial heave or prominent murmur, the underlying cardiac disease may remain undiagnosed until cardiomegaly is detected on chest radiograph.

Causes:

A variety of factors have been identified as causes of myocardial damage. These are presented in Table 1. In the vast majority of patients, however, no specific etiology is demonstrable (idiopathic). Systemic carnitine deficiency and anthracycline-induced cardiomyopathy are notable exceptions.

Table 1. Factors Identified as Causes of Myocardial Damage

Viral infections (myocarditis)	Coxsackievirus B, human immunodeficiency, echovirus, rubella, varicella, mumps, Ebstein-Barr virus, measles, polio
Bacterial infections	Diphtheria, Mycoplasma, tuberculosis, septicemia
Rickettsia	Psittacosis, Rocky Mountain spotted fever
Parasites	Toxoplasma, Toxocara, Cysticercus
Fungi	Histoplasma, coccidioidomycoses, Actinomyces
Neuromuscular disorders	Duchenne muscular dystropy, Friedreich ataxia, 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
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	Cat-cry syndrome (5p-)

Three major factors have been implicated in the pathogenesis of myocardial damage in DCM: preceding viral myocarditis, autoimmunity, and underlying genetic predisposition.

Viral myocarditis

Epidemiologic, serologic, and molecular studies have detected evidence of enteroviral infection and, in particular, coxsackievirus B in 20-25% of patients.

At present, we do not have methods to distinguish cardiovirulent strains of enteroviruses from those that are noncardiovirulent. Furthermore, the presence of a virus does not necessarily establish a causal relationship.

The mechanism of myocardial damage (rapid destruction or a long-term slowing of cardiomyocyte function) also remains unclear.

Autoimmunity

Animal studies have shown that DCM is an autoimmune disease in genetically predisposed strains of mice. Approximately 30-40% of adult patients with DCM have organ-specific and disease-specific autoantibodies. The absence of these antibodies in the remaining patients may be related to the stage of disease progression.

It has been postulated that an insult such as viral myocarditis initiates an autoimmune process with superantigen-triggered immune responses resulting in massive T-lymphocyte activation and myocardial damage.

Genetic predisposition

Genetic causes account for more than 30% of DCM.

The role of genetic factors is exemplified by the studies on familial dilated cardiomyopathy. There is an increased frequency of human leukocyte antigen (HLA)-DR4 in patients with familial DCM.

Autosomal dominant and recessive inheritance, X-linked transmission, and polygenic and mitochondrial inheritance have all been documented. Available literature on the genetic loci of DCM is summarized in Table 2.

Table 2. Summary of Genetic Loci and Disease Genes for Familial Dilated Cardiomyopathy

Clinical Pattern	Genetic Loci Identified	Disease Genes Identified
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

Anthracyclines and cardiomyopathy

Anthracyclines, widely used in the management of childhood malignancies, account for up to 30% of cases of dilated cardiomyopathy in the United States and a lesser percentage in other countries. Besides dilated cardiomyopathy, the other manifestations of anthracycline cardiotoxicity include restrictive cardiomyopathy (symptomatic and asymptomatic), asymptomatic left ventricular enlargement, and more subtle changes of cardiac function.

Early diagnosis requires periodic Doppler echocardiography (Echo) studies during therapy and for several years after cessation of treatment. It also requires more widespread use of load-independent measurements of cardiac contractility (like stress velocity index), which incorporate measurements of contractility, afterload, and preload.

Cardiotoxicity may be of two types: early onset or late onset. Early onset type may be acute nonprogressive or chronically progressive.

Acute onset type is defined as left ventricular dysfunction during or immediately following infusion of anthracycline and is attenuated by discontinuation of therapy. With widespread use of low dose regimens, this type is rare now. ECG changes include nonspecific ST segment and T wave changes, decreased QRS voltage, prolonged QT interval, sinus tachycardia and, rarely, ventricular, junctional, or supraventricular tachycardia or atrioventricular and bundle branch blocks. Blood levels of cardiac troponin T (cTnT) are a specific marker of this type of injury.

Early-onset chronically progressive toxicity presents within one year of completion of therapy and persists or progresses even after discontinuation of therapy. Clinical features are similar to any other type of cardiomyopathy and include ECG changes, left ventricular (LV) dysfunction, reduced exercise-stress capacity, and even overt signs of heart failure. Blood levels of cTnT are elevated. Presence of early onset cardiotoxicity is believed to be a harbinger of poor patient outcome.

Late onset toxicity clinically manifests after a latent period of one or more years following completion of therapy. This type of manifestation is presumably due to diminished left ventricular contractility and an inappropriately thin left ventricular wall, resulting in elevated wall stress and progressive LV dysfunction. Myocyte loss underlies all these sequelae, and alteration of myocellular protein transcription by anthracyclines may contribute. The latent period, thus, is not latent at all, and more sensitive markers may be able to detect the changes earlier. Late onset asymptomatic has also been reported, but more detailed questioning often reveals easy fatigability or dyspnea in many of these patients.

Risk factors contributing to the development of cardiotoxicity include the following: (1) the total cumulative dose of the drug received (20% mortality with cumulative dose >550 mg/m², 65% frequency of subtle Echo changes with dose >400 mg/m², and histologic evidence of toxicity with >240 mg/m²), (2) female sex (higher cellular concentrations because of higher body fat percentage), (3) young children, (4) rate of drug administration (maximum risk with doses >50 mg/m²/dose), (5) concomitant cardiac radiation exposure or use of amsacrine, (6) black race, and (7) trisomy 21.

Lab Studies:

Full blood counts, erythrocyte sedimentation rate, and C-reactive proteins may show evidence of acute inflammation in the presence of active myocarditis.

Similarly, creatine kinase–myocardial fraction may be elevated.

Rising titers of specific viral-neutralizing antibodies in the serum and positive viral cultures from nasopharyngeal or stool swabs may suggest a viral etiology; however, this need not mean a cause and effect relationship.

Serum carnitine levels (total and free) are low when the disease is due to systemic carnitine deficiency.

Arterial blood gas (ABG) reveals early stages of mild respiratory alkalosis and, later, mild hypoxemia secondary to pulmonary edema. In advanced disease, mixed acid-base disturbances with metabolic acidosis indicate the need for intravenous inotropes and ventilatory assistance.

Imaging Studies:

Chest radiograph

Chest radiograph (CXR) shows cardiomegaly with a prominent left ventricular apex and prominent pulmonary artery segment.

Elevation of left main bronchus reflects dilation of the left atrium. When combined with a dilated pulmonary artery, this can result in compression of the left lower lobe bronchus leading to collapse of the left lower lobe of the lung.

There is often evidence of pulmonary venous congestion and frank pulmonary edema. When present, pleural effusion is better appreciated in the erect and lateral decubitus films.

Massive cardiomegaly resembling pericardial effusion is the hallmark of established disease.

Rarely, in fulminant cases, cardiomegaly may not be prominent because the ventricle has not had time to dilate, despite the presence of features of pulmonary edema.

Doppler Echo studies

These form the basis for the diagnosis of DCM in the majority of patients. Marked dilation of the left ventricle with global hypokinesia is the hallmark of the disease. Left ventricular fractional shortening is usually less than 25% (ejection fraction <50%). Left ventricular walls are thin and areas of dyskinesis may be observed. The left atrium is also dilated, and mitral valve leaflets show sluggish movement; the anterior leaflet does not appose to the interventricular septum, giving an increased E point septal separation on the M-mode pictures. The M-mode also shows clearly the limited excursions of the anterior and posterior leaflets during diastole.

Doppler studies show varying degrees of mitral regurgitation secondary to left ventricular dilation and possible papillary muscle dysfunction. Mitral regurgitation is more prominent in follow-up studies after commencing therapy when the cardiac output has improved. Left ventricular ejection parameters show decrease in peak velocity and peak acceleration, prolongation of the pre-ejection period, and decrease in ejection time. These flow measurements are dependent on loading conditions.

Parameters of diastolic dysfunction are not reliable in presence of established systolic dysfunction and mitral regurgitation; however, they may be useful in the early stages of the disease. Diastolic dysfunction is not as typical or as pronounced as it is in hypertrophic cardiomyopathy.

Long-standing cases show evidence of pulmonary hypertension in the form of right ventricular dilation and hypertrophy and tricuspid regurgitation. Tricuspid regurgitation and pulmonary regurgitation velocities give an estimate of the pulmonary artery systolic and diastolic pressures respectively. In severe cases, swirling echodensity (smoke or spontaneous echo contrast) can be appreciated along the outer ventricular wall, moving from the mitral valve towards the aortic valve. Occasionally, thrombi can be visualized in the left ventricular apex and in the left atrium. Pericardial effusion also may be present.

Echo can exclude other heart diseases, both congenital and acquired. Cardiomyopathy secondary to severe aortic stenosis, coarctation of aorta or congenital mitral valve dysplasia, and anomalous left coronary artery arising from pulmonary artery (ALCAPA) are the major differential diagnoses. At times, it is difficult to identify cardiomyopathy secondary to congenital mitral regurgitation (dysplastic mitral valve without stenosis), but the abnormal anatomy of the mitral valve leaflets should help. The echo-dense papillary muscles along with dilated proximal right coronary artery and continuous retrograde flow of blood into the origin of pulmonary artery all direct the attention of the cardiologist to ALCAPA, a potentially treatable condition that mimics DCM.

Radionuclide imaging

First pass test and multiple gated acquisition (MUGA) scans help to measure the left and right ventricular stroke volumes and cardiac outputs. They are also helpful to document dyskinetic segments in the ventricular walls. Although theoretically superior to Echo measurements, their practical application is limited because of a lack of standardization and because of nonreproducibility, especially in children.

Thallium studies could identify areas of decreased myocardial perfusion, though this is seldom required.

Gallium citrate Ga 67 scintigraphy and indium In-111 altumomab pentetate antimyosin antibody cardiac imaging have been suggested to help identify ongoing inflammation noninvasively. They may be used to identify patients who might benefit from myocardial biopsy.

Other Tests:

Electrocardiogram

ECG changes are usually nonspecific.

The majority of patients have sinus tachycardia, downward frontal plane QRS axis, left atrial enlargement, left ventricular hypertrophy, deep q waves with ST segment depression and tall T waves in leads I, aVL, V₅, V₆ (the latter reflect left ventricular volume overload).

In more advanced disease, right axis deviation, right atrial enlargement, and right ventricular hypertrophy are seen (because of pulmonary hypertension).

The main role of ECG is to detect evidence of myocardial ischemia (pathologic Q waves with ST elevation and T wave inversion in leads I, aVL, V₅, V₆) that might point to anomalous coronary artery as the etiology of the cardiomyopathy. A segmental myocarditis may result in ECG features of myocardial infarction.

Cardiac arrhythmias, such as supraventricular/ventricular ectopy or tachycardia, may be revealed. These might indicate an underlying myocarditis or cardiomyopathy; however, if sustained, it is possible that the arrhythmia is the cause of the cardiomyopathy rather than the result.

Procedures:

Cardiac catheterization and angiography

Children with DCM are at special risk for complications during cardiac catheter studies and angiography. Procedures should be performed by experienced pediatric cardiologists and only when absolutely essential.

At present, preparation for cardiac transplant and need for myocardial biopsy are the main indications for performing the procedure.

Patients should be under optimum medical therapy and kept stable hemodynamically before and after catheterization. Careful observation is required during the procedure for ventricular arrhythmias and hemodynamic deterioration. Echo is recommended postcatheterization to identify any pericardial effusion secondary to subclinical perforation of the myocardium, especially if a biopsy has also been performed.

Study should be limited to measurement of pressures in the aorta and left ventricle, wedge position, and evaluation of pulmonary vascular resistance. Aortography may be performed to identify coronary artery anatomy, and left ventricular angiogram may be performed to assess mitral valve function. The number of biopsy specimens collected should be limited to the minimum required (usually 4-8).

Usual findings include elevated filling pressures in all the cardiac chambers (especially the left ventricle), elevated pulmonary wedge pressure, and reduced cardiac output and stroke volume. Mixed venous oxygen saturation and reduced arterial saturation reflect low cardiac output and pulmonary edema. Pulmonary and systemic vascular resistances are elevated. With end-stage disease, the peak systolic left ventricular and aortic pressures drop.

Myocardial biopsy

At present, preparation for cardiac transplant and post-transplant follow-up care are the main indications for biopsy. If facilities are available, molecular or metabolic studies could be additional indications for academic and research purposes. Rarely, suspected metabolic diseases (isolated myocardial carnitine deficiency, rare forms of glycogen storage disease, fatty acid oxidation defects) or persistent myocarditis might require biopsy for confirmation.

Special precautions, as mentioned above, should be taken to minimize complications.

Specimens should be subjected to both light and electron microscopy. Polymerase chain reaction (PCR) assay and metabolic studies should be performed as indicated.

The most important aspect is the availability of sufficient level of expertise for interpretation of the findings.

PCR has been used to aid the detection of viral antigens in myocardial tissue in patients with DCM. Studies have revealed an association between viral antigens and DCM. However, a proportion of the studies gave negative results. A recently published meta-analysis of the studies on DCM gave an odds ratio of 3.8 to the association between presence of viral antigens in DCM. The results are influenced by factors like contamination from the reference strain used in the laboratory and choice of the controls. It also is not clear whether these positive cases among DCM actually represented acute myocarditis rather than DCM.

Diagnostic evaluation: Flow charts (Tables 3 and 4) will guide evaluation of children with suspected DCM to arrive at a firm diagnosis.

Table 3. Flow Diagram for Diagnosis of DCM in Children

Step I: Diagnosis of DCM

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 radiograph	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
Electrocardiograph	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 Echo 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 hyper-echoic papillary muscles, retrograde continuous flow into proximal pulmonary artery	Diagnose anomalous left coronary artery from pulmonary artery
	Dilated left ventricle (>95^th percentile) with global hypokinesia (fractional shortening <25%, ejection fraction <50%), and no demonstrable structural heart disease	Diagnose dilated cardiomyopathy

Table 4. Flow Diagram for Diagnosis of DCM in Children

Step II: Identification of Any Underlying Etiology style="spacerun: yes">

Approach	Findings	Conclusion
Clinical features	Positive family history	Genetic cause for DCM
	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, low calcium and magnesium, electrolytes disturbances	Help in the initial management; occasionally point to a cause of DCM, especially in neonate
	Elevated acute phase reactants and cardiac enzymes	Myocarditis
	Positive viral titers	Viral myocarditis
	Low serum carnitine	Systemic carnitine deficiency
	Hypoglycemia with low or no acidosis (ketosis) High insulin, low free fatty acid Low insulin, high free fatty acid	Infant of diabetic mother, nesidioblastosis Defect in fatty acid oxidation or carnitine metabolism
	Hypoglycemia with moderate or high acidosis (ketosis) normal lactate and abnormal urine and serum organic acids High lactate	Organic (propionic, methylmalonic) acidemias, or b-ketothiolase deficiency 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 DCM
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

Histologic Findings: Histologic features are nonspecific in the majority of patients and include myocardial cell loss with varying degree of necrosis and fibrosis. In presence of myocarditis, lymphocytic infiltration of varying degree is also present (Dallas criteria).

Medical Care:

Perform general supportive measures during acute stage management: intubation, inotropes, fluid/acid-base management.

Treat chest infections appropriately.

Treat anemia appropriately.

Oxygen inhalation is of benefit only in presence of hypoxia (as with pneumonia or pulmonary edema).

Carnitine supplements (100 mg/kg IV infusion over 30 min followed by 100 mg/kg/d as continuous infusion for 24-72 h; 25-50 mg/kg/dose PO bid/tid, not to exceed 200 mg/kg/d) reverse the myocardial dysfunction in a majority of patients affected by systemic carnitine deficiency.

Surgical Care:

Cardiac transplantation is currently the optimal treatment for DCM-induced resistant chronic congestive heart failure in children.

Limiting factors include availability of a suitable donor, complications of rejection, and life-long immunosuppression.

Palliative surgical measures bear significant mortality and morbidity in spite of 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 tried as palliative measures. Cardiomyoplasty is the transposition of electrically transformed skeletal muscle to provide systolic and diastolic augmentation to the native heart.

Implantable mechanical support devices, modified for used in infants and children, have been introduced to support the failing heart until a suitable donor is available for transplantation (bridge to transplant). Major limitations include infection, thromboembolism, disturbance from noise, and the need to recharge batteries frequently.

Prolonged support of left ventricular function with these devices has shown restoration of the native cardiac function, enabling removal of the device in a few cases. This raises the possibility that mechanical intervention at an earlier stage in viral myocarditis and dilated cardiomyopathy might prevent the deterioration of cardiac function.

Consultations:

A multidisciplinary approach is a must for optimum management and should include the following:

Pediatric cardiologist

Pediatric cardiothoracic surgeon

Pharmacist

Dietitian and nutritionist

Family physician
Occupational therapist
Psychologist
School teacher
Specialist nurse
Religious advisor (terminal stages)

Diet:

Dietary requirements are high because of the 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.

Powerful diuretics have largely obviated the need for stringent restrictions on salt and fluid intake.

Activity:

Enforced bed rest is impractical and probably unnecessary.

Often, restriction of physical activity is self-enforced.

Infants might need intravenous alimentation for relief from feeding activity.

Apart from the above, activity to the limit of tolerance should be allowed and encouraged.

In chronically ill patients, regular graded exercise has been shown to improve effort tolerance and quality of life.

Psychopathology: 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.

Medical therapy is largely symptomatic and is aimed at the underlying heart failure. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and digoxin form the initial therapy. Diuretics and digoxin give symptomatic improvement while ACE inhibitors prolong survival. Intravenous infusions of sympathomimetic inotropes may be required in resistant heart failure. Recently, the use of beta-blockers has become more extensive in childhood dilated cardiomyopathy drug therapy.

Drug Category: Diuretics -- Elimination of retained fluid and preload reduction.

Drug Name	Furosemide (Lasix) -- This is the first DOC. It inhibits reabsorption of fluid from the ascending Loop of Henle in the renal tubule. Given IV, it has venodilator action and lowers preload even before diuresis sets in. It is the first DOC in acute heart failure and in exacerbations of chronic heart failure. In addition, it is used for long-term management of chronic heart failure.
Adult Dose	40 mg PO bid 20-50 mg IV; repeat q6-8h
Pediatric Dose	1-4 mg/kg PO qd or bid 1-4 mg/kg IV q8h
Contraindications	Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion
Interactions	Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides (hearing loss of varying degrees may occur); anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible; risk of hypokalemia with concurrent administration of amiodarone and flecainide; sotalol enhances hypotension and risk of cardiac arrhythmia
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypokalemia, hyponatremia and hypotension; aggravates diabetes mellitus, porphyria, and liver failure; use with caution in pregnancy and breastfeeding; may cause hyperuricemia; may produce deafness due to ototoxicity; administer oral dose with food or milk to decrease stomach upset

Drug Name	Spironolactone (Aldactone) -- A potassium-sparing diuretic, this drug acts on the distal convoluted tubule of the kidney as an aldosterone antagonist. It exhibits synergistic action with furosemide.
Adult Dose	100-200 mg PO qd
Pediatric Dose	0.5-1.5 mg/kg PO bid
Contraindications	Documented hypersensitivity; anuria, renal failure, hyperkalemia; Addison disease
Interactions	May decrease effect of anticoagulants; ACE inhibitors, cyclosporine, potassium, and potassium-sparing diuretics may increase toxicity of spironolactone; may increase the risk of digoxin toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	GI upset; hyponatremia; hyperkalemia; hepatotoxicity; lethargy; confusion; impotence; gynecomastia; avoid salt substitutes or natural licorice

Drug Name	Amiloride (Midamor) -- Potassium-sparing diuretic acting directly on the distal renal tubule. It is usually used with a potassium-losing diuretic.
Adult Dose	5-10 mg PO bid
Pediatric Dose	0.2 mg/kg PO bid
Contraindications	Documented hypersensitivity; hyperkalemia; potassium supplementation or the use of potassium-sparing diuretics; impaired renal function
Interactions	ACE inhibitors, cyclosporin, indomethacin, and potassium supplements increase risk of hyperkalemia; NSAIDs decrease effect; increased risk of toxicity with lithium and amantadine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	GI upset, dry mouth; skin rash; confusion; postural hypotension; hyperkalemia; hyponatremia; use with caution in patients with severe hepatic insufficiency

Drug Category: ACE inhibitors -- These drugs reduce afterload and decrease myocardial remodeling that worsens chronic heart failure.

Drug Name	Captopril (Capoten) -- Accepted as an essential part of any antifailure therapy; provides symptomatic improvement and prolonged survival; prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Adult Dose	6.25-25 mg PO tid; not to exceed 150 mg tid
Pediatric Dose	0.1-1 mg/kg PO tid
Contraindications	Documented hypersensitivity; renal impairment; renal artery stenosis
Interactions	NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment, valvular stenosis, or severe congestive heart failure; hypotension; tachycardia; renal failure; persistent dry cough has been reported in 5-20% of children

Drug Name	Enalapril (Vasotec) -- ACE Inhibitor with prolonged duration of action PO; competitive inhibitor of ACE; reduces angiotensin II levels, decreasing aldosterone secretion.
Adult Dose	20-40 mg PO qd or divided bid
Pediatric Dose	0.1-1 mg/kg/d PO; not to exceed 40 mg
Contraindications	Documented hypersensitivity
Interactions	NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment, valvular stenosis, or severe congestive heart failure

Drug Category: Cardiac glycosides -- These drugs give symptomatic improvement with chronic administration.

Drug Name	Digoxin (Lanoxin) -- Improves myocardial contractility, reduces heart rate, and lowers sympathetic stimulation in chronic heart failure. Digoxin inhibits Na⁺-K⁺ ATPase pump. Sodium preferentially exchanges with calcium, increasing the intracellular calcium and resulting in an increase in contractility.
Adult Dose	Total digitalizing dose (TDD): 0.75-1.5 mg PO 50% of TDD initially; remaining 2 doses at 25% TDD q6-12h (1/2, 1/4, 1/4) Maintenance dose: 0.125-0.5 mg PO qd
Pediatric Dose	Total digitalizing dose (TDD): Preterm infant: 20-30 mcg/kg PO Term infant: 25-35 mcg/kg PO 1 month to 2 years: 35-60 mcg/kg PO 2-5 years: 30-40 mcg/kg PO 5-10 years: 20-35 mcg/kg PO >10 years: Administer as in adults 50% of TDD initially; remaining 2 doses at 25% TDD q6-12h (1/2, 1/4, 1/4) Maintenance dose: Preterm infant: 5-7.5 mcg/kg PO divided bid Term infant: 6-10 mcg/kg PO divided bid 1 month to 2 years: 10-15 mcg/kg PO divided bid 2-5 years: 7.5-10 mcg/kg PO divided bid 5-10 years: 5-10mcg/kg divided bid >10 years: Administer as in adults
Contraindications	Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; and carotid sinus syndrome
Interactions	Medications that may increase levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil; medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete A-V block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis

Drug Category: Oral anticoagulant -- To prevent recurrence of thromboembolic episodes of cardiac origin.

Drug Name	Warfarin (Coumadin) -- Interferes with hepatic synthesis of vitamin K-dependent coagulation factors. It prevents thrombus formation within cardiac chambers and venous circulation. Tailor dose to maintain an INR in the range of 2-3.
Adult Dose	5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR
Pediatric Dose	0.05-0.34 mg/kg/d; adjust dose according to desired INR
Contraindications	Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers
Interactions	Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate; medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Pregnancy	D - Unsafe in pregnancy
Precautions	Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

Drug Category: Beta adrenoceptor blockers -- Block the beta-adrenergic receptor and are modulators of the autonomic system.

Drug Name	Propranolol (Inderal) -- Inhibits both beta1- and beta2-adrenergic receptors. This drug is a nonselective adrenergic antagonist.
Adult Dose	40-80 mg PO bid initially; increase to 160-320 mg/d (some patients require up to 640 mg/d)
Pediatric Dose	1-4 mg/kg/d PO divided bid/tid
Contraindications	Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; A-V conduction abnormalities
Interactions	Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; gradually taper over 1-2 wk when discontinuing

Drug Name	Carvedilol (Coreg) -- Nonselective beta-blocker with additional direct vasodilator action.
Adult Dose	25 mg PO bid; not to exceed 50 mg bid
Pediatric Dose	0.08 mg/kg PO qd initially; increase as tolerated over 12 wk; not to exceed 0.5 mg/kg/d
Contraindications	Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; A-V conduction abnormalities
Interactions	Coadministration with rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; gradually taper over 1-2 wk when discontinuing

Drug Category: Sympathomimetic inotropes -- These are used in resistant cases as intravenous infusions and are stimulators of beta1-adrenergic receptors in the myocardium. Also useful for periodic home inotropic therapy in end stage of disease, when cardiac transplant is not feasible, to improve the quality of life. However, studies have shown increased mortality related to arrhythmogenic potential.

Drug Name	Dobutamine hydrochloride (Dobutrex) -- Synthetic catecholamine with potent cardiac stimulating properties; in addition, has direct vasodilating action on peripheral blood vessels; infusion with or without additional dopamine infusion in renal dose would be appropriate therapy for cardiogenic shock secondary to dilated cardiomyopathy.
Adult Dose	0.5 mcg/kg/min IV infusion initially; titrate to effect; not to exceed 40 mcg/kg/min
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial fibrillation or flutter
Interactions	Beta-adrenergic blockers antagonize effects; general anesthetics may increase toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Close monitoring of heart rate, blood pressure and ECG are advisable during infusion; hypovolemic state should be corrected before use

Drug Category: Antibiotics, prophylactic -- Antibiotic prophylaxis is given to patients with cardiomyopathy before performing procedures that may cause bacteremia.

Drug Name	Amoxicillin (Amoxil, Trimox) -- Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Used as prophylaxis in minor procedures.
Adult Dose	2 g PO 1 h before procedure
Pediatric Dose	50 mg/kg PO 1 h before procedure; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	Reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Ampicillin (Marcillin, Omnipen) -- For prophylaxis in patients undergoing dental, oral, or respiratory tract procedures. Coadministered with gentamicin for prophylaxis in GI or genitourinary procedures.
Adult Dose	2 g IV/IM within 30 min before starting the procedure High-risk patients: 2 g ampicillin IV/IM plus gentamicin 1.5 mg/kg IV within 30 min before starting the procedure, followed 6 h later by 1 g ampicillin IV/IM or 1 g amoxicillin PO
Pediatric Dose	50 mg/kg IV/IM within 30 min before starting the procedure; not to exceed 2 g/dose High-risk patients: 50 mg/kg IV/IM ampicillin plus gentamicin 1.5 mg/kg IV within 30 min before starting the procedure, followed 6 h later by ampicillin 25 mg/kg IV/IM or amoxicillin 25 mg/kg PO
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Drug Name	Clindamycin (Cleocin) -- Used in penicillin-allergic patients undergoing dental, oral, or respiratory tract procedures. Useful for treatment against streptococcal and most staphylococcal infections.
Adult Dose	600 mg PO 1 h before procedure or 600 mg IV within 30 minutes before starting the procedure
Pediatric Dose	20 mg/kg PO 1 h or 20 mg/kg IV within 30 min before starting the procedure; not to exceed 600 mg/dose
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Name	Gentamicin (Garamycin) -- Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Used in conjunction with ampicillin or vancomycin for prophylaxis in GI or genitourinary procedures.
Adult Dose	1.5 mg/kg IV; not to exceed 120 mg/dose; administer with ampicillin 2 g IV 30 min before starting the procedure
Pediatric Dose	1.5 mg/kg IV; not to exceed 120 mg/dose; administer with ampicillin (50 mg/kg IV; not to exceed 2 g/dose) within 30 min before starting the procedure
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Vancomycin (Vancocin) -- Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. Use creatinine clearance to adjust dose in renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing GI or genitourinary procedures.
Adult Dose	Dental, oral, or upper respiratory tract surgery: 1 g IV, infused over 1 h, to complete infusion within 30 minutes before starting the procedure GI/GU procedures: 1 g IV, infused over 1 h, to complete infusion within 30 minutes before starting the procedure plus gentamicin 1.5 mg/kg IV within 30 minutes of starting the procedure.
Pediatric Dose	Dental, oral, or upper respiratory tract surgery: 20 mg/kg IV, infused over 1 h, to complete infusion within 30 minutes before starting the procedure GI/GU procedures: 20 mg/kg IV, infused over 1 h, to complete infusion within 30 minutes before starting the procedure plus gentamicin 1.5 mg/kg IV within 30 minutes of starting the procedure.
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal failure, neutropenia; red man syndrome is caused by too rapid IV infusion (dose given over a few minutes) but rarely happens when dose given IV over 2 h or as PO/IP administration; red man syndrome is not an allergic reaction

Further Inpatient Care:

Admission is necessitated with exacerbations of heart failure often precipitated by chest infection. Admission also may be necessary for reevaluation when the first line of medications fail to give significant relief to symptoms (resistant heart failure). During terminal illness, patients and parents might opt to stay in the hospital.

Besides taking aggressive steps to treat the precipitating factor (infection, anemia), compliance to 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. In the long-term, however, they increase myocardial irritability leading to arrhythmia.

Recently, use of beta-blocker therapy in children with chronic congestive heart failure (CHF) from DCM was shown to improve symptoms and left ventricular ejection fraction. Carvedilol is a beta-adrenergic blocker with additional vasodilating action but has not been tried in children.

Anticoagulants and antiarrhythmic agents, particularly amiodarone, are often used in patients with low myocardial contractility and symptomatic arrhythmias, respectively. Results are encouraging.

Automatic implantable cardioverter-defibrillators reduce sudden death in adults with chronic CHF. Their use in children has been limited, however.

Studies in adults who died from heart failure report significant fatigue, dyspnea, and pain in the days before death. It is logical to conclude similar problems in children.

Design a comprehensive program involving the family, specialist nurse, physician, and religious advisors to make the final days for the child and family more peaceful.

Transfer:

Transfer may be required for further diagnostic evaluation and surgical intervention (cardiac transplantation).

Complications:

Congestive heart failure

Pneumonia

Cardiac arrhythmias (supraventricular and ventricular)

Infective endocarditis

Thromboembolism

Venous thrombosis

Cardiac cirrhosis

Post-transplant complications

Sudden, unexplained death

Prognosis:

If a treatable cause is discovered, prognosis is better.

Prognosis is worst for cardiomyopathy secondary to storage diseases that do not have effective therapy.

History of viral illness in the 3 months before onset may point to a better prognosis.

For DCM with no obvious detectable etiology, outcome depends on severity of myocardial dysfunction, improvement during the first year after onset, compliance to therapy and availability of timely transplant.

Degree of depression of fractional shortening or ejection fraction at time of initial echocardiography, elevation of left ventricular end diastolic pressure, and cardiothoracic ratio have all been applied as predictors of outcome, although they are not often predictive. Other possible prognostic factors include age at onset (better for infants), presence of symptomatic arrhythmias, and thromboembolic episodes.

Arrhythmic death can occur even after the left ventricular ejection fraction has returned to normal.

Following cardiac transplant, survival rates as high as 77% at 1 year and 65% at 5 years have been reported in children.

Patient Education:

Education is a continuous process from the time of diagnosis. Explain disease process, management, and prognosis to parents and older patients.

Compliance to medication is an important factor in success of therapy. Compliance is affected by complexity of the dosing regime, perceptions of illness, benefits of treatment, and family dynamics.

Increased dosage frequency, timing of drug administration during school hours, and unpalatability increase noncompliance. Young children may not understand the benefits of treatment, whereas adolescents may exhibit independence or denial.

Family dynamics can include parental anxiety, parental preoccupation, and unstable marital relationships.

Effective communication is a confounding problem when a family member who is not the primary care provider accompanies the child to the hospital.

Educating and counseling parents and caretakers, with the help of models, diagrams, and written instructions, lessen the problem.

Concordance, in which the pediatrician forms a therapeutic alliance with the caretaker and the child, and negotiation with the family to choose the best-fit regime have been found to improve compliance.

Avoid competitive sports.

Avoid activity beyond tolerance.

In chronically ill patients, regular graded exercise has been shown to improve effort tolerance and quality of life.

Caption: Picture 1. Chest radiograph of a child with idiopathic dilated cardiomyopathy

Caption: Picture 2. Echocardiographic picture taken from apical 4-chamber view showing dilated left atrium and left ventricle in a child with idiopathic dilated cardiomyopathy display:none;hide:all'>

Caption: Picture 3. This is a color Doppler echocardiographic picture taken from apical 4-chamber view showing dilated left atrium and left ventricle with the blue jet of mitral regurgitation in a child with idiopathic dilated cardiomyopathy. Mild tricuspid regurgitation also is shown.

Caption: Picture 4. This is an echocardiographic picture taken from parasternal long axis view showing dilated left atrium and left ventricle in a child with idiopathic dilated cardiomyopathy.

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