Pediatric Dilated Cardiomyopathy 

Updated: Jan 25, 2019
Author: Poothirikovil Venugopalan, MBBS, MD, FRCPCH; Chief Editor: Syamasundar Rao Patnana, MD 

Overview

Practice Essentials

Dilated cardiomyopathy (DCM) refers to dilation and systolic dysfunction of the ventricles (predominantly the left ventricle) with or without congestive cardiac failure. It is the most common form of heart muscle disease in children. See the image below.

Chest radiograph of a child with idiopathic dilate Chest radiograph of a child with idiopathic dilated cardiomyopathy.

Signs and symptoms

Onset of DCM is usually insidious but may be acute in as many at 25% of patients. Approximately 50% of patients with DCM have a history of preceding viral illness.

Initial presenting symptoms typically include the following:

  • Cough

  • Poor feeding

  • Irritability

  • Shortness of breath

  • Pallor

  • Sweating

  • Fatigability

  • Failure to gain weight

  • Decreased urine output

Wheezing may be an important clinical sign, suggesting congestive heart failure in infants.

Other symptoms at presentation, found in approximately 20% of patients, are as follows:

  • Chest pain

  • Palpitations

  • Orthopnea

  • Hemoptysis

  • Frothy sputum

  • Abdominal pain

  • Syncope

  • Neurologic deficit

See Presentation for more detail.

Diagnosis

Echocardiography and Doppler studies form the basis for the diagnosis of DCM. They are the most informative noninvasive tests for diagnosing the type of cardiomyopathy and the degree of dysfunction in the heart muscle.

Chest radiography may reveal cardiomegaly and pulmonary edema. Cardiomegaly that is incidentally detected on a chest radiograph or an arrhythmia that is incidentally detected on an electrocardiogram (ECG) may be the basis for initial cardiac referral. ECG may show the degree of left ventricular enlargement and reveal any abnormal heart rhythm.

The complete blood count, erythrocyte sedimentation rate, and C-reactive protein level may show evidence of acute inflammation in patients with DCM in the presence of active myocarditis.

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 in documenting dyskinetic segments in the ventricular wall.

Invasive procedures

Invasive procedures such as cardiac catheterization should be performed by experienced pediatric cardiologists and only when absolutely essential. Children with DCM are at a particular risk for complications during cardiac catheterization studies and angiography. At present, preparation for cardiac transplantation and need for myocardial biopsy are the main indications for performing the procedure.

Myocardial biopsy is usually performed in preparation for cardiac transplant and post-transplant follow-up monitoring.

See Workup for more detail.

Management

Pharmacologic therapy

Initial therapy in DCM is largely directed at the symptoms of the underlying heart failure. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers are used. 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.

Device implantation

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.

Cardiac resynchronization therapy with AV synchronous biventricular pacing has been successful in some children with DCM and left bundle branch block (LBBB).

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

See Treatment and Medication for more detail.

Background

Idiopathic dilated cardiomyopathy (DCM) refers to congestive cardiac failure secondary to dilatation and systolic dysfunction (with or without diastolic dysfunction) of the ventricles (predominantly the left ventricle) 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 are sometimes 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 regurgitation, tricuspid regurgitation, or both.

Persistent mitral regurgitation leads to thickening of the mitral valve leaflets, and, at times, distinguishing this thickening from other causes of mitral regurgitation is difficult. Thrombus formation (secondary to the low-flow cardiac output state) is often seen in the left ventricular apex and, at times, is seen in the atria. Occasionally, the right ventricle is preferentially involved in the cardiomyopathic process; this often indicates a familial basis.

Onset is usually insidious but may be acute in as many as 25% of patients with DCM, especially if exacerbated by a complicating lower respiratory infection. Cough, poor feeding, irritability, and shortness of breath are usually the initial presenting symptoms. In a patient with established disease, features of congestive heart failure are dominant. (See Presentation.)

Echocardiography and Doppler studies form the basis for the diagnosis of dilated cardiomyopathy (DCM) in most patients (see Workup). Cardiac transplantation is currently the optimal treatment for DCM-induced resistant chronic heart failure in children (see Treatment).

Patient education is a continuous process from the time of diagnosis. Explain the disease process, management, and prognosis to parents and older patients. In cases of familial DCM, patients and their families should be told about the genetic implications. For patient education information, see the Heart Center, as well as Heart and Lung Transplant.

Pathophysiology

Injury to the myocardial cell is the initiating factor that leads to cell death. If considerable cell loss occurs, the myocardium fails to generate enough contractile force to produce adequate cardiac output. This results in the activation of the following compensatory mechanisms:

  • The renin-angiotensin-aldosterone system

  • Sympathetic stimulation

  • Antidiuretic hormone production

  • Release of atrial natriuretic peptide

These compensatory mechanisms help to maintain cardiac output in the initial phase; however, as myocardial damage progresses, persistent and excessive activation can be detrimental to cardiac function, leading to overt congestive heart failure.

The theory that left ventricular noncompaction is an underlying factor in the development of DCM in young infants has received much attention.[1, 2, 3]

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

Myocardial remodeling is an important contributor to worsening heart failure.[4] Lost myocyte cells are replaced with fibrous tissue, thereby decreasing the compliance of one or more ventricles and adversely affecting performance. Aldosterone, angiotensin II, catecholamines, endothelins, and mechanical factors, such as excessive myocardial stretch and ischemia, have been identified as mediators of remodeling. The degree of left ventricular dilatation has been reported to influence short-term outcome in children listed for transplant.[5]

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

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, downregulation of myosin or conversion 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.

Etiology

Various factors have been identified as causes of myocardial damage. These are presented in Table 1, below. However, in the vast majority of patients, no specific etiology is demonstrable (ie, idiopathic DCM). Systemic carnitine deficiency and anthracycline-induced cardiomyopathy are notable exceptions. Three major factors have been implicated in the pathogenesis of myocardial damage in DCM: preceding viral myocarditis, autoimmunity, and underlying genetic predisposition.

Table 1. Factors Identified as Causes of Myocardial Damage (Open Table in a new window)

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

Viral myocarditis

Epidemiologic, serologic, and molecular studies have detected evidence of enteroviral infection, in particular coxsackievirus B, in 20-25% of patients. Evidence also implicates various other viruses. In fact, the most common associated viruses appear to vary over time.[6, 7] Currently, coxsackievirus B is likely a less common cause of DCM than in the past.

Currently, no methods can be used to distinguish cardiovirulent strains of enteroviruses from those that are not virulent. Furthermore, the presence of a virus in a patient with DCM does not necessarily establish a causal relationship. Demonstration of viral DNA or RNA by polymerase chain reaction (PCR) is a more reliable method for revealing viral myocarditis. Unfortunately, obtaining myocardial tissue is invasive.

The exact mechanism of myocardial damage (rapid destruction or a long-term slowing of cardiomyocyte function) also remains unclear.[8]

Autoimmunity

Animal studies have shown that DCM is an autoimmune disease in genetically predisposed strains of mice. In humans, 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 25-50% of DCM cases.[9] The role of genetic factors is exemplified by the studies on familial DCM.[10, 11, 12] Patients with familial DCM have an increased frequency of human leukocyte antigen (HLA)-DR4. The frequency of HLA-DQA1 0501 alleles has been reported to be significantly higher in patients with idiopathic DCM.[13]

Autosomal dominant and recessive inheritance, X-linked transmission, and polygenic and mitochondrial inheritance have all been documented. Presently known DCM genetic loci are summarized in Table 2, below.

Table 2. Summary of Genetic Loci and Disease Genes for Familial Dilated Cardiomyopathy (Open Table in a new window)

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

Mutation screening of the exons that code for actin, β myosin heavy chain (MYH7 gene), cardiac troponin T (TNNT2 gene), phospholamban (PLN gene), titin, αβ-crystallin, and the cardio-specific exon of metavinculin (VCL gene) could be helpful in detecting some forms of familial DCM.

Anthracycline cardiotoxicity

Anthracyclines, which are widely used in the management of childhood malignancies, account for as many as 30% of cases of DCM in the United States and a lesser percentage in other countries.

Besides DCM, the other manifestations of anthracycline cardiotoxicity include restrictive cardiomyopathy (symptomatic and asymptomatic), cardiac arrhythmias[14] , asymptomatic left ventricular enlargement, and more subtle changes of cardiac function.

Cardiotoxicity has two types: early onset and late onset. The 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 use of low-dose regimens, this type is becoming rare.

Electrocardiographic (ECG) changes include nonspecific ST segment and T wave changes, decreased QRS voltage, prolonged QT interval, and sinus tachycardia. Less commonly, 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 dysfunction, arrhythmias, 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 left ventricular dysfunction.

Myocyte loss underlies all these sequelae, and alteration of myocellular protein transcription by anthracyclines may contribute. Thus, the latent period is not latent at all, and more sensitive markers may be able to detect the changes earlier. Late-onset asymptomatic toxicity 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 anthracycline cardiotoxicity include the following:

  • Total cumulative dose (20% mortality with cumulative dose >550 mg/m2, 65% frequency of subtle echocardiographic changes with dose >400 mg/m2, and histologic evidence of toxicity with >240 mg/m2)

  • Female sex (higher cellular concentrations because of higher body fat percentage)

  • Young age

  • Rate of drug administration (maximum risk with doses >50 mg/m2/dose)

  • Concomitant cardiac radiation exposure or use of amsacrine

  • Black race

  • Trisomy 21

Epidemiology

In the United States, the reported incidence rate of DCM is 0.57 cases per 100,000 children.[15] The incidence rate in Finland is 2.6 cases per 100,000 children.[16] In the United Kingdom, the incidence rate is 0.87 cases per 100,000 individuals older than 16 years.[17] No reliable figures are available for the rest of the world. Genetic causes account for more than 30% of DCM cases.

DCM is reportedly more common in boys than in girls, and some forms are clearly X-linked.[15] All age groups are affected. However, studies suggest that DCM is more common in infants (age < 1 y) than in children.[15] Fetal presentation is uncommon.

Prognosis

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.[18] 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.

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

The degree of depression of fractional shortening or ejection fraction on 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. A recent review of outcomes from the Pediatric Cardiomyopathy Registry places the incidence of sudden cardiac deaths at 3% and suggests age at diagnosis younger than 14.3 years, left ventricular dilation, and left ventricular posterior wall thinning as predictors of risk.[19]

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

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

Mortality and morbidity have greatly decreased because of advances in medical management. Studies from 1975-1990 reported 70% survival at 2 years and 52% survival at 11.5 years of follow-up.[20, 21, 22, 23, 16, 24] Studies from 1992-1997 document more than 85% survival at 5 years. However, a study from Texas that included patients diagnosed from 1990-2004 found reported a survival of only 40% at a mean followup of 6.2 years.[25]

 

Presentation

History

Onset is usually insidious but may be acute in as many as 25% of patients with dilated cardiomyopathy (DCM), especially if exacerbated by 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 observed. Wheezing may be an important clinical sign, suggesting congestive heart failure in infants.

Other symptoms at presentation, found in approximately 20% of patients, are as follows:

  • Chest pain

  • Palpitations

  • Orthopnea

  • Hemoptysis

  • Frothy sputum

  • Abdominal pain

  • Syncope

  • Neurologic deficit

Approximately 50% of patients with DCM have a history of preceding viral illness. A detailed family history for familial cardiomyopathy is revealing in as many as 25% of cases.

Physical Examination

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 the following:

  • Cardiomegaly

  • Quiet precordium

  • Tachycardia

  • Gallop rhythm (S3 and/or S4)

  • Accentuated P-2

  • Murmurs of mitral and tricuspid regurgitation

Murmurs may be inconspicuous initially if the patient presents with 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 a chest radiograph.

 

DDx

 

Workup

Approach Considerations

Echocardiography and Doppler studies form the basis for the diagnosis of dilated cardiomyopathy (DCM) in most patients. Cardiomegaly that is incidentally detected on a chest radiograph or an arrhythmia that is incidentally detected on an electrocardiogram (ECG) may be the reason for initial cardiac referral.

ECG changes are usually nonspecific. The main role of ECG is to detect evidence of myocardial ischemia that might point to an anomalous coronary artery as the etiology of the cardiomyopathy.

Cardiac catheterization studies, angiography, and myocardial biopsy are preformed principally as preparation for cardiac transplantation.

Blood Studies

The complete blood count, erythrocyte sedimentation rate, and C-reactive protein level may show evidence of acute inflammation in patients with dilated cardiomyopathy (DCM) 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 does not necessarily 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) analysis 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.

Chest Radiography

Chest radiography reveals cardiomegaly with a prominent left ventricular apex and prominent pulmonary artery segment. (See the image below.)

Chest radiograph of a child with idiopathic dilate Chest radiograph of a child with idiopathic dilated cardiomyopathy.

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

Pulmonary venous congestion and frank pulmonary edema are often evident. 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.

Echocardiography and Doppler Studies

These form the basis for the diagnosis of DCM in most 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. (See the images below.) The M-mode also clearly reveals the limited excursions of the anterior and posterior leaflets during diastole.

Echocardiogram obtained from apical 4-chamber view Echocardiogram obtained from apical 4-chamber view revealing a dilated left atrium and left ventricle in a child with idiopathic dilated cardiomyopathy.
This is an echocardiogram obtained from parasterna 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.

Doppler studies show varying degrees of mitral regurgitation secondary to left ventricular dilation and possible papillary muscle dysfunction. See image below. 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.

This is a color Doppler echocardiogram obtained fr 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.

The dilatation of the mitral valve ring and the altered shape of the left ventricle cavity, which lead to change in the direction of the papillary muscles, are used to explain the secondary mitral regurgitation seen in a large proportion of children with DCM. Tissue Doppler studies have recently been reported in children with DCM.

Parameters of diastolic dysfunction are not reliable in the 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.

More detailed evaluation of mechanical dyssynchrony and its association with clinical status in children with DCM is increasingly used in specialized centers in an attempt to predict outcome.[26] The standard deviation of QRS to peak systolic velocity interval using tissue Doppler can be measured in 12 left ventricular segments as a dyssynchrony index (DI). DI reference ranges for children have not been established; the current adult-defined DI reference ranges are used to define dyssynchrony.

Longitudinal function can be assessed by serial measurements of the mitral and tricuspid valve displacements in systole. Speckle tracking strain can complement tissue Doppler imaging in identification of dyssynchrony.[27] Real time 3-dimensional echocardiography also helps to assess for dyssynchrony.[28]

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 echocardiographic contrast) can be observed 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.

Echocardiography 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. These diagnoses should be excluded as the cause of cardiomegaly by careful data acquisition and interpretation.

At times, identifying cardiomyopathy secondary to congenital mitral regurgitation (dysplastic mitral valve without stenosis) is difficult, but the abnormal anatomy of the mitral valve leaflets should help. The echo-dense papillary muscles and the 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.

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

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 in documenting dyskinetic segments in the ventricular walls. Although theoretically superior to echocardiographic measurements, their practical application is limited because of a lack of standardization and because of nonreproducibility, especially in children.

Thallium studies may identify areas of decreased myocardial perfusion, although this is seldom required.

Gallium-67 citrate (Ga-67) scintigraphy and indium-111 (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.

Electrocardiography

ECG changes are usually nonspecific. Some patients have the following findings:

  • Sinus tachycardia

  • Downward frontal plane QRS axis

  • Left atrial enlargement

  • Left ventricular hypertrophy

  • Deep Q waves with ST segment depression

  • Tall T waves in leads I, aVL, V5, V6 (these reflect left ventricular volume overload)

In more advanced disease, right-axis deviation, right atrial enlargement, and right ventricular hypertrophy are seen. These result from 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. On the other hand, if the arrhythmia is sustained, it may be the cause of the cardiomyopathy rather than the result (ie, tachycardia-induced cardiomyopathy).

Cardiac Catheterization and Angiography

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

At present, preparation for cardiac transplantation and need for myocardial biopsy are the main indications for performing the procedure. Patients should be under optimum medical therapy and kept hemodynamically stable before and after catheterization. Careful observation is required during the procedure for ventricular arrhythmias and hemodynamic deterioration.

Echocardiography should be considered after catheterization to identify any pericardial effusion secondary to subclinical perforation of the myocardium, especially if a biopsy has also been performed. Aortography may be performed to identify coronary artery anatomy, and left ventricular angiography 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 monitoring for rejection are the main indications for biopsy. If facilities are available, molecular or metabolic studies can be additional indications for academic and research purposes. Rarely, suspected metabolic diseases (eg, isolated myocardial carnitine deficiency, rare forms of glycogen storage disease, fatty acid oxidation defects) or persistent myocarditis might require biopsy for confirmation. The most important aspect is the availability of a sufficient level of expertise for interpretation of the findings.

Specimens should be subjected to both light and electron microscopy. Polymerase chain reaction (PCR) and metabolic studies should be performed when indicated. Histologic features are nonspecific in most patients and include myocardial cell loss with varying degree of necrosis and fibrosis. In the presence of myocarditis, lymphocytic infiltration of varying degree is also present (Dallas criteria).

PCR has been used to aid the detection of viral antigens in myocardial tissue in patients with DCM.[6, 7] Studies have revealed an association between viral antigens and DCM. However, a proportion of the studies gave negative results. A meta-analysis of the studies on DCM gave an odds ratio of 3.8 to the association between presence of viral antigens and DCM.

The results of PCR studies are influenced by such factors as 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.

The Two Steps to Diagnosis

Step-by-step charts (see Tables 3 and 4, below) guide the evaluation of children with suspected DCM to help clinicians arrive at a firm diagnosis.

Making the diagnosis

Table 3. Diagnosis of Dilated Cardiomyopathy in Children - Step I: Diagnosis (Open Table in a new window)

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

*In all cases of suspected DCM, careful evaluation of coronary artery origin and distribution should be performed in multiple views to confirm/exclude anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA).

Identifying the etiology

Table 4. Diagnosis of Dilated Cardiomyopathy in Children - Step II: Identification of Any Underlying Etiology (Open Table in a new window)

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

 

 

Treatment

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.

 

Medication

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.