Pediatrics

Cardiomyopathies

OVERVIEW: What every practitioner needs to know

Are you sure your patient has a cardiomyopathy? What are the typical findings for this disease?

There are five different types of cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular dysplasia, and left ventricular noncompaction). The type of cardiomyopathy is primarily defined by characteristic findings on an echocardiogram. Not all patients with cardiomyopathy have symptoms. Regardless of the type of cardiomyopathy, if symptoms are present they are the result of congestion related to diastolic dysfunction and/or low cardiac output (heart failure). When a patient with cardiomyopathy experiences heart failure, the most common presenting symptoms are:

Shortness of breath

Exercise intolerance

Abdominal pain

What other disease/condition shares some of these symptoms?

Patients with cardiomyopathies can be asymptomatic and present with a murmur. The murmur could be secondary to mitral regurgitation in dilated cardiomyopathy or outflow obstruction in hypertrophic cardiomyopathy.

If a patient presents in acute decompensated heart failure with a cardiomyopathy, the signs and symptoms can resemble those of a viral respiratory infection, pneumonia, or viral gastroenteritis. Patients can be short of breath, complain of cough, vomiting, poor appetite, and poor energy level. Patients with cardiomyopathy can also present with syncope, palpitations, or chest pain.

What caused this disease to develop at this time?

A common cause of dilated cardiomyopathy is viral infection of the heart muscle (viral myocarditis). It is not clear why common viruses cause cardiomyopathy in some individuals and not in others. It is very uncommon for viral myocarditis to develop more than once.

Patients with viral myocarditis may have presenting signs and symptoms similar to a respiratory infection. The history may be significant for a viral infection 4-6 weeks before presentation, but this is not always the case. More importantly, families usually note fatigue, feeding intolerance, and increased work of breathing in the preceding days to weeks. On physical examination the patient is usually tachycardic and tachypneic with increased work of breathing, with or without murmur; wheezing or crackles can be heard and hepatomegaly or peripheral edema may be seen. A gallop or accentuated P2 may also be heard. A chest radiograph is usually notable for cardiomegaly with or without pulmonary edema.

Genetics can predispose a patient to the development of cardiomyopathy. Hypertrophic cardiomyopathy is commonly autosomal dominant and related to mutations in genes of the sarcomere. Dilated cardiomyopathy can also be familial, although the genetics are not as well defined as for hypertrophic cardiomyopathy. Any child with a first-degree relative with hypertrophic or dilated cardiomyopathy should have a screening echocardiogram and be evaluated by a cardiologist.

Although familial hypertrophic cardiomyopathy typically develops in adolescence, it can develop sooner in some children, so serial echocardiograms beginning in early childhood are recommended for patients considered at risk because of their family history. The onset of familial dilated cardiomyopathy is less predictable, so early evaluation by a cardiologist is recommended.

There are many syndromes that are associated with cardiomyopathy. In most of these instances, the child is diagnosed with the syndrome and associated cardiomyopathy in infancy. Noonan, Costello, and LEOPARD syndromes are associated with hypertrophic cardiomyopathy. Barth syndrome is associated with left ventricular noncompaction or dilated cardiomyopathy and can present with hypotonia or symptoms of heart failure in infancy. Barth syndrome is also associated with neutropenia and growth failure and is diagnosed by a genetic test detecting a mutation in the TAZgene.

Neuromuscular disorders are commonly associated with cardiomyopathy. Duchenne and Becker muscular dystrophy are associated with dilated cardiomyopathy. Friedrich ataxia is associated with hypertrophic cardiomyopathy. In these patients, the onset of cardiomyopathy can be in early childhood or adolescence, so serial evaluation by echocardiography is recommended at the time of diagnosis of the neuromuscular disorder.

Metabolic syndromes and disorders of the mitochondria are associated with varied forms of cardiomyopathy. Pompe disease is associated with hypertrophic cardiomyopathy and may present with hypotonia, feeding problems, or respiratory difficulties in the first few months of life. Mitochondrial diseases can cause dilated cardiomyopathy, but definitive diagnoses in these patients is very challenging and requires skeletal and/or heart biopsies.

Children exposed to cardiotoxic chemotherapy (anthracyclines) are at risk for the development of dilated cardiomyopathy. This risk increases with the cumulative dose of anthracycline, bolus/rapid adminstration of anthracyclines, and associated chest wall radiation. Anthracycline cardiomyopathy typically presents years after exposure, so serial echocardiograms should be considered for patients at highest risk or at any time signs or symptoms concerning for cardiomyopathy develop in an at-risk patient.

Although rare in developed countries, severe nutritional deficiencies of selenium, thiamine, and iron can lead to dilated cardiomyopathy. The history in these patients with respect to the mother's nutritional status if breast feeding or excessive whole milk intake can be clues to these underlying problems. These causes usually present in infancy and can be diagnosed by laboratory studies targeting these essential nutrients.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

In general, the diagnosis of cardiomyopathy is made by echocardiography. Laboratory testing should be tailored to the type of cardiomyopathy suspected based on the underlying condition or syndrome if present. Typically, ordering the most appropriate laboratory testing should be done in consultation with an expert in pediatric cardiomyopathy to avoid ordering unnecessary tests. Many of the metabolic and genetic tests can be extremely expensive and require expert interpretation.

Would imaging studies be helpful? If so, which ones?

A chest radiograph is a useful screening tool that can be helpful when the history or physical examination is suspicious for a cardiomyopathy. The presence of cardiomegaly or pulmonary edema would be suggestive of cardiomyopathy.

Echocardiography is the mainstay of diagnosing all forms of cardiomyopathy. Cardiac structure, function, and valve regurgitation can be defined. In some infants and toddlers, sedation may be necessary to attain a good quality study, but the test is noninvasive and does not involve radiation. A complete echocardiogram takes 20-30 minutes to complete and is costly because of the technical expertise required to perform and interpret the study.

Cardiac magnetic resonance imaging (MRI) is an evolving imaging modality that can help clarify the diagnosis of some types of cardiomyopathy as well as provide useful cardiac functional information. In hypertrophic cardiomyopathy, more complete and accurate assessment of the absolute thickness of all areas of the left ventricle can be determined. There are areas of the left ventricle that are not easily visualized on echocardiography but can be seen well with the use of MRI. In addition, areas of fibrosis within the left ventricle can be defined by cardiac MRI in the form of delayed gadolinium enhancement.

Although it is not yet clear, areas of fibrosis could be foci for abnormal rhythm development. Arrhythmogenic right ventricular dysplasia is difficult to diagnose definitively by echocardiography but can be well defined by cardiac MRI when specific imaging sequences are performed. Left ventricular noncompaction is also often difficult to define by echocardiography, but on MRI the presence of abnormal trabeculations within the left ventricle can be more easily seen. Cardiac MRI does not involve radiation, but because the study requires the patient to lie still for long periods, and breath holding on command is required, general anesthesia is necessary in infants and young children.

If you are able to confirm that the patient has a cardiomyopathy, what treatment should be initiated?

Acute treatment of cardiomyopathy is dependent on the clinical status of the patient. If a patient is acutely ill from heart failure, transfer to a center specializing in the care of children with heart disease should be instituted immediately. In general, first-line therapy for acute decompensated heart failure should be given in consultation with a center specializing in the care of children with heart disease but includes maintenance of an airway, diuresis as tolerated, and consideration of afterload reduction with milrinone .

Inotropes such as dopamine, dobutamine, and epinephrine should be avoided in patients with heart failure because they are associated with an increased risk of mortality. Because patients in heart failure are usually fluid overloaded, fluid adminstration is not usually recommended. However, aggressive diuresis also may not be well tolerated because these patients are dependent on a certain level of preload to maintain cardiac output.

An electrocardiogram should be obtained because identification of heart rhythm is critical. Arrhythmias such as supraventricular tachycardia, if long standing, can lead to a dilated cardiomyopathy and heart failure. Conversion to sinus rhythm can reverse this type of cardiomyopathy.

The risk of hypotension and cardiac arrest are significant if sedation or anesthesia is administered to a patient in heart failure because of withdrawal of intrinsic catecholamines. Therefore, intubation or central line placement that require sedation in infants and young children should be done only when absolutely necessary. Noninvasive ventilation or the use of peripheral intravenous lines could serve as alternatives in some patients in the acute setting.

In neonates and infants, structural abnormalities can result in heart failure or dilated cardiomyopathy. Coarctation of the aorta can be identified clinically by absence of femoral pulses or a greater than10 mm Hg difference between upper and lower extremity blood pressure readings. Initiation of prostaglandin infusion can be lifesaving in patients with a critical coarctation of the aorta. Anomalous origin of the left coronary artery from the pulmonary artery should be considered in infants 2-6 months old presenting with dilated cardiomyopathy or in cardiogenic shock. Both of these congenital heart problems can be diagnosed by echocardiography and are able to be surgically repaired.

Outpatient (or chronic) treatment for cardiomyopathies in children is dependent on the type of cardiomyopathy present and the patient's symptoms. Medical management of heart failure and cardiomyopathies in children should be performed in consultation with a cardiologist specializing in this area because of the complexity of these patients.

The mainstay of treatment for dilated cardiomyopathy is angiotensin-converting enzyme (ACE) inhibitors, which are used for afterload reduction and their beneficial effects on preventing adverse ventricular remodeling. Digoxin is recommended for patients with symptoms of heart failure, although no improvement in mortality has been demonstrated. Diuretics are used to control congestive symptoms such as dyspnea and peripheral edema. Diuretics may also help decrease wall stress in the setting of an extremely dilated ventricle. Beta-blockers are considered for patients with symptomatic heart failure based on their beneficial effects for adults with heart failure.

Patients with hypertrophic cardiomyopathy are sometimes treated with beta-blockers or calcium channel blockers if outflow tract obstruction is present. The decreased heart rate and therefore increased ventricular filling time associated with beta-blockers can result in decreased outflow obstruction, especially during exercise. The negative inotropic effect of calcium channel blockers is thought to be responsible for the improvement in outflow obstruction with that class of medication. Some patients with associated chest pain have also derived benefit from beta-blocker therapy. In general, volume depletion/dehydration should be avoided in patients with hypertrophic cardiomyopathy as this can exacerbate the outflow tract obstruction.

Frequent monitoring for abnormal heart rhythms—especially ventricular tachycardia—is important in all patients with cardiomyopathy because this could be associated with an increased risk of sudden death (Table I). Placement of an implantable cardioverter defibrillator is considered for patients with cardiomyopathy and an increased risk of sudden death. However, complications such as infection and inappropriate discharge are common in children, so this must be taken into consideration as well. Hypertrophic cardiomyopathy is the most common cause of sudden death in young persons and participation in high-intensity exercise as well as competitive sports is to be avoided.

Table I.

Risk Factors for Sudden Cardiac Death in Hypertrophic Cardiomyopathy
Aborted sudden death event
Nonsustained ventricular tachycardia
Syncope
Family history of sudden cardiac death
Extreme hypertrophy
Abnormal blood pressure response to exercise

What are the adverse effects associated with each treatment option?

The most common side effects of ACE inhibitors include dizziness, feeling lightheaded, or a nonproductive cough. These medications should be used with caution in combination with nonsteroidal antiinflammatory medications because of the possibility of renal toxicity.

Side effects of beta-blockers include fatigue, poor energy, and depression. Exacerbation of asthma and diabetes can occur, so this class of medications should be used with caution in patients with these comorbidities.

Side effects of diuretics are dizziness or feeling lightheaded (because of volume depletion) as well as thirst or craving of salt.

What are the possible outcomes of cardiomyopathy?

Fortunately cardiomyopathy is a rare condition in children, with an incidence of dilated cardiomyopathy (the most common form) of approximately 1/100,000 children younger than the age of 18 years. However, the outcome of dilated cardiomyopathy in general is quite poor, with a 5-year rate of death or transplantation of about 40%. Unfortunately there have been few improvements made in treatment options for dilated cardiomyopathy specific to children over the past few decades.

Counseling families of children with newly diagnosed cardiomyopathy varies depending on the form of cardiomyopathy present and the clinical presentation. Children presenting with new-onset dilated cardiomyopathy who are in cardiogenic shock may require the use of mechanical circulatory support (e.g., ventricular assist device or extracorporeal membrance oxygenation. There is a high rate of complications for patients supported with these types of devices, such as bleeding, stroke, infection, and death. Other patients may require mechanical ventilation and inotropic support, which will result in prolonged hospitalization.

Heart transplantation is an option for some patients with end-stage heart failure as a result of cardiomyopathy. A heart transplant is considered for patients who continue to experience heart failure despite maximal medical therapy. Although heart transplantation is not a cure, it is the best option for survival in patients with severe heart failure secondary to cardiomyopathy.

Patients who have had a heart transplant will require lifelong immune suppression, and complications include graft rejection, transplant coronary artery vasculopathy, secondary malignancies, infections, and death. The benefit of heart transplantation is that many pediatric heart recipients live full and happy lives after heart transplantation. These children can attend normal schools, participate in sports, and in general develop normally.

Are additional laboratory studies available; even some that are not widely available?

Commercial genetic testing is becoming more widely available for the different forms of cardiomyopathy. There are panels of genes that are designed to include the most common mutations associated with dilated cardiomyopathy, hypertrophic cardiomyopathy (including panels specific for Noonan and Costello syndromes), arrhythmogenic right ventricular dysplasia, and left ventricular noncompaction. All genetic testing should be done with the assistance of a cardiomyopathy specialist and/or a genetic counselor. The implications of genetic testing are an important consideration before ordering the test.

How can cardiomyopathy be prevented?

Unfortunately there is no effective method for preventing the development of most cardiomyopathies. Avoidance of toxic exposures or nutritional deficiencies that can cause cardiomyopathy obviously would be beneficial.

What is the evidence?

Because pediatric cardiomyopathy and heart failure are so rare, there is a paucity of controlled trials for the treatment options recommended. In fact, of the 49 recommendations included in the treatment guidelines for pediatric heart failure, none is based on level A evidence (multiple randomized trials), 7 are based on level B evidence (single randomized trial or multiple nonrandomized trials), whereas the remaining 42 recommendations are based on level C evidence (expert consensus).

In 2007, Shaddy et al reported the results from the first and only randomized controlled trial of medical therapy (carvedilol, a nonspecific beta-blocker) in children with heart failure. In the pediatric carvedilol trial, there was no significant clinical benefit of beta-blocker therapy over placebo for children with symptomatic heart failure. These results are in stark contrast to the improvement noted in adults with heart failure treated with beta-blockers. One of the criticisms of the pediatric carvedilol trial was the heterogeneous nature of the patients enrolled—patients with cardiomyopathy and congenital heart disease were included. For that reason there remains some controversy in the field as to the utility of beta-blockers for the treatment of children with heart failure.

Rosenthal, D, Chrisant, MR, Edens, E. "International Society for Heart and Lung Transplantation: Practice guidelines for management of heart failure in children". J Heart Lung Transplant. vol. 23. 2004. pp. 1313-33.

(Guidelines detailing treatment recommendations for children with heart failure.)

Shaddy, RE, Boucek, MM, Hsu, DT. "Carvedilol for children and adolescents with heart failure: a randomized controlled trial". JAMA. vol. 298. 2007. pp. 1171-9.

(A multicenter, randomized, placebo-controlled trial of low- and high-dose carvedilol for the treatment of children with symptomatic heart failure. There was no benefit of carvedilol over placebo in this study. However, there was a trend toward improvement in children with dilated cardiomyopathy and a trend toward worsening in response to carvedilol in children with a single systemic ventricle [e.g., hypoplastic left heart syndrome]).
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