Pediatric Dilated Cardiomyopathy Workup

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.

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

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.

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.

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.

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.

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.

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).

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.

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.

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)

*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)