Cardiomyopathy is defined as an intrinsic abnormality in systolic and/or diastolic function of the myocardium and represents a significant morbidity and mortality to both pediatric and adult populations. First introduced in 1957, cardiomyopathy encompasses a group of disorders characterized by myocardial disease in the absence of coronary arterial disease, hypertension, or valvar heart disease. Our understanding of the molecular and genetic mechanisms responsible for cardiomyopathy has increased exponentially over the last decade. Although the disease process may appear similar in adults and children, children represent a unique population, and data regarding predictors of adverse clinical outcomes in this group are lacking. Echocardiographic assessment of children with cardiomyopathy often represents the first line of investigation and proper assessment is critical in establishing the diagnosis, allowing a strategy of appropriate management and additionally providing prognostic information for the patient. This chapter aims to discuss the echocardiographic evaluation of all forms of cardiomyopathy excluding hypertrophic cardiomyopathy, which will be discussed in a separate chapter.
CLASSIFICATION OF CARDIOMYOPATHY
There are several classification systems for cardiomyopathy and some groups have even advocated a molecular classification. The Australian cardiomyopathy study, which studied all cases between 1987 and 1996, reported an annual incidence of 1.24 per 100,000 children <10 years of age. The most common forms of cardiomyopathy in this cohort include dilated cardiomyopathy (DCM) (58.6%), hypertrophic cardiomyopathy (HCM) (25.5%), restrictive cardiomyopathy (RCM) (2.5%), and left ventricular noncompaction cardiomyopathy (LVNC) (9.2%). Among the study population, lymphocytic myocarditis was present in 25 of 62 cases (40%) of dilated cardiomyopathy. Sudden cardiac death (SCD) occurred in 11 cases (3.5%). The North American Cardiomyopathy study, which looked at the northeastern and southern USA, reported similar findings to those reported in the Australian study.
GENETICS OF CARDIOMYOPATHY AMONG CHILDREN
There are characteristic racial and genetic factors which predispose to various forms of cardiomyopathy. For each form of cardiomyopathy, specific mutations have been identified which are responsible for encoding proteins which compose the cytoskeletal structure. A disruption in the cytoskeletal structure consequently translates to a defective phenotype in these children. Certain populations may have a predisposition to cardiomyopathy also. Arrhythmogenic right ventricular dysplasia (ARVD) has a dramatically increased prevalence among the Italian population and there have been reports of increased risk of HCM among North Americans, Western Europeans, and Japanese.
CHARACTERIZATION OF CARDIOMYOPATHIES
Cardiomyopathies can be classified into the following:
4.Left ventricular noncompaction cardiomyopathy
5.Arrhythmogenic right ventricular dysplasia/ cardiomyopathy
6.Neuromuscular disorders and storage disorder–induced cardiomyopathy
8.Others, including arrhythmia-induced and anthracycline- induced cardiomyopathies
Dilated cardiomyopathy (DCM) is the commonest form of cardiomyopathy and is defined as a patient having a dilated and poorly contracting left ventricle, namely a left ventricular ejection fraction (LVEF) <40% with a left ventricular end-diastolic dimension (LVEDD) >2 z-scores. These patients develop congestive heart failure as a consequence of impaired LV +/- RV systolic function. The etiology underlying this disease comprises multiple genetic and metabolic disorders and some are provided in Table 23.1. Differentiation from myocarditis is important, as in myocarditis there may be a significant recovery of LV contractility following resolution of the viral process.
Causes and Prevalence of DCM
Approximately 50% of cases are idiopathic, with an overall prevalence of 36.5 per 100,000 patients (Table 23.2). The majority of cases of DCM become manifest in the fourth decade of life, however the disease will often declare itself in childhood.
The Cardiac Cytoskeleton
The myocardium acts as a mechanical syncytium, coupling individual myocytes to provide a concerted myocardial contraction. Force is generated by the actin–myosin interaction and this energy is transmitted to adjacent sarcomeres at Z discs and between myocytes at the intercalated discs. There is an extensive network of proteins which link these sites. Dystrophin and actin represent two essential proteins in this process (Fig. 23.1), and mutations within these components often lead to defective force transmission, which is accompanied by progressive left ventricular dilatation and failure (Frank Starling curve exceeded). The progressive dilatation of the LV results in increased wall stress (Laplace’s law) and increased mismatch of myocardial oxygen supply and demand. With continued ventricular remodeling with ongoing heart failure, cardiac fibroblasts proliferate, and mechanically stable collagen is degraded by metalloproteinases and an excess of poorly cross-linked collagen accumulates within the interstitium. This results in increased muscle mass, ventricular dilatation, and wall thinning. Eventually cardiac apoptosis occurs with noninflammatory programmed cell death.
Genetics of DCM
Several genetic loci have been identified to be responsible for DCM. X-linked cardiomyopathy was one of the earliest detected genetic causes of DCM, highlighting the crucial role of dystrophin in maintaining integrity of the cytoskeleton. Other loci include 1p1–1q1, 1q32, 2q31, 3p22–p25, 9q13–q22, 10q21–23, and 15q14. Recently LMNA mutations have been associated with a poor prognosis in DCM.
Clinical Features of DCM
The most common symptoms are dyspnea, failure to thrive, and orthopnea in older children. Physical examination will reveal tachycardia, elevated JVP, a displaced apical beat and a gallop rhythm. There may be a mitral or tricuspid valve regurgitation murmur if there is significant atrioventricular valvar dilatation or elevated LV end-diastolic pressure. Hepatomegaly is common, although peripheral edema is rarely seen in children compared to adults. The chest radiograph demonstrates cardiomegaly with increased pulmonary venous congestion.
Two-Dimensional Echocardiographic Evaluation of DCM
Echocardiography is diagnostic in dilated cardiomyopathy demonstrating a dilated left ventricle with depressed left ventricular systolic function. Dilated cardiomyopathy is defined as a left ventricular end-diastolic dimension >2 z-scores and a left ventricular ejection fraction <40% (Fig. 23.2). The left ventricle assumes a more globular shape in DCM rather than the normal ellipsoid pattern. In the normal heart the LV long-axis to short axis ratio exceeds 1.6. In patients with dilated cardiomyopathy, this “sphericity index” ratio decreases to less than 1.5 and approaches 1.0. The left ventricular end-diastolic dimension progressively increases, resulting in mitral annular dilatation. This results in noncoaptation of the anterior and posterior mitral valve leaflets, which results in mitral regurgitation (Fig. 23.3). The presence of elevated left ventricular end-diastolic pressures exacerbates mitral regurgitation. With progressive mitral regurgitation there is left atrial enlargement and retrograde flow into the pulmonary veins, resulting in the development of pulmonary venous and arterial hypertension. Some studies have shown correlation between survival and the severity of mitral regurgitation.
M-mode echocardiography allows for excellent spatial resolution and calculation of left ventricular end-diastolic and end-systolic dimensions and hence derivation of the LV shortening fraction (Fig. 23.4). Using Simpson’s method, serial left ventricular volumes in systole and diastole are measured and a left ventricular ejection fraction is determined (Fig. 23.5). One limitation of calculating LVEF in DCM using Simpson’s method results from LV dilatation which may make it difficult to image the LV apex from the four-chamber and two-chamber views. Myocardial drop-out in the region of the LV apex may be improved using contrast echocardiography. The presence of pulmonary arterial hypertension should be assessed from the TR jet velocity (Bernoulli equation: RV systolic pressure = (TR velocity)2 + right atrial pressure). In adult patients, a characteristic M-mode finding in DCM is an increased E-point to septal separation (EPSS) which is indicative of a reduced left ventricular ejection fraction. EPSS is the distance in millimeters from the anterior septal myocardium to the maximal early opening point of the mitral valve (Fig. 23.6). As the left ventricular internal dimension is proportional to LV diastolic volume, and maximal diastolic mitral valve excursion relates to mitral stoke volume, a reduced LV ejection fraction correlates with a reduction in the mitral valve opening and hence an increased distance between E-point and septum. In normal adult patients the EPSS measures approximately 6 mm. In addition, with a reduced LV ejection fraction, the aortic valve opening points on M-mode become rounded rather than the crisp box-like pattern in the normal functioning heart (Fig. 23.7).
Doppler evaluation of the patient with dilated cardiomyopathy yields much data regarding systolic and diastolic parameters. The stroke volume and hence cardiac output can be calculated from the time velocity integral (TVI) in the left ventricular outflow tract. Cardiac output is a multiple of stroke volume and heart rate. The stroke volume is calculated by the product of the time velocity integral and the cross-sectional area of the left ventricular outflow tract (measured as r2, r = radius of LVOT) (Fig. 23.8). Errors in measurement of the LVOT radius will exponentially result in error as this measure is squared in calculation of the cross-sectional area.
FIGURE 23.1. The cardiac cytoskeleton demonstrating dystrophin associated glycoprotein complex linking actin and myosin. (From Towbin JA, Bowles NE. The failing heart. Nature 2002; 415:227–233.)
FIGURE 23.2. Apical four-chamber view demonstrating dilated LV with depressed LV systolic function.
FIGURE 23.3. Moderate mitral regurgitation in a patient with dilated cardiomyopathy.
FIGURE 23.4. M-mode tracing demonstrating reduced LV shortening fraction in DCM.
FIGURE 23.5. Simpson’s calculation of LV ejection fraction.
The transmitral inflow and pulmonary venous Doppler patterns are important in the evaluation of left ventricular diastolic relaxation. The patterns of inflow include normal mitral inflow, abnormal relaxation, and decreased left ventricular compliance (Fig. 23.9). With abnormal relaxation there is a decrease in early inflow (E wave) velocity, an increase in A wave velocity, and prolongation of the E wave deceleration time. The pulmonary venous Doppler inflow pattern normally demonstrates a predominant systolic flow but diastolic flow predominates in impaired relaxation states. The atrial reversal wave (Ar) duration and velocity are typically normal. There are various states of decreased compliance with an initial phase of pseudonormalization where E and A wave patterns are normal; however, there is predominant diastolic pulmonary venous flow, increased Ar wave velocity and duration, and a reduction in the mitral Ea tissue Doppler velocity at the lateral mitral annulus. With further reductions in LV compliance the E/A ratio increases, diastolic pulmonary venous filling predominates, and lateral mitral Ea and Aa tissue Doppler velocities are reduced further. End-stage (grade 4) diastolic dysfunction is characterized by a high E/A ratio (typically >3 in children), primary diastolic pulmonary venous filling, and severely reduced lateral mitral Ea and Aa tissue Doppler velocities that are irreversible regardless of medical therapies. One group has reported limited utility of mitral and pulmonary venous Doppler in classifying the degree of diastolic dysfunction in children with cardiomyopathy.
FIGURE 23.6. EPSS derived from M-mode echocardiography.
FIGURE 23.7. Rounded aortic valve opening by M-mode in DCM.
FIGURE 23.8. Cardiac output derived from TVI and cross-sectional area of LVOT.
Tissue Doppler Imaging Velocities in DCM Patients
Descent of the base of the heart toward the ventricular apex provides a nonvolumetric assessment of longitudinal LV systolic function. Tissue Doppler imaging velocities at the lateral and septal mitral annuli measure the velocity of relaxation (Ea and Aa velocities) and contractility (Sa velocity) (Fig. 23.10). These are relatively load independent indices of systolic and diastolic relaxation. Sa and Ea velocities are both decreased in patients with DCM, while patients with HCM have greater decreases in Ea compared to Sa velocities. Combining the transmitral E wave velocity and the lateral mitral Ea velocity as a ratio (E/Ea ratio) allows an indirect measurement of left heart filling pressures (Fig. 23.11). In adult patients this E/Ea ratio has shown good correlation with LVEDP (r = 0.86, PCWP = 1.55 + 1.47(E/Ea)) (Fig. 23.12). Nagueh et al. demonstrated an E/Ea ratio >10 predicted LVEDP >15mm Hg with a sensitivity of 85% and specificity 93% in adult patients in normal sinus rhythm or sinus tachycardia. Accurate acquisition of tissue Doppler velocities requires consistent perpendicular interrogation of the area of myocardium being examined. Changes in angle of interrogation will result in widely varying values. Color tissue Doppler imaging may be used to assess differential myocardial velocities throughout the LV wall which is then analyzed using offline analysis.
FIGURE 23.9. Transmitral inflow patterns in patients with impaired LV relaxation.
Myocardial Performance Index (Tei Index)
In the 1990s, a novel combined index of systolic and diastolic function, the myocardial performance index, was reported in several cohorts of patients with abnormal LV systolic and diastolic function. This ratio was measured as the summation of isovolumetric relaxation and contraction times divided by the left ventricular ejection time (Fig. 23.13). Although this has shown some clinical utility in adult studies, its utility in providing prognostic information in children with DCM remains contentious.
dP/dt Measurement and Flow Propagation
Other indices of left ventricular systolic function in patients with mitral regurgitation include measurement of the dP/dt derived from continuous wave Doppler signal of the mitral regurgitant jet (Fig. 23.14). A high quality Doppler signal is required with a high sweep speed. The time change in milliseconds is determined from the point at which the velocity is 1m/s and 3 m/s. This represents the time required for a 32 mm Hg pressure change within the LV cavity. The dP/dt is then calculated = 32 ÷ time in milliseconds. A significantly reduced positive or negative dP/dt is associated with poor prognosis.
FIGURE 23.10. Tissue Doppler imaging velocities in a normal patient. Note the Ea, Aa, and Sa velocities.
FIGURE 23.11. Transmitral E/Ea as a predictor of LVEDP.
Color flow propagation (Vp) is measured using a combination of color Doppler and transmitral M-mode echocardiography. Mitral inflow propagation velocity is measured from the LV apex (Fig. 23.15). Reduced left ventricular filling velocity is associated with delayed LV filling and a reduced slope of the color M-mode signal (Fig. 23.16). With progressive LV dysfunction the propagation velocity decays, indicating a reduction in LV velocity with propagation to the apex. A reduced depth of propagation correlates with LV diastolic dysfunction. Although flow propagation has shown correlation with LV dysfunction in adults, its role in pediatric patients appears more limited, presumably due to the limited size of the distance of propagation (LV cavity) in this younger population.
FIGURE 23.12. Correlation of PCWP and E/Ea. (From Nagueh SF, Mikati I, Kopelen HA, et al. Doppler estimation of left ventricular filling pressure in sinus tachycardia. A new application of tissue Doppler imaging. Circulation. 1998;98:1644–1650.)
Strain and Strain Rate Imaging in DCM
Strain and strain rate imaging allow high resolution interrogation of regional and global left ventricular function. Strain rate is defined as the instantaneous rate of change in the two velocities divided by the instantaneous distance between the two points (Fig. 23.17). Negative values denote active myocardial relaxation and positive values denote active contraction. Strain imaging has proven more robust than most other methodologies as an early and sensitive indicator of regional wall dysfunction. Subtle alterations in ventricular regional wall systolic and diastolic function are detectable using this technique due to its excellent spatial and temporal resolution. Three-dimensional speckle tracking has been shown to be a useful tool in the evaluation of longitudinal, circumferential, and radial strain in patients with nonischemic dilated cardiomyopathy.
FIGURE 23.13. Derivation of myocardial performance index (Tei index). (From Eidem BW, Tei C, O’Leary PW, et al. Right and left ventricular function: myocardial performance index in normal children and patients with Ebstein anomaly. J Am Soc Echocardiogr.1998;11:849–856.)
FIGURE 23.14. Measurement of dP/dt.
Treatment of DCM
The mainstay of medical therapy includes diuretics, cardiac glycosides, and angiotensin-converting enzyme inhibitors (afterload reduction) if tolerated. Beta-blockers (carvedilol, metoprolol) are increasingly used to support the failing myocardium as they reduce myocardial wall stress and myocardial oxygen consumption. Carvedilol is a particularly attractive agent as it has beta-blocker and vasodilating actions. Patients in cardiogenic shock may require inotropic support. Dobutamine and milrinone (phosphodiesterase inhibitor) are the most appropriate inotropic agents. Adrenaline is associated with poorer outcomes in adult patients with congestive heart failure and likely results in further damage to the cytoskeleton. Optimizing preload and minimizing afterload appear to be the optimal means of supporting the myocardium. Occasionally patients on high inotropic support who continue to demonstrate end-organ failure require support of the myocardium using ECMO or ventricular assist devices.
In a subgroup of patients with severe mitral regurgitation, surgical repair of the atrioventricular valve is associated with an improvement in NYHA class and a reduction in left heart dimensions. Vatta et al. have provided convincing evidence that resting the myocardium results in dystrophin remodeling in patients with dilated cardiomyopathy (Fig. 23.18). The mean survival for children with DCM is 63%–90% at one year to 20%–80% at five years.
FIGURE 23.15. Calculation of flow propagation using color Doppler M-mode.
FIGURE 23.16. Reduced Vp slope in patient with depressed LV systolic and diastolic function.
Mechanical Dyssynchrony and DCM
Friedberg et al. reported a longer systole and shorted diastole in patients with heart failure. They also studied mechanical dyssynchrony and its association with clinical status in children with idiopathic dilated cardiomyopathy. The standard deviation of the time from QRS peak on the ECG to peak systolic velocity interval by tissue Doppler imaging was measured in 12 left ventricular segments as a dyssynchrony index (DI) in each child with DCM over a 12-month period. A cutpoint of 32.6 ms was used to define patients with idiopathic dilated cardiomyopathy as “dyssynchronous” or “synchronous.” Patients with DCM had a higher DI than controls. A DI >32.6 ms defined mechanical dyssynchrony in 65% of patients. The number of synchronous and dyssynchronous patients reaching the end point of death or transplantation was similar, although synchronous patients had poorer actuarial survival from the time of diagnosis. Although left ventricular mechanical dyssynchrony is prevalent in DCM, the QRS duration was not sufficient to define dyssynchrony in pediatric DCM, whereas the adult-derived DI of >32.6 ms appeared to be useful. However, in this study, the presence of mechanical dyssynchrony was not associated with a worse prognosis.
FIGURE 23.17. Strain imaging in a patient with DCM.
FIGURE 23.18. Dystrophin remodeling in patients with dilated cardiomyopathy.
A later study demonstrated that the diastolic dyssynchrony index was significantly higher in children with DCM than in control subjects with a 17-ms threshold, indicating the presence of diastolic dyssynchrony. Patients who died or underwent transplantation had greater diastolic dyssynchrony and the rate of transplant-free survival was worse for DCM patients with diastolic dyssynchrony than for patients with synchronous DCM. Cardiac resynchronization therapy may have a role to play in patients with evidence of dyssynchrony, particularly in those with echocardiographic evidence of septal flash.
Echocardiographic Predictors of Outcomes in Children with DCM
Several studies have evaluated echocardiographic parameters associated with a poor prognosis. These include older age at presentation (>2 years of age), elevated LVEDP >20mm Hg, presence of mural thrombus, coexistent atrial or ventricular arrhythmias, histologic evidence of endocardial fibroelastosis, right ventricular failure (in addition to LV dysfunction), and reduced heart rate variability. Echocardiographic predictors included lower LV ejection fraction, moderate-severe MR, decreased lateral mitral Ea velocities, and LV wall thinning.
In 40% of patients presenting with acute dilated cardiomyopathy, a viral etiology or myocarditis will be responsible. It is crucial to differentiate a genetic etiology of dilated cardiomyopathy from viral mediated cytoskeletal disruption, as this has major implications for medical therapies and prognosis. There is the potential for cytoskeletal remodeling in cases of viral myocarditis, as resting the myocardium may result in full recovery of myocyte function. One would defer cardiac transplantation if at all possible in this subset of patients. Echocardiographically at this time it is not possible to differentiate myocarditis from genetic dilated cardiomyopathy. The echocardiographic findings are comparable, although early presentation may not be associated with severe LV dilatation. Regional wall motion abnormalities are common, although generalized hypocontractility is the most common presentation. Pericardial effusions are often present in the setting of myocarditis.
In the future, tissue Doppler imaging and strain rate imaging may provide some role in differentiating these diseases. Currently cardiac magnetic resonance imaging with delayed contrast hyperenhancement has been used to identify hot spots of viral myocyte infiltration. This can then be used for targeted endomyocardial biopsy to confirm the presence of virus using PCR (polymerase chain reaction). Viral agents causing myocarditis are outlined in Table 23.1.
Restrictive cardiomyopathy is characterized by impaired diastolic relaxation, abnormal ventricular compliance, and elevated left and right ventricular end-diastolic pressures. Although these latter indices can only be quantified at cardiac catheterization, echocardiography can demonstrate particular transmitral Doppler inflow characteristics such as an elevation in the E:A ratio and increased E wave deceleration time (DT). Later findings include severe biatrial enlargement. In some cases the atrial volumes may actually exceed ventricular volumes (Fig. 23.19).
The findings in RCM are similar to constrictive pericarditis (see Table 23.2). The ventricular volumes are decreased, and due to impaired relaxation, progressive enlargement of both atria occurs. Restrictive cardiomyopathy is relatively rare in children. Recent evidence has demonstrated a particularly poor prognosis once children become symptomatic, and certain institutions advocate early transplantation, especially in the setting of acute abdominal or thoracic pain, which is associated with sudden cardiac death. Mutations within desmin have been implicated in the development of RCM. Tissue Doppler imaging has also been reported to be of use in identifying subclinical ventricular dysfunction in children with RCM.
FIGURE 23.19. Apical four-chamber view demonstrating severe biatrial enlargement in restrictive cardiomyopathy.
Left Ventricular Noncompaction Cardiomyopathy
Noncompaction of the ventricular myocardium, also known as left ventricular noncompaction (LVNC), represents an arrest in the normal embryonic process of myocardial compaction, resulting in the persistence of multiple prominent ventricular trabeculations and deep intertrabecular recesses. This disorder has only recently been recognized as a distinct form of cardiomyopathy. It was previously termed “spongy myocardium,” although this term has been abandoned, as it underscores the hypothesis that the basic morphogenetic abnormality may be arrest of normal compaction of the loose interwoven meshwork of myocardial fibers in the embryo. It typically involves the left ventricle (LV), although involvement of the right ventricle has been reported. Clinical presentations include depressed systolic and diastolic function, systemic embolism, and the development of ventricular tachyarrhythmias both in adult and pediatric populations. Children with LVNC may manifest an undulating phenotype with initial DCM which progresses to HCM. The medical management of LVNC depends upon the clinical phenotype. To date a small number of patients have been identified with mutations in G4.5 (tafazzin gene) and in CYPHER/ZASP, but in the majority of cases there is no identified genetic locus. A small number of patients may also manifest Barth’s syndrome, characterized by a dilated phenotype, neutropenia, and elevated 3,5 methylgluconic aciduria. Mutations in the NOTCH pathway regulator MIB1 have also been reported.
Echocardiographic Features of LVNC
Characteristic features include multiple apical trabeculations (>3), deep recesses between the trabeculations, and a noncompacted:compacted myocardial thickness ratio exceeding 2:1 (Fig. 23.20). The location of the trabeculations may vary but are characteristically found in the cardiac apex, LV free wall, septum, and LV posterior wall. The transmitral inflow Doppler pattern may demonstrate a restrictive pattern with an increased E wave velocity, decreased A wave velocity, increased E/A ratio, and a shortened E wave deceleration time. The transmitral E/Ea ratio is often increased, reflecting elevated left ventricular end-diastolic pressure. Color Doppler imaging is useful, focusing on blood flow into the recesses between the trabeculations. Tissue Doppler imaging velocities are often decreased in children with LVNC compared to age- and gender-matched controls (Fig. 23.21). One study of children with LVNC demonstrated a decreased ejection fraction and decreased lateral mitral Ea velocity to be useful in predicting risk of death, transplantation, and need for hospital admission. Interestingly, one recent study showed preserved regional deformation in the basal segments in LVNC compared to DCM, which showed that strain and strain rate values were homogenously reduced in all LV segments.
FIGURE 23.20. Apical four-chamber view demonstrating characteristic findings of LVNC with multiple apical trabeculations, deep trabecular recesses, and a noncompacted:compacted ratio of 2:1.
Arrhythmogenic Right Ventricular Dysplasia (ARVD)
ARVD is a highly lethal disease and well-recognized cause of sudden cardiac death. There is a high prevalence of this disease in the Italian population and it is characterized by RV regional wall motion abnormalities, replacement of the right ventricular outflow tract by fibrofatty infiltration, and dilatation of the right ventricle and right atrium. These findings are best delineated by cardiac MRI using fat saturation sequences. Familial occurrence is well recognized with an autosomal dominant inheritance pattern. Genetic heterogeneity has been established with linkage analysis identifying four specific loci on chromosomes 14q23–q24 (ARVD 1), 1q42–q43 (ARVD 2), 14q12–q22 (ARVD 3), and 2q32.1–q32.3 (ARVD 4). The VT associated with this disorder has an LBBB morphology, indicating its origin from the right ventricle.
FIGURE 23.21. Decreased lateral mitral Ea velocity in a patient with LVNC requiring hospitalization for management of heart failure.
Echocardiographic evaluation of children with ARVD is challenging, and cardiac MRI is more sensitive in detecting right ventricular dilatation, regional RV systolic and diastolic abnormalities, and fibrofatty infiltration of the RV outflow tract as well. Right atrial and ventricular dilatation may, however, be recognized on routine 2D echocardiography. Complete evaluation for this condition does warrant cardiac magnetic resonance imaging. Speckle tracking imaging at rest and stress has been shown to potentially enable quantification of early RV dysfunction in ARVD.
Dilated Cardiomyopathy Associated with Duchenne Muscular Dystrophy
Duchenne’s muscular dystrophy arises secondary to a mutation in the dystrophin gene located at Xp21. This results in cytoskeletal disruption and impaired force transmission, which leads to progressive LV dilatation and LV systolic dysfunction. The echocardiographic findings are consistent with dilated cardiomyopathy. An echocardiographic marker of the onset of LV deterioration is the typical ballooning of basal segments with this “ballooning” appearance observed in the parasternal long-axis view (Fig. 23.22). Earlier detection of DCM in patients with DMD has resulted in earlier treatment of these patients. Some investigators maintain that earlier medical intervention in this disease may delay the progression of LV systolic dysfunction, although this remains contentious.
FIGURE 23.22. Parasternal long-axis view of Duchenne’s patient with classic ballooning (arrows) of posterior cardiac segments.
Storage Disorders Associated with Cardiomyopathy
Several storage disorders may result in cardiomyopathy, the majority associated with hypertrophic cardiomyopathy. Pompe’s disease (acid maltase deficiency), Danon disease (lysosomal-associated protein-2 mutation), and Fabry’s disease (alpha-galactosidase A deficiency) are among the most common metabolic disorders associated with hypertrophic phenotypes. Mitochondrial disorders are also commonly associated with cardiomyopathy, manifesting either as dilated or hypertrophic phenotypes.
This condition mimics myocarditis following infection with Trypanosoma cruzi. This demonstrates a propensity to involve the apical segment of the left ventricle and may even give rise to aneurysm formation. However, this condition is endemic to South America and is rarely encountered in the U.S. or Europe.
The etiology of this condition remains poorly understood, with some women developing cardiomyopathy late in the third trimester or soon after childbirth. The findings are similar to DCM with progressive LV dilatation, depressed LV systolic function, and significant mitral regurgitation. Potential causes may be related to preeclampsia or a viral etiology, or may be idiopathic. The prognosis is variable, with some women experiencing a full recovery and others having long-standing LV dysfunction.
Anthracyclines (doxorubicin and epirubicin) are well-established agents in chemotherapy which have cardiac toxicity as a major side effect. This cardiac toxicity is mediated via oxygen free radicals. With higher cumulative doses there is a substantial risk of cardiac dysfunction, which may occur many years after the cessation of treatment. Administration of oxygen free radical scavengers (dexrazoxane) may reduce the risk of cardiomyopathy and is undergoing clinical trials. Echocardiographic findings in anthracycline cardiomyopathy are similar to those found in dilated cardiomyopathy. Interestingly, a recent study has demonstrated strain rate abnormalities in patients after a single dose of anthracycline therapy.
Intractable atrial or ventricular tachyarrhythmias may induce LV or RV dysfunction. The most common tachycardia in this setting is atrial ectopic tachycardia. It may be difficult to prove whether the tachycardia or the cardiomyopathy is the initial insult. Echocardiographic parameters are similar to those presenting with dilated cardiomyopathy. Termination of the arrhythmia and medical therapy with beta-blockade, afterload reduction, and cardiac glycosides often result in normalization of the ventricular function.
In recent years a new form of cardiomyopathy was recognized in association with chest pain, ST segment ECG changes, and transient left ventricular apical ballooning in the absence of coronary arterial disease. Rarely, left ventricular outflow tract obstruction may occur in association with systolic anterior motion of the mitral valve. Takotsubo cardiomyopathy is typically a benign and reversible process. Differentiation from acute coronary syndrome is essential, as inotropic support may exacerbate the condition. Echocardiographic findings may include apical distension of the left ventricle and LVOT obstruction secondary to SAM.
Response of Dilated Cardiomyopathy to Assist Devices
Echocardiographic evaluation of patients with DCM who have undergone mechanical support using ventricular assist devices have demonstrated improvements in left ventricular indices and systolic function. This is corroborated by regeneration of dystrophin in patients who have undergone mechanical assistance.
Fetal Echocardiographic Diagnosis of Cardiomyopathy
Several forms of cardiomyopathy may be diagnosed prenatally. This is often the case in dilated cardiomyopathy secondary to parvovirus, which may be associated with a pericardial effusion, pleural effusions, and hydrops fetalis.
Echocardiography, including two-dimensional imaging, M-mode echocardiography, color Doppler, tissue Doppler imaging, and strain and strain rate imaging, is crucial in the complete evaluation of children with cardiomyopathy. Further studies are required to clarify prognostic factors which will allow stratification of patients into high-risk groups who require closer evaluation and potentially more aggressive intervention. Increasingly, the application of cardiac resynchronization therapy and ventricular assist devices will improve outcomes for this cohort of patients.
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1.Which of the following features are NOT characteristic of left ventricular noncompaction cardiomyopathy?
A.Greater than three trabeculations in the LV
B.Noncompaction:compaction ratio >2 in systole
C.Elevated E:A ratio on transmitral inflow Doppler
D.Restrictive physiology pattern
E.Absence of color flow between trabeculations
2.Which of the following are NOT characteristics of ARVD?
A.Dilation of the right ventricle
C.Premature ventricular contractions
D.Right-bundle branch-block type ventricular tachycardia
E.Fibrofatty replacement of the myocardium
3.Which of the following are NOT characteristics of constrictive pericarditis rather than restrictive cardiomyopathy?
A.Ea < 8 cm/s
B.Respiratory variation in IVRT
E.RVSP <40 mmHg
4.Which of the following variables are NOT involved in the Tei index ?
C.LV ejection time
5.What is apical hypertrophic cardiomyopathy associated with?
B.Involvement of the interventricular septum
C.Low voltage T waves in precordial leads
D.Development of apical aneurysms
E.Massive dilatation of both atria
6.What are the risk factors for poor prognosis in hypertrophic cardiomyopathy?
B.Absence of LVOT gradient
C.Absence of ventricular tachycardia
D.LVH on electrocardiogram
E.Normal tissue Doppler velocities
7.With what is Takosubo hypertrophic cardiomyopathy associated?
B.Reduced E/Ea ratio
D.Anomalous left coronary artery
8.Which of the following does NOT characterize end-stage (Grade 4) diastolic dysfunction?
A.Elevated E/A ratio
B.Elevated Ea lateral mitral tissue Doppler velocities
C.Elevated Aa lateral mitral tissue Doppler velocities
D.Predominant systolic pulmonary venous filling
E.Hyperdynamic LV systolic function
9.Pseudonormalization of mitral inflow Doppler is characterized by:
A.normal Doppler E and A wave patterns.
B.systolic pulmonary venous filling.
C.increased transmitral Ea velocity at lateral mitral annulus.
D.reduced Ar wave velocity.
E.elevated E/A ratio.
10.Color flow propagation (Vp) is measured using a combination of:
A.color Doppler and transmitral M-mode echocardiography.
B.tissue Doppler at the lateral mitral annulus and M-mode.
C.E/A ratio and IVCT.
D.E/A ratio and left ventricular ejection time.
E.color Doppler and Tei index.
1.ANSWER: E. There is evidence of color flow between trabeculations in patients with LV noncompaction.
2.ANSWER: D. There is a left-bundle branch-block ventricular tachycardia pattern in patients with ARVD.
3.ANSWER: A. Ea >8 cm/s in patients with constrictive pericarditis. The Ea velocity is reduced in RCM.
4.ANSWER: D. The formula for MPI is (IVCT + IVRT) / LV ET.
5.ANSWER: D. The development of apical aneurysms may occur in apical hypertrophic cardiomyopathy.
6.ANSWER: A. Myocardial bridging is associated with a risk of sudden cardiac death.
7.ANSWER: C. Apical ballooning is classically associated with Takosubo cardiomyopathy.
8.ANSWER: D. Diastolic pulmonary venous filling typically occurs in Grade 4 diastolic dysfunction.
9.ANSWER: A. Both normal diastolic function and pseudonormal filling are characterized by a normal mitral inflow E and A wave velocity.
10.ANSWER: A. Color Doppler and M-mode echocardiography are used to measure Vp.