A. Pathology and Pathophysiology

• 1.
  

  A massive ventricular hypertrophy is present. Although asymmetric septal hypertrophy (ASH), formerly known as IHSS, is the most common type, a concentric hypertrophy with symmetric thickening of the LV sometimes occurs. Occasionally an intracavitary obstruction may develop during systole, partly because of systolic anterior motion (SAM) of the mitral valve against the hypertrophied septum, called hypertrophic obstructive cardiomyopathy (HOCM). In some patients, midcavity obstruction is caused by anomalous insertion of anterolateral papillary muscle into the anterior mitral leaflet, rather than SAM.

  
  
• 2.
  

  So-called apical hypertrophic cardiomyopathy is a variant of HCM in which hypertrophy is confined to the left ventricular apex, without intracavitary obstruction (and with giant negative T waves on the electrocardiogram [ECG]). This subtype is present in about 25% of patients with HCM in Japan and less than 10% in other parts of the world.

  
  
• 3.
  

  The myocardium itself has an enhanced contractile state, but diastolic ventricular filling is impaired because of abnormal stiffness of the LV. This may lead to LA enlargement and pulmonary venous congestion, producing congestive symptoms (exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea).

  
  
• 4.
  

  About 80% of LV stroke volume occurs in the early part of systole when little or no obstruction exists, resulting in a sharp upstroke of arterial pulse.

  
  
• 5.
  

  A unique aspect of HOCM is the variability of the degree of obstruction from moment to moment.

  
  
  
  
  • a.
    

    The obstruction to LV output worsens when LV volume is reduced (as seen with positive inotropic agents, reduced blood volume, lowering of SVR).

    
    
  • b.
    

    The obstruction lessens when the LV systolic volume increases (negative inotropic agents, leg raising, blood transfusion, increasing SVR).

  
  
  
  
• 6.
  

  Ten percent to 20% of infants of diabetic mothers develop a transient form of HCM with or without LVOT obstruction. Children with Noonan syndrome commonly have HOCM (see Table 1.1 ).

B. Clinical Manifestations

• 1.
  

  Easy fatigability, dyspnea, palpitation, anginal chest pain, or syncope may be the presenting complaint. Some 30% to 60% of cases are seen in adolescents and young adults with positive family history.

  
  
• 2.
  

  A sharp upstroke of the arterial pulse is characteristic. A late systolic ejection murmur may be audible at the MLSB and LLSB or at the apex. A holosystolic murmur (of MR) is occasionally present. The intensity and even the presence of the heart murmur vary from examination to examination in patients with HOCM.

  
  
• 3.
  

  The ECG may show LVH, ST-T changes, abnormally deep Q waves with diminished or absent R waves in the left precordial leads (LPLs), and arrhythmias. Occasionally “giant” negative T waves are seen in the LPLs in patients with apical hypertrophic cardiomyopathy. Occasionally, cardiac arrhythmia or first-degree AV block is seen.

  
  
• 4.
  

  Chest radiographs may show mild LV enlargement with globular heart.

  
  
• 5.
  

  Echo studies may demonstrate the following.

  
  
  
  
  • a.
    

    LV hypertrophy can be seen as concentric hypertrophy, localized segmental hypertrophy, ASH, or localized to the apex. ASH is present when the septal thickness is 1.4 times or greater than the posterior LV wall thickness.

    
    
  • b.
    

    In obstructive type, SAM of the mitral valve may be demonstrated. Doppler peak gradient in the LVOT of ≥30 mm Hg indicates an obstructive type.

    
    
  • c.
    

    In adults, LV diastolic wall thickness ≥15 mm (or on occasion, 13 or 14 mm), usually with LV dimension <45 mm, is accepted as HCM. For children, z score of ≥2 relative to body surface area (BSA) is compatible with the diagnosis.

    
    
  • d.
    

    Highly trained athletes may show LV hypertrophy, but the LV wall thickness ≥13 mm is very uncommon. In addition, it is always associated with an enlarged LV cavity (with LV diastolic dimension >54 mm, with ranges of 55 to 63 mm). Therefore trained adult athletes with LV wall thickness >16 mm and a nondilated LV cavity are likely to have HCM.

    
    
  • e.
    

    The Doppler examination of the mitral inflow demonstrates signs of diastolic dysfunction with a decreased E velocity, an increased A velocity, and a decreased E:A ratio (usually <0.8) ( Fig. 11.2 ). These abnormalities are, however, nonspecific for HCM; they are also seen with dilated cardiomyopathy.

    
    

    
    

    
    

    

    
    

    
    

    Examples of diastolic dysfunction seen in different types of cardiomyopathy. A , A wave (the velocity of a second wave that coincides with atrial contraction); DT , deceleration time (time from the peak of the E wave to the point where the decelerating diastolic velocity reaches the baseline); E , E wave (the velocity of an early peak that coincides with the early ventricular filling); E:A, ratio of E wave to A wave velocity; IVRT , isovolumic relaxation time (measured from the cessation of ventricular outflow to the onset of the E wave; between the two small arrows ).

    
    

    From Park, M. K., & Salamat, M. (2020). Park’s pediatric cardiology for practitioners (7th ed.). Philadelphia: Mosby.

    
    

  
  
  
  
• 6.
  

  Natural history.

  
  
  
  
  • a.
    

    Obstruction may be absent, stable, or progressive (especially in genetically predisposed individuals).

    
    
  • b.
    

    Sudden and unexpected death may occur during sports or vigorous exercise, due to ventricular fibrillation.

    
    
  • c.
    

    Atrial fibrillation may cause stroke or heart failure.

  
  

C. Management

• 1.
  

  The goals of management are to (a) reduce LVOT obstruction (by reducing LV contractility and by increasing LV volume), (b) increase ventricular compliance, and (c) prevent sudden death (by preventing or treating ventricular arrhythmias). However, most therapeutic modalities used do not significantly reduce mortality rate.

  
  
• 2.
  

  General care.

  
  
  
  
  • a.
    

    Patients with HCM should avoid strenuous exercise or competitive sports, regardless of age, gender, symptoms, LVOT obstruction, or treatment.

    
    
  • b.
    

    Genetic testing for HCM sequencing and deletion/duplication panels are available from blood, oral rinse, or buccal (cheek) swabs.

    
    
  • c.
    

    First-degree relatives and other family members should be screened.

  
  
  
  
• 3.
  

  A β-adrenergic blocker (such as propranolol, atenolol, or metoprolol) or a calcium channel blocker (principally verapamil) is the drug of choice in the obstructive subgroup. These drugs reduce the degree of obstruction, decrease the incidence of anginal pain, and have antiarrhythmic actions.

  
  
  
  
  • a.
    

    A combination therapy with atenolol and verapamil may be considered in those patients with excessive LV hypertrophy and severe LVOT obstruction.

    
    
  • b.
    

    In small children, propranolol is the drug of choice due to liquid formulation and a low side effect profile. The dosage is 2 to 4 mg/kg/day given in three divided doses, with the heart rate goal of 80 to 100 beats/min.

    
    
  • c.
    

    In older children, metoprolol is typically used.

    
    
  • d.
    

    In infants of diabetic mothers, β-adrenergic blockers are used when the LVOT obstruction is present. In most of these infants, LV hypertrophy spontaneously resolves within the first 6 to 12 months of life.

  
  
  
  
• 4.
  

  Prophylactic therapy with either β-adrenergic blockers or verapamil is controversial in patients without LVOT obstruction. Some favor prophylactic use of these drugs even in the absence of LVOT obstruction; others limit prophylactic drug therapy to young patients with a family history of premature sudden death and those with particularly marked LVH.

  
  
• 5.
  

  The following drugs are contraindicated: digitalis, other inotropic agents, and vasodilators tend to increase LVOT obstruction; diuretics may reduce LV volume and increase LVOT obstruction (but may be used in small doses to improve respiratory symptoms).

  
  
• 6.
  

  For drug-refractory patients with obstruction, Morrow’s myotomy-myectomy or percutaneous alcohol ablation may be considered.

  
  
  
  
  • a.
    

    In Morrow’s procedure, hypertrophied LV septum is resected through a transaortic approach to reduce the obstruction.

    
    
  • b.
    

    In alcohol ablation, absolute alcohol is injected into a target septal perforator branch of the left anterior descending coronary artery to produce “controlled” myocardial infarction.

  
  
  
  
• 7.
  

  Implantable cardioverter defibrillator (ICD) has been proved to be effective in preventing sudden death. The following are risk factors for sudden death in HCM and may be indications for an ICD.

  
  
  
  
  • a.
    

    Prior cardiac arrest (ventricular fibrillation)

    
    
  • b.
    

    Spontaneous sustained ventricular tachycardia (defined as three or more beats at ≥120 beats/min on Holter ECG)

    
    
  • c.
    

    Family history of premature sudden death

    
    
  • d.
    

    Unexplained syncope, particularly in young patients

    
    
  • e.
    

    LV thickness ≥30 mm, particularly in adolescents and young adults

    
    
  • f.
    

    Nonsustained VT

    
    
  • g.
    

    Abnormal exercise blood pressure (BP) (attenuated response or hypotension)

  
  
  
  
• 8.
  

  Cardiac arrhythmias.

  
  
  
  
  • a.
    

    Ventricular arrhythmias are treated with propranolol, amiodarone, and other antiarrhythmic agents, guided by serial ambulatory ECG monitoring.

    
    
  • b.
    

    Atrial fibrillation (AF) occurs more often in patients with LA enlargement. For new-onset AF, electrical cardioversion followed by anticoagulation with warfarin (superior to aspirin) is recommended. Amiodarone is generally considered as the most effective agent for preventing recurrence of AF.

  
  
  
  
• 9.
  

  Infants of diabetic mothers

In most cases, the LV hypertrophy spontaneously resolves within the first 6 to 12 months of life. β-Adrenergic blockers, such as propranolol, may help the LVOT obstruction, but treatment usually is not necessary. Digitalis and other inotropic agents are contraindicated because they may worsen the obstruction.

A. Causes

• 1.
  

  The cause of the condition is idiopathic in about 50% of the cases. Twenty percent to 35% of patients with idiopathic cardiomyopathy have been shown to have inherited familial DCM. Among the familial types, an autosomal dominant inheritance pattern is most frequent (occurring in 30% to 50%); X-linked, autosomal recessive; and mitochondrial inheritance patterns are less common.

  
  
• 2.
  

  Among the known causes of DCM are myocarditis (46%) and neuromuscular diseases (≈25%), followed by familial cardiomyopathy, active myocarditis, and others. The most frequently recognized familial form is Duchenne muscular dystrophy. Some cases of idiopathic dilated cardiomyopathy may be the result of subclinical myocarditis.

  
  
• 3.
  

  Some patients with idiopathic DCM may have tachycardia-induced cardiomyopathy, which is related to chronic tachycardia (usually atrial or supraventricular tachycardia).

  
  
• 4.
  

  Other rare causes of DCM include infectious causes other than viral infection (bacterial, fungal, protozoan, rickettsial), endocrine-metabolic disorders (hyperthyroidism and hypothyroidism, excessive catecholamines, diabetes, hypocalcemia, hypophosphatemia, glycogen storage disease, mucopolysaccharidoses), and nutritional disorders (kwashiorkor, beriberi, carnitine deficiency).

  
  
• 5.
  

  Cardiotoxic agents such as doxorubicin and systemic diseases (such as connective tissue diseases) can also cause dilated cardiomyopathy.

B. Pathology and Pathophysiology

• 1.
  

  In DCM, a weakening of systolic contraction is associated with dilatation of all four cardiac chambers. Dilatation of the atria is in proportion to ventricular dilatation.

  
  
• 2.
  

  Intracavitary thrombus formation is common in the apical portion of the ventricular cavities and in atrial appendages, and it may give rise to pulmonary and systemic embolization.

  
  
• 3.
  

  Histologic examinations from endomyocardial biopsies show varying degrees of myocyte hypertrophy and fibrosis. Inflammatory cells are usually absent, but a varying incidence of inflammatory myocarditis has been reported.

C. Clinical Manifestations

• 1.
  

  Fatigue, weakness, and symptoms of left heart failure (e.g., dyspnea on exertion, orthopnea) may be present.

  
  
• 2.
  

  On physical examination, signs of CHF (e.g., tachycardia, pulmonary crackles, weak pulses, distended neck veins, hepatomegaly) may be present. A prominent S3 with or without gallop rhythm is present. A soft systolic murmur of MR or TR may be audible.

  
  
• 3.
  

  The ECG commonly shows sinus tachycardia, LVH, and ST-T changes.

  
  
• 4.
  

  Chest radiographs show generalized cardiomegaly, often with signs of pulmonary venous congestion.

  
  
• 5.
  

  Echo studies are diagnostic and may include unexpected findings in an asymptomatic patient.

  
  
  
  
  • a.
    

    The LV and RV are markedly dilated with poor contractility. The LA may be enlarged.

    
    
  • b.
    

    Fractional shortening (FS) and ejection fraction (EF) are reduced.

    
    
  • c.
    

    Intracavitary thrombus and pericardial effusion may be present.

    
    
  • d.
    

    The mitral inflow Doppler tracing demonstrates a reduced E velocity and a decreased E:A ratio: nonspecific signs (see Fig. 11.2 ).

  
  
  
  
• 6.
  

  Laboratory tests: The following lab tests may help identify the causes of DCM.

  
  
  
  
  • a.
    

    Urine for organic and amino acids, 3-methylglutaconic acid (i.e., Barth syndrome)

    
    
  • b.
    

    Blood studies for complete blood count, comprehensive metabolic panel, lactate, calcium, magnesium, carnitine/acylcarnitine, thyroid function, creatine kinase and its MB fraction (CK-MB), troponin, brain natriuretic peptide (BNP) or its N-terminal fragment (NT-proBNP)

    
    
  • c.
    

    Genetic testing for DCM sequencing and deletion/duplication panels are available from blood, oral rinse or buccal (cheek) swabs.

  
  
  
  
• 7.
  

  Although echo study is diagnostic, cardiac catheterization can be helpful (1) to exclude anomalous coronary artery, (2) to predict etiology and prognosis by obtaining endomyocardial biopsy, and (3) to evaluate for possible cardiac transplantation including measurement of pulmonary vascular resistance.

  
  
• 8.
  

  Natural history. Progressive deterioration is the rule rather than the exception for many patients. Cardiac arrhythmias, systemic or pulmonary embolization, and CHF are common causes of death. Review of literature in children has suggested approximately one-third of patients die, one-third recover completely, and one-third improve with some residual cardiac dysfunction.

D. Management

When no identifiable and treatable cause of DCM is found, therapy is supportive and consists of (a) anticongestive regimens, (b) control of significant arrhythmias, and (c) minimizing the risk of thromboembolic complications.

• 1.
  

  Anticongestive treatment. Angiotensin-converting enzyme (ACE) inhibitors, β-adrenergic blockers, or combination of both are used. Diuretics and digoxin may also be added.

  
  
  
  
  • a.
    

    ACE inhibitors (captopril, enalapril) are the first line of drug to use, along with pulsed use of diuretics. ACE inhibitors reduce congestive symptoms by moving the Frank-Starling curve to the left and upward with resulting reduction in cardiac afterload and increase in stroke volume (see Fig 19.1 ) .

    
    
  • b.
    

    The beneficial effects of carvedilol, a β-adrenergic blocking agent, have been reported in adult patients as well as children with DCM. The use of β-adrenergic blocking agents is somewhat unorthodox, given poor contractility of the ventricle. Studies suggest that activation of the sympathetic nervous system may have deleterious cardiac effects (rather than being an important compensatory mechanism, as traditionally thought). β-Adrenergic blockers may exert beneficial effects by a negative chronotropic effect with reduced oxygen demand, reduction in catecholamine toxicity, inhibition of sympathetically mediated vasoconstriction, or reduction of potentially lethal ventricular arrhythmias.

    
    
  • c.
    

    Diuretics (furosemide) and digoxin are also frequently added to the treatment. Aldosterone antagonists (spironolactone) have also been shown to be beneficial with a decrease in the risk of death.

  
  
  
  
• 2.
  

  Antiplatelet agents (aspirin) should be initiated. The propensity for thrombus formation in these patients may prompt use of anticoagulation with warfarin. If thrombi are detected, they should be treated aggressively with heparin initially and later switched to long-term warfarin therapy.

  
  
• 3.
  

  Control of significant arrhythmias.

  
  
  
  
  • a.
    

    Amiodarone is effective and relatively safe in children.

    
    
  • b.
    

    For symptomatic bradycardia, a cardiac pacemaker may be necessary.

    
    
  • c.
    

    An implantable ICD may be considered for high-risk patients. Children who are considered to have risk factors for sudden death in DCM include (a) LV end-diastolic dimension z score >2.6, (b) age at diagnosis <14 years, and (c) an LV posterior wall thickness–to–end-diastolic dimension ratio of <0.14.

  
  
  
  
• 4.
  

  If carnitine deficiency is considered as the cause for the cardiomyopathy, carnitine supplementation should be started.

  
  
• 5.
  

  Beneficial effects of growth hormone (for 3 to 6 months) were reported in adults as well as children with DCM. Administration of recombinant human growth hormone (0.025-0.04 mg/kg/day for 6 months) may improve LVEF, increase LV wall thickness, reduce the chamber size, and improve cardiac output.

  
  
• 6.
  

  Many of these children may become candidates for cardiac transplantation.

A. Etiology and Pathology

• 1.
  

  Doxorubicin cardiomyopathy, a form of dilated cardiomyopathy, is one of the common causes of chronic CHF in children. Its prevalence is nonlinearly dose related, occurring in 2% to 5% of patients who have received a cumulative dose of 400 to 500 mg/m ² and up to 50% of patients who have received more than 1000 mg/m ² of doxorubicin (Adriamycin).

  
  
• 2.
  

  Risk factors for developing doxorubicin cardiomyopathy include the following.

  
  
  
  
  • a.
    

    Patients who received cumulative dose of anthracyclines >360 mg/m ² are 40 times more likely to die than those who received <240 mg/m ² .

    
    
  • b.
    

    Age younger than 4 years.

    
    
  • c.
    

    Concomitant cardiac irradiation.

    
    
  • d.
    

    A dosing regimen with larger and less frequent doses has been raised as a risk factor but not proved.

  
  
  
  
• 3.
  

  Dilated LV, decreased contractility, and elevated LV filling pressure are present.

B. Clinical Manifestations

• 1.
  

  Patients have a history of receiving doxorubicin, with the onset of symptoms 2 to 4 months, and rarely years, after completion of therapy.

  
  
• 2.
  

  Patients are usually asymptomatic until signs of CHF develop. Tachypnea and exertional dyspnea are the usual presenting complaints. Signs of CHF may be present on physical examination.

  
  
• 3.
  

  Chest radiographs show cardiomegaly with or without pulmonary congestion or pleural effusion.

  
  
• 4.
  

  The ECG frequently shows sinus tachycardia with occasional ST-T changes. During doxorubicin therapy, a prolonged QTc interval occurs in 40% of patients immediately after a single dose.

  
  
• 5.
  

  Echocardiographic abnormalities of DCM occur within a year after doxorubicin treatment and may include the following.

  
  
  
  
  • a.
    

    The LV size is slightly increased and the LV wall thickness slightly decreased.

    
    
  • b.
    

    LV contractility (either EF or fractional shortening) is decreased. Cardiotoxicity is defined as an LVEF decline of ≥5% to <55% with heart failure symptoms or an asymptomatic decrease of LVEF ≥10% to <55%

    
    
  • c.
    

    During doxorubicin therapy, echo may show reduced EF or fractional shortening (but stopping therapy based on these changes may not be justified).

  
  
  
  
• 6.
  

  Symptomatic patients have a high mortality rate. The 2-year survival rate is about 20%, and almost all patients die by 9 years after the onset of the illness.

C. Management

• 1.
  

  Attempts to reduce anthracycline cardiotoxicity have been directed toward (a) anthracycline dose limitation; (b) method of drug administration; (c) developing less cardiotoxic analogs; (d) concurrently administering cardioprotective agents to attenuate the cardiotoxic effects of anthracycline to the heart; and (e) secondary prevention strategies of early detection of cardiotoxicity and early initiation of therapy.

  
  
  
  
  • a.
    

    Limiting the total cumulative dose to 400 to 500 mg/m ² reduces the incidence of CHF to 5%, but this dose may not be effective in treating some malignancies.

    
    
  • b.
    

    Continuous infusion therapy may reduce cardiac injury by avoiding peak levels, but a recent study reports no cardioprotection of continuous infusion.

    
    
  • c.
    

    Liposomal doxorubicin (which contains doxorubicin wrapped up in a fatty covering called liposome) preserves anticancer properties of the drug but reduces cardiotoxicity.

    
    
  • d.
    

    Concurrent administration of the cardioprotective agents such as dexrazoxane (an iron chelator), carvedilol (a β-receptor antagonist with antioxidant property), and coenzyme Q10 have shown some protective effects, without attenuating the antimalignancy effect of the drug. Among these, dexrazoxane appears to be most cardioprotective.

    
    
  • e.
    

    Early detection of cardiotoxicity by echo study (LVEF<55%) and early initiation of drug therapy with enalapril + carvedilol appear to make LV systolic function recovery more likely.

  
  
  
  
• 2.
  

  When anthracycline cardiomyopathy is diagnosed, management is the same as discussed earlier for dilated cardiomyopathy in general. Currently, the following medications are used.

  
  
  
  
  • a.
    

    Afterload-reducing agents (ACE inhibitors [e.g., enalapril]), diuretics, and digoxin are useful.

    
    
  • b.
    

    β-Blockers have been shown to be beneficial in some children with chemotherapy-induced cardiomyopathy, similar to what has been reported in adults. Carvedilol, a nonselective β-blocker, also has vasodilator effect and antioxidant activity.

  
  
  
  
• 3.
  

  Cardiac transplantation may be an option for selected patients.

A. Prevalence and Causes

• 1.
  

  Restrictive cardiomyopathy is an extremely rare form of cardiomyopathy, accounting for 5% of cardiomyopathy cases in children.

  
  
• 2.
  

  It may be idiopathic, or it may be associated with a systemic infiltrative disease (such as scleroderma, amyloidosis, and sarcoidosis) or an inborn error of metabolism (mucopolysaccharidosis). Malignancies or radiation therapy may result in restrictive cardiomyopathy.

B. Pathology and Pathophysiology

• 1.
  

  This condition is characterized by markedly dilated atria and normal or decreased volume of both ventricles. Ventricular diastolic filling is impaired, resulting from excessively stiff ventricular walls. Systolic function of the ventricle is normal (or near normal). Therefore this condition resembles constrictive pericarditis in clinical presentation and hemodynamic abnormalities.

  
  
• 2.
  

  There are areas of myocardial fibrosis and hypertrophy of myocytes, or the myocardium may be infiltrated by various materials, as seen in such conditions as amyloidosis, sarcoidosis, hemochromatosis, glycogen deposit, Fabry disease (with deposition of glycosphingolipids), or neoplastic infiltration

  
  
• 3.
  

  Development of pulmonary hypertension due to diastolic dysfunction is a significant problem in children as is in adults.

C. Clinical Manifestations

• 1.
  

  History of exercise intolerance, weakness and dyspnea, or chest pain may be present.

  
  
• 2.
  

  Jugular venous distention, hepatomegaly, a loud S2 (P2), gallop rhythm, and a systolic murmur of MR or TR may be present.

  
  
• 3.
  

  Chest radiographs show cardiomegaly, pulmonary congestion, and pleural effusion.

  
  
• 4.
  

  The ECG usually shows RAH and/or LAH. It may show atrial fibrillation and paroxysms of SVT.

  
  
• 5.
  

  Echo studies reveal the following:

  
  
  
  
  • a.
    

    Marked biatrial enlargement with normal dimension of the LV and RV, almost diagnostic signs.

    
    
  • b.
    

    Normal LV systolic function (EF) until the late stages of the disease.

    
    
  • c.
    

    Abnormal diastolic function (with increased E velocity and increased E:A ratio, and shortened deceleration time (see Fig. 11.2 ).

    
    
  • d.
    

    Possible atrial thrombus.

  
  
  
  
• 6.
  

  Differentiation of restrictive cardiomyopathy from constrictive pericarditis is important because the latter can be treated successfully with pericardiotomy.

  
  
  
  
  • a.
    

    In constrictive pericarditis, echo shows a thickened pericardium and Doppler studies show a marked respiratory variation in the filling phase, although both conditions show similar Doppler findings of diastolic dysfunction.

    
    
  • b.
    

    Cardiac catheterization shows similar hemodynamic data in both conditions, although pulmonary hypertension is worse in restrictive cardiomyopathy.

    
    
  • c.
    

    Endomyocardial biopsy reveals myocyte hypertrophy and interstitial fibrosis; it may also reveal a specific cause.

    
    
  • d.
    

    Rarely, surgical exploration may be needed.

  
  

D. Management

Treatment is directed at alleviating symptoms. In general, medical therapy does not improve survival. The prognosis is poor.

• 1.
  

  Diuretics are beneficial by relieving congestive symptoms, but they should be used judiciously because they can reduce end-diastolic pressure, making symptoms worse.

  
  
• 2.
  

  Calcium channel blockers may be used to increase diastolic compliance.

  
  
• 3.
  

  Digoxin is not indicated, because systolic function is unimpaired.

  
  
• 4.
  

  ACE inhibitors should not be used because they may reduce systemic BP without increasing cardiac output.

  
  
• 5.
  

  Anticoagulants (warfarin) and antiplatelet drugs (aspirin and dipyridamole) may help prevent thrombosis.

  
  
• 6.
  

  Permanent pacemaker is indicated for complete heart block.

  
  
• 7.
  

  Cardiac transplantation may be an option before pulmonary hypertension develops.

A. Prevalence and Pathology

• 1.
  

  This rare anomaly of unknown etiology is more prevalent in northern Italy.

  
  
• 2.
  

  The myocardium of the RV is partially or totally replaced by fibrous or adipose tissue. The RV wall may rarely assume a paper-thin appearance because of the total absence of myocardial tissue, but in others, RV wall thickness is normal or near normal. The LV is also often affected.

  
  
• 3.
  

  Histologic sections show a variable reduction in myofibrils and inflammation associated with interstitial infiltration by histiocytes and lymphocytes.

B. Clinical Manifestations

• 1.
  

  The onset is in infancy, childhood, or adulthood (but usually before age 20 years), with history of palpitation, syncopal episodes, or both. It accounts for about 5% of sudden cardiac death.

  
  
• 2.
  

  Presenting manifestations may be arrhythmias (VT, SVT) or signs of CHF.

  
  
• 3.
  

  The ECG is helpful in suspecting the diagnosis.

  
  
  
  
  • a.
    

    Tall P waves in lead II (RAH) and decreased RV forces may be present.

    
    
  • b.
    

    Inverted T waves in the right precordial leads (V1-V4) may be significant (although this pattern is normally seen in young children).

    
    
  • c.
    

    The ECG may show PVCs or ventricular tachycardia with LBBB morphology.

    
    
  • d.
    

    An incomplete RBBB pattern may be present (in >30% of the cases).

  
  
  
  
• 4.
  

  Chest radiographs usually show cardiomegaly.

  
  
• 5.
  

  Echo studies show selective RV enlargement, extreme thinning of the RV free wall, often with systolic bulging, the hallmark of the condition.

  
  
• 6.
  

  Cardiac MRI and RV angiogram show similar findings as echo studies.

  
  
• 7.
  

  Cardiac catheterization may show an elevated right atrial “a” wave. An RV angiogram usually shows RV systolic dysfunction. The hallmark of the disease is systolic bulging of the RV free wall. Endomyocardial biopsy of the RV septum shows classic pathologic changes in more than 90% of the patients but with a high false-negative rate.

  
  
• 8.
  

  A substantial portion of patients die before 5 years of age from CHF and intractable ventricular tachycardia.

C. Management

• 1.
  

  Various antiarrhythmic agents are often unsuccessful in abolishing ventricular arrhythmias.

  
  
• 2.
  

  Surgical intervention (ventricular incision or complete electrical disarticulation of the RV free wall) may be tried if antiarrhythmic therapy is unsuccessful.

  
  
• 3.
  

  ICD may be indicated in selected patients.

A. Cause

This condition results from an intrauterine arrest of normal compaction of the loose interwoven meshwork of the ventricular myocardium (which normally occurs during the first month of fetal life). Several gene mutations in patients with noncompaction cardiomyopathy have been reported; thus the genetic testing of the relatives of an index case is recommended. Familial occurrence has been reported in up to 25% with a less severe form of the disease.

B. Clinical Manifestations

• 1.
  

  Most patients with this disorder are asymptomatic. Occasionally, they may present with signs and symptoms of heart failure during infancy.

  
  
• 2.
  

  Cardiac examination may be entirely normal. Signs of LV dysfunction may be present or eventually develop. Associated dysmorphic facial features may be seen in 14%. Nearly 30% of the patients have neurologic disorders, including seizures, hypotonia, myopathy, or mental/motor retardation.

  
  
• 3.
  

  The ECG may show giant QRS complexes, sometimes with WPW preexcitation.

  
  
• 4.
  

  Chest radiographs are usually normal.

  
  
• 5.
  

  Echo findings:

  
  
  
  
  • a.
    

    Characteristic echo findings are segmental thickening of the LV wall consisting of two layers with a thin, compacted epicardial layer and an extremely thickened noncompacted endocardial layer with prominent trabeculations and deep recesses. Apical and midventricular segments of both the inferior and lateral walls are most commonly affected.

    
    
  • b.
    

    LV systolic dysfunction is seen in 35% to 90% of pediatric patients. LV diastolic dysfunction is often present.

  
  
  
  
• 6.
  

  Natural history. Heart failure usually worsens despite optimal treatment. Arrhythmias and thromboembolic events are mostly seen in adults, but they may also be seen in children.

C. Treatment

• 1.
  

  Anticongestive measures with digoxin, diuretic, and afterload-reducing agents are usually used. The use of carvedilol, a β-blocker, should be considered in patients with LV dysfunction; it has been shown to improve LV dysfunction.

  
  
• 2.
  

  All patients should be on an antiplatelet dose of aspirin. If thrombosis is detected, anticoagulation with warfarin should be started.

  
  
• 3.
  

  Appropriate antiarrhythmic therapy is indicated. Implantation of ICD may be considered for life-threatening ventricular arrhythmias.

  
  
• 4.
  

  Patients with dysmorphic features or neurologic manifestations may need detailed metabolic screening (e.g., fatty acid oxidation disorder or mitochondrial disease).

  
  
• 5.
  

  Heart transplantation is a possible option for selected patients.