Pediatric Restrictive Cardiomyopathy

Updated: Dec 27, 2015
  • Author: Kimberly Y Lin, MD; Chief Editor: Syamasundar Rao Patnana, MD  more...
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Overview

Background

Restrictive cardiomyopathy (RCM) is a rare disorder in children that is characterized by restrictive filling and reduced diastolic volume of one or both ventricles with normal or near-normal systolic function and wall thickness. [1] The heart is structurally normal, although histologic abnormalities are often present, depending on the etiology of the restrictive cardiomyopathy. 

RCM may manifest as a solitary abnormality, although restrictive filling patterns of the left ventricle can be seen in patients with dilated or hypertrophic cardiomyopathy. Because this disease is so rare, its pathogenesis, natural history, and treatment are not well defined. Associated syndromes and noncardiac conditions include scleroderma, amyloidosis, sarcoidosis, Gaucher disease, Hurler disease, glycogen storage diseases, hypereosinophilic syndrome, and carcinoid syndrome.

Some investigators have divided RCM into the following subtypes: (1) pure restrictive cardiomyopathy, (2) hypertrophic-restrictive cardiomyopathy, and (3) mildly dilated restrictive cardiomyopathy. [2]

Therapy for idiopathic restrictive cardiomyopathy (RCM) is limited to symptomatic treatment and is often ineffective in improving outcome. Surgical options are limited to heart transplantation. A healthy lifestyle is recommended, although there is an increased risk of sudden death and worsening heart failure, which generally precludes competitive sports participation.

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Pathophysiology

The pathophysiology of RCM is diverse. This condition can be associated with diseases such as amyloidosis, hemosiderosis, hypereosinophilia, and endocardial fibroelastosis; it can also occur secondary to radiation therapy and certain medications. However, these may be considered separate diseases because the etiology is known.

In true idiopathic RCM, endomyocardial biopsy and pathologic specimen findings are usually abnormal, although they may not be diagnostic for any single disease. Findings include myofibrillar disarray, myocyte hypertrophy, and interstitial fibrosis. Morphologic findings include atrial enlargement without increased ventricular wall thickness or ventricular cavity dilation, the absence of eosinophilic infiltration, and the absence of pericardial disease. [2, 3]

The physiologic consequences of RCM are more uniform than those of its diverse etiologies. Typically, there is abrupt premature cessation of ventricular filling in early diastole, causing a dip-and-plateau or square-root pattern on ventricular pressure tracings. Therefore, ventricular filling is limited to early diastole. Thisis probably related to decreased compliance of the ventricle and ultimately results in the development of atrial dilatation. Typical hemodynamic characteristics include normal systolic function and equalization of increased ventricular end-diastolic pressures.

The natural history of RCM varies and is at least partially dependent on the etiology, if any is identified. Because the number of patients that have subclinical RCM is unknown, the natural history can be determined only when symptoms develop. Once symptoms develop, the morbidity and mortality are high (see Prognosis and Complications).

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Etiology

In most pediatric cases of RCM, the etiology is unknown. Risk factors are also unknown.

RCM can be divided into 2 main types, myocardial and endomyocardial. The myocardial type, in turn, can be further classified into 2 subtypes, noninfiltrative and infiltrative.

Noninfiltrative myocardial forms of RCM include the following:

  • Idiopathic (the most common etiology of RCM in children)
  • Familial
  • Post–cardiac transplant
  • Diabetic cardiomyopathy with a restrictive component

Infiltrative myocardial causes of RCM include the following:

  • Amyloidosis (the most common cause of RCM in adults outside of the tropics) [4]
  • Hemochromatosis
  • Lysosomal storage diseases such as Gaucher disease, Hurler disease, and Fabry disease

Endomyocardial causes of RCM include the following:

  • Endomyocardial fibrosis (EMF; the most common cause of restrictive cardiomyopathy in adults and children in certain tropical areas of Africa, Asia, and South America) [5]
  • Hypereosinophilic syndrome (also known as Loeffler endocarditis)
  • Carcinoid heart disease
  • Metastatic cancers
  • Pseudoxanthoma elasticum
  • Certain drugs, including anthracyclines and methysergide
  • Mediastinal radiation

Most cases of RCM (including idiopathic ones) are not known to be inherited, although there have been reports of families in whom multiple members are affected by a combination of hypertrophic and restrictive cardiomyopathies. [6] Additionally, some inherited infiltrative disorders can cause restrictive cardiomyopathy. These include Fabry disease (X-linked recessive), Gaucher disease (autosomal recessive), glycogen storage diseases, and autosomal recessive hemochromatosis.

Significant progress has been made in defining the genetic causes of RCM. These causes include mutations in the following genes: troponin I, troponin T, alpha-cardiac actin, myosin, myosin-binding protein C, filamin-C, and desmin. [7, 8, 9, 10, 11, 12, 13, 14, 15, 16]  Genetic mutations have also been identified in several diseases associated with RCM, including lamin A/C in Emery-Dreifuss muscular dystrophy, transthyretin in amyloidosis, and RSK2 in Coffin-Lowry syndrome. [17, 18, 19]

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Epidemiology

Although its exact prevalence is unknown, RCM is the least common cardiomyopathy and represents approximately 2-5% of pediatric cardiomyopathies in the United States. [20, 21, 22] Reports from Europe and Australia suggest similar international infrequency. [23, 24] However, in tropical areas of Africa, Asia, and South America where endomyocardial fibrosis is endemic, the prevalence may be much higher. [25, 26]

Idiopathic RCM has been described in children of all ages. Some studies suggest that idiopathic RCM may be slightly more common in girls than in boys. [27, 28] No racial predilection is known.

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Prognosis

The prognosis of RCM can be very poor in children. Patients are at risk for various acute and chronic complications that require close monitoring. Those who ultimately require and undergo heart transplantation before development of severe, irreversible pulmonary hypertension have a reasonably good prognosis after transplantation, comparable to those with other types of cardiomyopathy.

Mortality in children with idiopathic RCM is high, particularly in the absence of heart transplantation. Rates have been reported to be as high as 63% within 3 years of diagnosis and 75% within 6 years of diagnosis. [20] Actuarial survival range is 44-50% at 1-2 years after presentation. [20, 28] This decreases to 29-39% at 3-5 years after presentation. [22, 28]

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