Description

• Restrictive cardiomyopathy (RCM) is a heterogeneous group of myocardial diseases characterized by decreased left ventricular compliance, leading to an increase in end-diastolic filling pressures of the left ventricle or both ventricles. The ventricular cavity is usually not dilated and may be small; wall thickness may be normal or increased.
• Ejection fraction is usually normal but may deteriorate late in any of the disease processes that cause an RCM.

Epidemiology

Prevalence

• RCM accounts for approximately 5% of all cases of primary heart muscle disease.
• Of the three major cardiomyopathy phenotypes (dilated, hypertrophic, and restrictive), RCM is the least common form in Western countries.
• Amyloidosis is the most common cause of RCM in the United States.
• Endomyocardial fibrosis (EMF) is common in tropical climates and sub-Saharan Africa, accounting up to a quarter of deaths due to heart disease in those regions.

Pediatric Considerations

• RCM prognosis is especially poor in children who have progressed to heart failure.
• EMF occurs most commonly in children in sub-Saharan Africa.

Pathophysiology

• RCM is often related to myocardial infiltration or fibrosis leading to increased ventricular stiffness.
• Increased ventricular stiffness leads to increases in ventricular filling pressures.
• Heart failure symptoms are related to the increased filling pressures and inability to augment stroke volume with exercise.

Etiology and Pathophysiology

Myocardial

• Infiltrative
  • Amyloidosis: deposition of abnormally folded protein fibrils. The predominant amyloid types which involve the myocardium and progress to heart failure include light-chain (AL) (formerly “primary”) amyloidosis, wild-type transthyretin (TTR) (formerly “senile” amyloidosis), and mutant-type TTR (formerly “hereditary TTR” amyloidosis).
  • Cardiac sarcoidosis may rarely cause an RCM.
• Noninfiltrative
  • Diabetic cardiomyopathy/metabolic syndrome/obesity associated: spectrum of disease ranging from mild diastolic dysfunction to severe restrictive phenotype
  • Idiopathic cardiomyopathy: described in children and adults, but median age of diagnosis is approximately 68 years. Prognosis appears to be worse in children than in adults. Diagnosis of exclusion and biopsy are indicated to rule out other causes.
  • Familial RCM
  • Scleroderma
  • Churg-Strauss syndrome
  • Pseudoxanthoma elasticum
• Storage disease
  • Iron overload cardiomyopathy
  • Fabry disease
  • Glycogen storage disease
  • Gaucher disease
  • Hurler disease (mucopolysaccharidosis type I)
• Endomyocardial
  • EMF: marked by intense endomyocardial fibrotic thickening of the apex and subvalvular regions, markedly enlarged atria
  • Hypereosinophilic syndrome (HES) (Loffler endocarditis)
  • Carcinoid heart disease
  • Metastatic cancers
  • Radiation carditis
  • Drug induced: anthracycline (especially if treated during childhood), serotonin, methysergide, ergotamine, chloroquine, busulfan

Genetics
RCM is commonly associated with systemic diseases, some of which are inherited (i.e., hereditary amyloidosis, hemochromatosis), whereas others are multifactorial (i.e., diabetic cardiomyopathy). Familial RCM are rare and may share genetic abnormalities with hypertrophic obstructive cardiomyopathy but with different phenotypic expression.

Risk Factors

• Family history of RCM
• Inherited diseases (such as hereditary hemochromatosis, Fabry disease, mutant-type [hereditary] TTR amyloidosis, etc.)
• Frequent blood transfusions—secondary hemochromatosis
• Prior anthracycline use in childhood, exposure to other toxic agents (as noted above)
• Eosinophilic syndrome or chronic parasitic infection
• Thoracic radiation

Commonly Associated Conditions

• Heart failure, biventricular
• Pleural effusion, ascites
• Thromboembolism is common due to stasis, atrial arrhythmias, and elevated proinflammatory cytokines.
• Atrial arrhythmias
• Conduction system disease
• Extracardiac manifestations depending on underlying etiology