What is restrictive cardiomyopathy?

Restrictive Cardiomyopathy

Restrictive cardiomyopathy is a cardiac disorder characterized by impaired ventricular filling with normal or near-normal systolic function, leading to elevated diastolic pressures and poor prognosis with 50% mortality at 5 years after diagnosis. 1

Definition and Pathophysiology

Restrictive cardiomyopathy (RCM) is defined by:

• Abnormal diastolic function with restrictive ventricular filling pattern
• Exaggerated increases in diastolic pressures with small increases in ventricular filling volumes
• Normal or near-normal ejection fraction
• Normal or mildly increased ventricular wall thickness
• Normal or reduced ventricular chamber size
• Significant biatrial enlargement (classic morphological pattern)

The key pathophysiologic feature is increased myocardial stiffness, resulting in rapid pressure rises with minimal volume changes during diastole. 1, 2

Clinical Presentation

Patients with restrictive cardiomyopathy typically present with:

• Dyspnea due to elevated diastolic pressures
• Prominent signs of fluid retention
• Fatigue and weakness reflecting impaired cardiac output reserve
• No evidence of cardiomegaly on chest radiography
• Massive biatrial enlargement with normal ventricular size on imaging

This presentation can be similar to constrictive pericarditis, making differential diagnosis crucial. 1

Etiology

Restrictive cardiomyopathy can be classified by four main disease mechanisms:

1. Interstitial fibrosis and intrinsic myocardial dysfunction

   • Idiopathic restrictive cardiomyopathy
   • Scleroderma
   • Radiation-induced fibrosis

2. Infiltration of extracellular spaces

   • Cardiac amyloidosis
   • Sarcoidosis

3. Accumulation of storage material within cardiomyocytes

   • Hemochromatosis
   • Fabry's disease
   • Glycogen storage diseases

4. Endomyocardial fibrosis

   • Eosinophilic cardiomyopathy
   • Endomyocardial fibrosis

Additional causes include familial/genetic forms with sarcomeric protein mutations (troponin I, troponin T, desmin, and α-crystallin). 1, 2, 3

Diagnostic Evaluation

Diagnosis requires a multimodal approach:

• Echocardiography: Shows restrictive filling pattern, biatrial enlargement, normal ventricular size, and normal/near-normal systolic function
• Cardiac MRI: Helps identify specific etiologies (e.g., amyloidosis, sarcoidosis, hemochromatosis)
• ECG: May show conduction defects (common in amyloidosis), atrial fibrillation, or ventricular arrhythmias
• Endomyocardial biopsy: Often required to establish specific diagnosis
• Genetic testing: For familial forms, especially in childhood-onset cases
• Cardiac catheterization: Demonstrates restrictive hemodynamics with rapid early diastolic pressure drop followed by plateau (square root sign)

Histological findings vary by etiology and can be diagnostic (e.g., amyloid or iron deposition). 1, 2, 4

Associated Features and Complications

• Atrial fibrillation is common across most etiologies
• Ventricular arrhythmias are prevalent in sarcoidosis and some familial forms
• Cardiac conduction defects often accompany amyloidosis
• Sudden cardiac death risk is significant, with up to half of cardiac amyloidosis patients dying suddenly 1

Treatment

Treatment options are limited and often challenging:

• Heart failure management: Diuretics for congestion, but careful monitoring is needed as they may reduce cardiac output
• Arrhythmia management: Rate control for atrial fibrillation
• ICD implantation: Recommended for patients with sustained ventricular arrhythmias causing hemodynamic instability who have good functional status and >1 year life expectancy 1
• Disease-specific therapies:
  • Tafamidis for transthyretin amyloidosis (reduces mortality by 30% and cardiovascular hospitalizations by 32%) 5
  • Iron chelation therapy for hemochromatosis
  • Stem cell transplantation for certain amyloidosis cases

Most pharmacological therapies used in other forms of heart failure (digoxin, calcium channel blockers, beta-blockers, ACE inhibitors) have limited value or may be harmful in RCM. 1, 6

Prognosis

The prognosis for restrictive cardiomyopathy is generally poor:

• 50% survival at 5 years after diagnosis
• In children, transplant-free survival rates are 48%, 34%, and 22% at 1,2, and 5 years, respectively
• Risk factors for mortality include NYHA functional class, left atrial size, and male sex 1

Important Clinical Considerations

• Early recognition is critical but often delayed
• Differentiation from constrictive pericarditis is essential, as constrictive pericarditis can be surgically treated
• Comprehensive evaluation for underlying systemic diseases is mandatory as some causes have specific treatments
• Cardiac transplantation may be considered in selected cases without significant systemic involvement