Restrictive Cardiomyopathy

Cardiomyopathy is defined as a 'myocardial disorder in which heart muscle is structurally and functionally abnormal without coronary artery disease, hypertension, valvular or congenital heart diseases'.^[1]

There are five types, namely hypertrophic, dilated, arrhythmogenic, restrictive and unclassified. Cardiomyopathy is a significant cause of sudden cardiac death in young people.

What is restrictive cardiomyopathy?^[2]

Restrictive cardiomyopathy is a heterogeneous group of diseases characterised by restrictive ventricular function with a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness.

The defining feature is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function.

Beyond this shared haemodynamic hallmark, the phenotypic spectrum of restrictive cardiomyopathy is wide. There are 4 main disease mechanisms:

• Interstitial fibrosis and intrinsic myocardial dysfunction.
• Infiltration of extracellular spaces.
• Accumulation of storage material within cardiomyocytes.
• Endomyocardial fibrosis.

There are separate articles which discuss Cardiomyopathies, Dilated Cardiomyopathies and Arrhythmogenic Right Ventricular Cardiomyopathy.

How common is restrictive cardiomyopathy? (Epidemiology)

• Restrictive cardiomyopathy is the least common of the major cardiomyopathies, representing 2% to 5% of cases.^[3]
• However, restrictive cardiomyopathy is a leading cause of heart transplantation.
• Familial inheritance is not characteristic of restrictive cardiomyopathy.
• Restrictive cardiomyopathy is more prevalent in tropical Africa than in the Western world.

Causes of restrictive cardiomyopathy

Often no underlying cause is found. The causes of restrictive cardiomyopathies include:^[2]

Familial:

• Familial, unknown gene.
• Sarcomeric protein mutations.
• Troponin I (restrictive cardiomyopathy ± hypertrophic cardiomyopathy).
• Essential light chain of myosin.
• Familial amyloidosis.
• Transthyretin (restrictive cardiomyopathy and neuropathy).
• Apolipoprotein (restrictive cardiomyopathy and nephropathy).
• Desminopathy.
• Pseuxanthoma elasticum.
• Haemochromatosis.
• Anderson–Fabry disease.
• Glycogen storage disease.

Non-familial:

• Amyloid (AL/prealbumin).
• Scleroderma.
• Endomyocardial fibrosis.
• Hypereosinophilic syndrome.
• Carcinoid heart disease.
• Metastatic cancers.
• Radiation.
• Drugs (anthracyclines).
• Idiopathic.
• Löffler's eosinophilic endocarditis.
• Infiltrative myocardial disease.
• Cardiac amyloidosis - the most common cause of restrictive cardiomyopathy in the Western World.
• Sarcoidosis.
• The myocardium may be infiltrated by iron in haemochromatosis, glycogen in Pompe’s disease and Cori’s disease, or glycolipids in Fabry’s disease.

Restrictive cardiomyopathy symptoms (presentation)

• Usually presents with heart failure but normal systolic function: dyspnoea, fatigue, loud third heart sound, pulmonary oedema, murmurs due to valve incompetence.
• Heart size is usually normal or slightly enlarged.
• Features of right ventricular failure predominate: raised JVP, with prominent x and y descents, hepatomegaly, oedema, ascites.
• The clinical presentation of restrictive cardiomyopathy and constrictive pericarditis patients may be strikingly similar.^[4]
• Up to 75% of patients with idiopathic restrictive cardiomyopathy develop atrial fibrillation.^[5]

Investigations^[2]

Restrictive pathophysiology can be demonstrated by cardiac catheterisation or Doppler echocardiography.

The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiac MRI, but further investigations may be needed, such as endomyocardial biopsy and genetic evaluation.

Differential diagnosis

Apart from constrictive pericarditis, which is the main differential diagnosis to consider, other constrictive diseases may mimic restrictive cardiomyopathy, so the following are often considered:

• Metastases.
• Carcinoid.
• Radiation.
• Cardiac tamponade - constrictive only.

Restrictive cardiomyopathy treatment and management^[2]

• Disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.
• In children, restrictive cardiomyopathy is primarily idiopathic, and transplantation is the treatment of choice.
• Management of heart failure, including diuretics and angiotensin-converting enzyme (ACE) inhibitors. Loop diuretics to reduce pulmonary and peripheral oedema and ascites.
• Amiodarone can reduce ventricular arrhythmias in high-risk patients.
• All patients with restrictive cardiomyopathy and atrial fibrillation should be anticoagulated unless contra-indicated.^[5]
• Beta-blockers and non-dihydropyridine calcium-channel blockers may be used for rate control in those with atrial fibrillation.^[5] Beta-blockades may not be tolerated due to their negative chronotropic and, to a lesser extent, inotropic impact.
• A pacemaker may be required (patients are often not able to tolerate the cardiac dysfunction associated with arrhythmias).
• Implantable cardioverter defibrillator: to prevent sudden death in high-risk patients.^[6]
• Heart transplantation may be indicated for some patients.

Prognosis

• Variable, depending on the underlying cause.
• Restrictive cardiomyopathy due to amyloid has a worse prognosis.^[7]
• Cardiac amyloidosis is difficult to treat due to poor tolerance of most cardiovascular medication and poor outcome for transplantation.^[8]
• Recent advances in diagnosis and treatment of amyloid are, however, associated with improved prognosis.^[9]