eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Cardiomyopathy, Restrictive

Author: Vivek J Goswami, MD, Cardiologist, Austin Heart, PA
Contributor Information and Disclosures

Updated: Oct 9, 2008

Introduction

Background

Restrictive cardiomyopathy (RCM) is a rare disease of the myocardium and is the least-encountered form of cardiomyopathy. RCM accounts for approximately 5% of all cases of primary heart muscle disease. The World Health Organization (WHO) defines RCM as a myocardial disease characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. Increased interstitial fibrosis may be present. This disease may be idiopathic or associated with other diseases (eg, amyloidosis, endomyocardial disease with or without hypereosinophilia). The disease course varies depending on the pathology and treatment but is often unsatisfactory. However, the importance of an accurate diagnosis of RCM is to distinguish it from constrictive pericarditis, which also presents with restrictive physiology but is frequently curable by surgical intervention.

RCM closely mimics constrictive pericarditis in its clinical and hemodynamic profile. In the past, the correct diagnosis was frequently not made until surgical inspection demonstrated the pericardium of normal thickness and appearing normal. A subsequent myocardial biopsy would prove the diagnosis of RCM. With the improvement in diagnostic imaging, the necessity of progressing to surgical intervention to confirm the diagnosis of RCM (or constrictive pericarditis) should decrease.

Pathophysiology

This heart muscle disease creates increased stiffness of the myocardium, which causes pressure within the ventricles to rise precipitously with small increases in volume. Thus, accentuated filling occurs in early diastole, which terminates abruptly at the end of the rapid filling phase. When pressure tracings are taken at this point, they show a characteristic diastolic dip and a plateau or a square-root sign.

Patients typically have diastolic heart failure, meaning systolic function is normal, but the left ventricle has increased diastolic stiffness (reduced compliance) and cannot fill adequately at normal diastolic pressures, leading to a reduction in cardiac output due to reduced left ventricular filling volume. Systolic function usually remains normal, at least early in the disease; wall thickness is typically increased secondary to myocardial infiltration with amyloidosis, but it is usually not as pronounced as that observed in hypertrophic cardiomyopathy.

A variable reduction in systolic function may be present as the disease progresses. Reduced left ventricular filling volume leads to reduced stroke volume and low cardiac output symptoms (eg, fatigue, lethargy), whereas increased filling pressures cause pulmonary and systemic congestion. Thus, restrictive cardiomyopathy (RCM) causes symptoms and signs of left- and/or right-sided failure because it affects both ventricles, but amyloidosis typically presents with dominant right-sided fluid retention.

Some patients may have complete heart block due to fibrosis encasing the sinoatrial or the atrioventricular nodes. Interestingly, amyloid deposition in the bundle branches is rare.

Based on pathology, RCM can be classified as obliterative (ie, thrombus-filled ventricles) or nonobliterative/idiopathic.

Obliterative RCM is very rare. It may result from the end stage of the eosinophilic syndromes, in which an intracavitary thrombus fills the left ventricular apex and hampers the filling of the ventricles. The fibrosis of the endocardium may extend to involve the atrioventricular valves and cause regurgitation. Two forms of endomyocardial fibrosis exist—an active inflammatory eosinophilia and chronic endomyocardial fibrosis.

In idiopathic, or primary, RCM, progressive fibrosis of the myocardium but no thrombus formation occurs. This entity also is said to lack specific histopathologic changes.

Frequency

United States

Idiopathic restrictive cardiomyopathy is observed mainly in the United States.

International

Loeffler endocarditis is common in the temperate zone, and chronic endomyocardial fibrosis is observed in the tropics.

Clinical

History

• Patients usually complain of gradually worsening shortness of breath, progressive exercise intolerance, and fatigue.
• Fatigue and weakness are results of decreased stroke volume and cardiac output.
• Patients with restrictive cardiomyopathy (RCM) may have distention of the abdomen secondary to ascites, but they frequently have profound bilateral peripheral edema.
• Chest pain secondary to angina or chest pain mimicking myocardial ischemia can be observed, primarily in patients with amyloidosis, possibly due to myocardial compression of small vessels.
• Patients may complain of palpitations, frequently due to atrial fibrillation, which is common in idiopathic RCM.
• As many as one third of patients with idiopathic RCM may present with thromboembolic complications, especially pulmonary emboli secondary to blood clots in the legs. If atrial fibrillation is present, high risk of left atrial clots and systemic emboli is present.
• Patients may have a history of syncopal attacks from a variety of causes, but orthostatic hypotension secondary to a peripheral and/or autonomic neuropathy should be excluded.
• Syncope and sudden death are common in AL amyloidosis, but ventricular arrhythmias are uncommon. Electrical-mechanical dissociation is more common.
• Conduction disturbances are particularly common in some forms of infiltrative RCM, but not in amyloidosis.
• Depending on the etiology, patients may have a prior history of radiation therapy, heart transplantation, chemotherapy, or a systemic disease.

Physical

In respect to history and clinical profile, pericardial constriction and restrictive cardiomyopathy (RCM) may be indistinguishable. Remember that the 2 conditions can coexist in the same patient; for example, radiation therapy affects the myocardium as well as the pericardium. However, clinical features that help to differentiate the 2 conditions are described in Table 1 below.

• General examination
  • Patients may be more comfortable in the sitting position because of fluid in the abdomen and/or lungs. Weight loss and cardiac cachexia is not uncommon. Easy bruising, periorbital purpura, macroglossia, and other systemic findings, such as carpal tunnel syndrome, should advise the clinician to consider amyloidosis.
  • Increased jugular venous pressure is present, with rapid x and y descents; the most prominent finding is usually the rapid y descent. The degree of elevation of the jugular venous pressure indicates the severity of impaired filling of the right ventricle.
  • The jugular venous pulse fails to fall during inspiration and may actually rise (Kussmaul sign) in constrictive pericarditis. Although less common in RCM, Kussmaul sign cannot be used as an absolute means to distinguish RCM and constrictive pericarditis.
  • The pulse volume is decreased, consistent with decreased stroke volume and cardiac output.
  • Patients frequently have ascites and pitting edema of the lower extremities. The liver is usually enlarged and full of fluid, which may be painful. However, the liver may be enlarged and firm due to amyloid infiltration. Splenomegaly is rare.
• Cardiovascular system examination
  • Heart sounds S₁ and S₂ are normal, with a normal S₂ split.
  • A loud early diastolic filling sound (S₃) may be present but is uncommon in amyloidosis. A fourth heart sound is almost never present, possibly secondary to amyloid infiltration of the atria.
  • Murmurs due to mitral and tricuspid valve regurgitation may be heard, but they are secondary to the myocardial disease and usually not hemodynamically significant.
• Respiratory system examination
  • Breath sounds are decreased due to pleural effusion, frequently bilateral, and large in amyloidosis.
  • Crepitations or rales are rarely heard, even in advanced heart failure of amyloidosis.
• Table 1. Clinical Features of Constrictive Pericarditis and Restrictive Cardiomyopathy

  Open table in new window

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  Table

  Clinical Features	Constrictive Pericarditis	Restrictive Cardiomyopathy
  History	Prior history of pericarditis or condition that causes pericardial disease	History of systemic disease (eg, amyloidosis, hemochromatosis)
  General examination	…	Peripheral stigmata of systemic disease
  Systemic examination - Heart sounds	Pericardial knock, high-frequency sound	Presence of loud diastolic filling sound S3, Low-frequency sound
  Murmurs	No murmurs	Murmurs of mitral and tricuspid insufficiency
  Prior chest radiograph	Pericardial calcification	Normal results of prior chest radiograph

  Clinical Features	Constrictive Pericarditis	Restrictive Cardiomyopathy
  History	Prior history of pericarditis or condition that causes pericardial disease	History of systemic disease (eg, amyloidosis, hemochromatosis)
  General examination	…	Peripheral stigmata of systemic disease
  Systemic examination - Heart sounds	Pericardial knock, high-frequency sound	Presence of loud diastolic filling sound S3, Low-frequency sound
  Murmurs	No murmurs	Murmurs of mitral and tricuspid insufficiency
  Prior chest radiograph	Pericardial calcification	Normal results of prior chest radiograph

Causes

Restrictive myocardial disease may be caused by various local and systemic disorders; many of them are rare and unlikely to be observed in the United States. However, primary amyloidosis is the most common cause of restrictive cardiomyopathy (RCM) in the United States. The etiology of RCM can be listed as follows:

• Idiopathic
• Specific heart muscle disease, such as primary amyloidosis
  • Endomyocardial fibrosis
  • Eosinophilic or Loeffler endomyocarditis
  • Infiltrative
    • Amyloidosis - Common
    • Hemochromatosis (dilated left ventricle with restrictive physiology) - Rare
    • Glycogen storage disease - Rare
  • Treatment-induced
    • Following heart transplantation (See Medscape's Heart and Lung Transplant Resource Center.)
    • Following mediastinal radiation
  • Malignancy
    • Metastatic endocardial and myocardial infiltration
    • Carcinoid heart disease
• Idiopathic/primary restrictive cardiomyopathy
  • A subset of patients have heart muscle disease of unknown cause that is manifested by heart failure and restrictive hemodynamics but without significant ventricular hypertrophy, endocardial thickening or fibrosis, associated eosinophilia, or other diagnostically distinct histopathological changes.
  • Males and females have been affected equally, but the prognosis appears to be worse in children than in adults. Children require relatively high filling pressures for maintenance of systolic output, and the therapeutic margin between volume depletion (leading to low output) and volume overload (leading to congestive heart failure) is narrow.
  • A familial pattern has been noted in some cases.
  • In addition to the presenting symptoms of right and left heart failure, as many as one third of patients with idiopathic RCM may present with thromboembolic complications. Pathologically, these patients have strikingly dilated atria, which may account for the increased cardiothoracic ratio observed on a chest radiograph. Echocardiography shows bilateral atrial enlargement with normal ventricular size but significant diffuse left ventricular hypertrophy, especially with amyloidosis. The histologic features include interstitial fibrosis, which is minimal in some and extensive in others.
• Amyloidosis
  • Amyloidosis is characterized by intercellular accumulation of amyloid material in amounts sufficient to impair the function of the involved organs. Depending on the amyloid protein composition, 4 different varieties of amyloidosis exist—(1) primary or myeloma-related amyloidosis, (2) secondary amyloidosis (ie, secondary to chronic diseases), (3) senile amyloidosis, and (4) familial amyloidosis.
  • The cardiac involvement in primary amyloidosis most commonly is associated with restrictive physiology. Amyloid infiltration of the heart is common in the elderly population (systemic senile amyloidosis) and may exhibit impaired diastolic filling properties but has other features that are more typical of a dilated cardiomyopathy.
  • The myeloma protein fibrils composed of immunoglobulin light chains are deposited diffusely throughout the myocardium and create a firm and rubbery consistency. Typically, the heart does not collapse when removed from the chest during autopsy.
  • On histologic examination, interstitial deposition of insoluble amyloid fibrils in all 4 cardiac chambers is observed. This can result in increased wall thickness without cavity dilatation.
• Involvement of the valves may create regurgitant lesions, but hemodynamically and clinically significant degree of regurgitation is unusual.
  • The granular sparkling (ie, scintillating) appearance on 2-dimensional echocardiography may be present and is typical, but not diagnostic, of cardiac amyloidosis. Echocardiography more typically shows biventricular thickening out of proportion to current or prior hypertension, biatrial enlargement, a restrictive filling pattern by Doppler echocardiography, and normal systolic function/EF until late in the disease.
  • In the early stages of the disease, typical restrictive hemodynamics may not be evident; however, in more advanced cases, typical restrictive hemodynamics are more likely. A corollary of these observations is that restrictive diastolic dynamics strongly predict cardiac death in patients with amyloidosis.
  • Cardiac biopsy is needed to confirm the diagnosis if doubt remains after noninvasive tests.
• Eosinophilic cardiomyopathy and endomyocardial fibrosis
  • Severe prolonged eosinophilia due to any cause (eg, allergic, autoimmune, parasitic, leukemic, idiopathic) can lead to eosinophilic infiltration of the myocardium. The intracytoplasmic granular content of activated eosinophils is believed to be responsible for the toxic damage to the heart. This eosinophilic cardiomyopathy, also known as Loeffler endocarditis, is associated with dense endomyocardial fibrosis, intraventricular thrombus formation, and obliteration of the ventricular cavity in its late stages; therefore, it is included in obliterative RCM.
  • Endomyocardial fibrosis, which is observed exclusively in equatorial Africa and less frequently in Asia and South America, was believed to be the end stage of eosinophilic endomyocarditis. However, endomyocardial fibrosis now is considered a separate entity because it does not exhibit eosinophilia. This condition demonstrates pathology that is similar to that described above (Loeffler endocarditis) and is grouped under obliterative RCM.
  • The prognosis is poor for patients with diffuse involvement of the heart in endomyocardial fibrosis, but localized lesions involving the valves are amenable to surgical repair or removal and replacement.
• Postirradiation fibrosis
  • Radiation-induced myocardial and endocardial fibrosis also can cause RCM. However, this complication of radiotherapy, like pericardial constriction, is evident several years after treatment.
  • The differential between constriction and restriction may be particularly difficult in these patients because the 2 conditions may coexist.

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