DESCRIPTION

Various primary myocardial vs. systemic diseases, including infiltrative and storage diseases, cause stiffening of one or both ventricles, resulting in heart failure due to severely impaired diastolic function with preserved ventricular ejection fraction.

EPIDEMIOLOGY

• Restrictive cardiomyopathies are much less common than dilated and hypertrophic forms in developed countries.
• Most common forms of restrictive cardiomyopathy include: Idiopathic cardiomyopathy; amyloidosis; sarcoidosis; endomyocardial fibrosis; radiation-induced; anthracycline-induced.
• ~1/2 of restrictive cardiomyopathy cases are idiopathic.
• Most cases of idiopathic restrictive cardiomyopathy are diagnosed after age 60.

RISK FACTORS

Depends on etiology

Genetics

Genetic tests should be directed at suspected underlying etiology.

PATHOPHYSIOLOGY

• Increased stiffness in one or both ventricular walls leads to impaired diastolic relaxation. Heart failure occurs due to elevated ventricular diastolic pressures resulting in elevated atrial pressures, and congestion of the pulmonary and systemic venous systems.
• The atria typically dilate, and atrial arrhythmias such as atrial fibrillation are common.
• Ventricular systolic function is usually preserved, but may be reduced in end-stage disease.

ETIOLOGY

• Primary restrictive cardiomyopathies:
  • Idiopathic restrictive cardiomyopathy
  • Endomyocardial fibrosis
  • Loeffler endocarditis
• Secondary restrictive cardiomyopathies:
  • Infiltrative diseases:
    • Amyloidosis
    • Sarcoidosis
    • Gaucher disease
    • Hurler disease
    • Fatty infiltration
  • Storage diseases:
    • Hemochromatosis
    • Fabry disease
    • Glycogen storage disease
  • Scleroderma
  • Hypereosinophilic syndrome
  • Carcinoid heart disease
  • Metastatic cancers
  • Familial cardiomyopathy
  • Hypertrophic cardiomyopathy
  • Pseudoxanthoma elasticum
  • Churg-Strauss syndrome
  • Noonan syndrome
  • Reactive arthritis
  • Werner syndrome
  • Diabetic cardiomyopathy
  • Radiation carditis
  • Drug-induced: Anthracycline; serotonin; methysergide; ergotamine; chloroquine; busulfan

COMMONLY ASSOCIATED CONDITIONS

• Heart failure
• Atrial fibrillation
• Sudden cardiac death
• Pleural effusions
• Thromboembolism
• Other associated conditions are specific to the underlying etiology.

Outline

• Description
• Epidemiology
• Risk Factors
  • Genetics
• Pathophysiology
• Etiology
• Commonly Associated Conditions

History

• A full review of systems is key to determining etiology of restrictive cardiomyopathy.
• Inquire about: Previous malignancies and treatments; medications (serotonin; methysergide; ergotamine; chloroquine; busulfan); pulmonary, gastrointestinal, neurological, and renal problems (scleroderma; amyloidosis; carcinoid; Churg-Strauss); diabetes (hemochromatosis).
• For all etiologies, symptoms of heart failure may be present: Dyspnea; fatigue; peripheral edema; orthopnea; PND.

Physical Exam

• Signs of heart failure: S3; S4; pulmonary rales; peripheral edema; pulsatile hepatomegaly; ascites; elevated JVP.
• Kussmaul’s sign (paradoxical elevation in jugular venous pressure upon inspiration) is relatively specific, but can also be seen in constrictive pericarditis.
• A thorough physical including cardiac, pulmonary, GI, neurologic, ophthalmologic, rheumatologic, and dermatologic exam is essential to diagnosing etiology of restrictive cardiomyopathy.
• Neurologic exam: Peripheral neuropathy and carpal tunnel syndrome may suggest amyloidosis
• Ophthalmologic exam: Anterior uveitis may suggest sarcoidosis
• Dermatologic: Cutaneous flushing is seen with carcinoid syndrome; hyperpigmentation is seen with hemochromatosis; erythema nodosum is seen with sarcoidosis

DIAGNOSTIC TESTS & INTERPRETATION

Lab

• Potential lab tests are extensive, and should be directed at suspected etiology: CBC to look for anemia, eosinophilia, thrombocytopenia; hepatic and renal function tests; serum muscle enzyme levels; serum and urine protein electrophoresis and immunoelectrophoresis
• Plasma brain-natriuretic peptide may help differentiate restrictive cardiomyopathy from constrictive pericarditis.
• In hemochromatosis, serum ferritin levels are markedly elevated, along with iron levels and transferrin saturation.
• The ACE level may be elevated with sarcoidosis, although it can be within the normal range.
• Eosinophilia is associated with eosinophilic heart disease.
• Urinary 5-hydroxyindoleacetic acid levels are elevated in carcinoid.
• EKG commonly shows ST-T-wave abnormalities and atrial fibrillation, and sometimes intraventricular conduction delay.

Imaging

• Transthoracic echo:
  • Ventricles are typically nonhypertrophied (although some infiltrative processes cause hypertrophy) and nondilated (sarcoid can cause LV aneurysm). Atria are usually notably enlarged. Ventricular systolic function is typically preserved (except in terminal stages).
  • Doppler demonstration of severe diastolic dysfunction (Grade 3–4) is essential to defining restrictive cardiomyopathy:
    • The mitral inflow pattern shows a high E-to-A ratio (>2), and short deceleration time (<160 msec) and isovolumic relation time (<70 msec).
    • The pulmonary venous flow reveals a blunted systolic waveform.
    • Impaired myocardial relaxation causes blunted mitral annular tissue velocities (e’ <7 cm/sec) and high E-to-e’ ratio (>15).
    • In contrast to constrictive pericarditis, there is no significant respiratory variation in mitral and tricuspid Doppler inflow patterns.
• Cardiac MRI:
  • Can be used to identify diastolic function by analysis of LV filling rate, diastolic strains, and chamber sizes; can also differentiate constrictive pericarditis by the presence of pericardial thickening.
  • Can distinguish among various etiologies of restrictive cardiomyopathy:
    • Amyloidosis: Thickened interatrial septum and RA free wall; subendocardial delayed enhancement.
    • Endomyocardial fibrosis: LV and RV apical filling; delayed enhancement of the LV or RV apical endocardial surface; can differentiate apical hypertrophy from thrombus or tumor.
    • Hemochromatosis: Quantity of iron deposition can be reproducibly measured using T2-star mode.
• CXR:
  • Cardiac silhouette is typically normal in size.
  • Pulmonary congestion and pleural effusions may be present.
  • Bilateral hilar lymphadenopathy may be seen with sarcoid.
  • In differentiating constrictive pericarditis, look for pericardial calcification.

Diagnostic Procedures/Surgery

Right heart catheterization:

• Usually reveals a dip-and-plateau pattern ("square root sign") in ventricular pressure.
• The atrial pressure tracing may have an "M" or "W" waveform, due to rapid X and Y descents.
• LV and RV pressures are not interdependent, unlike constrictive pericarditis (in which RV pressure increases with inspiration while LV pressure decreases).

Pathological Findings

Endomyocardial biopsy:

• Necessary in many cases to determine the underlying etiology (eg, amyloidosis; Churg-Strauss; endomyocardial fibrosis; pseudoxanthoma elasticum; anthracycline).
• Idiopathic restrictive cardiomyopathy reveals interstitial fibrosis (predominantly peri-cellular), perivascular fibrosis, myocyte hypertrophy, attenuation, and degeneration.

DIFFERENTIAL DIAGNOSIS

Constrictive pericarditis also demonstrates impaired diastolic function with preserved systolic function. It can appear clinically similar in terms of symptoms and physical exam findings.

Outline

• History
• Physical Exam
• Diagnostic Tests & Interpretation
  • Lab
  • Imaging
  • Diagnostic Procedures/Surgery
  • Pathological Findings
• Differential Diagnosis

• Diuretics are useful to treat pulmonary congestion, but overly aggressive diuresis can lead to a marked decline in cardiac output.
• Digoxin can lead to toxicity at lower than usual doses in amyloidosis.
• Amiodarone can be used for treatment of atrial fibrillation.
• Chelation therapy with desferrioxamine or phlebotomy may be useful in restrictive cardiomyopathy due to hemochromatosis.
• Steroid therapy can treat sarcoidosis successfully.
• Warfarin therapy is indicated in the presence of thrombi or atrial fibrillation.

• Treatment is directed at the underlying etiology, if determined.
• Management of heart failure involves reducing congestion with diuretics, and controlling heart rate to allow adequate filling time.

ADDITIONAL TREATMENT

Additional Therapies

• Heart transplantation should be considered for end-stage restrictive cardiomyopathies, although some etiologies may preclude transplant or recur in the transplanted heart.
• Permanent pacemakers may be implanted for advanced heart block or symptomatic bradyarrhythmias.
• Implantable cardioverter-defibrillators should be considered on a case-by-case basis for primary and secondary prevention of sudden cardiac death.
• Electrical cardioversion may be necessary for atrial fibrillation; atrial fibrillation is typically poorly tolerated.

PATIENT EDUCATION

Patient should be taught the importance of daily weights and vigilant sodium and fluid intake to maintain a stable volume status.

PROGNOSIS

• Prognosis depends on the etiology, but is poor in general.
• Median survival in 1 small study was 68 mo, with roughly 1/2 of deaths due to heart failure and roughly 1/4 of deaths due to arrhythmia/sudden death.

Outline

• Patient Education
• Prognosis

CODES

ICD9

• 425.4 Other primary cardiomyopathies
• 425.8 Cardiomyopathy in other diseases classified elsewhere

SNOMED

• 415295002 restrictive cardiomyopathy (disorder)
• 39041004 restrictive cardiomyopathy secondary to sarcoidosis (disorder)

CLINICAL PEARLS

• Comprehensive review of systems and physical exam are essential to determining the underlying etiology.
• 50% of restrictive cardiomyopathy cases are idiopathic.
• Other common causes include amyloidosis, sarcoidosis, endomyocardial fibrosis, radiation carditis, and anthracycline therapy.
• Echo and right heart catheterization are key diagnostic tools to distinguish restrictive cardiomyopathy from constrictive pericarditis.
• Treatment and prognosis vary depending on the underlying etiology, but prognosis is poor in general.

Outline

• Codes
  • ICD9
  • SNOMED
• Clinical Pearls

ADDITIONAL READING

• Ammash N, Seward JB. Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circulation. 2000;101(21):2490–2496.
• Daly RP. Heart Failure with Preserved Left Ventricular Ejection Fraction. In: Griffin BP & Topol EJ, eds., Manual of Cardiovascular Medicine, 3rd ed. Philadelphia: Lippincott, 2009;1739–1762.
• Hare JM. The Dilated, Restrictive, and Infiltrative Cardiomyopathies. In: Libby P, ed., Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed. Philadelphia: Saunders, 2008; 122–137.
• Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. 1997;336:267–276.
• Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336:1224–1234.
• Rochitte CE. Tassi EM, et al. The emerging role of MRI in the diagnosis and management of cardiomyopathies. Curr Cardiol Rep. 2006;8(1):44–52.
• Stollberger C, Finsterer J. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy. Clin Cardiol. 2007;30(8):375–380.

Thomas M. Tadros

Deepak L. Bhatt

Gary S. Francis