Cardiomyopathy, Restrictive

Nathan Riddell, M.D.
Christopher P. Blomberg, D.O.

Basic Information

Definition

Restrictive cardiomyopathy refers to either an idiopathic or a systemic myocardial disorder (in the absence of ischemic, hypertensive, valvular, or congenital heart disease) characterized by restrictive filling (Fig. 1), normal or reduced left ventricular (LV) and right ventricular (RV) volumes, and normal or near normal systolic LV and RV function. Pathophysiologically, the heart muscle is abnormally stiff, resulting in decreased compliance, abnormal relaxation in diastole, and increased filling pressures. Except for primary nonhypertrophic cardiomyopathy and a few infiltrative diseases, restrictive cardiomyopathies are secondary.

FIG.1

Cardiomyopathies.

A, Normal. B, Dilated. C, Hypertrophic. D, Restrictive. Ao, Aorta; LA, left atrium; LV, left ventricle.

Modified from Roberts WC, Ferrans VJ: Pathologic anatomy of the cardiomyopathies. *Hum Pathol* 6:289–342, 1975.

Synonyms

Idiopathic restrictive cardiomyopathy
Infiltrative cardiomyopathy

ICD-10CM CODES
D86.XX	Sarcoidosis-related codes
E83.11X	Hemochromatosis-related codes
E85.X	Amyloidosis-related codes
I42.5	Other restrictive cardiomyopathy
I42.8	Other cardiomyopathies
I43.1	Cardiomyopathy in metabolic diseases
I42.9	Cardiomyopathy, unspecified

Epidemiology & Demographics

•

A relatively uncommon cardiomyopathy, accounting for 5% of all primary myocardial diseases.
•

Most frequently caused by amyloidosis or myocardial fibrosis (following open heart surgery, transplantation or radiation).
•

Patients classified as having “idiopathic” restrictive cardiomyopathy may have mutations in the gene for cardiac troponin I, and restrictive cardiomyopathy may represent an overlap with hypertrophic cardiomyopathy in many familial cases.

Physical Findings & Clinical Presentation

Restrictive cardiomyopathy presents with symptoms of progressive left-sided and right-sided heart failure:

•

Fatigue, weakness (caused by low output as patients are unable to augment cardiac output by increasing heart rate without compromising ventricular filling).
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Progressively worsening exercise intolerance and dyspnea.
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Anginal chest pain can be seen (particularly in patients with amyloidosis) from myocardial compression of small coronaries.
•

Palpitations (atrial fibrillation is common), dizziness or syncope (from orthostasis, heart block, or malignant arrhythmia).
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Edema, ascites, hepatomegaly, distended neck veins (from elevated right heart pressures).
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Kussmaul sign may be present (rise, or failure to fall, of the jugular veins on inspiration).
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On auscultation: murmurs of mitral or tricuspid regurgitation may be heard; an S3 may be present.
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Apical impulse may be palpable (can help distinguish it from constrictive pericarditis) and nondisplaced.

Etiology

Disease may be classified according to pathophysiologic processes:

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Infiltrative:
1. 1.
  
  Amyloidosis (most common overall): The main types include AA, AL, Aß (ß amyloid), and ATTR (transthyretin-mutated or wild type [commonly known as senile systemic]).
2. 2.
  
  Sarcoidosis (more commonly causing a dilated cardiomyopathy with regional wall motion abnormalities)
•
Noninfiltrative:
1. 1.
  
  Idiopathic (familial subtypes may have genetic overlap with hypertrophic cardiomyopathy)
2. 2.
  
  Scleroderma
3. 3.
  
  Diabetic cardiomyopathy
4. 4.
  
  Pseudoxanthoma elasticum
•
Storage diseases:
1. 1.
  
  Hemochromatosis (more commonly associated with a dilated cardiomyopathy)
2. 2.
  
  Glycogen or other storage diseases (Gaucher, Hurler, Fabry—all rare)
•
Endomyocardial:
1. 1.
  
  Endomyocardial fibrosis
2. 2.
  
  Hypereosinophilic syndrome (Loeffler’s syndrome)
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Carcinoid heart disease
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Radiation
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Metastatic cancers
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Drug related (anthracyclines, serotonin, ergotamine, busulfan, methysergide)

Diagnosis

Differential Diagnosis

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Constrictive pericarditis (see Table E1)

TABLEE1 Differentiation between Restrictive Cardiomyopathy and Constrictive PericarditisFrom Andreoli TE, et al., [eds]: Andreoli and Carpenter’s Cecil essentials of medicine, ed 8, Philadelphia, 2010, Saunders.

Type of Evaluation	Restrictive Cardiomyopathy	Constrictive Pericarditis
Physical examination	Kussmaul sign present Apical impulse may be prominent Regurgitant murmurs are common	Kussmaul sign may be present Apical impulse usually not palpable Pericardial knock may be present Pulsus paradoxus may be present
Electrocardiography	Low QRS voltage (especially in amyloidosis) Pseudoinfarction pattern Bundle branch blocks AV conduction disturbances Atrial fibrillation	Low QRS voltage Repolarization abnormalities
Chest radiography		Calcification of the pericardium may be present
Echocardiography	Marked enlargement of the atria Increased wall thickness (especially in amyloidosis) Valvular thickening (especially in hypereosinophilia)	Atria usually of normal size Normal wall thickness Pericardial thickening may be seen
Doppler echocardiography	Restrictive mitral inflow (dominant E wave with short deceleration time) No significant variation of transvalvular velocities with respiration (<10%) Reversal of forward flow in hepatic veins during inspiration Low tissue Doppler velocities	Restrictive mitral inflow (dominant E wave with short deceleration time) Increased velocity of RV filling and decreased velocity of LV filling with inspiration; opposite with expiration; variation in velocity exceeds 15% Reversal of forward flow in hepatic veins during expiration High tissue Doppler velocities
Cardiac catheterization	Prominent atrial x and y descents (w sign) Dip-and-plateau appearance of ventricular diastolic pressure Diastolic pressures increased but not equalized (LV diastolic pressure higher than RV diastolic pressure)	Prominent atrial x and y descents (w sign) Dip-and-plateau appearance of ventricular diastolic pressure Increase and equalization of diastolic pressures Discordance of RV and LV peak systolic pressures (with inspiration, RV systolic pressure increases and LV systolic pressure decreases)
Endomyocardial biopsy	May reveal specific cause of restrictive cardiomyopathy	No specific findings on endomyocardial biopsy Pericardial biopsy may reveal abnormality
Computed tomography, magnetic resonance imaging	Late gadolinium myocardial enhancement in certain conditions	Pericardial thickening >4 mm
Laboratory testing	BNP is elevated	BNP may be normal to slightly elevated
AV, Atrioventricular; BNP, brain natriuretic peptide; LV, left ventricular; RV, right ventricular.

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Valvular dysfunction (especially aortic stenosis)
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Hypertrophic cardiomyopathy
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Hypertensive heart disease

Workup

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Complete blood count with differential (to identify eosinophilia), iron studies, serum renal function studies, chest x-ray, ECG, echocardiogram.
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Right and left heart catheterization, magnetic resonance imaging, and computed tomography (in select cases).
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Aspiration biopsy of subcutaneous fat to detect amyloidosis.
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Endomyocardial biopsy if diagnostic confirmation needed.
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Brain natriuretic peptide (BNP) serum levels (>400 pg/ml): there is data suggesting that BNP levels are markedly elevated in restrictive cardiomyopathy but near normal in constrictive pericarditis, most likely resulting from the lack of myocardial stretching in constriction that is required for BNP release
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Genetic testing.

Imaging Studies

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Chest x-ray:
1. 1.
  
  Ranges from normal cardiomediastinal silhouette to moderate cardiomegaly (primarily because of biatrial enlargement).
2. 2.
  
  Evidence of heart failure may be present.
3. 3.
  
  Presence of pericardial calcification favors alternative diagnosis of constrictive pericarditis.
•
ECG:
1. 1.
  
  Nonspecific ST-T wave abnormalities are the most common finding. Voltage may be low in infiltrative etiologies such as amyloidosis.
2. 2.
  
  Frequent atrial and ventricular ectopy are often present. Atrial fibrillation may be present.
3. 3.
  
  High-degree atrioventricular block, intraventricular conduction delay may be seen in advanced cases.
•
Echocardiogram (Fig. 2):
1. 1.
  
  Biatrial enlargement almost always present.
2. 2.
  
  Wall thickness depends on etiology; often thickened in infiltrative disease.
3. 3.
  
  Myocardial appearance may be altered (speckled pattern suggestive of infiltration).
4. 4.
  
  Ventricular chamber sizes and systolic function are often normal or reduced.
5. 5.
  
  Echo Doppler shows evidence of diastolic dysfunction. Tissue Doppler demonstrates low mitral annular velocities.
FIG.2

Echocardiogram of a patient with restrictive cardiomyopathy.

The optical four-chamber view shows the markedly enlarged right and left atria, compared to the normal-sized left and right ventricular chambers. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

From Kliegman RM, et al.: Nelson textbook of pediatrics, ed 19, Philadelphia, 2011, Saunders.
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Cardiac catheterization:
1. 1.
  
  Characteristic hemodynamic findings are a dip and plateau, or square-root sign, in the left ventricular tracing where a deep and rapid decline in ventricular pressure at the onset of diastole is immediately followed by rapid rise and plateau in early diastolic phase.
2. 2.
  To distinguish restrictive cardiomyopathy from constrictive processes (Fig. 3):
  1. ○
    
    Constrictive: Usually involves both ventricles and leads to equalization of diastolic pressures between all four cardiac chambers to within 5 mm Hg. There is discordance in RV and LV pressures generated during inspiration, which is due to increased ventricular interdependence and decreased left atrial filling (caused by a decreased gradient in inspiration between the pulmonary veins, which are outside the constrictive process and the left atrium).
  2. ○
    
    Restrictive cardiomyopathy: Impairs the left ventricle more than the right, often with left-sided end-diastolic pressures of 5 mm Hg greater than the right. The presence of increased pulmonary arterial systolic pressures is also suggestive of restrictive disease. Simultaneous RV and LV pressure tracings demonstrate concordant patterns during the respiratory cycle.
  FIG.3
  
  Differentiation of restrictive cardiomyopathy from constrictive pericarditis.
  
  CT, Computed tomography; MRI, magnetic resonance imaging; EDP, end-diastolic pressure.
  
  From Pereira NL, Dec GW: Restrictive and infiltrative cardiomyopathies. In Crawford MH, et al.: Cardiology, Philadelphia, 2010, Elsevier.
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Cardiac computed tomographic scan may be helpful to identify a thickened and calcified pericardium, consistent with constrictive pericarditis.
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Cardiac magnetic resonance imaging (CMRI) may also be useful to distinguish restrictive cardiomyopathy from constrictive pericarditis (thickness of the pericardium greater than 4 mm in the latter). CMRI is particularly helpful in the diagnosis of the amyloid or sarcoid variants and may have value in other variants as well. Late gadolinium enhancement can be seen with infiltrative diseases.

Treatment

Nonpharmacologic Therapy

Congestive symptoms may respond to dietary sodium restriction (<2 g/day).

Acute General Rx

Treatment of volume overload and heart failure symptoms with diuretic therapy.

Chronic Rx

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Treatment involves management of the underlying disease if it exists:
1. 1.
  
  Hemochromatosis may respond to repeated phlebotomy and iron chelators to decrease iron deposition in the heart.
2. 2.
  
  Sarcoidosis may respond to corticosteroid therapy.
3. 3.
  
  Primary amyloidosis may respond to chemotherapy (high-dose melphalan with autologous stem cell therapy or bortezomib-based regimens). ATTR may be treated with liver transplant or other promising novel therapeutic agents that are currently being tested in clinical trials.
4. 4.
  
  Eosinophilic cardiomyopathy may respond to corticosteroid and cytotoxic drugs.
5. 5.
  
  There is no effective therapy for other causes of restrictive cardiomyopathy.
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Overall, the goal of treatment is to reduce symptoms by decreasing filling pressures while preserving cardiac output. Since there is currently no drug available to specifically act on myocardial relaxation, therapy centers on low-dose diuretics to lower the preload.
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Beta-blockers or calcium channel blockers have not been demonstrated to improve symptoms or alter the course of disease. Must be careful not to decrease HR too far, as this will affect cardiac output (CO = HR × stroke volume).
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ACE inhibitors (or angiotensin receptor blockers [ARBs]) and vasodilators should be avoided in patients with amyloidosis as they are poorly tolerated. Even small doses can trigger profound hypotension (probably due to associated autonomic neuropathy).
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Atrial fibrillation is common and patients with it or with a history of embolization should be anticoagulated. Tachycardia (of any cause) is poorly tolerated and a common cause of decompensation. Rate control is of paramount importance. Cardioversion in case of rapid atrial fibrillation should be considered. Of note, digoxin should be used with caution as it is potentially arrhythmogenic (particularly in patients with amyloidosis).
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Fibrosis of the cardiac conduction system may result in complete heart block presenting as dizziness or syncope (especially in amyloidosis) and pacemaker implantation may be required. The course of restrictive cardiomyopathy is variable and depends on the underlying etiology. Death usually results from heart failure or arrhythmias, and interventions aimed at addressing these are recommended.
1. 1.
  
  For the amyloid variant, an implantable cardiac defibrillator offers little prophylactic benefit beyond the ability to pace because the cause of sudden cardiac death is usually electromechanical disassociation.

Disposition

Prognosis varies with the etiology of the cardiomyopathy but is poor overall as disease is rarely detected before advanced stages.

Referral

Cardiac transplantation can be considered in patients with refractory symptoms and idiopathic or familial restrictive cardiomyopathies.

Ferri – Cardiomyopathy, Restrictive