eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Cardiomyopathy, Restrictive

Vivek J Goswami, MD, Cardiologist, Austin Heart, PA

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

  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.

Differential Diagnoses

Aortic Stenosis
Cardiac Tamponade
Cardiomyopathy, Hypertrophic
Hypertensive Heart Disease

Other Problems to Be Considered

All causes of diastolic dysfunction are included in the differential diagnosis.

Constrictive pericarditis is the most important disease to consider, since it is potentially curable. The physical findings of constriction and restriction are similar and may be confusing to the less-experienced clinician.

Systemic hypertension, valvular aortic stenosis, and hypertrophic cardiomyopathy all cause impaired diastolic distensibility secondary to left ventricular hypertrophy (LVH). The thickened LV could be confused with amyloidosis on echocardiography, but the clinical findings are completely different.

Workup

Laboratory Studies

Laboratory studies are performed to establish the diagnosis of restrictive cardiomyopathy, to quantitate the severity of the disease, and to monitor the patient.

• Complete blood count with peripheral smear helps establish eosinophilia.
• Blood gas analysis is performed to monitor hypoxia.
• Obtain serum electrolytes, BUN and creatinine, and a liver function profile.
• Serum iron concentrations, percent saturation of total iron-binding capacity, and serum ferritin levels are all increased in hemochromatosis.
• Serum brain natriuretic peptide (BNP) level: Recent data suggest that serum BNP levels are nearly normal in patients with constrictive physiology of heart failure and grossly elevated in patients with restrictive physiology, despite nearly identical clinical and hemodynamic presentation.¹

Imaging Studies

• Chest radiograph: This typically shows cardiomegaly with bilateral pleural effusions.
• Two-dimensional echocardiography
  • This shows a nondilated, normally contracting, nonhypertrophied left ventricle and marked dilatation of both atria. However, amyloidosis typically shows diffuse increased LV thickening.
  • The ventricular cavity size may be normal or reduced. The wall thickness may be increased in patients with infiltrative diseases. Mural thrombus and cavity obliteration are features of obliterative cardiomyopathy. In contrast, dilated cardiomyopathy shows dilatation of all the chambers of the heart, and increased wall thickness, especially of the ventricular septum, is observed in hypertrophic cardiomyopathy.
  • Abnormal myocardial textures can also be appreciated using echocardiography. For example, granular speckling of the ventricular walls suggests the presence of infiltrative disease, such as amyloidosis.
  • Pericardial thickening is not reliably observed on echocardiography; MRI is suggested for exclusion of a thick pericardium.
• Doppler echocardiography
  • Doppler echocardiogram shows features of restriction to diastolic filling. Accentuated early diastolic filling of the ventricles (E), shortened deceleration time, and diminished atrial filling (A), which results in a high E-to-A ratio on the mitral inflow velocities, are present.
  • Variations of this diastolic (transmitral) blood flow with respiration help to differentiate between constrictive pericarditis and restrictive cardiomyopathy (RCM).
  • Because both of the ventricles are encased in a common constricting pericardial sac, an inspiratory increase in inflow to the right ventricle causes a reciprocal reduction in the transmitral inflow to the left ventricle. Thus, a pattern of respiratory variation, with a diminished peak transmitral diastolic flow during inspiration, is characteristic of pericardial constriction but not of myocardial restriction.
  • In contrast, in RCM, the left-sided filling pressures are elevated further in inspiration.
• Tissue Doppler imaging: The use of pulsed-wave Doppler imaging is used in some centers as a noninvasive approach to distinguishing RCM and constrictive pericarditis. In addition to the information obtained by Doppler imaging, pulsed-wave Doppler imaging can define myocardial contraction and relaxation. This results in a measure referred to as the myocardial velocity gradient. Small studies have suggested that the myocardial velocity gradient is a specific measure that distinguishes these 2 entities well.
• Cardiac catheterization
  • Ventricular pressure tracings of increased right heart pressures, typical venous wave pattern, and the dip-plateau or square-root contour of the ventricular diastolic pressures (deep and rapid early decline in ventricular pressure at the onset of diastole, with a rapid rise to a plateau in early diastole) obtained by cardiac catheterization are the same in pericardial constriction and RCM. This dip and plateau or square-root sign of ventricular pressure is manifested in the atrial pressure tracing as a prominent descent followed by a rapid rise to a plateau.
  • A few criteria favor the pericardial disorder, as follows:
    • Equalization of left and right ventricular filling pressures, with a difference of no more than 5 mm Hg between the 2 sides
    • Right ventricular end-diastolic pressure (RVEDP) equal to or exceeding one third of the level of the right ventricular systolic pressure (RVSP)
    • RVSP lower than 50 mm Hg
    • Persistence of diastolic equalization of pressures under stress or exercise or fluid challenge
  • In RCM, variance between right and left ventricular diastolic pressures is more likely to be greater than 5 mm Hg, RVEDP is more likely to be less than one third the RVSP, and the ventricular systolic pressure is more likely to be higher than 50 mm Hg.
• Radionuclide imaging: Radionuclide imaging shows increased diffuse uptake of technetium-99m (^99m Tc) pyrophosphate and indium-111 (¹¹¹ In) antimyosin in cardiac amyloidosis.
• Angiography: Angiography may show a small, thick-walled cavity in eosinophilic endomyocardial disease, which may be distorted significantly by a mural thrombus.
• Cardiovascular magnetic resonance (CMR): More recently, CMR has been used to assess abnormal myocardial interstitium. Preliminary reports suggest a characteristic pattern of global subendocardial late gadolinium enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics in RCM.

Table 2. Investigation of Constrictive Cardiomyopathy and Restrictive Cardiomyopathy

*Left ventricular end-diastolic pressure

Other Tests

Electrocardiography (ECG): The findings on ECG depend on the stage of the disease and the specific diagnosis. The ECG may be normal or just show some nonspecific ST-T wave changes, but rhythm disorders (notably atrial fibrillation) are common. Conduction abnormalities are uncommon in amyloidosis. Low QRS voltage is common in amyloidosis, out of proportion to the thick LV on echocardiography. A pseudo-infarct pattern is possible, secondary to myocardial infiltration and/or small vessel induced ischemia or infarction.

Procedures

• Cardiac biopsy: Ventricular biopsy obtained from either the right or the left ventricle has proved useful in certain cases in establishing whether endocardial or myocardial disease is present. Growing experience in this technique indicates a high diagnostic yield in diseases that may present with restriction hemodynamics, when noninvasive studies have failed to establish a clear-cut diagnosis. Amyloidosis demonstrates apple-green birefringence, stained with Congo red, viewed under a polarizing microscope.
• Liver biopsy is performed for diagnosis of hemochromatosis.
• Fine-needle aspiration of abdominal fat is easier and safer than myocardial biopsy to determine amyloidosis.
• Confirmation of the diagnosis of AL amyloidosis demands a search for a plasma cell dyscrasia.

Treatment

Medical Care

The goal of treatment in restrictive cardiomyopathy (RCM) is to reduce symptoms by lowering elevated filling pressures without significantly reducing the cardiac output. Presently, no drugs selectively enhance myocardial relaxation. Therefore, current therapy consists predominately of low-dose diuretics to lower the preload. Small initial doses should be administered to avoid hypotension because these patients are frequently extremely sensitive to alterations in left ventricular volume. Higher doses may be needed if the serum albumin level is low secondary to concomitant nephrotic syndrome.

• ACE inhibitors and angiotensin II inhibitors are poorly tolerated in patients with amyloidosis. Even small doses may result in profound hypotension, probably secondary to an autonomic neuropathy.
• Beta-blockers and calcium channel blockers are not documented to improve day-to-day symptoms or to favorably alter the natural history in patients with diastolic heart failure.
• No published data are available on the use of intravenous inotropic or vasodilator drugs.
• Patients with a history of embolization or atrial fibrillation should be anticoagulated. In patients with atrial fibrillation, the rate should be controlled adequately. Removal of the atrial contribution to ventricular filling may worsen the existing diastolic dysfunction, and a rapid ventricular response may further compromise diastolic filling, creating a crisis. Therefore, maintaining sinus rhythm is important, and medications such as amiodarone and beta-blocker are often used. Digoxin should be used with caution because it is potentially arrhythmogenic, particularly in patients with amyloidosis.
• Specific therapy
  • Antiplasma cell therapy with melphalan may slow the progress of systemic amyloidosis by stopping production of the paraprotein responsible for the formation of amyloid. The prognosis of patients with primary systemic amyloidosis remains poor, with a median survival of approximately 2 years despite intervention with alkylating-based chemotherapy in selected cases. In specific cases, chemotherapy has dramatic benefits, with improvement in systemic and cardiac manifestations.
  • Medical therapy with corticosteroids, cytotoxic agents (eg, hydroxyurea), and interferon is appropriate during the early phase of Loeffler endocarditis and improves symptoms and survival.
  • Chelation therapy or venesection is effective in patients with hemochromatosis to decrease the iron overload.
  • The treatment of Loeffler endocarditis consists of correctly identifying the condition before the end-stage fibrosis occurs; administration of corticosteroids, cytotoxic agents (eg, hydroxyurea), and interferon to suppress the intense eosinophilic infiltration of the myocardium; and conventional heart failure medication.

Surgical Care

• Patients with idiopathic restrictive cardiomyopathy (RCM) may have fibrosis of the sinoatrial and atrioventricular nodes that result in complete heart block, and, therefore, require permanent pacing. If cardioversion to treat atrial fibrillation is attempted, particularly in patients with amyloidosis, the abnormal sinus node may fail as an effective pacemaker. Patients with sinus node dysfunction and/or advanced conduction system disease also require treatment with implantation of a pacemaker.
• Cardiac transplantation can be considered in highly selected patients with refractory symptoms in idiopathic or familial RCM and amyloidosis. When noncardiac organ involvement is absent, a few patients with amyloidosis have undergone successful cardiac transplantation, combined with postoperative high-dose chemotherapy, to abolish recurrent amyloid production.
• Loeffler endocarditis: Surgical therapy, with excision of the fibrotic endocardium and replacement of the mitral and tricuspid calves, is palliative in the fibrotic stage of the disease but may provide symptomatic improvement. The operative mortality rate is in the range of 15-25%.
• Combined heart and liver transplantation in patients with heart and liver failure due to hemochromatosis has been successful in small numbers of patients. However, early morbidity and mortality is higher in dual organ transplantation than in single organ transplantation.
• Transplantation is a treatment option for cardiac sarcoidosis, but recurrence of sarcoid granulomas can occur in the transplanted heart.
• A surgical approach offers a cure for pericardial constriction but carries a potential for significant morbidity for RCM. Thus, establishing a clear diagnosis is crucial, and the advent of current sophisticated imaging technology helps in that regard. Fewer patients are now needing exploratory open-heart surgery to establish the correct diagnosis.
• Stem cell transplantation used in conjunction with high-dose chemotherapy is still considered experimental by most cardiologists. Its routine use has not yet been established.
• Finally, whether patients who have radiation-induced cardiac diseases are candidates for heart transplant is uncertain. Concerns have been raised as to whether their immune system would allow them to receive the immunosuppressive therapy necessary following the surgical procedure and whether relapse of their malignancy might occur.

Medication

The goals of pharmacotherapy for restrictive cardiomyopathy are to reduce morbidity and prevent complications.

Diuretics

Symptomatic treatment may improve symptoms of venous congestion through elimination of retained fluid and preload reduction.

Hydrochlorothiazide (HydroDIURIL, Esidrix, Microzide)

Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions.

Dosing

Adult

12.5-100 mg PO qd or in divided doses; may administer qod

Pediatric

Not established

Interactions

Thiazides may decrease effects of anticoagulants, antigout agents, and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants; ACTH, corticosteroids, and amphotericin B increase hypokalemia risk; orthostatic hypotension may occur with alcohol ingestion

Contraindications

Documented hypersensitivity; anuria; renal decompensation

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with renal and hepatic disease, gout, diabetes mellitus, asthma, postsympathectomy, excessive fluid loss, and SLE; not recommended in breastfeeding women; monitor electrolytes and BUN; potassium supplements or potassium-sparing diuretics may be needed; discontinue if electrolyte disorder develops rapidly; adverse effects include electrolyte disorders (especially hypokalemia), hyperglycemia, hyperuricemia, photosensitivity, orthostatic hypotension, GI disturbances, and adverse lipid values

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg no sooner than 6-8 h after the previous dose until desired diuresis occurs. When treating infants, titrate with 1-mg/kg/dose increments until satisfactory effect achieved.

Dosing

Adult

20-80 mg/d PO/IV/IM; may repeat or increase after 6-8 h; not to exceed 600 mg/d; watch for volume depletion, electrolyte imbalance, and orthostatic hypotension

Pediatric

Not established

Interactions

Metformin decreases furosemide concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently; alcohol and CNS depressants may increase orthostatic hypotension; antagonized by indomethacin; may alter excretion of salicylates; hypokalemia may occur with corticosteroids or ACTH; potentiates antihypertensive effects of succinylcholine

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, CO₂, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter; caution in renal or hepatic dysfunction, diabetes, gout, SLE, breastfeeding, and elderly patients; potassium supplementation may be needed; discontinue if progressive renal dysfunction occurs; adverse effects include excessive diuresis, fluid or electrolyte imbalance, GI upset, dizziness, vertigo, paresthesias, orthostatic hypotension, hyperglycemia, jaundice, hyperuricemia, rash, photosensitivity, tinnitus, hearing loss, blood dyscrasias, and renal calcification in premature infants

Nitrates

Used to reduce preload in diastolic dysfunction.

Long-acting Nitroglycerin (Deponit, Nitrostat, Nitrol, Nitro-Bid)

Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Result is a decrease in blood pressure.
Available as lingual pump spray, sublingual tablets, oral tablets, patches, and ointments.

Dosing

Adult

Spray: 1-2 sprays; dose may be repeated q3-5min as hemodynamics permit; not to exceed 3 sprays in 15 min
Ointment (15 mg/in): Apply 1/2 in every am to chest wall; repeat in 6 h; may increase to 1 in, then to 2 in bid
Patch: Apply 0.2-mg/h patch or 0.4-mg/h patch for 12-14 h/d; remove patch for 10-12 h/d
Sublingual tablets: 0.3- to 0.6-mg tab, 1 tab SL, may repeat in 5 min; not to exceed 3 tab in 15 min

Pediatric

Not recommended

Interactions

Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary); hypotension potentiated by sildenafil, calcium channel blockers, alcohol, vasodilators, antihypertensives, beta-blockers, phenothiazines, and aspirin; may antagonize alteplase or heparin; drugs that cause dry mouth (eg, TCAs, anticholinergics) may interfere with SL dissolution; avoid ergots; tolerance to other forms of nitrates may blunt effects; may interfere with cholesterol tests

Contraindications

Documented hypersensitivity; early MI; severe anemia; shock; postural hypotension; head trauma; increased intracranial pressure; concomitant sildenafil; closed-angle glaucoma; cerebral hemorrhage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in acute MI, hypotensive or volume-depleted patients, elderly patients, breastfeeding women, and patients with hypertrophic cardiomyopathy; monitor in heart failure; avoid abrupt cessation; discontinue if blurred vision or dry mouth occurs; adverse reactions include headache, weakness, vertigo, palpitations, orthostatic hypotension, tachycardia, syncope, flushing, rash, and exfoliative dermatitis

Cardiac glycosides

Used to treat atrial fibrillation and systolic dysfunction in RCM.

Digoxin (Lanoxin, Lanoxicaps)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Dosing

Adult

Loading dose: 0.5-0.75 mg PO over 12-24h; 0.25-1.0 mg IV over 12-24h
Maintenance dose: 0.125 mg/d PO

Pediatric

Not established

Interactions

Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil; medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid

Contraindications

Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patients to digitalis toxicity; hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; caution in patients with hypothyroidism, hypoxia, and acute myocarditis; in patients with renal dysfunction, reduce dose; caution in premature infants, neonates, and breastfeeding women; adverse reactions include GI effects (eg, anorexia, vomiting, diarrhea), CNS effects (eg, blurred or yellow vision, mental disturbances, confusion, headache, weakness, dizziness, apathy), gynecomastia, rash, heart block, and arrhythmias; in children, arrhythmia is the earliest sign of toxicity

Follow-up

Prognosis

The course of restrictive cardiomyopathy varies depending on the pathology, and treatment is often unsatisfactory.

Miscellaneous

Medicolegal Pitfalls

• All causes of diastolic dysfunction are included in the differential diagnosis of restrictive cardiomyopathy (RCM). Establishing the diagnosis of RCM, and excluding constrictive pericarditis, is imperative.
• The etiology of RCM has been confused with constrictive pericarditis because patients can present with findings typical of constrictive pericarditis but they may actually have RCM. In the past, diagnosis of RCM was often made during surgery. Now, with wider knowledge of clinical findings and better imaging techniques, correct diagnosis can be strongly suggested and exploratory surgery can be avoided. The final diagnosis is most commonly made on biopsy of fat tissue, such as abdominal wall fat.

References

1. Leya FS, Arab D, Joyal D, Shioura KM, Lewis BE, Steen LH, et al. The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy. J Am Coll Cardiol. Jun 7 2005;45(11):1900-2. [Medline].

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Keywords

restrictive cardiomyopathy, RCM, myocardium, Loeffler's endocarditis, chronic endomyocardial fibrosis, diastolic heart failure, primary amyloidosis, eosinophilic, hemochromatosis, glycogen storage disease

Contributor Information and Disclosures

Author

Vivek J Goswami, MD, Cardiologist, Austin Heart, PA
Vivek J Goswami, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians-American Society of Internal Medicine, American Heart Association, American Medical Association, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Gary E Sander, MD, PhD, Professor, Department of Internal Medicine, Division of Cardiology, Tulane University Health Sciences Center
Gary E Sander, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Hypertension, Heart Failure Society of America, Louisiana State Medical Society, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Frank M Sheridan, MD, Cardiology, Providence Everett Medical Center
Frank M Sheridan, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

CME Editor

Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Chief Editor

Patrice Delafontaine, MD, FACC, FAHA, FACP, FESC, Sidney W and Marilyn S Lassen Professor of Cardiovascular Medicine, Chief, Section of Cardiology, Director, Cardiovascular Center of Excellence, Tulane University; Professor of Physiology, Chair, Department of Medicine, Tulane University School of Medicine
Patrice Delafontaine, MD, FACC, FAHA, FACP, FESC is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Cardiology, American College of Physicians, American Diabetes Association, American Federation for Clinical Research, American Federation for Medical Research, American Heart Association, American Medical Association, American Society for Clinical Investigation, Association of American Physicians, Association of Professors of Cardiology, Association of Professors of Medicine, Endocrine Society, European Society of Cardiology, Louisiana State Medical Society, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Sarath Reddy, MD; Alan Forker, MD; Gunateet Goswami, MD; and Nafisa Kuwajerwala, MD to the development and writing of this article.

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