AUTHOR INFORMATION	Section 1 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Author: Murat Celebi, MD, Section of Cardiovascular Medicine, Louisiana State University Health Sciences Center Coauthor(s): Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital; Gary E Sander, MD, Professor, Department of Internal Medicine, Division of Cardiology, Louisiana State University School of Medicine and Medical Center

Editor(s): Robert E Fowles, MD, Clinical Professor of Medicine, University of Utah College of Medicine; Consulting Staff, LDS Hospital; Director and Consulting Staff, Department of Cardiology, Salt Lake Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ronald J Oudiz, MD, Director of Pulmonary Hypertension, Associate Professor, Department of Medicine, Division of Cardiology, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA; Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital; and Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice

Disclosure

	INTRODUCTION	Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: Cardiomyopathy is a complex disease process that can affect the heart of a person of any age. It is a common problem throughout the world and is the most common diagnosis in persons receiving supplemental medical financial assistance via the US Medicare program. Cardiomyopathy is an important cause of morbidity and mortality among the world's aging population. Cardiomyopathies are conditions in which the normal muscular function of the myocardium has been altered by specific or multiple etiologies, with varying degrees of physiologic compensation for that malfunction. Cardiomyopathies have multiple etiologies. The degree and time course of malfunction are variable and do not always coincide with a linear expression of symptoms. Persons with cardiomyopathy may have asymptomatic left ventricular systolic dysfunction, left ventricular diastolic dysfunction, or both.

When the balance between malfunction and compensation is disrupted such that cardiac output can no longer be maintained at normal left ventricular filling pressures, the disease process is expressed with symptoms that collectively compose the disease state known as congestive heart failure (CHF). This article addresses etiologies and pathophysiology in addition to diagnostic and treatment modalities not discussed in other articles. General considerations and the direction of heart failure therapy are also reviewed.

Pathophysiology: Because the etiology for cardiomyopathies varies, so does the pathophysiology that may lead to its clinical expression as CHF. Although the pathophysiologic mechanisms are different, the hemodynamic consequences and neurohormonal abnormalities associated with the different causes of cardiomyopathies remain very similar. Dilated cardiomyopathy (DCM) manifests hemodynamically as decreased cardiac output and increased pulmonary venous pressure. The pathophysiologic mechanisms associated with CHF may be considered secondary to a dilated physiology or to a restrictive physiology.

Anatomically, the heart has greater left ventricular cavity size with little or no wall hypertrophy. Hypertrophy is judged as the ratio of left ventricular mass to cavity size, which is decreased in persons with DCMs. The enlargement of the remaining heart chambers is primarily due to left ventricular failure, but it may be secondary to the primary cardiomyopathic process. DCMs are associated with both systolic and diastolic dysfunction. The decrease in systolic function of the myocardium is by far the primary abnormality. This leads to an increase in the end-diastolic and end-systolic volumes.

Progressive dilation can lead to significant mitral and tricuspid regurgitation, which may further diminish the cardiac output and increase end-systolic volumes and ventricular wall stress, thus leading to further dilation and myocardial dysfunction. Early compensation for systolic dysfunction and decreased cardiac output is accomplished by increasing the stroke volume, the heart rate, or both (cardiac output = stroke volume X heart rate), which is also accompanied by an increase in peripheral tone.

The basis for compensation of low cardiac output is explained by the Frank-Starling Law, which states that myocardial force at end-diastole compared with end-systole increases as muscle length increases, thereby generating a greater amount of force as the muscle is stretched. Overstretching, however, leads to failure of the myocardial contractile unit. These compensatory mechanisms are blunted in persons with DCMs compared with persons with hearts with normal left ventricular systolic function. Additionally, these compensatory mechanisms lead to further myocardial injury, dysfunction, and geometric remodeling (concentric or eccentric).

Compensatory mechanisms

The 2 most important initial mechanisms of compensation involve alterations in stroke volume and heart rate (increases in heart rate and venous filling). The increase in peripheral tone noted with decreased cardiac output maintains appropriate blood pressure. Also observed is an increased tissue oxygen extraction rate with a shift in the hemoglobin dissociation curve.

Neurohormonal activation

At the CNS level, decreased cardiac output with resultant reductions in organ perfusion results in neurohormonal activation, including stimulation of the adrenergic nervous system and the renin-angiotensin-aldosterone system (RAAS). Additional factors important to compensatory neurohormonal activation include the release of arginine vasopressin and the secretion of natriuretic peptides (eg, atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], C-type natriuretic peptide). Unfortunately, initially compensatory mechanisms ultimately lead to further disease progression.

Alterations in the adrenergic nervous system induce significant increases in circulating levels of dopamine and, especially, norepinephrine. By increasing sympathetic tone and decreasing parasympathetic activity, an increase in cardiac performance (beta-adrenergic receptors) and peripheral tone (alpha-adrenergic receptors) is attempted. Unfortunately, long-term exposure to high levels of catecholamines leads to down-regulation of receptors in the myocardium and blunting of this response. The response to exercise in reference to circulating catecholamines is also blunted. On a theoretical level, the increased catecholamine levels observed in cardiomyopathies due to compensation may in themselves be cardiotoxic and lead to further dysfunction. In addition, stimulation of the alpha-adrenoreceptors, which leads to increased peripheral vascular tone, increases the myocardial work load, which can further decrease cardiac output. Circulating norepinephrine levels have been inversely correlated with survival.

Activation of the RAAS is critically important when discussing neurohormonal alterations in persons with CHF. Angiotensin II potentiates the effects of norepinephrine by increasing systemic vascular resistance. It also increases the secretion of aldosterone, which facilitates sodium and water retention and may contribute to myocardial fibrosis.

The release of arginine vasopressin from the hypothalamus is controlled by both osmotic (hyponatremia) and nonosmotic stimuli (eg, diuresis, hypotension, angiotensin II). Arginine vasopressin may potentiate the peripheral vascular constriction because of the aforementioned mechanisms. Its actions in the kidneys reduce free-water clearance.

Natriuretic peptide levels are elevated in individuals with DCM. Natriuretic peptides in the human body include ANP (source is mostly right atrium), BNP (source is ventricles), and C-type natriuretic peptide.

ANP is primarily released by the atria. Right atrial stretch is an important stimulus for its release. The effects of ANP include vasodilation, possible attenuation of cell growth, diuresis, and inhibition of aldosterone.

BNP was initially identified in brain tissue and is a 32–amino acid polypeptide neurohormone. BNP is secreted from cardiac ventricles in response to volume or pressure overload, and it causes vasodilation and natriuresis. As a result, BNP levels are elevated in patients with CHF.

Counterregulatory processes to neurohormonal activation involve the increase in release of prostaglandins and bradykinins. These mechanisms do not significantly counteract the previously mentioned compensatory mechanisms. The body's compensatory mechanisms for a failing heart are evidently short sighted. Compensation of decreased cardiac output cannot be sustained without inducing further decompensation. The rationale for the most successful medical treatment modalities for cardiomyopathies is therefore based on altering these neurohormonal responses.

Circulating cytokines as mediators of myocardial injury

Tissue necrosis factor-alpha (TNF-alpha) is involved in all forms of cardiac injury. In cardiomyopathies, TNF-alpha has been implicated in the progressive worsening of ventricular function, but the complete mechanism of its actions is poorly understood. Progressive deterioration of left ventricular function and cell death (TNF plays a role in apoptosis) are implicated as some of the mechanisms of TNF-alpha. It also directly depresses myocardial function in a synergistic manner with other interleukins.

Several interleukins have been found at elevated levels in patients with left ventricular dysfunction. Interleukin (IL)–1b has been shown to depress myocardial function. One theory is that elevated levels of IL-2R in patients with class IV CHF suggest that T lymphocytes play a role in advanced stages of heart failure. IL-6 stimulates hepatic production of C-reactive protein, which serves as a marker of inflammation. IL-6 has also been implicated in the development of myocyte hypertrophy, and its level has been found to be elevated in patients with CHF. IL-6 has been found to correlate with hemodynamic measures in persons with left ventricular dysfunction.

Frequency:

• In the US: The true incidence of cardiomyopathies is unknown. As with other diseases, authorities depend on reported cases (at necropsy or as a part of clinical disease coding) to define the prevalence and incidence rates. The inconsistency in nomenclature and disease coding classifications for cardiomyopathies has led to collected data that only partially reflect the true incidence of these diseases. Whether secondary to improved recognition or other factors, the incidence and prevalence of cardiomyopathy appears to be increasing. The reported incidence is 400,000-500,000 cases per year, with a prevalence of 2-3 million people.

Mortality/Morbidity: Cardiomyopathy is an important cause of morbidity and mortality among the world's aging population.

Age: Cardiomyopathy is a complex disease process that can affect the heart of a person of any age.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History: Details of specific causes of cardiomyopathies are covered within their respective articles. For example, see Cardiomyopathy, Alcoholic; Cardiomyopathy, Cocaine; Cardiomyopathy, Diabetic; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; and Cardiomyopathy, Peripartum.

One manifestation of CHF is decreased exercise tolerance, depending on the level of compensation. This leads to symptoms of shortness of breath, orthopnea, dyspnea upon exertion, and edema. However, these symptoms occur primarily in the late stages of cardiomyopathy. The clinician should pay special attention to details in the history that suggest an increased risk for developing cardiomyopathy or early stages of cardiomyopathy, such as angina, indicative family history, social history (eg, alcohol or drug use), and palpitations. Notably, atrial fibrillation and ventricular dysrhythmias may be early signs of myocardial disease.

Physical: The level of compensation (or decompensation) determines which signs are present.

• Neck

• Jugular venous distention (as an estimate of central venous pressure)

• Hepatojugular reflux

• a wave

• Large cv wave (observed with tricuspid regurgitation)

• Goiter

• Lungs: Crackles (pulmonary rales) or signs of pleural effusion may be noted.

• Heart

• Inspection and palpation
  • Palpate for heaves, shifted point of maximal impulse, and cardiomegaly (broad and displaced point of maximal impulse, right ventricular heave).

  • The normal apical impulse should be approximately the size of a quarter and should be located in one (fourth or fifth) intercostal space. The apical impulse is normally within 10 cm of the midsternal line. In a person with DCM, the clinician may be able to palpate an apical presystolic impulse.

  • Observe for signs of previous surgery.

• Auscultation
  • Murmurs (with appropriate maneuvers), tachycardia, S₂ at the base (paradoxical splitting, prominent P₂), S₃, and S₄ may be noted.

  • Remember that S₃/S₄ are low-frequency sounds heard best with the bell and that a prominent pulmonic component of the S₂ audible at the apex can be misinterpreted as an S₃ if care is not taken to distinguish the frequency of the sound.

  • An irregularly irregular rhythm (atrial fibrillation) may be noted. Gallops are almost always present in persons with DCM.

• Abdomen: Percussion and palpation of the liver may reveal hepatomegaly due to elevated venous pressure, infiltrative disease, hepatojugular reflux, or ascites.

• Musculoskeletal system: Most muscular diseases can involve myocardium. Observe for cardiac cachexia, peripheral edema, cyanosis, and clubbing.

Causes: The classification of cardiomyopathy has varied over the past century. Cardiomyopathies may be simply divided into dilated or nondilated categories. Within each of these groups, the myocardium may be hypertrophic or nonhypertrophic, and it may be accompanied by a restrictive (diastolic ventricular dysfunction) and/or congestive (systolic ventricular dysfunction) physiology. This form of classification may assist in specifying a cause for a cardiomyopathy based on the predominant clinical picture. However, this classification has a significant degree of overlap compared with a specific etiology for a cardiomyopathy. For example, in ischemic cardiomyopathy, diastolic and systolic dysfunction often coexist.

Cardiomyopathy has many causes. Finding a specific cause for a cardiomyopathy is often difficult, especially when it is multifactorial. Traditionally, ischemic cardiomyopathy is listed as the most common cause of cardiomyopathy in North America and Europe.

Idiopathic cardiomyopathy is the second most common cause, although this may partially reflect undiagnosed etiologies such as infectious (viral) or toxic (ethanol-induced) cardiomyopathies. The idiopathic category should continue to diminish as more information explaining pathophysiological mechanisms, specifically genetic-environmental interactions, becomes available. Hypertensive disease is also a prime cause of cardiomyopathy in North America and Europe. Every cardiomyopathy has a cause for which the specific incidence varies with geographic location. For example, in Africa, idiopathic congestive cardiomyopathy, endomyocardial fibrosis, and rheumatic heart disease all are more prevalent than disease due to atherosclerotic coronary artery disease.

Cardiomyopathies

• Idiopathic
  • Dilated
    • Sporadic

    • Genetic (familial)

    • Mitral valve prolapse

  • Hypertrophic - With or without asymmetric septal hypertrophy

  • Nondilated, nonhypertrophic - Endomyocardial fibrosis, Löffler endocarditis

• Specific cardiomyopathies
  • Secondary to other cardiovascular disease
    • Ischemia

    • Hypertension

    • Valvular disease

    • Tachycardia induced

  • Infectious
    • Viral

    • Rickettsial

    • Bacterial

    • Metazoal

    • Protozoal

    • Probable infectious - Whipple disease, Lyme disease

  • Metabolic
    • Endocrine diseases - Hyperthyroidism, hypothyroidism, acromegaly, myxedema, hypoparathyroidism, hyperparathyroidism, other

    • Diabetes mellitus

    • Electrolyte imbalance - Potassium, phosphate, magnesium, other

    • Nutritional - Thiamine deficiency (beriberi), protein deficiency, starvation, carnitine deficiency

  • Toxic
    • Drugs

    • Poisons

    • Foods

    • Anesthetic gases

    • Heavy metals

    • Alcohol

  • Collagen vascular disease
    • Systemic lupus erythematosus

    • Rheumatoid arthritis

    • Progressive systemic sclerosis

    • Polymyositis

    • HLA-B12–associated cardiac disease

  • Infiltrative
    • Hemochromatosis

    • Amyloidosis

    • Glycogen storage disease

  • Granulomatous (sarcoidosis)

  • Physical agents
    • Extreme temperatures

    • Ionizing radiation

    • Electric shock

    • Nonpenetrating thoracic injury

  • Neuromuscular disorders
    • Muscular dystrophy - Limb-girdle (Erb dystrophy), Duchenne dystrophy, fascioscapulohumeral (Landouzy-Dejerine dystrophy)

    • Friedreich disease

    • Myotonic dystrophy

  • Primary cardiac tumor (myxoma)

  • Senile

  • Peripartum

  • Immunological
    • Postvaccination

    • Serum sickness

    • Transplant rejection

• Specific cardiomyopathies: These include cardiomyopathies of infectious origin (eg, viral cardiomyopathy). Infectious cardiomyopathies can occur as a result of bacterial, viral, rickettsial, fungal, or parasitic infection of the heart. Viral myocarditis is an important entity within the category of infectious cardiomyopathy. Viruses have been implicated in cardiomyopathies as early as the 1950s, when coxsackievirus B was isolated from the myocardium of a newborn baby with a fatal infection. Advancements in genetic analysis, such as polymerase chain reaction, have aided in the discovery of several viruses that are believed to have roles in viral cardiomyopathies.

• Viral infections and viruses associated with myocardial disease

• Coxsackievirus (A and B)

• Influenza virus (A and B)

• Adenovirus

• Echovirus

• Rabies

• Hepatitis

• Yellow fever

• Smallpox

• Lymphocytic choriomeningitis

• Epidemic hemorrhagic fever

• Chikungunya fever

• Dengue fever

• Cytomegalovirus

• Epstein-Barr virus

• Rubeola

• Rubella

• Mumps

• Respiratory syncytial virus

• Varicella-zoster virus

• Human immunodeficiency virus

• Viral myocarditis: Viral myocarditis can produce variable degrees of illness, ranging from focal disease to diffuse pancarditis involving myocardium, pericardium, and valve structures. Viral myocarditis is usually a self-limited, acute-to-subacute disease of the heart muscle that most often leads to the dilated type of cardiomyopathy. Symptoms are similar to those of CHF and often are subclinical. Many patients experience a flulike prodrome. Confirming the diagnosis can be difficult because symptoms of heart failure can occur several months after the initial infection. Patients with viral myocarditis (median age, 42 y) are generally healthy and have no systemic disease.

  Myocarditis is almost always a clinically presumed diagnosis because it is not associated with any pathognomonic sign or specific, acute diagnostic laboratory test result. In the past, percutaneous transvenous right ventricular endomyocardial biopsy has been used, but the Myocarditis Treatment Trial revealed no advantage for immunosuppressive therapy in biopsy-proven myocarditis, so biopsy is not routinely performed in most cases. Importantly, note that myocarditis can mimic acute myocardial infarction, with patients sometimes presenting in the emergency department with chest pain, nonspecific ECG changes, and abnormal, often highly elevated serum markers such as troponin, creatine kinase, and creatine kinase-MB.

• Diagnosis
  • The diagnosis of viral myocarditis is mainly indicated by a compatible history and the absence of other potential etiologies, particularly if it can be confirmed with acute or convalescent sera.

  • An ECG demonstrates varying degrees of ST-T wave changes reflecting myocarditis and, sometimes, varying degrees of conduction disturbances.

  • Echocardiography is a crucial aid in classifying this disease process, which manifests mostly as a dilated type of cardiomyopathy.

  • The utility of endomyocardial biopsy is very limited. If a patient is thought to have viral myocarditis, the initial diagnostic strategies should be to evaluate cardiac troponin I or T levels and to perform antimyosin scintigraphy. Positive troponin I or T findings in the absence of myocardial infarction and the proper clinical setting confirm acute myocarditis. Negative antimyosin scintigraphy findings exclude active myocarditis.

• Pathophysiology
  • The exact mechanism for myocardial injury in viral cardiomyopathy is controversial.

  • Several mechanisms have been proposed based on animal models. Viruses affect myocardiocytes by direct cytotoxic effects and by cell-mediated (T-helper cells) destruction of myofibers. Other mechanisms include disturbances in cellular metabolism, vascular supply of myocytes, and other immunologic mechanisms.

• Prognosis
  • Viral myocarditis may resolve over several months during the treatment of left ventricular systolic dysfunction. However, it can progress to a chronic cardiomyopathy. The main issue in recovery is ventricular size. Reduction of ventricular size is associated with long-term improvement; otherwise, the course of the disease is characterized by progressive dilation.

  • Because of an immunologic mechanism of myocyte destruction, several trials have investigated the use of immunomodulatory medications. (Other trials are currently being conducted.) According to Mason et al in 1995, the Myocarditis Treatment Trial demonstrated no survival benefit with prednisone plus cyclosporine or azathioprine in patients with viral (lymphocytic) myocarditis. Randomized trials are underway to evaluate intravenous immunoglobulin as treatment for viral myocarditis.

• Familial cardiomyopathy: Familial cardiomyopathy is a term that collectively describes several different inherited forms of heart failure.

• Diagnosis
  • Familial DCM is diagnosed in patients with idiopathic cardiomyopathy who have 2 or more first- or second-degree relatives with the same disease (without defined etiology).

  • Establishing a diagnosis with more-distant affected relatives (third degree and greater) simply requires identifying more family members with the same disease. Genetic screening has been recommended for patients fulfilling the above criteria.

• Pathophysiology
  • This form of cardiomyopathy has a poorly characterized etiology. Several forms have been described, and theories postulate its association with other causes of cardiomyopathy. Inheritance is autosomal dominant; however, autosomal recessive and sex-linked inheritance have been reported.

  • Several different diseased genes and chromosomal aberrations have been described in studied families. One example is associated with actin, a cardiac muscle fiber component. Other forms of familial cardiomyopathy involve a strong association with active or previous conduction system disease. As research continues, the knowledge database of etiologies for familial cardiomyopathies is likely to expand.

• Toxic cardiomyopathy (doxorubicin induced): Toxic cardiomyopathies can be difficult to diagnose. The common use of anthracyclines as antineoplastic agents and their high degree of cardiotoxicity predispose these patients to a characteristic form of dose-dependent toxic cardiomyopathy. Both an early acute cardiotoxicity and chronic cardiomyopathy have been described for these agents. Anthracyclines can also be associated with acute coronary spasm. The acute toxicity can occur at any point from the onset of exposure to several weeks after drug infusion. Radiation and other agents may potentiate the cardiotoxic effects of anthracyclines. Cardiac injury occurs even at doses below the empiric limitation of 550 mg/m². However, whether injury translates to clinical CHF varies. The development of heart failure is very rare at total doses less than 450 mg/m² but is dose dependent.

• History: The history of these patients, in addition to classic heart failure symptoms or symptoms of acute myocarditis, involves a previous history of malignancy and treatment with doxorubicin.

• Pathophysiology
  • Anatomically, these patients' hearts vary from having bilaterally dilated ventricles to being of normal size.

  • The mechanism of myocardial injury is related to degeneration and atrophy of myocardial cells, with loss of myofibrils and cytoplasmic vacuolization. The generation of free radicals by doxorubicin has also been implicated.

• Prognosis: Progressive deterioration is the norm for this toxic cardiomyopathy.

• Prevention
  • Prevention is based on limiting dosing after 450 mg/m² and on serial functional assessments (ie, resting and exercise evaluation of ejection fraction).

  • The drug should be discontinued if the ejection fraction is less than 0.45, if it falls by more than 0.05 from baseline, or if it fails to increase by more than 0.05 with exercise.

  • Dexrazoxane is an iron-chelating agent approved to reduce toxicity; however, it increases the risk of severe myelosuppression.

• Cardiomyopathy associated with collagen-vascular disease: Several collagen-vascular diseases have been implicated in the development of cardiomyopathies. These include rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, and polymyositis. Diagnosis is based on identification of the underlying disease in conjunction with appropriate clinical findings of heart failure.

• Granulomatous cardiomyopathy (sarcoidosis): Endomyocardial biopsy may be helpful in establishing the diagnosis, especially in sarcoidosis in which the myocardium may be involved. Involvement may be patchy, resulting in a negative biopsy finding. The diagnosis can also be made if some other tissue diagnosis is possible or available in conjunction with the appropriate clinical picture for heart failure. The following discussion concentrates on cardiomyopathy associated with sarcoidosis. Cardiac involvement in sarcoidosis reportedly occurs in approximately 20% of cases.

• History
  • Patients have signs and symptoms of sarcoidosis and CHF. Patients rarely present with CHF without evidence of systemic sarcoid.

  • Look for bilateral mediastinal, paratracheal, and/or hilar lymphadenopathy.

• Pathophysiology
  • Noncaseating granulomatous infiltration of the myocardium occurs as with other organs affected by this disease.

  • Sarcoid granulomas can show a localized distribution within the myocardium. The granulomas particularly affect the conduction system of the heart, left ventricular free wall, septum, papillary muscles, and, infrequently, heart valves.

  • Fibrosis and thinning of the myocardium occurs as a result of the infiltrative process affecting the normal function of the myocardium.

• Diagnosis
  • Diagnosis involves finding noncaseating granulomas from cardiac biopsy or other tissues.

  • Often, patients present with conduction disturbances or ventricular arrhythmias. In fact, in patients with normal left ventricular function, these conduction disturbances may be the primary clinical feature.

• Prognosis
  • Treatment of cardiac sarcoidosis with low-dose steroids may be beneficial, especially in patients with progressive disease, conduction defects, or ventricular arrhythmias.

  • The true benefit is unknown because of the lack of placebo-controlled studies. This also holds true for the use of other immunosuppressive agents (eg, chloroquine, hydroxychloroquine, methotrexate) in the treatment of cardiac sarcoidosis.

• Carnitine deficiency: A carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with DCM or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy, which results in prolonged prevention of cardiac failure. The prognosis for long-term survival in pediatric DCM is poor.

• Tachycardia-induced cardiomyopathy: Generally, this type of cardiomyopathy is reversible once treatment of the tachycardia is successful. Persistent tachycardia is known to lead to myocyte dysfunction and cardiomyopathy. The exact mechanisms by which tachycardia affects cell function are poorly understood. The following are possible mechanisms by which myocyte dysfunction arises from tachycardia:

• Depletion of energy stores

• Abnormal calcium channel activity

• Abnormal subendocardial oxygen delivery secondary to abnormalities in blood flow

• Reduced responsiveness to beta-adrenergic stimulation

	DIFFERENTIALS	Section 4 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Amyloidosis, AA (Inflammatory)
Amyloidosis, Familial Renal
Amyloidosis, Immunoglobulin-Related
Amyloidosis, Overview
Amyloidosis, Transthyretin-Related
Anemia
Aortic Regurgitation
Aortic Stenosis
Beriberi (Thiamine Deficiency)
Cardiac Tamponade
Cardiomyopathy, Restrictive
Glycogen Storage Disease, Type II
Glycogen Storage Disease, Type III
Glycogen Storage Disease, Type IV
Glycogen Storage Disease, Type Ia
Glycogen Storage Disease, Type Ib
Glycogen Storage Disease, Type V
Glycogen Storage Disease, Type VI
Glycogen Storage Disease, Type VII
Graves Disease
HIV Disease
Heart Failure
Hyperthyroidism
Hypophosphatemia
Hypothyroidism
Infective Endocarditis
Myocardial Infarction
Myocarditis
Pericarditis, Acute
Pericarditis, Constrictive
Pericarditis, Constrictive-Effusive
Pericarditis, Uremic
Pulmonary Edema, Cardiogenic
Toxicity, Cocaine
Toxicity, Iron
Toxicity, Lead

Other Problems to be Considered:

Alcohols
Amphetamine toxicity
Collagen-vascular disorders
Congestive heart failure
Ischemic and hypertensive heart disease
Neuromuscular disorders
Other drugs (emetine, doxorubicin, cobalt)
Thyroid hormone toxicity