Causes of dilated cardiomyopathy

INTRODUCTION — Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of one or both ventricles [1-5]. Affected patients have impaired systolic function and may or may not develop overt heart failure (HF). The presenting manifestations can include atrial and/or ventricular arrhythmias, and sudden death can occur at any stage of the disease. (See "Definition and classification of the cardiomyopathies".)

DCM is currently responsible for approximately 10,000 deaths and 46,000 hospitalizations each year in the United States. Furthermore, idiopathic DCM is the primary indication for cardiac transplantation [6].

The definition, clinical presentation, and causes of DCM will be reviewed here. The initial evaluation of the patient with suspected HF and the subsequent evaluation to determine the cause are discussed separately. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

DEFINITION — A diagnosis of dilated cardiomyopathy requires evidence of dilation and impaired contraction of the left ventricle or both ventricles (eg, left ventricular ejection fraction <40 percent or fractional shortening less than 25 percent) [1,2]. The disease is considered idiopathic if primary and secondary causes of heart disease (eg, myocarditis and coronary artery disease) are excluded by evaluation including history and physical examination, laboratory testing, coronary angiography (to exclude >50 percent obstruction of one or more coronary arteries), echocardiography, and endomyocardial biopsy when indicated. (See "Endomyocardial biopsy".)

CLINICAL PRESENTATION — Most patients present between the ages of 20 and 60, but dilated cardiomyopathy can occur in children and older adults [3]. Affected patients can present in a number of different ways [3,7]. Symptoms of heart failure (progressive dyspnea with exertion, impaired exercise capacity, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema) are most common. Other presentations include the incidental detection of asymptomatic cardiomegaly and symptoms related to coexisting arrhythmia, conduction disturbance, thromboembolic complications, or sudden death [7]. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Clinical presentation'.)

The clinical course is largely unpredictable in the individual patient and may depend in part upon the cause of the heart disease. There are also disease-independent predictors of survival, the most important of which are New York Heart Association functional class, left ventricular ejection fraction, and maximal oxygen consumption (peak VO₂). These prognostic determinants assume that the cause of the myocardial dysfunction cannot be treated. (See "Predictors of survival in heart failure with reduced ejection fraction".)

ETIOLOGY — Dilated cardiomyopathy (DCM) can be caused by a variety of disorders (table 1). These conditions will be briefly reviewed here; many are discussed in detail elsewhere. In many cases, however, no etiology can be found and the cardiomyopathy is deemed idiopathic.

Ischemic cardiomyopathy — Coronary atherosclerosis is the most common cause of heart failure (HF) in the United States, comprising 50 to 75 percent of patients with HF (see "Epidemiology of heart failure"). Although the term "ischemic cardiomyopathy" has been used to describe ischemic myocardial dysfunction (particularly in North America), this term is not supported by the 2006 American Heart Association or 2007 European Society of Cardiology cardiomyopathy classification systems. (See "Definition and classification of the cardiomyopathies".)

Most patients with ischemic cardiomyopathy have known coronary heart disease. However, occult disease is not an uncommon cause of DCM, accounting for as many as 7 percent of otherwise unexplained cases [8]. These observations plus the potential reversibility of hibernating myocardium (figure 1) constitute the rationale for performing angiography in most patients with HF of uncertain etiology. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Issues related to the detection of hibernating myocardium and the management of such patients are discussed separately. (See "Evaluation of hibernating myocardium" and "Treatment of ischemic cardiomyopathy".)

Stress-induced cardiomyopathy — An uncommon but increasingly reported cause of an acute, usually ST elevation coronary syndrome occurring in the absence of critical coronary artery disease is stress-induced cardiomyopathy, also called transient left ventricular apical ballooning, takotsubo cardiomyopathy, and broken heart syndrome. This disorder is typically precipitated by intense psychologic stress and primarily occurs in postmenopausal women. The characteristic finding of apical ballooning is seen on left ventriculography or echocardiography (movie 1). Despite frequent hemodynamic compromise or even cardiogenic shock, almost all patients recover completely within one to four weeks. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)

Infectious cardiomyopathy — A variety of infectious organisms can lead to myocarditis and DCM (table 2):

Viral cardiomyopathy — Viral infection is the most common cause of myocarditis and has been implicated in the development of DCM. Viruses known to involve the myocardium include parvovirus B19, human herpesvirus 6, coxsackievirus, influenza virus, adenovirus, echovirus, cytomegalovirus, and HIV. (See "Myocarditis: Causes and pathogenesis".)

The initial immune response limits the degree of viremia early during infection and protects against myocarditis. If, however, this response is insufficient, the virus may not be eliminated and myocyte injury may ensue via one or two mechanisms:

●Direct cytotoxicity via receptor-mediated entry of the virus into cardiac myocytes.

●An adverse autoimmune response induced by persisting viral genomic fragments that may not be capable of replicating as intact virus.

Other aspects of viral myocarditis, including clinical manifestations, diagnosis, and therapy, are discussed elsewhere. (See "Clinical manifestations and diagnosis of myocarditis in adults" and "Treatment and prognosis of myocarditis in adults".)

HIV infection — Although the prevalence of HIV-associated myocardial disease has dropped significantly in resource-rich areas since the widespread use of antiretroviral therapy (ART), subtle abnormalities in myocardial structure and function are still observed among treated HIV-infected individuals. Cardiomyopathy associated with HIV infection remains a major issue in resource-limited settings. The proposed mechanisms of cardiac damage include drug toxicity, secondary infection, myocardial damage by HIV itself, and an autoimmune process induced by HIV itself or in association with other cardiotropic viruses such as coxsackievirus, cytomegalovirus, or Epstein-Barr virus. (See "Cardiac and vascular disease in patients with HIV", section on 'Myocardial disease'.)

Chagas disease — Chagas disease, which is a protozoan infection due to Trypanosoma cruzi, is the leading cause of DCM in Central and South America. It is characterized clinically by acute myocarditis, cardiac enlargement, tachycardia, and nonspecific electrocardiogram abnormalities including right bundle branch block and premature ventricular contractions. Patients can develop left ventricular apical aneurysms that are pathognomonic for this disease. (See "Chronic Chagas cardiomyopathy: Clinical manifestations and diagnosis".)

Lyme disease — Cardiac involvement with Lyme disease is usually manifested as a conduction abnormality. Cardiac muscle dysfunction can also occur; it is often self-limited and mild, leading to transient cardiomegaly or pericardial effusion on echocardiogram or chest radiograph. However, occasional patients develop symptomatic myocarditis and DCM. (See "Lyme carditis".)

Genetic causes of dilated cardiomyopathy — Among patients with idiopathic DCM, it is estimated that up to 50 percent have familial disease. No clinical or histologic criteria, other than family history and careful examination of relatives (including those who are asymptomatic), have been derived to distinguish familial from nonfamilial disease. The mode of inheritance is usually autosomal dominant, although autosomal recessive, X-linked, and mitochondrial inheritance have also been described. These disorders, as well as recommendations for screening and counseling family members, are discussed elsewhere. (See "Genetics of dilated cardiomyopathy" and "Familial dilated cardiomyopathy: Prevalence, diagnosis and treatment".)

Antibodies to a variety of cardiac proteins are present in approximately 30 percent of patients with DCM. These antibodies are also present in 20 to 30 percent of the first and second degree relatives of DCM patients, compared with 1 to 2 percent of control subjects. Furthermore, among relatives of DCM patients, the presence of such antibodies is associated with a greater likelihood of developing DCM. (See 'Autoimmunity' below.)

DCM in patients who do not have a known family history of disease may also have a genetic basis. (See "Genetics of dilated cardiomyopathy", section on 'Nonfamilial dilated cardiomyopathy'.)

Inherited syndromes — DCM can be a common and important component of a number of inherited disorders, including a number of neuromuscular diseases (eg, muscular dystrophies and myotonic dystrophy), hereditary hemochromatosis, and the hereditary sideroblastic anemias and thalassemias. (See "Inherited syndromes associated with cardiac disease".)

Hypertrophic cardiomyopathy — A small proportion of patients with hypertrophic cardiomyopathy who survive the early risk of sudden death develop progressive myocardial wall thinning, a reduction in systolic performance, and an increase in left ventricular dimensions in the long term, resembling the morphologic and functional features of DCM [9]. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'HCM with LV systolic dysfunction (ejection fraction <50 percent)'.)

Left ventricular noncompaction — Left ventricular noncompaction (LVNC), also called isolated ventricular noncompaction and left ventricular hypertrabeculation, is a rare unclassified cardiomyopathy with an altered myocardial wall due to intrauterine arrest of compaction of the loose interwoven meshwork that makes up the fetal myocardial primordium. LVNC has been identified in 0.05 percent of patients undergoing echocardiography. Affected patients present with HF, thromboembolism, or ventricular arrhythmias. The diagnosis is established by echocardiography, although the changes can also be seen on magnetic resonance imaging. (See "Isolated left ventricular noncompaction in adults: Clinical manifestations and diagnosis".)

Toxic cardiomyopathy — DCM can be a direct result of toxic exposure from a variety of agents, most notably alcohol, cocaine, medications, particularly chemotherapeutic drugs, and radiation.

Alcohol — Excessive alcohol consumption can lead to myocardial dysfunction, although the pathogenesis and factors that determine patient susceptibility are still poorly understood. Alcohol is believed to be toxic to cardiac myocytes via oxygen free radical damage and defects in cardiac protein synthesis.

The risk of developing alcoholic DCM is related to both mean daily alcohol intake and the duration of drinking. However, individual susceptibility remains important. The typical finding in patients with alcoholic DCM is left ventricular dilation with reduced ejection fraction. More advanced cases have biventricular failure. (See "Alcohol-induced cardiomyopathy".)

Abstinence can lead to a dramatic improvement in cardiac function if the disease is diagnosed early. Thus, careful questioning for a history of alcohol use is an important part of the evaluation of a patient with DCM.

Distinction from cirrhotic cardiomyopathy — While alcoholic cardiomyopathy is one cause of heart disease in patients with cirrhosis, experimental and observational studies have found that cirrhosis is associated with myocardial dysfunction independent of alcohol exposure. The causes and manifestations of cirrhotic cardiomyopathy are not well defined. The condition has been defined as otherwise unexplained chronic cardiac dysfunction in patients with cirrhosis with impaired contractile responsiveness to stress and/or diastolic dysfunction with associated electrophysiologic abnormalities. The left atrium may be dilated but the left ventricular cavity size is generally normal, although dilation may develop in some cases. (See "Definition and classification of the cardiomyopathies", section on 'Unclassified cardiomyopathies'.)

Cocaine — The use of cocaine is associated with cardiomyopathy, but the relationship is less well understood than that between cocaine and coronary ischemia. Nevertheless, cardiomegaly with otherwise unexplained HF in a young person should raise the possibility of cocaine abuse. Possible mechanisms include a direct toxic effect, the cocaine-induced hyperadrenergic state, and, in parenteral cocaine abusers, an infectious cardiomyopathy. Abstinence usually leads to complete reversal of the myocardial dysfunction. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)

Medications — A number of medications are associated with cardiomyopathy, and discontinuation of the implicated drug may result in significant improvement (table 1). Anthracycline-induced cardiomyopathy has been the most extensively studied. Another chemotherapeutic agent associated with frequent cardiotoxicity is trastuzumab, particularly in patients also treated with an anthracycline plus cyclophosphamide. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity" and "Cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines" and "Cardiotoxicity of trastuzumab and other HER2-targeted agents".)

Trastuzumab is a monoclonal antibody directed against the c-erbB-2 (HER2/neu) receptor that is used in the treatment of breast cancer. There is biologic plausibility for cardiac toxicity, since HER2 signaling appears to play an important role in cardiac development and cardioprotection [10]. Direct evidence of such an effect was provided in a study of mice with ventricular restricted deletion of the HER2 gene [11]. These mice developed multiple signs of a cardiomyopathy. In addition, cardiomyocytes from these mice showed enhanced susceptibility to anthracycline toxicity. Cardiomyopathy also develops after a loss of function mutation in HER2 in ventricular myocytes [12].

Trace elements — Trace elements are known to have an important role in myocardial metabolism and their accumulation (cobalt, arsenic) or deficiency (selenium) can be responsible for a form of DCM that is indistinguishable from an idiopathic cardiomyopathy. (See "Overview of dietary trace elements", section on 'Selenium'.)

The role of trace elements was assessed in a study in which myocardial and skeletal muscle biopsies were obtained from 13 patients with an idiopathic DCM, 35 patients with valvular or ischemic heart disease, and 4 normal subjects [13]. Compared with normals, patients with a DCM had a significant increase in myocardial concentration of mercury (22,000 times normal), antimony (12,000-fold higher), gold (increased 11-fold), chromium (13-fold higher), and cobalt (4 times higher). By comparison, patients with valvular or ischemic heart disease had myocardial concentrations of trace elements that were ≤5 times greater than normal. Skeletal muscle concentrations of trace elements were normal in all groups of patients.

Cobalt cardiomyopathy has been reported in drinkers of beer containing cobalt sulphate for foam stabilization (known as Quebec beer-drinkers’ cardiomyopathy) [14], individuals with work-related cobalt exposure, and in some individuals exposed to cobalt from metal hip prostheses [15]. Although some patients with elevated cobalt levels three or more years following metal-on-metal hip arthroplasty lack clinical evidence of cobalt toxicity [16], reports suggest that in some cases degeneration of metallic hip implants can lead to cobalt cardiomyopathy [17,18]. (See "Total hip arthroplasty".)

Peripartum cardiomyopathy — Peripartum cardiomyopathy is a rare cause of DCM of unclear etiology that occurs in late pregnancy and the early postpartum period. The diagnosis requires exclusion of other causes of cardiomyopathy. A variety of definitions have been proposed for this disorder [19]. This condition is discussed in detail separately. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis".)

Tachycardia-mediated cardiomyopathy — A cardiomyopathy has been reported in patients with chronic supraventricular tachycardias with ventricular rates of 130 to 200 beats/minute including atrial fibrillation, atrioventricular nodal reentry, and preexcitation syndromes [20-23]. The rate of the tachycardia appears to correlate with the degree of left ventricular dysfunction [24]. (See "Arrhythmia-induced cardiomyopathy".)

The mechanism of myocardial dysfunction in this setting is not clear. Among the changes that have been observed are a reduction in myocyte contractility, abnormalities in myocardial architecture, and a decrease in calcium responsiveness [25,26]. Left ventricular dysfunction can occur without dilation. Definitive treatment of the arrhythmia results in complete reversal of the myocardial dysfunction (generally within three months) [24].

Sarcoidosis — The clinical manifestations of cardiac sarcoidosis depend upon the location and extent of granulomatous inflammation. In addition to a reversible form of DCM, other cardiac manifestations include conduction abnormalities, ventricular and supraventricular arrhythmias, pericarditis, and valvular dysfunction due to papillary muscle involvement. Cardiac involvement may precede, follow, or occur concurrently with involvement of the lungs or other organs. Antecedent pulmonary or other organ involvement may be absent or not apparent and presentation may be limited to cardiac abnormalities. An acute cardiac presentation may resemble hypertrophic cardiomyopathy with asymmetric septal hypertrophy, which is caused by edema rather than myocyte hypertrophy. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

The clinician should consider the possibility of sarcoid heart disease when confronted with an otherwise healthy young or middle-aged person with cardiac symptoms or a patient with known sarcoidosis who develops arrhythmias, conduction disease, or HF. Diagnosis depends upon recognition of the multisystem features of sarcoidosis and securing the evidence of noncaseating granuloma either in the myocardium or in other affected tissues.

End-stage kidney disease — Patients with end-stage kidney disease being treated with hemodialysis can develop a DCM via an uncertain mechanism [27]. (See "Overview of screening and diagnosis of heart disease in patients on dialysis".)

Autoimmunity — Autoimmunity may be a cause of DCM [28], and the presence of autoantibodies may identify family members of patients with DCM who are at a greater risk of developing cardiomyopathy. Autoimmunity has also been implicated in the pathogenesis of myocarditis. (See "Myocarditis: Causes and pathogenesis", section on 'Autoimmune disorders'.)

A number of cardiac autoantibodies have been identified. These antibodies target a variety of antigens, including the following:

●Beta-1 adrenoceptor

●Alpha-myosin heavy chain

●Beta-myosin heavy chain

●Myosin light chain

●Troponin

Collectively, these autoantibodies are sometimes referred to as anti-heart antibodies (AHAs).

Evidence of pathogenicity — AHAs have not been established as causing DCM in humans, but this is a provocative hypothesis based on animal data. In a rabbit model, immunization with sequences of the beta-1 adrenoreceptor induced the production of beta-1 adrenoceptor autoantibodies and resulted in anatomic and histologic changes in the myocardium resembling those seen in human DCM [29]. A similar study in rats also demonstrated the production of autoantibodies as well as severe left ventricular dilation and dysfunction in vivo [30]. These findings appear to be applicable to humans since these autoantibodies can be detected in as many as 38 percent of patients with an idiopathic DCM [31,32].

Support for a pathogenetic role of beta-1 adrenoceptor autoantibodies comes from the efficacy of eliminating them by immunoadsorption. In one report, immunoadsorption completely eliminated the beta-1 adrenoceptor autoantibodies in the 17 patients undergoing this therapy [32]. After one year, the mean left ventricular ejection fraction increased from 22 to 38 percent, left ventricular end-diastolic volume decreased by 15 percent, and the autoantibodies did not reappear. In contrast, there were no changes in antibody levels or left ventricular function in 17 patients with these antibodies who received only standard medical therapy.

Similar improvement in left ventricular ejection fraction was noted in a later report of eight patients with DCM and beta-1 adrenoceptor antibodies treated with selective immunoadsorption [33]. The advantage of selective immunoadsorption is that immunoglobulin replacement is not required.

A potential pathogenic mechanism for beta-1 adrenoceptor autoantibodies was demonstrated in a study of murine DCM induced by beta-1 adrenoceptor autoantibodies [34]. The autoantibodies acted as agonists, shifting endogenous beta-1 adrenoceptors into the agonist-coupled high-affinity state, thereby triggering an intracellular protein kinase A-dependent signaling cascade in cardiomyocytes. Sustained activation caused intracellular calcium mishandling, cardiomyocyte apoptosis, and DCM with HF.

In addition to a role in some cases of DCM, beta-1 adrenoceptor autoantibodies have also been linked to myocarditis. (See 'Autoimmunity' above.)

Familial disease — AHAs are found in approximately 30 percent of DCM patients [31,32,35], and in 20 to 30 percent of their asymptomatic relatives [36]. The significance of AHAs in the healthy relatives of patients with DCM was evaluated in a series of 169 probands and 592 of their first and second degree relatives [37]. The following findings were noted:

●AHAs were significantly more common in family members of DCM patients than in patients with noninflammatory heart disease, patients with ischemic heart disease, or normal blood donors (32 versus 1, 1, and 2.5 percent, respectively).

●Relatives of DCM patients who later developed DCM were more likely to have AHAs than were relatives who did not progress (69 versus 37 percent).

Thus, AHAs were more common in family members of DCM patients than in control subjects, and the presence of AHAs in asymptomatic family members was associated with an increased likelihood of developing disease. However, fully defining the role of autoimmune factors in familial cardiomyopathy requires further study.

Systemic lupus erythematosus — Cardiac disease is common in systemic lupus erythematosus. Affected patients can develop valvular, pericardial, or coronary disease or myocarditis. Patients with myocardial involvement can present with resting tachycardia disproportionate to body temperature, electrocardiographic abnormalities (such as ST-T wave abnormalities), and unexplained cardiomegaly. Immunosuppressive therapy does not always lead to improved myocardial function in this setting. (See "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults".)

Celiac disease — Two reports from Italy suggest that celiac disease, which is often clinically unsuspected, accounts for as many as 5 percent of patients with autoimmune myocarditis or idiopathic DCM [38,39]. In one report of nine such patients, none had classic gastrointestinal symptoms of celiac disease (recurrent abdominal pain, diarrhea, and weight loss), but all had iron deficiency anemia refractory to iron replacement [38]. Cardiac function improved following a gluten-free diet with or without immunosuppressive therapy. (See "Myocarditis: Causes and pathogenesis", section on 'Celiac disease'.)

Although these findings are intriguing, it is premature to screen all patients with otherwise unexplained cardiomyopathy for celiac disease. However, it is reasonable to question for a history of gastrointestinal complaints or refractory iron deficiency.

Endocrine dysfunction — Thyroid dysfunction, excess sympathetic activity in pheochromocytoma, and rarely Cushing's syndrome and growth hormone (GH) excess or deficiency can cause cardiac dysfunction, which can usually be reversed by correction of the endocrine disorder [40-43].

●The exact mechanisms by which hyperthyroidism or hypothyroidism can lead to DCM are not known. Thyroid hormone is known to alter preload, afterload, heart rate, and contractility, each of which may contribute to cardiac dysfunction. There is also some evidence in experimental animals that excess T3 causes myocyte hypertrophy and changes in specific protein synthesis [40]. (See "Cardiovascular effects of hyperthyroidism" and "Cardiovascular effects of hypothyroidism".)

●Excess sympathomimetic amines in pheochromocytoma can cause focal direct myocyte injury followed by inflammation, downregulation of beta receptors, and a net reduction of viable myofibrils [41].

●As many as 10 percent of patients with newly diagnosed acromegaly have HF, usually with a high cardiac output [42].

●Most of the biologically active effects of GH on the heart appear to be mediated via local production of insulin-like growth factor 1 (IGF-1), which in turn regulates tissue growth by paracrine and/or autocrine mechanisms. In an analysis from the Framingham Heart Study, patients with serum IGF-1 concentrations below the median (<140 microg/L) were found to have an increased likelihood of developing HF at five years (10.2 versus 5.3 percent) [44].

Nutritional deficiencies — Deficiencies in thiamine, selenium, and carnitine have been reported to produce HF and replacement therapy results in improvement in cardiac function [7,45].

●Thiamine plays an important role in normal oxidative phosphorylation and therefore myocardial energy production. Thiamine deficiency initially presents as a high output state secondary to vasodilation; this is followed by eventual depression of myocardial function and the development of a low output state [7].

●Selenium (Se) deficiency decreases the activity of glutathione peroxide, resulting in increased free radicals that are toxic to cardiac myocytes. The development of Keshan disease, an endemic cardiomyopathy that affects children and women of childbearing age in areas of China, has been linked to Se deficiency [46]. The geographical distribution of Keshan disease is associated with local diets, which are nearly devoid of Se. An animal model of Keshan disease in Se deficient mice infected with Coxsackievirus has been described [47]. The mice have increased mutations in the viral genome, leading to a virus with greater cardiac virulence, causing a cardiomyopathy similar to that seen in Keshan disease. (See "Overview of dietary trace elements", section on 'Selenium'.)

●Carnitine deficiency impairs the oxidation of fatty acids, resulting in lipid accumulation in the myocyte cytoplasm. This problem is reversed with carnitine supplements.

Obstructive sleep apnea — Sleep disturbances, including obstructive and nonobstructive sleep apnea, can contribute to the impairment of left ventricular dysfunction. A history of snoring, daytime somnolence, and obesity should alert the clinician to the diagnosis. Effective therapy, as with nasal continuous positive airway pressure during sleep, can lead to a significant improvement in left ventricular dysfunction [48]. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy".)

SUMMARY

●Definition – Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of one or both ventricles. (See 'Definition' above.)

●Causes – DCM is caused by a variety of disorders (table 1), although frequently no etiology can be found and the cardiomyopathy is deemed idiopathic.

Causes of DCM include stress, infections, toxins, genetics, pregnancy, tachycardia, sarcoidosis, end-stage kidney disease, autoimmune disease, endocrine dysfunction, and nutritional deficiencies.

Coronary artery disease, valve disease, and congenital heart disease are not considered causes of dilated cardiomyopathy by major societies.