Definition and classification of the cardiomyopathies

INTRODUCTION — Cardiomyopathies are diseases of heart muscle [1]. A contemporary definition for cardiomyopathy is a myocardial disorder in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to explain the observed myocardial abnormality. Cardiomyopathies include a variety of myocardial disorders that manifest with various structural and functional phenotypes and are frequently genetic. Although some have defined cardiomyopathy to include myocardial disease caused by known cardiovascular causes (such as hypertension, ischemic heart disease, or valvular disease), current major society definitions of cardiomyopathy exclude heart disease secondary to such cardiovascular disorders.

Definitions and classification systems for cardiomyopathies are described here. The individual disorders and the evaluation of the patient with heart failure (HF) or cardiomyopathy are discussed separately. (See "Determining the etiology and severity of heart failure or cardiomyopathy" and "Causes of dilated cardiomyopathy" and "Restrictive cardiomyopathies" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations" and "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)

DEFINITION AND CLASSIFICATION — In 1980, the World Health Organization (WHO) defined cardiomyopathies as "heart muscle diseases of unknown cause" to distinguish cardiomyopathy from cardiac dysfunction due to known cardiovascular entities such as hypertension, ischemic heart disease, or valvular disease [2]. In clinical practice, however, the term "cardiomyopathy" has also been applied to diseases of known cardiovascular cause (eg, "ischemic cardiomyopathy" and "hypertensive cardiomyopathy").

As a result, the 1995 WHO/International Society and Federation of Cardiology (ISFC) Task Force on the Definition and Classification of the Cardiomyopathies expanded the classification to include all diseases affecting heart muscle and to take into consideration etiology as well as the dominant pathophysiology [3]. In this 1995 classification, the cardiomyopathies were defined as "diseases of the myocardium associated with cardiac dysfunction." They were classified according to anatomy and physiology into the following types, each of which has multiple different causes:

●Dilated cardiomyopathy (DCM)

●Hypertrophic cardiomyopathy (HCM)

●Restrictive cardiomyopathy (RCM)

●Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D)

●Unclassified cardiomyopathies

Cardiomyopathies that are associated with specific cardiac or systemic disorders generally fall into one or more of the above morphologic types. These categories are included in subsequent American Heart Association/European Society of Cardiology (AHA/ESC) classification systems. Etiologies include a host of genetic, inflammatory, metabolic, toxic, and other diseases (table 1A-B and table 2). The 1995 WHO/ISFC classification system included ischemic, valvular, and hypertensive disease among the causes of cardiomyopathy.

A 2006 AHA scientific statement proposed a contemporary definition and classification of the cardiomyopathies [4]. The expert consensus panel proposed the following definition: "Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. Cardiomyopathies either are confined to the heart or are a part of generalized systemic disorders, often leading to cardiovascular death or progressive heart failure-related disability." Cardiomyopathies are categorized into two groups: primary cardiomyopathies (predominantly involving the heart) and secondary cardiomyopathies (accompanied by other organ system involvement). The primary cardiomyopathies are subdivided into those which are genetic, mixed (predominantly nongenetic; less commonly genetic), or acquired. The genetic cardiomyopathies include HCM, arrhythmogenic cardiomyopathy (ACM; including ARVC), left ventricular noncompaction, PRKAG2, lamin and Danon glycogen storage diseases, conduction defects, mitochondrial myopathies, and ion channel disorders. The mixed cardiomyopathies include DCM and RCM. The acquired cardiomyopathies include myocarditis, stress-induced (takotsubo), peripartum, tachycardia-induced, and infants of insulin-dependent diabetic mothers.

The AHA definition and classification are not intended to provide methodologies for clinical diagnosis, but are rather a scientific scheme that aims to aid in the understanding of this complex group of disorders. The main departure of the proposed AHA Scientific Statement definition from previous classifications is the inclusion of the ion channelopathies as primary cardiomyopathies, despite the absence of gross structural abnormalities.

Genes contributing to HCM are more frequently identified than are genes contributing to DCM or RCM. However, data suggest a small fraction of cardiomyopathies classified as acquired in the AHA schema including myocarditis have genetic contributions [5,6].

In 2008, the ESC working group on myocardial and pericardial diseases presented an update to the WHO/ISFC classification in which cardiomyopathy was defined as: "A myocardial disorder in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to explain the observed myocardial abnormality" (table 3A-B) [7]. The ESC classification is meant to be particularly useful in everyday clinical practice.

The AHA and ESC classification systems differ from the earlier WHO/ISFC classification in emphasizing the distinction between familial/genetic and nonfamilial/non-genetic causes of cardiomyopathy and excluding heart disease secondary to coronary artery disease, valvular, or congenital heart disorders (table 3A-B) [7]. The ESC classification differs from the AHA classification in also excluding ion channelopathies.

The MOGE(S) classification for a phenotype-genotype-based nomenclature of cardiomyopathy was endorsed by the World Heart Federation and published in 2013 [8]. This proposed system was inspired by the TNM staging of malignant tumors and does not include ion channelopathies. The clinical applicability of this system has not yet been defined [9]. This system involves notation of five attributes:

●The morphofunctional (M) notation indicates a descriptive phenotypic diagnosis (eg, M_D = DCM).

●The organ involvement (O) notation indicates if heart and/or extracardiac involvement related to the cause of heart disease is present (eg, O_H+K = heart and kidney involvement).

●The genetic or familial inheritance (G) notation indicates the nature of genetic transmission (eg, G_AD = autosomal dominant).

●The etiological annotation (E) provides description of the specific cause (eg, the specific gene and mutation as in E_{G-MYH7[p.Arg403Glu]}).

●The addition of a functional status (S) term is considered optional (eg, S_C-II = stage C disease in New York Heart Association [NYHA] functional class II).

A study using a MOGE(S) scoring system ranging from 0 to 4 (assigning one point for each attribute, ie, extracardiac involvement, genetic etiology, environmental etiology, NYHA functional class ≥III) found that a MOGE(S) score ≥2 was associated with worse outcomes in patients with DCM, supporting this classification for predicting risk of cardiovascular events [10].

In summary, cardiomyopathies were originally defined as disorders that were idiopathic. Nevertheless, in clinical practice, the terms "ischemic," "valvular," and "hypertensive cardiomyopathy" have been used commonly, particularly in North America. The 1995 WHO/ISFC Task Force used the term "specific cardiomyopathy" to reflect this reality and the fact that the genetic basis of the cardiomyopathies was being elucidated. The 2008 ESC proposal provides a clinical approach to diagnosing a patient who presents with symptoms, a family history of cardiomyopathy, or electrocardiographic (ECG) and echocardiographic abnormalities that are otherwise unexplained. Like the 2006 AHA proposal, it focuses on the established morphological types described by the 1995 WHO/ISFC Task Force (HCM, DCM, ARVC, RCM). The AHA, ESC, and MOGE(S) classification systems then go on to define the familial and, if possible, genetic basis of disease.

The use of the term "cardiomyopathy" to describe valvular, ischemic, or hypertensive heart disease unnecessarily broadens a term best suited to predominantly reflect genetically determined diseases with recognizable phenotypes. However, the term "ischemic cardiomyopathy" continues to be used by some, including the 2013 American College of Cardiology Foundation/American Heart Association HF guidelines [11].

The classification systems described are based on the predominant clinical, morphological and functional characteristics exhibited by the patient. Though symptoms of exercise limitation, HF and arrhythmia are features of all of the cardiomyopathies, the distinctive presentation with arrhythmia of right ventricular origin (LBBB VT) and characteristic morphological and histological features at postmortem led to incorporation of ARVC as a distinctive cardiomyopathy in previous classifications. Left ventricular (LV) involvement, though recognized clinically (T wave inversion in lateral leads) and at postmortem was considered an aspect of disease progression. The finding of mutations in genes encoding desmosomal proteins, important constituents of the gap junction, confirmed the incorporation of ARVC as an ACM. However, recognition of predominant and even isolated LV disease caused by desmosomal mutations has led to use of the terms LV arrhythmogenic cardiomyopathy (LVAC) and left dominant arrhythmogenic cardiomyopathy (LDAC) [12,13]. In addition, genes encoding other cytoskeletal, sarcomeric, nuclear and ion channel proteins has led to the recognition of other conditions in which there were structural abnormalities of the heart which were not explained by ischemic, hypertensive, or valvular heart disease, and in which arrhythmias were the predominant clinical manifestation. Guidelines of the Heart Rhythm Society incorporate these inherited as well as other systemic/acquired conditions as ACMs [14]. With the increasing availability of mutation analysis there are likely to be additional conditions that fall under the label of ACM [14].

ECHOCARDIOGRAPHIC EVALUATION — Identification of various cardiomyopathy phenotypes relies primarily upon echocardiographic evaluation. Two-dimensional and Doppler echocardiography can, in most cases, define the anatomic and functional characteristics of the heart that are diagnostic of DCM, HCM, ARVC, or RCM. (See "Echocardiographic recognition of cardiomyopathies".)

In select cases, cardiac magnetic resonance imaging or computed tomography may be useful to identify and localize fat, iron, or amyloid infiltration, inflammation, scar/fibrosis, focal hypertrophy, LV apical aneurysm, and right ventricular structure and function. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Cardiomyopathy' and "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".)

Systolic dysfunction — Systolic dysfunction is characterized by a decrease in myocardial contractility. When myocardial contractility is decreased globally (ie, throughout the LV), a reduction in the LV ejection fraction (LVEF) results. While a variety of approaches are available for the quantitative measurement of LV systolic function, the LVEF is often assessed qualitatively. (See "Tests to evaluate left ventricular systolic function".)

When systolic dysfunction occurs, cardiac output is initially maintained in two ways:

●LV enlargement, which results in a higher stroke volume

●The Frank-Starling relationship (an increase in contractility in response to increasing stretch)

However, these compensatory mechanisms are eventually exceeded and cardiac output decreases, resulting in the physiologic manifestations of HF. (See "Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and remodeling".)

Systolic dysfunction is characteristic of DCM. It is also seen in some patients with HCM who develop progressive LV wall thinning, a small increase in diastolic dimension, and a decrease in LVEF. (See "Hypertrophic cardiomyopathy: Natural history and prognosis".)

Diastolic dysfunction — Diastolic dysfunction refers to cardiac dysfunction in which LV relaxation and filling is abnormal and is accompanied by elevated filling pressures. Diastolic dysfunction may occur with or without associated systolic dysfunction. When systolic dysfunction is present, diastolic dysfunction is also present. (See "Echocardiographic evaluation of left ventricular diastolic function in adults".)

In patients presenting with HF but without systolic dysfunction, diastolic dysfunction is one of the potential causes. Causes of HF with a normal or near normal LVEF include cardiomyopathies with preserved ejection fraction (eg, HCM, RCM, LV noncompaction), valvular heart disease, pericardial disease, right HF, and HF with preserved ejection fraction (HFpEF) (table 4). HFpEF is a clinical syndrome of HF in patients with an LVEF ≥50 percent and evidence of cardiac dysfunction as a cause of symptoms; diagnosis of HFpEF requires exclusion of other causes of HF including cardiomyopathies. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis", section on 'Introduction'.)

The LV diastole includes two components (figure 1). LV relaxation is a dynamic process that takes place during isovolumic relaxation (the period between aortic valve closure and mitral valve opening) and then during early rapid filling of the ventricle. Later in diastole, after relaxation is complete, further LV filling is a passive process that is dependent on the compliance or distensibility of the myocardium and ends in the atrial filling phase. Either active relaxation or passive compliance or both may be impaired in a patient with diastolic dysfunction. (See "Pathophysiology of heart failure with preserved ejection fraction".)

Diastolic dysfunction is more difficult to identify and quantitate echocardiographically than systolic dysfunction, and may be missed or underestimated in many cases. Echocardiographic evaluation of LV diastolic dysfunction includes Doppler assessment of transmitral flow and pulmonary venous flow as well as tissue Doppler imaging. (See "Echocardiographic evaluation of left ventricular diastolic function in adults".)

Diastolic dysfunction is characteristic of both HCM and RCM.

ANATOMIC AND PHYSIOLOGIC CLASSIFICATION — Cardiomyopathies are classified into the following categories based upon morphology and physiology.

Some cardiac disorders may present as more than one type of cardiomyopathy or may cross classification categories as they progress, as illustrated by the following examples:

●Amyloid cardiomyopathy, which may present as an HCM or as an RCM. (See "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis".)

●Cardiac sarcoidosis that may progress from manifesting as a focal wall motion abnormality to a DCM or RCM, often with heart block and ventricular arrhythmias as early presenting features. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

●Left ventricular dilation and impaired systolic function may present as a DCM with fatigue, dyspnea, and exercise limitation, or as an ACM with arrhythmia.

Dilated cardiomyopathy — DCM is characterized by dilation and impaired contraction of one or both ventricles [15]. The dilation often becomes severe and is invariably accompanied by an increase in total cardiac mass (hypertrophy) (image 1). Affected patients have impaired systolic function and clinical presentation is usually with features of HF. When the presenting manifestations include conduction abnormalities, atrial and/or ventricular arrhythmias, and sudden death, then an ACM caused by mutations in desmosomal, ion channel, and the lamin gene should be considered.

The incidence of DCM has been estimated to be five to eight cases per 100,000 population, with a prevalence of 36 per 100,000 [15]. These figures may underestimate the frequency of the disorder because so many patients with DCM have incomplete disease expression, which goes unrecognized. Evaluation with ECG and echocardiogram of 767 relatives of 189 probands with DCM revealed unrecognized disease in 4.6 percent of relatives [16]. Also, LV systolic dysfunction may be more prevalent than previously estimated as suggested by a study finding that 14 percent of the middle-aged and older adult population have asymptomatic left ventricular (LV) systolic dysfunction [17].

The complete list of causes of DCM is extensive [18]. The common causes include viruses and gene mutations (table 5), which are now recognized to be relatively common among patients with idiopathic DCM. In addition, the later stages of hypertrophic heart disease may resemble DCM with mild dilation and moderate to severe impairment of systolic function (such as genetic HCM). (See "Causes of dilated cardiomyopathy" and "Genetics of dilated cardiomyopathy" and "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'HCM with LV systolic dysfunction (ejection fraction <50 percent)'.)

The echocardiogram in DCM shows LV cavitary dilation (with a tendency for the shape of the cavity to become less ovoid and more spherical), normal or decreased wall thickness, poor wall thickening, and/or reduced inward endocardial systolic motion (movie 1). In addition to these changes in the LV, other findings include left atrial enlargement and, less often, right ventricular enlargement and dysfunction. In such patients, all four chambers may be dilated. (See "Echocardiographic recognition of cardiomyopathies", section on 'Dilated cardiomyopathy'.)

Coronary artery disease and valve disease are other causes of ventricular dilation with systolic dysfunction (commonly called "ischemic cardiomyopathy" or "valvular cardiomyopathy," although these are not defined as cardiomyopathies under current American Heart Association/European Society of Cardiology [AHA/ESC] classification systems). These causes of heart disease should be distinguished from DCM for appropriate genetic counseling and clinical management. (See "Treatment of ischemic cardiomyopathy" and "Chronic primary mitral regurgitation: General management" and "Natural history and management of chronic aortic regurgitation in adults".)

Hypertrophic cardiomyopathy — HCM is a clinically heterogeneous disorder caused by a variety of mutations associated with hypertrophy of the LV, and occasionally of the right ventricle [19]. The term "HCM" is also used in a broader sense in the 2006 AHA and 2008 ESC classification system to include a variety of conditions (eg, Fabry, Noonan, Friedreich ataxia) with increased ventricular wall thickness or mass not caused by pathologic loading conditions (eg, hypertension or valve disease) (table 3A and table 3B). The prevalence of HCM in the absence of aortic valve disease or systemic hypertension is at least 1:500 of the adult population [20]. The interventricular septum is typically more prominently involved than the LV free wall, but concentric and apical hypertrophy can occur (movie 2). (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction" and "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".)

The LV volume is normal or reduced in HCM, and diastolic dysfunction is usually present. Systolic pressure gradients in the left ventricular outflow tract during resting conditions are found in approximately one-quarter of patients. Characteristic histologic changes include myocyte hypertrophy and disarray, which usually corresponds to the areas of greatest hypertrophy (picture 1) [21,22].

In approximately 60 to 70 percent of patients, HCM is caused by mutations in sarcomeric contractile protein genes and is transmitted as an autosomal dominant trait with incomplete penetrance. The most common mutations are in the beta myosin heavy chain and the cardiac myosin-binding protein C genes [23]. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".)

The clinical manifestations and natural history of HCM are discussed in detail separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)

Athlete's heart — In response to intensive endurance training, there can be physiologic increases in LV wall thickness, cavity size and mass, often referred to as "athlete's heart." Intensive athletic training has also been associated with a number of arrhythmias, also usually benign. (See "Athletes with arrhythmias: Treatment and returning to athletic participation".)

In athletes, the distinction of physiological LV hypertrophy (LVH) from HCM has been emphasized. In individuals with athlete's heart, LVH is generally symmetric and wall thickness is ≤12 mm; however, in some endurance athletes, LVH reaches 14 to 16 mm. Ethnic differences also affect the degree of LVH and echocardiographic abnormalities. Black women athletes have a greater degree of LVH and repolarization abnormalities than White women athletes [24]. Reliance on LV wall thickness alone may be problematic and diagnostic evaluations of athletes with suspected cardiovascular disease should include a family history, 12-lead ECG, and echocardiographic assessment of the distinguishing features of athlete's heart versus HCM. United States and European Cardiovascular Societies differ in their recommendations for preparticipation screening of competitive athletes [25,26].

Criteria for distinguishing athlete's heart from HCM are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Athlete's heart'.)

Other causes of hypertrophy — Other genetic causes of cardiac hypertrophy include other genetically determined syndromes (eg, Noonan), metabolic disease (eg, Friedreich ataxia, Pompe's, AMP-kinase), mitochondrial disease, and Fabry disease, an X-linked recessive glycolipid storage disease. Although classic multisystem Fabry disease is rare, isolated cardiac involvement may be relatively common in patients with otherwise unexplained concentric LVH. (See "Fabry disease: Cardiovascular disease".)

Not pypertrophic cardiomyopathy — As noted above, cardiac hypertrophy with resulting ventricular dysfunction can also be caused by cardiovascular disease. The most common causes of LVH are hypertension and aortic stenosis. Cardiomyopathy as defined by the 2006 AHA and 2008 ESC classification systems does not include hypertrophy secondary to cardiovascular disorders. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Diagnostic echocardiography'.)

Restrictive cardiomyopathy — RCM is characterized by nondilated ventricles with impaired ventricular filling [27]. Hypertrophy is typically absent, although infiltrative disease (such as amyloidosis) and storage disease (such as Fabry disease) may cause an increase in LV wall thickness. Systolic function usually remains normal, at least early in the disease.

On two-dimensional echocardiogram, RCM is characterized by nondilated, nonhypertrophied (nonthickened) ventricles with moderate to marked biatrial enlargement, which is secondary to the elevated atrial pressures (image 2). However, the physiologic abnormality RCM (impaired ventricular filling) is difficult to discern from two-dimensional imaging. Doppler assessment of diastolic transmitral flow velocity is more sensitive for the detection of filling abnormalities (waveform 1); tissue Doppler echocardiogram is also an effective diagnostic tool. (See "Echocardiographic recognition of cardiomyopathies", section on 'Hypertrophic cardiomyopathy' and "Echocardiographic evaluation of left ventricular diastolic function in adults".)

Causes of RCM can be classified as familial noninfiltrative, infiltrative, storage diseases, and others disorders (eg, diabetic cardiomyopathy, scleroderma, endomyocardial fibrosis). The etiology and differential diagnosis of RCM is discussed separately. (See "Restrictive cardiomyopathies", section on 'Differential Diagnosis'.)

RCM is much less common than either DCM or HCM outside the tropics, but is a frequent cause of death in Africa, India, South and Central America, and Asia, primarily because of the high incidence of endomyocardial fibrosis in those regions [27]. (See "Endomyocardial fibrosis".)

Endomyocardial fibrosis — Endomyocardial fibrosis (EMF) occurs mainly in children and adolescents in the tropics. The cause is unknown, but proposed contributing factors include infection, environmental exposure, immunologic processes, and genetics. In some patients, it is associated with severe hypereosinophilia in the early stages of the illness. Disease progression includes endocardial fibrosis and thrombosis, particularly affecting the apical ventricles and subvalvular apparatus. In the later stages, restrictive physiology is prominent, with HF and atrioventricular valve regurgitation. (See "Endomyocardial fibrosis".)

Arrhythmogenic cardiomyopathy — ACM is defined as an arrhythmogenic heart muscle disorder with structural abnormalities of the myocardium and clinical presentation with arrhythmia which is not explained by ischemic, hypertensive, or valvular heart disease. Clinical presentation may be with documented arrhythmia (eg, atrial fibrillation, conduction disease, ventricular tachycardia) or arrhythmia symptoms. The etiology of ACM may be genetic (eg, desmosomal or arrhythmogenic left ventricular cardiomyopathy [ALVC], lamin A/C, filamin C, phospholamban, TMEM43), or part of a systemic disorder (eg, sarcoidosis, amyloidosis), an apparently isolated cardiac abnormality (eg, myocarditis), or an infection (eg, Chagas disease). ARVC was the first and is the best characterized of the ACMs in relation to diagnosis, treatment, and outcomes. ARVC is a genetically determined heart muscle disease characterized by ventricular arrhythmias and a specific myocardial pathology [28]. The myocardium of the right ventricular free wall (and frequently the LV as well) is replaced by fibrous and/or fibro-fatty tissue, with scattered residual myocardial cells (picture 2). Right ventricular function is abnormal, with regional akinesis or dyskinesis and, in severe cases, global right ventricular dilation and dysfunction. Mutations in desmosomal genes cause disease in 40 to 60 percent of cases, and also cause arrhythmogenic left ventricular cardiomyopathy with similar arrhythmic and pathological manifestations. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics" and "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".)

Unclassified cardiomyopathies — The term "unclassified cardiomyopathy" was included in the 2008 ESC classification system to describe disorders that do not readily fit into any of the above phenotypic categories [3]. Examples cited include LV noncompaction and stress-induced (takotsubo) cardiomyopathy.

Left ventricular noncompaction — LV noncompaction, also called isolated ventricular noncompaction, is a rare unclassified cardiomyopathy with an altered myocardial wall due to intrauterine arrest of compaction of the loose interwoven meshwork. There is continuity between the LV cavity and deep intratrabecular recesses that are filled with blood from the ventricular cavity without evidence of communication to the epicardial arterial system (picture 3). When the morphological changes are severe, LV noncompaction may be associated with HF, thromboembolism, and ventricular arrhythmias in adults. (See "Isolated left ventricular noncompaction in adults: Clinical manifestations and diagnosis".)

Stress-induced cardiomyopathy — Stress-induced cardiomyopathy, also called apical ballooning syndrome, broken heart syndrome, and takotsubo cardiomyopathy, is an increasingly reported syndrome generally characterized by transient systolic dysfunction of the apical and/or mid segments of the LV that is often provoked by stress. Basal and other morphologic variants have been described. This condition is discussed in detail separately. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)

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 established. The condition has been defined as an otherwise unexplained chronic cardiac dysfunction in patients with cirrhosis with impaired contractile responsiveness to stress and/or diastolic dysfunction [29-32]. Electrical abnormalities include QT interval prolongation, electrical and mechanical dyssynchrony, and chronotropic incompetence [31]. The left atrium may be dilated but the LV cavity size is generally normal, although dilation may develop in some cases.

Other

Endocardial fibroelastosis — Endocardial fibroelastosis (EFE) is characterized by diffuse thickening of the LV endocardium secondary to proliferation of fibrous and elastic tissue. Two forms have been described: a dilated form (DCM phenotype), in which the LV is enlarged, and a contracted form (RCM phenotype), in which the LV cavity is small [33].

EFE, which occurs primarily in infants during the first year of life, is often seen in conjunction with congenital heart disease, particularly LV outflow obstructive lesions and hypoplastic LV. It appears to represent a nonspecific response to various kinds of cardiac injury [34]. Anoxia, endocarditis, viral infection, and genetic factors have all been implicated [33]. Familial EFE has been reported in association with systemic carnitine deficiency [35]. In addition, an association with maternal autoantibody-mediated congenital heart block (neonatal lupus) has been described [36]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Specific fatty acid oxidation disorders", section on 'Carnitine transporter deficiency'.)

On echocardiogram, LV cavity size may be normal, small, or dilated, and systolic function may be preserved or depressed. Diastolic dysfunction may be detected. Dense echoes along the endocardial surface of the LV (and right ventricle) may be seen on echocardiogram, but endomyocardial biopsy is necessary for definitive diagnosis [37]. Case reports suggest that endocardial late gadolinium enhancement on cardiac magnetic resonance imaging can help identify EFE [38,39].

Survival in one series of 52 patients at six months, one year, and four years was 93, 83, and 77 percent, respectively; however, only approximately one-third of these patients had histologic confirmation of the diagnosis [40]. By contrast, in another report of 13 infants with neonatal lupus, congenital heart block, and EFE, 11 either died or required cardiac transplantation because of EFE [36]. A report identified EFE as a cause of HF with preserved ejection fraction in teenagers who had undergone successful balloon aortic valvuloplasty in infancy [39].

SUMMARY

●Definition – Cardiomyopathies include a variety of myocardial disorders that manifest with various structural and functional phenotypes and are frequently genetic. Myocardial disease caused by known cardiovascular causes (such as hypertension, ischemic heart disease, or valvular disease) should be distinguished from cardiomyopathies for classification and management purposes. (See 'Definition and classification' above.)

●Broad classification by phenotype – The main cardiomyopathy phenotypes are dilated, hypertrophic, restrictive, arrhythmogenic right ventricular, and unclassified cardiomyopathies. Each cardiomyopathy phenotype is caused by a variety of familial and nonfamilial disorders (table 3A and table 3B). (See 'Anatomic and physiologic classification' above.)

●Echocardiographic evaluation – Identification of various cardiomyopathy phenotypes is primarily reliant upon echocardiographic evaluation. In select cases, cardiac magnetic resonance imaging or computed tomography may be useful to identify and localize fatty infiltration, inflammation, scar/fibrosis, focal hypertrophy, and better visualize the left ventricular apex and right ventricle. (See 'Echocardiographic evaluation' above.)