Definition and Classification of The Cardiomyopathies

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Definition and classification of the cardiomyopathies

Author: Leslie T Cooper, Jr, MD
Section Editor: William J McKenna, MD
Deputy Editor: Susan B Yeon, MD, JD, FACC
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature rev iew current through: Mar 2020. | This topic last updated: Apr 22, 2019.
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 or cardiomyopathy are discussed
separately. (See "Determining the etiology and severity of heart failure or cardiomyopathy" and
"Causes of dilated cardiomyopathy" and "Idiopathic restrictive cardiomyopathy" and
"Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical
manifestations" and "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and
evaluation".)
DEFINITION
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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
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(predominantly nongenetic; less commonly genetic), or acquired. The genetic cardiomyopathies

include HCM, ARVC/D, left ventricular noncompaction, PRKAG2 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 hypertrophic cardiomyopathy are more frequently identified than are genes
contributing to dilated or restrictive cardiomyopathy. 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, MD =

dilated cardiomyopathy).
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● The organ involvement (O) notation indicates if heart and/or extracardiac involvement related
to the cause of heart disease is present (eg, OH+K = heart and kidney involvement).
● The genetic or familial inheritance (G) notation indicates the nature of genetic transmission
(eg, GAD = autosomal dominant).
● The etiological annotation (E) provides description of the specific cause (eg, the specific
gene and mutation as in EG-MY H7[p.Arg403Glu] ).
● The addition of a functional status (S) term is considered optional (eg, SC-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 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 heart failure guidelines [11].
ECHOCARDIOGRAPHIC EVALUATION
Identification of various cardiomyopathy phenotypes relies primarily upon echocardiographic

evaluation. Two-dimensional and Doppler echocardiography can, in most cases, define the
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anatomic and functional characteristics of the heart that are diagnostic of dilated, hypertrophic,
arrhythmogenic right ventricular, or restrictive cardiomyopathy. (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, left ventricular (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 heart failure (HF). (See
"Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and
remodeling".)
Systolic dysfunction is characteristic of dilated cardiomyopathy. It is also seen in some patients

with hypertrophic cardiomyopathy (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.
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, hypertrophic cardiomyopathy, restrictive cardiomyopathy, LV
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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 "Clinical
manifestations and diagnosis of heart failure with preserved ejection fraction", 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".)
Diastolic dysfunction is characteristic of both HCM and restrictive cardiomyopathy (RCM).

However, some component of diastolic dysfunction is also common in patients with dilated
cardiomyopathy (DCM).
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 a hypertrophic cardiomyopathy or as a

restrictive cardiomyopathy.
● Cardiac sarcoidosis that may progress from manifesting as a focal wall motion abnormality
to a dilated or restrictive cardiomyopathy often with heart block and ventricular arrhythmias
as early presenting features. (See "Clinical manifestations and diagnosis of cardiac
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sarcoidosis".)
Dilated cardiomyopathy — Dilated cardiomyopathy (DCM) is characterized by dilation and

impaired contraction of one or both ventricles [12]. 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 heart
failure (HF). When the presenting manifestations include conduction abnormalities, atrial and/or
ventricular arrhythmias, and sudden death, then an arrhythmogenic cardiomyopathy 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 [12]. These figures may underestimate the frequency of the
disorder because so many patients with DCM have incomplete disease expression, which goes
unrecognized. It has been suggested that up to 14 percent of the middle-aged and elderly
population have asymptomatic left ventricular (LV) systolic dysfunction [13].
The complete list of causes of DCM is extensive [14]. 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 (such as genetic hypertrophic cardiomyopathy [HCM]). (See "Causes of dilated
cardiomyopathy" and "Genetics of dilated cardiomyopathy" and "Hypertrophic cardiomyopathy:
Natural history and prognosis", section on 'End-stage HCM (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
"Ischemic cardiomyopathy: Treatment and prognosis" and "Management of chronic primary
mitral regurgitation" and "Natural history and management of chronic aortic regurgitation in
adults".)
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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
[15]. 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 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 [16]. The interventricular septum is typically
more prominently involved than the LV free wall, but concentric and apical hypertrophy can occur
(image 2 and 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) [17,18].
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 [19]. (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: Prevalence, pathophysiology, and management of concurrent atrial
arrhythmias" 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 athletes, LVH reaches 14 to 16 mm. Ethnic differences also affect
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the degree of LVH and echocardiographic abnormalities. Black women athletes have a greater
degree of LVH and repolarization abnormalities than white women athletes [20]. 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 electrocardiogram, 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 [21,22].
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's 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 HCM — 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 "Definition
and pathogenesis of left ventricular hypertrophy in hypertension" and "Clinical manifestations
and diagnosis of aortic stenosis in adults", section on 'Diagnostic echocardiography'.)
Restrictive cardiomyopathy — Restrictive cardiomyopathy (RCM) is characterized by nondilated

ventricles with impaired ventricular filling [23]. 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 3). 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".)
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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 "Idiopathic restrictive
cardiomyopathy", 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 [23]. (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 right ventricular cardiomyopathy — Arrhythmogenic right ventricular

cardiomyopathy is a genetically determined heart muscle disease characterized by ventricular
arrhythmias and a specific myocardial pathology [24]. 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
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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 [25-28]. Electrical
abnormalities include QT interval prolongation, electrical and mechanical dyssynchrony, and
chronotropic incompetence [27]. 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 [29].
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 [30]. Anoxia,
endocarditis, viral infection, and genetic factors have all been implicated [29]. Familial EFE has
been reported in association with systemic carnitine deficiency [31]. In addition, an association
with maternal autoantibody-mediated congenital heart block (neonatal lupus) has been
described [32]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and
diagnosis" and "Specific fatty acid oxidation disorders", section on 'Carnitine transporter
deficiency'.)
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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 [33]. Case reports suggest that
endocardial late gadolinium enhancement on cardiac magnetic resonance imaging can help
identify EFE [34,35].
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 [36]. 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 [32]. A report identified EFE as a cause of HF with preserved ejection fraction in
teenagers who had undergone successful balloon aortic valvuloplasty in infancy [35].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain
language, at the 5 th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10 th to 12 th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Dilated cardiomyopathy (The Basics)")
● Beyond the Basics topic (see "Patient education: Dilated cardiomyopathy (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● 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
12 of 39 4/29/2020, 5:46 PM
management purposes. (See 'Definition' above.)
● Identification of various cardiomyopathy phenotypes relies primarily 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.)
● 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.)
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REFERENCES
1. McKenna WJ, Maron BJ, Thiene G. Classification, Epidemiology, and Global Burden of
Cardiomyopathies. Circ Res 2017; 121:722.
2. Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies.
Br Heart J 1980; 44:672.
3. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health

Organization/International Society and Federation of Cardiology Task Force on the
Definition and Classification of cardiomyopathies. Circulation 1996; 93:841.
4. Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the
cardiomyopathies: an American Heart Association Scientific Statement from the Council on
Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and
Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary
Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;
113:1807.
5. Belkaya S, Kontorovich AR, Byun M, et al. Autosomal Recessive Cardiomyopathy

Presenting as Acute Myocarditis. J Am Coll Cardiol 2017; 69:1653.
6. Ware JS, Li J, Mazaika E, et al. Shared Genetic Predisposition in Peripartum and Dilated
13 of 39 4/29/2020, 5:46 PM
Cardiomyopathies. N Engl J Med 2016; 374:233.
7. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position

statement from the European Society Of Cardiology Working Group on Myocardial and
Pericardial Diseases. Eur Heart J 2008; 29:270.
8. Arbustini E, Narula N, Dec GW, et al. The MOGE(S) classification for a phenotype-genotype
nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J Am Coll
Cardiol 2013; 62:2046.
9. Elliott PM. Classification of cardiomyopathies: evolution or revolution? J Am Coll Cardiol

2013; 62:2073.
10. Hazebroek MR, Moors S, Dennert R, et al. Prognostic Relevance of Gene-Environment

Interactions in Patients With Dilated Cardiomyopathy: Applying the MOGE(S) Classification.
J Am Coll Cardiol 2015; 66:1313.
11. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, et al. 2013 ACCF/AHA guideline
for the management of heart failure: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on practice guidelines. Circulation
2013; 128:e240.
12. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994; 331:1564.
13. Devereux RB, Roman MJ, Paranicas M, et al. A population-based assessment of left
ventricular systolic dysfunction in middle-aged and older adults: the Strong Heart Study. Am
Heart J 2001; 141:439.
14. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in
patients with initially unexplained cardiomyopathy. N Engl J Med 2000; 342:1077.
15. Braunwald E, Seidman CE, Sigwart U. Contemporary evaluation and management of

hypertrophic cardiomyopathy. Circulation 2002; 106:1312.
16. Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a
general population of young adults. Echocardiographic analysis of 4111 subjects in the
CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 1995;
92:785.
17. St John Sutton MG, Lie JT, Anderson KR, et al. Histopathological specificity of hypertrophic
14 of 39 4/29/2020, 5:46 PM
obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis. Br Heart J

1980; 44:433.
18. Maron BJ, Wolfson JK, Roberts WC. Relation between extent of cardiac muscle cell
disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy. Am J
Cardiol 1992; 70:785.
19. Richard P, Charron P, Carrier L, et al. Hypertrophic cardiomyopathy: distribution of disease

genes, spectrum of mutations, and implications for a molecular diagnosis strategy.
Circulation 2003; 107:2227.
20. Rawlins J, Carre F, Kervio G, et al. Ethnic differences in physiological cardiac adaptation to
intense physical exercise in highly trained female athletes. Circulation 2010; 121:1078.
21. Corrado D, Pelliccia A, Bjørnstad HH, et al. Cardiovascular pre-participation screening of

young competitive athletes for prevention of sudden death: proposal for a common
European protocol. Consensus Statement of the Study Group of Sport Cardiology of the
Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group
of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J
2005; 26:516.
22. Thompson PD, Franklin BA, Balady GJ, et al. Exercise and acute cardiovascular events
placing the risks into perspective: a scientific statement from the American Heart
Association Council on Nutrition, Physical Activity, and Metabolism and the Council on
Clinical Cardiology. Circulation 2007; 115:2358.
23. Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med 1997;
336:267.
24. Basso C, Corrado D, Marcus FI, et al. Arrhythmogenic right ventricular cardiomyopathy.
Lancet 2009; 373:1289.
25. Milani A, Zaccaria R, Bombardieri G, et al. Cirrhotic cardiomyopathy. Dig Liver Dis 2007;
39:507.
26. Møller S, Henriksen JH. Cirrhotic cardiomyopathy. J Hepatol 2010; 53:179.
27. Zardi EM, Abbate A, Zardi DM, et al. Cirrhotic cardiomyopathy. J Am Coll Cardiol 2010;
56:539.
28. Timoh T, Protano MA, Wagman G, et al. A perspective on cirrhotic cardiomyopathy.
15 of 39 4/29/2020, 5:46 PM
Transplant Proc 2011; 43:1649.
29. Denfield, SW, Gajarski, et al. Cardiomyopathies. In: Science and Practice of Pediatric Cardi
ology, 2nd Ed, Garson, A Jr, Bricker, JT, Fisher, DJ, Neish, SR (Eds), Williams and Wilkins,
Baltimore 1998. p.1851.
30. Lurie PR. Endocardial fibroelastosis is not a disease. Am J Cardiol 1988; 62:468.
31. Tripp ME, Katcher ML, Peters HA, et al. Systemic carnitine deficiency presenting as familial
endocardial fibroelastosis: a treatable cardiomyopathy. N Engl J Med 1981; 305:385.
32. Nield LE, Silverman ED, Taylor GP, et al. Maternal anti-Ro and anti-La antibody-associated
endocardial fibroelastosis. Circulation 2002; 105:843.
33. Mahle WT, Weinberg PM, Rychik J. Can echocardiography predict the presence or absence
of endocardial fibroelastosis in infants <1 year of age with left ventricular outflow
obstruction? Am J Cardiol 1998; 82:122.
34. Tworetzky W, del Nido PJ, Powell AJ, et al. Usefulness of magnetic resonance imaging of
left ventricular endocardial fibroelastosis in infants after fetal intervention for aortic valve
stenosis. Am J Cardiol 2005; 96:1568.
35. Robinson JD, Del Nido PJ, Geggel RL, et al. Left ventricular diastolic heart failure in
teenagers who underwent balloon aortic valvuloplasty in early infancy. Am J Cardiol 2010;
106:426.
36. Ino T, Benson LN, Freedom RM, Rowe RD. Natural history and prognostic risk factors in
endocardial fibroelastosis. Am J Cardiol 1988; 62:431.
Topic 4943 Version 27.0
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GRAPHICS
Etiologic classification of cardiomyopathy-I
Infectious Viral (cont'd) Helminthic (cont'd)
Coxsackievirus* Schistosomiasis*
Bacterial
Echovirus* Ascariasis
Diptheria*
Cytomegalovirus* Heterophydiasis
Tuberculosis*
Hepatitis* Filariasis
Typhoid fever*
Rabies* Paragonimiasis
Rheumatic fever*
Mycoplasma* Strongyloidiasis
Scarlet fever*
Psittacosis* Cysticercosis
Meningococcal*
Herpes Visceral larva migrans
Pneumococcal
Encephalitis Toxins and drugs
Gonococcal
Arboviruses*
Brucellosis Adriamycin*
Tetanus Mycotic Amphetamine*
Meliodosis Actinomycosis Antimony
Tularemia Blastomycosis Arsenic*
Pertussis Moniliasis Carbon monoxide

Aspergiliosis Carbon tetrachloride
Spirochetal
Histoplasmosis* Catecholamines*
Syphilis
Coccidiomycosis Cobalt*
Leptospirosis*
Cryptococcosis* Cocaine*
Lyme disease*
Candidiasis Cyclophosphamide
Rickettsial
Protozoal Emetine
Typhus
South American Ethyl alcohol*
Rocky mountain spotted fever*
trypanosomiasis* Lithium
Q fever
African trypanosomiasis* Lead
Viral
Toxoplasmosis* Methysergide
Parvovirus B19*
Malaria Phenothiazine drugs
Human herpesvirus 6*
Amebiasis Phosphorus*
Poliomyelitis*
Leishmaniasis Tricyclic antidepressants
Influenza*
Balantidiasis Zidovudine*
Mumps*
Sarcosporidiosis Radiation* ¶
Rubella*
Helminthic
Rubeola*
Trichiniasis*
Variola*
Echinococcosis
Varicella*
Epstein-Barr*
* Conditions that may manifest clinically as dilated cardiomyopathy.

¶ Conditions that may manifest clinically as restrictive cardiomyopathy.
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Adapted with permission from: Abelmann, WH. Introduction to Atlas of Heart Diseases, Vol. II: Cardiomyopathies,
Myocarditis and Pericardial disease, Abelmann, WH (Ed), Current Medicine, Philadelphia, 1995, p. 1.
Graphic 78298 Version 6.0
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Etiologic classification of cardiomyopathy-II
Genetic Hematologic/oncologic Endomyocardial

Genetic hypertrophic
diseases
Hematologic disorders
cardiomyopathy* ¶ Endomyocardial fibrosis ¶Δ
Leukemia Δ
Genetic dilated Hypereosiinophilic heart
Myeloma
cardiomyopathy Δ disease
Sickle cell anemia Δ
Metabolic (Loffler's) ¶
Anemia Δ
Endocrine Endocardial
Henoch-Schonlein purpura Δ fibroelastosis ¶Δ
Acromegaly* ¶Δ
Neoplastic diseases
Inflammatory
Thyrotoxicosis Δ
Primary neoplasms ¶
Hypothyroidism* ¶Δ Connective tissue
Metastatic neoplasms ¶ diseases
Pheochromocytoma* ¶Δ
Deposits Rheumatoid heart
Diabetes melllitus disease Δ
Hemochromatosis ¶Δ
Familial storage diseases Ankylosing spondylitis
Oxalosis
Glycogen storage Systemic lupus
diseases* Δ Ochronosis erythematosus Δ
Refsum disease Amyloid disease ¶ Scleroderma ¶Δ
Niemann-Pick disease Heredofamilial neurologic and Dermatomyositis Δ
Hand-Schuller-Christian neuromuscular diseases Periarteritis nodosa
disease
Progressive muscular dystrophy (Duchenne) Δ Granulomatous
Fabry's disease* Δ
Limb-girdle muscular dystrophy (Erb) Δ Sarcoid Δ
Gangliosiderosis
Fascioscapulohumeral dystrophy (Landouzy- Wegener's
Gaucher's disease ¶Δ Dejerine) granulomatosis Δ
Sandhoff's disease Δ Humeroperoneal ataxia Granulomatous
Mucopolysaccharidosis Δ Friedreich's ataxia* myocarditis Δ
Hunter's syndrome Myotonia atrophica (Steinert) Δ Other inflammation
Hurler's syndrome Myasthenia gravis Giant cell myocarditis Δ
Nutritional Chronic progressive external opthmoplegia Hypersensitivity

(Kearns-Savre) myocarditis Δ
Beriberi Δ
Familial centronuclear myopathy
Kwashiokor Δ
Juvenile progressive spinal muscular atrophy
Pellagra
(Kugelberg-Welander)
Selenium deficiency
Neurofibromatosis*
(Keshan's disease) Δ
Other
Hypokalemia Δ
Carnitine deficiency Δ
Uremia Δ
* Conditions that may manifest clinically as hypertrophic cardiomyopathy. (These designations are neither obligatory nor
exclusive).
¶ Conditions that may manifest clinically as restrictive cardiomyopathy.
Δ Conditions that may manifest clinically as dilated cardiomyopathy.
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Adapted with permission from: Abelmann WH. Introduction to Atlas of Heart Diseases, Vol. II: Cardiomyopathies,
Myocarditis and Pericardial disease, Abelmann, WH (Ed), Current Medicine, Philadelphia, 1995, p.1.
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Major causes of dilated cardiomyopathy
Infectious Medications Inflammatory/autoimmune

diseases Chemotherapeutic agents Systemic lupus erythematosis
Viral Anthracyclines Dermatomyositis
Adenovirus Cyclophosphamide Scleroderma
Coxsackie virus Trastuzumab
Rheumatoid arthritis
Cytomegalovirus Antiretroviral drugs
Sarcoidosis
HIV Zidovudine
Hypersensitivity myocarditis
Influenza virus Didanosine
Other autoimmune myocarditis
Varicella Zalcitabine
Hepatitis Giant cell arteritis
Phenothiazines
Epstein-Barr Kawasaki disease
Chloroquine
Echovirus
Hydroxychloroquine
Endocrinologic disorders
Parvovirus
Clozapine Thyroid hormone excess or deficiency
Other
Growth hormone excess or deficiency
Bacterial Toxins
Diabetes mellitus
Streptococci-rheumatic Ethanol
fever Cushing's syndrome
Cocaine
Typhoid fever Pheochromocytoma or other catecholamine
Amphetamines
Diphtheria excess
Cobalt
Brucellosis Genetic with or without
Lead
Psitticosis neuromuscular disease
Mycobacteria Lithium
Familial (and sporadic) genetic cardiomyopathies
Rickettsial Mercury
Duchenne's muscular dystrophy
Spirochetal Carbon monoxide
Myotonic dystrophy
Leptospirosis Beryllium
Friedreich's ataxia
Syphilis Methysergide
Arrhythmogenic right ventricular cardiomyopathy
Lyme disease Electrolyte and
Miscellaneous
Fungal renal abnormalities
Peripartum cardiomyopathy
Histoplasmosis Hypocalcemia
Tachycardia
Cryptococcosis Hypophosphatemia
Heat stroke
Parasitic Uremia
Hypothermia
Toxoplasmosis
Nutritional deficiencies
Sleep apnea
Trypanosomiasis
(Chagas disease) Thiamine
Radiation
Shistosomiasis Selenium
(Calcium overload)
Trichinosis Carnitine
(Oxygen free radical damage)
Deposition Niacin (pellagra)
Differential diagnosis
diseases
Ischemic heart disease
Hemochromatosis
Amyloidosis
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Familial types of cardiomyopathy
A rrhythmogenic
HCM DCM A RVC RCM Unclassified
CM
Familial, unknown Familial, Familial, Familial, unknown Familial, unknown Left ventricular
gene unknown gene unknown gene gene gene non-compaction
Sarcomeric protein Sarcomeric Intercalated Intercalated disc Sarcomeric protein Barth
mutations protein disc protein protein mutations (see mutations syndrome
Β myosin mutations (see mutations ARVC) Troponin I Lamin A/C
heavy chain HCM) Plakoglobin Lamin A/C (RCM +/- ZASP
Cardiac myosin Z-band Desmoplakin HCM) α-dystrobrevin
SCN5A
binding protein Muscle LIM Plakophilin 2 Essential light
Phospholamban
C protein Desmoglein chain of myosin
Cardiac TCAP 2 Familial
troponin I Cytoskeletal Desmocollin amyloidosis
Troponin-T genes 2 Transthyretin
α-tropomyosin Titin Transforming (RCM +
Essential growth factor- neuropathy)
Dystrophin
myosin light β3 (TGF-β3) Apolipoprotein
Desmin
chain Transmembrane (RCM +
Metavinculin
Regulatory protein 43 nephropathy)
Sarcoglycan
myosin light (TMEM43) Desminopathy
complex
chain Pseuxanthoma
CRYAB
Cardiac actin elasticum
Epicardin
α-myosin Haemochromatosis
Nuclear
heavy chain
membrane Anderson-Fabry
Titin
Lamin A/C disease
Troponin C
Emerin Glycogen storage
Muscle LIM
Mildly dilated disease
protein
CM
Glycogen storage
disease (eg, Intercalated
Pompe; PRKAG2, disc protein
Forbes', Danon) mutations (see
ARVC)
Lysosomal storage
diseases (eg, Mitochondrial
Anderson-Fabry, cytopathy
Hurler's)
Disorders of fatty
acid metabolism
Carnitine
deficiency
Phosphorylase B
kinase deficiency
Mitochondrial
cytopathies
Syndromic HCM
Noonan's
syndrome
LEOPARD
syndrome
Friedreich's
ataxia
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Beckwith-
Wiedemann
syndrome
Swyer's
syndrome
Other
Phospholamban
promoter
Familial
amyloid
HCM: hypertrophic cardiomyopathy; DCM: dilated cardiomyopathy; ARVC: arrhythmogenic right ventricular
cardiomyopathy; RCM: restrictive cardiomyopathy.
Modified with permission from: Elliott P, Anderson B, Arbustini E, et al. Classification of the cardiomyopathies: a position
statement from the European Society of Cardiology working group on myocardial and pericardial disease. Eur Heart J 2008;
29:270. Copyright © 2008 Oxford University Press.
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Non-familial types of cardiomyopathy
HCM DCM A RVC RCM Unclassified
Obesity Myocarditis Inflammation? Amyloid Takotsubo

Infants of diabetic (infective/toxic (AL/prealbumin) cardiomyopathy
mothers /immune) Scleroderma
Athletic training Kawasaki disease Endomyocardial
Amyloid Eosinophilic (Churg fibrosis
(AL/prealbumin) Strauss syndrome) Hypereosinophilic
Viral persistence syndrome
Drugs Idiopathic
Chromosomal
Pregnancy
cause
Endocrine
Drugs (serotonin,
Nutritional - methysergide,
thiamine, carnitine, ergotamine,
selenium, mercurial agents,
hypophosphataemia, busulfan)
hypocalcaemia Carcinoid heart
Alcohol disease
Tachycardiomyopathy Metastatic cancers

Radiation
Drugs
(anthracyclines)
HCM: hypertrophic cardiomyopathy; DCM: dilated cardiomyopathy; ARVC: arrhythmogenic right ventricular
cardiomyopathy; RCM: restrictive cardiomyopathy.
Reproduced with permission from: Elliott P, Anderson B, Arbustini E, et al. Classification of the cardiomyopathies: a position
statement from the European Society of Cardiology working group on myocardial and pericardial disease. Eur Heart J 2008;
29:270. Copyright © 2008 Oxford University Press.
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Differential diagnosis of heart failure with preserved ejection fraction
Heart failure with preserved ejection fraction (HFpEF)
HFpEF (contributing factors include hypertension, aging, coronary heart disease, diabetes mellitus, sleep-
disordered breathing, chronic kidney disease, and obesity)
Cardiomyopathies with preserved ejection fraction
Restrictive cardiomyopathy
Familial causes include sarcomeric gene mutations, familial amyloidosis (TTR or apolipoprotein mutation),
unknown gene mutation, familial causes of iron overload (hereditary hemochromatosis, hereditary anemias),
Fabry disease, glycogen storage disease, desminopathy, and pseudoxanthoma elasticum
Non-familial causes include amyloid (AL or wild-type TTR), systemic sclerosis, endomyocardial fibrosis
(idiopathic, caused by hypereosinophilic syndrome, or drugs), carcinoid heart disease, metastatic cancer,
radiation, non-familial iron overload (eg, acquired iron-loading anemia, high-dietary intake), and drug
toxicity (anthracycline)
Hypertrophic cardiomyopathy
Familial causes in addition to sarcomere gene mutations include unknown mutations, glycogen storage
disease, lysosomal storage disease (including Fabry disease), syndromic hypertrophic cardiomyopathy (eg,
Noonan's syndrome, LEOPARD syndrome, Friedreich's ataxia), and familial amyloidosis (TTR or
apolipoprotein mutation)
Non-familial causes include non-familial amyloidosis (AL or wild-type TTR)
Noncompaction cardiomyopathy
Valvular heart disease
Valvular stenosis
Valvular regurgitation
Right heart failure
Pulmonary hypertension
Right ventricular infarction
Arrhythmogenic right ventricular cardiomyopathy
Pericardial disease
Cardiac tamponade
Constrictive pericarditis
Effusive-constrictive pericardial disease
Obstructive lesion in heart or great vessel
Atrial myxoma
Pulmonary vein stenosis
High-output heart failure
Transient left ventricular systolic dysfunction
Adapted from: Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-
dimensional and Doppler echocardiography. J Am Coll Cardiol 2006; 47:500.
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Phases of diastole
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Dilated cardiomyopathy chest radiograph
T his plain frontal radiograph of the c hes t in a 5 1 - y ear- old male

demons trates mark ed enlargement of the c ardiac s ilhouette
c ompatible with a dilated c ardiomy opathy. C ardiomegaly is
nons pec ific and c an be s een with any etiology of c ardiomy opathy.
Courtesy of Jonathan Kruskal, MD, PhD.
Normal chest radiograph
P os teroanterior v iew of a normal c hes t radiograph.
Courtesy of Carol M Black, MD.
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Genes considered clinically relevant for dilated cardiomyopathy
Estimated
Gene Protein OMIM fraction of Reference*
DCM
Strongest evidence ¶
LMNA Lamin A/C 150330 0.06 [1-14]
MYH7 Beta-myosin heavy 160760 0.04 [15-18]

chain
TNNT2 Cardiac troponin T 191045 0.03 [15,17-23]
RBM20 (hotspot) Δ RNA binding protein 613171 0.02 [24,25]

20
Strong evidence
TTN – truncating Titin 188840 0.15 to 0.20 [26-32]

variants
BAG3 BCL-associated 603883 0.03 [33-35]

athanogene 3
SCN5A Sodium channel 600163 0.02 [18,36,37]
FLNC Filamin C 102565 0.02 to 0.04 [38,39]
TPM1 Alpha-tropomyosin 191010 <0.01 [40-42]
PLN Phospholamban 172405 <0.01 [17,43-47]
TNNC1 Cardiac troponin C 191040 <0.01 [21,41,48]
TNNI3 Cardiac troponin I 191044 <0.01 [41,49,50]
EYA4 Eyes-absent 4 603550 ? [51]
Variable evidence
MYPN Myopalladin 608517 0.03 [52]
MYBPC3 Myosin-binding 600958 0.02 [16,41]

protein C
MYH6 Alpha-myosin heavy 160710 0.04 [41,53]

chain
LAMA4 Laminin alpha-4 600133 <0.01 [54]
VCL Metavinculin 193065 <0.01 [17,55]
LDB3 Cypher/ZASP 605906 <0.01 [18,56]
TCAP Titin-cap or 604488 <0.01 [18,57]

telethonin
ACTN2 Alpha-actinin-2 102573 <0.01 [58]
CRYAB Alpha B crystalin 123590 <0.01 [59]
RBM20 (non- RNA binding protein 613171 ? [25]

hotspot) 20
ABCC9 SUR2A 601439 <0.01 [60]
ACTC1 Cardiac actin 102540 <0.01 [61-66]
PDLIM3 PDZ LIM domain 605889 <0.01 [67]

protein 3
28 of 39 4/29/2020, 5:46 PM
ILK Integrin-linked 602366 <0.01 [54]

kinase
SGCD Delta-sarcoglycan 601411 <0.01 [68-70]
DES Desmin 125660 <0.01 [64,69,71]
CSRP3 Muscle LIM protein 600824 <0.01 [18,72]
ANKRD1 Ankyrin repeat 609599 ? [73,74]

domain-containing
protein 1
NEXN Nexilin 613121 ? [75]
NEBL Nebulette 605491 ? [76]
ARVC genes
DSP Desmoplakin 125660 ? [77-81]
PKP2 Plakophilin 2 602861 ? [77-79]
DSG2 Desmoglein 2 125671 ? [77-79]
G enes hav e been c ategorized bas ed on s trength of ev idenc e.
OMIM: Online Mendelian Inheritance in Man; DCM: dilated cardiomyopathy; ARVC: arrhythmogenic right ventricular
cardiomyopathy.
* References not necessarily exhaustive, especially on genes with strongest or strong evidence. Syndromic genes (eg, TAZ,
DMD) not included.
¶ Most variants shown to be DCM disease-causing have been rare missense variants.
Δ Restricted to the RBM20 6 amino acid hotspot.
References:
1. Fatkin D, MacRae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of
dilated cardiomyopathy and conduction-system disease. N Engl J Med 1999; 341:1715.
2. Brodsky G, Muntoni F, Miocic S, et al. Lamin A/C gene mutation associated with dilated cardiomyopathy with
variable skeletal muscle involvement. Circulation 2000; 101:473.
3. Becane HM, Bonne G, Varnous S, et al. High incidence of sudden death with conduction system and myocardial
disease due to lamins A and C gene mutation. Pacing Clin Electrophysiol 2000; 23:1661.
4. Jakobs PM, Hanson E, Crispell KA, et al. Novel lamin A/C mutations in two families with dilated cardiomyopathy and
conduction system disease. J Card Fail 2001; 7:249.
5. Arbustini E, Pilotto A, Repetto A, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a
lamin A/C defect-related disease. J Am Coll Cardiol 2002; 39:981.
6. Hershberger RE, Hanson E, Jakobs PM, et al. A novel lamin A/C mutation in a family with dilated cardiomyopathy,
prominent conduction system disease, and need for permanent pacemaker implantation. Am Heart J 2002;
144:1081.
7. Taylor MR, Fain PR, Sinagra G, et al. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J
Am Coll Cardiol 2003; 41:771.
8. Sebillon P, Bouchier C, Bidot LD, et al. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and
functional consequences of these mutations. J Med Genet 2003; 40:560.
9. MacLeod HM, Culley MR, Huber JM, McNally EM. Lamin A/C truncation in dilated cardiomyopathy with conduction
disease. BMC Med Genet 2003; 4:4.
10. Sylvius N, Bilinska ZT, Veinot JP, et al. In vivo and in vitro examination of the functional significances of novel lamin
gene mutations in heart failure patients. J Med Genet 2005; 42:639.
11. Pethig K, Genschel J, Peters T, et al. LMNA mutations in cardiac transplant recipients. Cardiology 2005; 103:57.
12. Karkkainen S, Reissell E, Helio T, et al. Novel mutations in the lamin A/C gene in heart transplant recipients with
end stage dilated cardiomyopathy. Heart 2006; 92:524.
13. Parks SB, Kushner JD, Nauman D, et al. Lamin A/C mutation analysis in a cohort of 324 unrelated patients with
idiopathic or familial dilated cardiomyopathy. Am Heart J 2008; 156:161.
14. Pasotti M, Klersy C, Pilotto A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am
Coll Cardiol 2008; 52:1250.
15. Kamisago M, Sharma SD, DePalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated
cardiomyopathy. N Engl J Med 2000; 343:1688.
29 of 39 4/29/2020, 5:46 PM
16. Daehmlow S, Erdmann J, Knueppel T, et al. Novel mutations in sarcomeric protein genes in dilated cardiomyopathy.
Biochem Biophys Res Commun 2002; 298:116.
17. Villard E, Duboscq-Bidot L, Charron P, et al. Mutation screening in dilated cardiomyopathy: prominent role of the
beta myosin heavy chain gene. Eur Heart J 2005; 26:794.
18. Hershberger RE, Parks SB, Kushner JD, et al. Coding sequence mutations identified in MYH7, TNNT2, SCN5A,
CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clin Transl Sci 2008;
1:21.
19. Hanson E, Jakobs P, Keegan H, et al. Cardiac troponin T lysine-210 deletion in a family with dilated
cardiomyopathy. J Card Fail 2002; 8:28.
20. Li D, Czernuszewicz GZ, Gonzalez O, et al. Novel cardiac troponin T mutation as a cause of familial dilated
cardiomyopathy. Circulation 2001; 104:2188.
21. Mogensen J, Murphy RT, Shaw T, et al. Severe disease expression of cardiac troponin C and T mutations in patients
with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2004; 44:2033.
22. Moller DV, Andersen PS, Hedley P, et al. The role of sarcomere gene mutations in patients with idiopathic dilated
cardiomyopathy. Eur J Hum Genet 2009; 17:1241.
23. Hershberger RE, Pinto JR, Parks SB, et al. Clinical and functional characterization of TNNT2 mutations identified in
patients with dilated cardiomyopathy. Circ Cardiovasc Genet 2009; 2:306.
24. Brauch KM, Karst ML, Herron KJ, et al. Mutations in ribonucleic acid binding protein gene cause familial dilated
cardiomyopathy. J Am Coll Cardiol 2009; 54:930.
25. Li D, Morales A, Gonzalez Quintana J, et al. Identification of novel mutations In RBM20 in patients with dilated
cardiomyopathy. Clin Transl Sci 2010; 3:90.
26. Gerull B, Gramlich M, Atherton J, et al. Mutations of TTN, encoding the giant muscle filament titin, cause familial
dilated cardiomyopathy. Nat Genet 2002; 30:201.
27. Gerull B, Atherton J, Geupel A, et al. Identification of a novel frameshift mutation in the giant muscle filament titin in
a large Australian family with dilated cardiomyopathy. J Mol Med 2006; 84:478.
28. Herman DS, Lam L, Taylor MR, et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med 2012;
366:619.
29. Norton N, Li D, Rampersaud E, et al. Exome Sequencing and Genome-Wide Linkage Analysis in 17 Families
Illustrates the Complex Contribution of TTN Truncating Variants to Dilated Cardiomyopathy. Circ Cardiovasc Genet
2013; 6:144.
30. Roberts AM, Ware JS, Herman DS, et al. Integrated allelic, transcriptional, and phenomic dissection of the cardiac
effects of titin truncations in health and disease. Sci Transl Med 2015; 7:270ra6.
31. Ware JS, Li J, Mazaika E, et al. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. N Engl J
Med 2016; 374:233.
32. Schafer S, de Marvao A, Adami E, et al. Titin-truncating variants affect heart function in disease cohorts and the
general population. Nat Genet 2017; 49:46.
33. Norton N, Li D, Reider MJ, et al. Genome-wide studies of copy number variation and exome sequencing identify rare
variants in BAG3 as a cause of dilated cardiomyopathy. Am J Hum Genet 2011; 88:273.
34. Villard E, Perret C, Gary F, et al. A genome-wide association study identifies two loci associated with heart failure
due to dilated cardiomyopathy. Eur Heart J 2011; 32:1065.
35. Arimura T, Ishikawa T, Nunoda S, et al. Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly
and enhance sensitivity to apoptosis in cardiomyocytes. Hum Mutat 2011; 32:1481.
36. McNair WP, Ku L, Taylor MR, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder,
and arrhythmia. Circulation 2004; 110:2163.
37. Olson TM, Michels VV, Ballew JD, et al. Sodium channel mutations and susceptibility to heart failure and atrial
fibrillation. JAMA 2005; 293:447.
38. Begay RL, Tharp CA, Martin A, et al. FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy. JACC Basic Transl
Sci 2016; 1:344.
39. Ortiz-Genga MF, Cuenca S, Dal Ferro M, et al. Truncating FLNC Mutations Are Associated With High-Risk Dilated and
Arrhythmogenic Cardiomyopathies. J Am Coll Cardiol 2016; 68:2440.
40. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter the surface charge of alpha-tropomyosin are
associated with dilated cardiomyopathy. J Mol Cell Cardiol 2001; 33:723.
41. Hershberger RE, Norton N, Morales A, et al. Coding sequence rare variants identified in MYBPC3, MYH6, TPM1,
TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet
2010; 3:155.
42. Lakdawala NK, Dellefave L, Redwood CS, et al. Familial dilated cardiomyopathy caused by an alpha-tropomyosin
mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. J Am Coll Cardiol 2010; 55:320.
43. Schmitt JP, Kamisago M, Asahi M, et al. Dilated cardiomyopathy and heart failure caused by a mutation in
phospholamban. Science 2003; 299:1410.
30 of 39 4/29/2020, 5:46 PM
44. Haghighi K, Kolokathis F, Pater L, et al. Human phospholamban null results in lethal dilated cardiomyopathy
revealing a critical difference between mouse and human. J Clin Invest 2003; 111:869.
45. DeWitt MM, MacLeod HM, Soliven B, McNally EM. Phospholamban R14 deletion results in late-onset, mild, hereditary
dilated cardiomyopathy. J Am Coll Cardiol 2006; 48:1396.
46. Medin M, Hermida-Prieto M, Monserrat L, et al. Mutational screening of phospholamban gene in hypertrophic and
idiopathic dilated cardiomyopathy and functional study of the PLN –42 C>G mutation. Eur J Heart Fail 2007; 9:37.
47. Liu GS, Morales A, Vafiadaki E, et al. A novel human R25C-phospholamban mutation is associated with super-
inhibition of calcium cycling and ventricular arrhythmia. Cardiovasc Res 2015; 107:164.
48. Pinto JR, Siegfried JD, Parvatiyar MS, et al. Functional characterization of TNNC1 rare variants identified in dilated
cardiomyopathy. J Biol Chem 2011; 286:34404.
49. Murphy RT, Mogensen J, Shaw A, et al. Novel mutation in cardiac troponin I in recessive idiopathic dilated
cardiomyopathy. Lancet 2004; 363:371.
50. Carballo S, Robinson P, Otway R, et al. Identification and functional characterization of cardiac troponin I as a novel
disease gene in autosomal dominant dilated cardiomyopathy. Circ Res 2009; 105:375.
51. Schonberger J, Wang L, Shin JT, et al. Mutation in the transcriptional coactivator EYA4 causes dilated
cardiomyopathy and sensorineural hearing loss. Nat Genet 2005; 37:418.
52. Duboscq-Bidot L, Xu P, Charron P, et al. Mutations in the Z-band protein myopalladin gene and idiopathic dilated
cardiomyopathy. Cardiovasc Res 2008; 77:118.
53. Carniel E, Taylor MR, Sinagra G, et al. Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and
hypertrophic phenotypes of cardiomyopathy. Circulation 2005; 112:54.
54. Knoll R, Postel R, Wang J, et al. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy
via simultaneous defects in cardiomyocytes and endothelial cells. Circulation 2007; 116:515.
55. Olson TM, Illenberger S, Kishimoto NY, et al. Metavinculin mutations alter actin interaction in dilated
cardiomyopathy. Circulation 2002; 105:431.
56. Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left
ventricular non-compaction. J Am Coll Cardiol 2003; 42:2014.
57. Hayashi T, Arimura T, Itoh-Satoh M, et al. Tcap gene mutations in hypertrophic cardiomyopathy and dilated
cardiomyopathy. J Am Coll Cardiol 2004; 44:2192.
58. Mohapatra B, Jimenez S, Lin JH, et al. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated
cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab 2003; 80:207.
59. Inagaki N, Hayashi T, Arimura T, et al. Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem Biophys Res
Commun 2006; 342:379.
60. Bienengraeber M, Olson TM, Selivanov VA, et al. ABCC9 mutations identified in human dilated cardiomyopathy
disrupt catalytic KATP channel gating. Nat Genet 2004; 36:382.
61. Olson TM, Michels VV, Thibodeau SN, et al. Actin mutations in dilated cardiomyopathy, a heritable form of heart
failure. Science 1998; 280:750.
62. Mayosi B, Khogali S, Zhang B, Watkins H. Cardiac and skeletal actin gene mutations are not a common cause of
dilated cardiomyopathy. J Med Genet 1999; 36:796.
63. Takai E, Akita H, Shiga N, et al. Mutational analysis of the cardiac actin gene in familial and sporadic dilated
cardiomyopathy. Am J Med Genet 1999; 86:325.
64. Tesson F, Sylvius N, Pilotto A, et al. Epidemiology of desmin and cardiac actin gene mutations in a european
population of dilated cardiomyopathy. Eur Heart J 2000; 21:1872.
65. Zolty R, Brodsky G, Perryman B, et al. Epidemiology of cardiac actin gene mutations in dilated cardiomyopathy. J
Cardiac Failure 1999; 5:Supple 1:23.
66. Taylor MR, Slavov D, Ku L, et al. Prevalence of desmin mutations in dilated cardiomyopathy. Circulation 2007;
115:1244.
67. Arola AM, Sanchez X, Murphy RT, et al. Mutations in PDLIM3 and MYOZ1 encoding myocyte Z line proteins are
infrequently found in idiopathic dilated cardiomyopathy. Mol Genet Metab 2007; 90:435.
68. Tsubata S, Bowles KR, Vatta M, et al. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated
cardiomyopathy. J Clin Invest 2000; 106:655.
69. Karkkainen S, Miettinen R, Tuomainen P, et al. A novel mutation, Arg71Thr, in the delta-sarcoglycan gene is
associated with dilated cardiomyopathy. J Mol Med 2003; 15:15.
70. Sylvius N, Duboscq-Bidot L, Bouchier C, et al. Mutational analysis of the beta- and delta-sarcoglycan genes in a
large number of patients with familial and sporadic dilated cardiomyopathy. Am J Med Genet A 2003; 120A:8.
71. Li D, Tapscoft T, Gonzalez O, et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation
1999; 100:461.
72. Knoll R, Hoshijima M, Hoffman HM, et al. The Cardiac Mechanical Stretch Sensor Machinery Involves a Z Disc
Complex that Is Defective in a Subset of Human Dilated Cardiomyopathy. Cell 2002; 111:943.
73. Duboscq-Bidot L, Charron P, Ruppert V, et al. Mutations in the ANKRD1 gene encoding CARP are responsible for
31 of 39 4/29/2020, 5:46 PM
human dilated cardiomyopathy. Eur Heart J 2009; 30:2128.

74. Moulik M, Vatta M, Witt SH, et al. ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated
cardiomyopathy gene. J Am Coll Cardiol 2009; 54:325.
75. Hassel D, Dahme T, Erdmann J, et al. Nexilin mutations destabilize cardiac Z-disks and lead to dilated
cardiomyopathy. Nat Med 2009; 15:1281.
76. Purevjav E, Varela J, Morgado M, et al. Nebulette mutations are associated with dilated cardiomyopathy and
endocardial fibroelastosis. J Am Coll Cardiol 2010; 56:1493.
77. Elliott P, O'Mahony C, Syrris P, et al. Prevalence of desmosomal protein gene mutations in patients with dilated
cardiomyopathy. Circ Cardiovasc Genet 2010; 3:314.
78. Garcia-Pavia P, Syrris P, Salas C, et al. Desmosomal protein gene mutations in patients with idiopathic dilated
cardiomyopathy undergoing cardiac transplantation: a clinicopathological study. Heart 2011; 97:1744.
79. Marcus FI, Edson S, Towbin JA. Genetics of arrhythmogenic right ventricular cardiomyopathy: a practical guide for
physicians. J Am Coll Cardiol 2013; 61:1945.
80. Lopez-Ayala JM, Gomez-Milanes I, Sanchez Munoz JJ, et al. Desmoplakin truncations and arrhythmogenic left
ventricular cardiomyopathy: characterizing a phenotype. Europace 2014; 16:1838.
81. Rasmussen TB, Hansen J, Nissen PH, et al. Protein expression studies of desmoplakin mutations in cardiomyopathy
patients reveal different molecular disease mechanisms. Clin Genet 2013; 84:20.
Adapted from: Kinnamon DD, Morales A, Bowen DJ, et al. Toward Genetics-Driven Early Intervention in Dilated
Cardiomyopathy: Design and Implementation of the DCM Precision Medicine Study. Circ Cardiovasc Genet 2017;
10:e001826. DOI: 10.1161/CIRCGENETICS.117.001826. Copyright © 2017 American Heart Association. Reproduced with
permission from Wolters Kluwer Health. Unauthorized reproduction of this material is prohibited.
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Subcostal long axis view in hypertrophic

cardiomyopathy
T he s ubc os tal v iew from the two- dimens ional ec hoc ardiogram s hows
ex tremely hy pertrophied and as y mmetric s eptum, whic h is 3 5 mm in
thic k nes s . T he s ubc os tal v iew often prov ides images from whic h the
interv entric ular s eptum is mos t eas ily meas ured.
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Myocyte disarray in hypertrophic cardiomyopathy
M ic ros c opic appearanc e of the my oc ardium in hy pertrophic

c ardiomy opathy, s tained with hematox y lin and eos in, s hows my oc y te
dis array with an irregular arrangement of abnormal s haped my oc y tes
that c ontain bizarre nuc lei and s urrounding areas of inc reas ed
c onnec tiv e tis s ue.
Courtesy of Professor Michael Davies, St. George's Hospital, London.
Normal endomyocardial biopsy
N ormal endomy oc ardial biops y in longitudinal s ec tion.
Courtesy of Helmut Rennke, MD.
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Echocardiography of restrictive cardiomyopathy
T he ec hoc ardiographic features ty pic al of an idiopathic res tric tiv e

c ardiomy opathy inc lude a nondilated, nonhy pertrophied v entric le with
dilated atria. P anel A s hows the left paras ternal long ax is v iew and
panel B is a r apic al four c hamber v iew.
LA: left atrium; LV: left ventricle; RA: right atrium; RV: right ventricle; AO: aorta.
Courtesy of Naser Ammash, MD.
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Doppler in restrictive cardiomyopathy
T he puls e wav e D oppler in a patient with an idiopathic res tric tiv e

c ardiomy opathy demons trates an inc reas ed E /A ratio (2 .4 ), with s hortened
dec eleration time (D T = 1 2 8 millis ec onds ).
Courtesy of Naser Ammash MD.
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Morphologic features in arrhythmogenic right ventricular

cardiomyopathy (ARVC)
M orphologic features in a 2 5 - y ear- old man who died s uddenly from arrhy thmogenic
right v entric ular c ardiomy opathy (A R V C ).
P anel A : F our c hamber v iew c ut of the heart s pec imen s howing the trans mural fatty
replac ement of the right v entric ular free wall and the trans luc ent infundibulum.
P anel B : P anoramic his tologic v iew of the s ame heart c onfirming that the
replac ement of the my oc ardium by fat is largely c onfined to the right v entric le
(arrow) and s ubs tantially s pares the interv entric ular s eptum as well as the left
v entric ular free wall (tric hrome H eidenhain x 3 ).
Reproduced with permission from: Basso C, Corrado D, Rossi L, et al. Morbid anatomy. In:
Arrhythmogenic right ventricular cardiomyopathy - dysplasia, Nava A, Rossi L, Thiene G (Eds),
Elsevier, Amsterdam 1997. p.71-86, Elsevier Science.
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Left ventricular noncompaction
I s olated left v entric ular nonc ompac tion in an autops y s pec imen, s hown in
s hort- ax is v iew. N ote the c ompac ted epic ardial lay er and nonc ompac ted
endoc ardial lay er with mark ed hy pertrabec ulation and deep rec es s es .
Courtesy of William D. Edwards, MD, Department of Laboratory Medicine and Pathology, Mayo
Clinic, Rochester, MN.
38 of 39 4/29/2020, 5:46 PM
Contributor Disclosures
Leslie T Cooper, Jr, MD Nothing to disclose William J McKenna, MD Nothing to disclose Susan B
Yeon, MD, JD, FACC Nothing to disclose
Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy
39 of 39 4/29/2020, 5:46 PM

Definition and Classification of The Cardiomyopathies - UpToDate

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Definition and classification of the cardiomyopathies - UpToDate https://www.uptodate.com/contents/definition-and-classification-of-the-c...

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Cardiomyopathies are diseases of heart muscle [1]. A contemporary definition for

● Dilated cardiomyopathy (DCM)

(predominantly nongenetic; less commonly genetic), or acquired. The genetic cardiomyopathies

The MOGE(S) classification for a phenotype-genotype-based nomenclature of cardiomyopathy

● The morphofunctional (M) notation indicates a descriptive phenotypic diagnosis (eg, MD =

In summary, cardiomyopathies were originally defined as disorders that were idiopathic.

Identification of various cardiomyopathy phenotypes relies primarily upon echocardiographic

Systolic dysfunction — Systolic dysfunction is characterized by a decrease in myocardial

● LV enlargement, which results in a higher stroke volume

Systolic dysfunction is characteristic of dilated cardiomyopathy. It is also seen in some patients

Diastolic dysfunction — Diastolic dysfunction refers to cardiac dysfunction in which LV relaxation

Diastolic dysfunction is more difficult to identify and quantitate echocardiographically than

Diastolic dysfunction is characteristic of both HCM and restrictive cardiomyopathy (RCM).

ANATOMIC AND PHYSIOLOGIC CLASSIFICATION

● Amyloid cardiomyopathy, which may present as a hypertrophic cardiomyopathy or as a

Dilated cardiomyopathy — Dilated cardiomyopathy (DCM) is characterized by dilation and

Hypertrophic cardiomyopathy — HCM is a clinically heterogeneous disorder caused by a

In approximately 60 to 70 percent of patients, HCM is caused by mutations in sarcomeric

Athlete's heart — In response to intensive endurance training, there can be physiologic

Restrictive cardiomyopathy — Restrictive cardiomyopathy (RCM) is characterized by nondilated

On two-dimensional echocardiogram, RCM is characterized by nondilated, nonhypertrophied

Endomyocardial fibrosis — Endomyocardial fibrosis (EMF) occurs mainly in children and

Arrhythmogenic right ventricular cardiomyopathy — Arrhythmogenic right ventricular

Unclassified cardiomyopathies — The term "unclassified cardiomyopathy" was included in the

Left ventricular noncompaction — LV noncompaction, also called isolated ventricular

Stress-induced cardiomyopathy — Stress-induced cardiomyopathy, also called apical

Cirrhotic cardiomyopathy — While alcoholic cardiomyopathy is one cause of heart disease

Endocardial fibroelastosis — Endocardial fibroelastosis (EFE) is characterized by diffuse

● Basics topic (see "Patient education: Dilated cardiomyopathy (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Cardiomyopathies include a variety of myocardial disorders that manifest with various

management purposes. (See 'Definition' above.)

● Identification of various cardiomyopathy phenotypes relies primarily upon echocardiographic

● The main cardiomyopathy phenotypes are dilated, hypertrophic, restrictive, arrhythmogenic

Use of UpToDate is subject to the Subscription and License Agreement.

3. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health

5. Belkaya S, Kontorovich AR, Byun M, et al. Autosomal Recessive Cardiomyopathy

Cardiomyopathies. N Engl J Med 2016; 374:233.

7. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position

9. Elliott PM. Classification of cardiomyopathies: evolution or revolution? J Am Coll Cardiol

10. Hazebroek MR, Moors S, Dennert R, et al. Prognostic Relevance of Gene-Environment

15. Braunwald E, Seidman CE, Sigwart U. Contemporary evaluation and management of

obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis. Br Heart J

19. Richard P, Charron P, Carrier L, et al. Hypertrophic cardiomyopathy: distribution of disease

21. Corrado D, Pelliccia A, Bjørnstad HH, et al. Cardiovascular pre-participation screening of

26. Møller S, Henriksen JH. Cirrhotic cardiomyopathy. J Hepatol 2010; 53:179.

28. Timoh T, Protano MA, Wagman G, et al. A perspective on cirrhotic cardiomyopathy.

Transplant Proc 2011; 43:1649.

Topic 4943 Version 27.0

Etiologic classification of cardiomyopathy-I

Infectious Viral (cont'd) Helminthic (cont'd)

Tetanus Mycotic Amphetamine*

Meliodosis Actinomycosis Antimony

Tularemia Blastomycosis Arsenic*

Pertussis Moniliasis Carbon monoxide

* Conditions that may manifest clinically as dilated cardiomyopathy.

Graphic 78298 Version 6.0

Etiologic classification of cardiomyopathy-II

Genetic Hematologic/oncologic Endomyocardial

Hunter's syndrome Myotonia atrophica (Steinert) Δ Other inflammation