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Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), most commonly is an inherited
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
. ACM is caused by genetic defects of the parts of
heart muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...
(also called ''myocardium'' or ''cardiac muscle'') known as
desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
s, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, and many of those proteins can have harmful
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s. ARVC can also develop in intense
endurance Endurance (also related to sufferance, resilience, constitution, fortitude, and hardiness) is the ability of an organism to exert itself and remain active for a long period of time, as well as its ability to resist, withstand, recover from a ...
athletes in the absence of desmosomal abnormalities. Exercise-induced ARVC cause possibly is a result of excessive right ventricular wall stress during high intensity exercise. The disease is a type of non-ischemic
cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
that primarily involves the
right ventricle A ventricle is one of two large chambers toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium, an adjacent chamber in the upper ...
, though cases of exclusive left ventricular disease have been reported. It is characterized by hypokinetic areas involving the free wall of the ventricle, with fibrofatty replacement of the myocardium, with associated
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s often originating in the right ventricle. The nomenclature ARVD is currently thought to be inappropriate and misleading as ACM does not involve dysplasia of the ventricular wall. Cases of ACM originating from the left ventricle led to the abandonment of the name ARVC. ACM can be found in association with diffuse palmoplantar keratoderma, and
woolly hair Woolly hair is a difficult to brush hair, usually present since birth and typically most severe in childhood. It has extreme curls and kinks and occurs in non-black people. The hairs come together to form tight locks, unlike in afro-textured hai ...
, in an autosomal recessive condition called
Naxos disease __notoc__ Naxos disease (also known as "diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy" or "diffuse palmoplantar keratoderma with woolly hair and arrhythmogenic right ventricular cardiomyopathy", first desc ...
, because this genetic abnormality can also affect the integrity of the superficial layers of the skin most exposed to pressure stress. ACM is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30–50% of cases have a familial distribution.


Signs and symptoms

Those affected by arrhythmogenic cardiomyopathy may not have any symptoms at all despite having significant abnormalities in the structure of their hearts. If symptoms do occur, the initial presentation is often due to abnormal heart rhythms (arrhythmias) which in arrhythmogenic cardiomyopathy may take the form of palpitations, or blackouts. Sudden death may be the first presentation of ACM without any preceding symptoms. These symptoms often occur during
adolescence Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
and early adulthood, but signs of ACM may rarely be seen in infants. As ACM progresses, the muscle tissue within the ventricles may dilate and weaken. The right ventricle typically weakens first, leading to fatigue and ankle swelling. In the later stages of the disease in which both ventricles are involved shortness of breath may develop, especially when lying flat. The first clinical signs of ACM are usually during
adolescence Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
and early adulthood. However, rarely, signs of ACM have been demonstrated in infants.


Causes


Genetics

ACM is usually inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
pattern, with variable expression. Only 30% to 50% of individuals affected by ACM will test positive to one of the known genetic mutations in
chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
loci associated with the disease. Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see
intercalated disc Intercalated discs or lines of Eberth are microscopic identifying features of cardiac muscle. Cardiac muscle consists of individual heart muscle cells (cardiomyocytes) connected by intercalated discs to work as a single functional syncytium. By con ...
) are the main causatives for the development of this disease. Recently it has been shown, that mutations in the
desmin Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture. Str ...
DES gene could cause ACM. Desmin is an intermediate filament protein, which is linked to the
desmosomes A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
. Different ''DES'' mutations cause an abnormal aggregation of desmin and associated proteins. The
penetrance Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype). In medical genetics, the penetrance of a disease-causing mutation is t ...
is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ACM. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals. Types include:


Exercise-induced ARVC

In recent years, several studies have found excessive long-term sports activity to be a cause of exercise-induced arrhythmogenic right ventricular cardiomyopathy (EIARVC). For some athletes ARVC might develop due to high-endurance exercise and it most often develops without an underlying desmosomal abnormalities, possibly only as a result of excessive right ventricular (RV) wall stress during very high volumes of training, which is known to be causing a disproportionate remodeling of RV. In a 2003 study, 46 endurance athletes (mostly cyclists) presented with various symptoms suggestive of arrhythmia of RV origin. 59% of participants testing met criteria for ARVC and another 30% for possible ARVC. And only 1 athlete of the group had a family history of hereditable ARVC. Exercise-induced ARVC and
athlete's heart Athletic heart syndrome (AHS) is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal. The athlete's heart is associated with physiological cardiac ...
has an overlapping features.


Pathogenesis

The
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of ACM is largely unknown.
Apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
(programmed cell death) appears to play a large role. It was previously thought that only the right ventricle is involved, but recent cohorts have shown many cases of left ventricular disease and biventricular disease. The disease process starts in the subepicardial region and works its way towards the endocardial surface, leading to transmural involvement (possibly accounting for the aneurysmal dilatation of the ventricles). Residual myocardium is confined to the subendocardial region and the trabeculae of the ventricles. These trabeculae may become hypertrophied. Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The left ventricle is involved in 50–67% of individuals. If the left ventricle is involved, it is usually late in the course of disease, and confers a poor prognosis. There are two pathological patterns seen in ACM, Fatty infiltration and fibro-fatty infiltration.


Fatty infiltration

The first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-complete substitution of myocardium with fatty tissue ''without'' wall thinning. It involves predominantly the apical and infundibular regions of the RV. The left ventricle and ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty infiltration. There is evidence of
myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
(myocardial cell) degeneration and death seen in 50% of cases of fatty infiltration.


Fibro-fatty infiltration

The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue. A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates (mostly
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s) seen on microscopy. Myocardial atrophy is due to injury and
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
. This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the RV outflow tract, and the RV apex. However, the LV free wall may be involved in some cases. Involvement of the ventricular septum is rare. The areas involved are prone to aneurysm formation.


The Role of Exercise

Recently, some studies have identified strenuous exercise as a novel risk for accelerated progression of the disease. One retrospective study on 301 patients conclusively demonstrated that the subpopulations participating in strenuous physical activity (professional athletes for example) had an earlier onset of symptoms and earlier mortality compared to other populations.


Ventricular arrhythmias

Ventricular arrhythmias due to ACM typically arise from the diseased right ventricle. The type of arrhythmia ranges from frequent premature ventricular complexes (PVCs) to
ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...
(VT) to
ventricular fibrillation Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and no p ...
(VF). While the initiating factor of the ventricular arrhythmias is unclear, it may be due to triggered activity or reentry. Ventricular arrhythmias are usually exercise-related, suggesting that they are sensitive to catecholamines. The ventricular beats typically have a right axis deviation. Multiple morphologies of ventricular tachycardia may be present in the same individual, suggesting multiple
arrhythmogenic Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the Cardiac cycle, heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per mi ...
foci or pathways. Right ventricular outflow tract (RVOT) tachycardia is the most common VT seen in individuals with ACM. In this case, the EKG shows a
left bundle branch block Left bundle branch block (LBBB) is a conduction abnormality in the heart that can be seen on an electrocardiogram (ECG). In this condition, activation of the left ventricle of the heart is delayed, which causes the left ventricle to contract late ...
(LBBB) morphology with an inferior axis.


Diagnosis

The
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
for the ventricular tachycardia due to ACM include: * Congenital heart disease ** Repaired
tetralogy of Fallot Tetralogy of Fallot (TOF), formerly known as Steno-Fallot tetralogy, is a congenital heart defect characterized by four specific cardiac defects. Classically, the four defects are: *pulmonary stenosis, which is narrowing of the exit from the ri ...
**
Ebstein's anomaly Ebstein's anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the right ventricle of the heart. It is classified as a critical congenital heart defect accounting ...
** Uhl's anomaly **
Atrial septal defect Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...
** Partial anomalous venous return * Acquired heart disease ** Tricuspid valve disease ** Pulmonary hypertension ** Right ventricular infarction ** Bundle-branch re-entrant tachycardia * Miscellaneous ** Pre-excited AV re-entry tachycardia ** Idiopathic RVOT tachycardia **
Sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
In order to make the diagnosis of ACM, a number of clinical tests are employed, including the electrocardiogram (EKG),
echocardiography An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in t ...
, right ventricular angiography, cardiac MRI, and
genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
.


Electrocardiogram

90% of individuals with ARVD have some EKG abnormality. The most common EKG abnormality seen in ACM is T wave inversion in leads V1 to V3. However, this is a non-specific finding, and may be considered a normal variant in
right bundle branch block A right bundle branch block (RBBB) is a heart block in the right bundle branch of the electrical conduction system. During a right bundle branch block, the right ventricle is not directly activated by impulses travelling through the right bu ...
(RBBB), women, and children under 12 years old. RBBB itself is seen frequently in individuals with ACM. This may be due to delayed activation of the right ventricle, rather than any intrinsic abnormality in the right bundle branch. The epsilon wave is found in about 50% of those with ACM. This is described as a terminal notch in the QRS complex. It is due to slowed intraventricular conduction. The epsilon wave may be seen on a surface EKG; however, it is more commonly seen on signal averaged EKGs. Ventricular ectopy seen on a surface EKG in the setting of ACM is typically of
left bundle branch block Left bundle branch block (LBBB) is a conduction abnormality in the heart that can be seen on an electrocardiogram (ECG). In this condition, activation of the left ventricle of the heart is delayed, which causes the left ventricle to contract late ...
(LBBB) morphology, with a QRS axis of −90 to +110 degrees. The origin of the ectopic beats is usually from one of the three regions of fatty degeneration (the "triangle of dysplasia"): the RV outflow tract, the RV inflow tract, and the RV apex. Signal averaged ECG ( SAECG) is used to detect late potentials and epsilon waves in individuals with ACM.


Echocardiography

Echocardiography may reveal an enlarged, hypokinetic right ventricle with a paper-thin RV free wall. The dilatation of the RV will cause dilatation of the tricuspid valve annulus, with subsequent
tricuspid regurgitation Tricuspid regurgitation (TR), also called tricuspid insufficiency, is a type of valvular heart disease in which the tricuspid valve of the heart, located between the right atrium and right ventricle, does not close completely when the right ventri ...
. Paradoxical septal motion may also be present.


MRI

Fatty infiltration of the RV free wall can be visible on cardiac MRI. Fat has increased intensity in T1-weighted images. However, it may be difficult to differentiate intramyocardial fat and the epicardial fat that is commonly seen adjacent to the normal heart. Also, the sub-tricuspid region may be difficult to distinguish from the atrioventricular sulcus, which is rich in fat. Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall. However, the normal RV free wall may be about 3 mm thick, making the test less sensitive.


Angiography

Right ventricular angiography is considered the
gold standard A gold standard is a monetary system in which the standard economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the early 1920s, and from the la ...
for the diagnosis of ACM. Findings consistent with ACM are an akinetic or dyskinetic bulging localized to the infundibular, apical, and subtricuspid regions of the RV. The specificity is 90%; however, the test is observer dependent.


Biopsy

Transvenous biopsy of the right ventricle can be highly specific for ACM, but it has low sensitivity. False positives include other conditions with fatty infiltration of the ventricle, such as long-term excessive alcohol use and Duchenne or
Becker muscular dystrophy Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes ...
. False negatives are common, however, because the disease progresses typically from the epicardium to the endocardium (with the biopsy sample coming from the endocardium), and the segmental nature of the disease. Also, due to the paper-thin right ventricular free wall that is common in this disease process, most biopsy samples are taken from the ventricular septum, which is commonly ''not'' involved in the disease process. A biopsy sample that is consistent with ACM would have > 3% fat, >40% fibrous tissue, and <45% myocytes. A post mortem histological demonstration of full thickness substitution of the RV myocardium by fatty or fibro-fatty tissue is consistent with ACM.


Genetic testing

ACM is an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
trait with reduced
penetrance Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype). In medical genetics, the penetrance of a disease-causing mutation is t ...
. Approximately 40–50% of ACM patients have a mutation identified in one of several genes encoding components of the
desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
, which can help confirm a diagnosis of ACM. Since ACM is an autosomal dominant trait, children of an ACM patient have a 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified by genetic testing, family-specific genetic testing can be used to differentiate between relatives who are at-risk for the disease and those who are not. ACM genetic testing is clinically available.


Diagnostic criteria

There is no pathognomonic feature of ACM. The diagnosis of ACM is based on a combination of major and minor criteria. To make a diagnosis of ACM requires either 2 major criteria ''or'' 1 major and 2 minor criteria ''or'' 4 minor criteria. Major criteria * Right ventricular dysfunction ** Severe dilatation and reduction of RV
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, ...
with little or no LV impairment ** Localized RV aneurysms ** Severe segmental dilatation of the RV * Tissue characterization ** Fibrofatty replacement of myocardium on endomyocardial biopsy * Electrocardiographical abnormalities ** Epsilon waves in V1 – V3 ** Localized prolongation (>110 ms) of QRS in V1 – V3 ** Inverted T waves in V1 -V3 in an individual over 12 years old, in the absence of a
right bundle branch block A right bundle branch block (RBBB) is a heart block in the right bundle branch of the electrical conduction system. During a right bundle branch block, the right ventricle is not directly activated by impulses travelling through the right bu ...
(RBBB) **
Ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...
with a
left bundle branch block Left bundle branch block (LBBB) is a conduction abnormality in the heart that can be seen on an electrocardiogram (ECG). In this condition, activation of the left ventricle of the heart is delayed, which causes the left ventricle to contract late ...
(LBBB) morphology, with superior axis * Family history ** Familial disease confirmed either clinically or on autopsy or surgery Minor criteria * Right ventricular dysfunction ** Mild global RV dilatation and/or reduced ejection fraction with normal LV. ** Mild segmental dilatation of the RV ** Regional RV hypokinesis * Tissue characterization * Electrocardiographical abnormalities ** Late potentials on signal averaged EKG. ** Ventricular tachycardia with a
left bundle branch block Left bundle branch block (LBBB) is a conduction abnormality in the heart that can be seen on an electrocardiogram (ECG). In this condition, activation of the left ventricle of the heart is delayed, which causes the left ventricle to contract late ...
(LBBB) morphology, with inferior or unknown axis ** Frequent PVCs (> 500 PVCs / 24 hours)


Management

The goal of management of ACM is to decrease the incidence of sudden cardiac death. This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient who was diagnosed during family screening. A certain subgroup of individuals with ACM are considered at high risk for sudden cardiac death. Associated characteristics include: * Young age * Competitive sports activity * Malignant familial history * Extensive RV disease with decreased right ventricular ejection fraction. * Left ventricular involvement * Syncope * Episode of ventricular arrhythmia Management options include pharmacological, surgical, catheter ablation, and placement of an
implantable cardioverter-defibrillator An implantable cardioverter-defibrillator (ICD) or automated implantable cardioverter defibrillator (AICD) is a device implantable inside the body, able to perform defibrillation, and depending on the type, cardioversion and pacing of the ...
. Prior to the decision of the treatment option,
programmed electrical stimulation A cardiac electrophysiology study (EP test or EP study) is a minimally invasive procedure using catheters introduced through a vein or artery to record electrical activity from within the heart. This electrical activity is recorded when the hear ...
in the
electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology that studies the electrical properties of b ...
laboratory may be performed for additional prognostic information. Goals of programmed stimulation include: * Assessment of the disease's arrhythmogenic potential * Evaluate the hemodynamic consequences of sustained VT * Determine whether the VT can be interrupted via antitachycardia pacing (ATP). Regardless of the management option chosen, the individual is typically advised to undergo lifestyle modification, including avoidance of strenuous exercise, cardiac stimulants (i.e.: caffeine, nicotine, pseudoephedrine) and alcohol. Regarding physical activity and exercise, ARVC patients, as well as gene carriers of pathogenic ARVC-associated desmosomal mutations, should not participate in competitive sports. These patients should be advised to limit their exercise programmes to leisure-time activities and remain under clinical surveillance.


Medications

Pharmacologic management of ACM involves arrhythmia suppression and prevention of thrombus formation.
Sotalol Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. It is only recommended in those with significant abnormal heart rhythms due to potentially serious side effects. Evidence ...
, a
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
and a class III
antiarrhythmic agent Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular ta ...
, is the most effective antiarrhythmic agent in ACM. Other antiarrhythmic agents used include
amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...
and conventional beta blockers (i.e.: metoprolol). If antiarrhythmic agents are used, their efficacy should be guided by series ambulatory Holter monitoring, to show a reduction in arrhythmic events. While
angiotensin converting enzyme inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood vol ...
s (ACE Inhibitors) are well known for slowing progression in other cardiomyopathies, they have not been proven to be helpful in ACM. Individuals with decreased RV ejection fraction with dyskinetic portions of the right ventricle may benefit from long term anticoagulation with
warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
to prevent thrombus formation and subsequent
pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
.


Catheter ablation

Catheter ablation may be used to treat intractable ventricular tachycardia. It has a 60–90% success rate. Unfortunately, due to the progressive nature of the disease, recurrence is common (60% recurrence rate), with the creation of new arrhythmogenic foci. Indications for catheter ablation include drug-refractory VT and frequent recurrence of VT after ICD placement, causing frequent discharges of the ICD.


Implantable cardioverter-defibrillator

An ICD is the most effective prevention against sudden cardiac death. Due to the prohibitive cost of ICDs, they are not routinely placed in all individuals with ACM. Indications for ICD placement in the setting of ACM include: * Cardiac arrest due to VT or VF * Symptomatic VT that is not inducible during programmed stimulation * Failed programmed stimulation-guided drug therapy * Severe RV involvement with poor tolerance of VT * Sudden death of immediate family member Since ICDs are typically placed via a transvenous approach into the right ventricle, there are complications associated with ICD placement and follow-up. Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during implantation, potentially causing
pericardial tamponade Cardiac tamponade, also known as pericardial tamponade (), is the buildup of fluid in the pericardium (the sac around the heart), resulting in compression of the heart. Onset may be rapid or gradual. Symptoms typically include those of obstruct ...
. Because of this, every attempt is made at placing the defibrillator lead on the ventricular septum. After a successful implantation, the progressive nature of the disease may lead to fibro-fatty replacement of the myocardium at the site of lead placement. This may lead to undersensing of the individual's electrical activity (potentially causing inability to sense VT or VF), and inability to pace the ventricle.


Heart transplant

Heart transplant A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease when other medical or surgical treatments have failed. , the most common proce ...
may be performed in ACM. It may be indicated if the arrhythmias associated with the disease are uncontrollable or if there is severe bi-ventricular heart failure that is not manageable with pharmacological therapy.


Family screening

All first degree family members of the affected individual should be screened for ACM. This is used to establish the pattern of inheritance. Screening should begin during the teenage years unless otherwise indicated. Screening tests include: *
Echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...
*
EKG Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...
* Signal averaged EKG *
Holter monitor In medicine, a Holter monitor (often simply Holter) is a type of ambulatory electrocardiography device, a portable device for cardiac monitoring (the monitoring of the electrical activity of the cardiovascular system) for at least 24 hours. T ...
ing *
Cardiac MRI Cardiac magnetic resonance imaging (cardiac MRI), also known as cardiovascular MRI, is a magnetic resonance imaging (MRI) medical imaging, technology used for non-invasive assessment of the function and structure of the cardiovascular system. Condi ...
*
Exercise stress test A cardiac stress test (also referred to as a cardiac diagnostic test, cardiopulmonary exercise test, or abbreviated CPX test) is a cardiological test that measures the heart's ability to respond to external stress in a controlled clinical environ ...


Prognosis

There is a long asymptomatic lead-time in individuals with ACM. While this is a genetically transmitted disease, individuals in their teens may not have any characteristics of ACM on screening tests. Many individuals have symptoms associated with ventricular tachycardia, such as palpitations, light-headedness, or syncope. Others may have symptoms and signs related to right ventricular failure, such as lower extremity edema, or liver congestion with elevated hepatic enzymes. ACM is a progressive disease. Over time, the right ventricle becomes more involved, leading to right ventricular failure. The right ventricle will fail before there is left ventricular dysfunction. However, by the time the individual has signs of overt right ventricular failure, there will be histological involvement of the left ventricle. Eventually, the left ventricle will also become involved, leading to bi-ventricular failure. Signs and symptoms of left ventricular failure may become evident, including congestive heart failure, atrial fibrillation, and an increased incidence of thromboembolic events.


Epidemiology

The prevalence of ACM is about 1/10,000 in the general population in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, although some studies have suggested that it may be as common as 1/1,000. Recently, 1/200 were found to be carriers of mutations that predispose to ACM. Based on these findings and other evidence, it is thought that in most patients, additional factors such as other genes, athletic lifestyle, exposure to certain viruses, etc. may be required for a patient to eventually develop signs and symptoms of ACM. It accounts for up to 17% of all sudden cardiac deaths in the young. In
Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
, the prevalence is 40/10,000, making it the most common cause of sudden cardiac death in the young population.


Society and culture


Notable cases

*
Columbus Crew The Columbus Crew, formerly known as Columbus Crew SC, is an American professional soccer club based in Columbus, Ohio. The Crew competes in Major League Soccer (MLS) as a member of the league's Eastern Conference and began play in 1996 as one ...
midfielder
Kirk Urso Kirk Jon Urso (March 6, 1990 – August 5, 2012) was an American professional Association football, soccer player who played as a midfielder. A product of Glenbard East High School and the IMG Soccer Academy, Urso played four years of college s ...
collapsed out with friends on August 5, 2012, and was pronounced dead an hour later. An autopsy later revealed the disease to be the likely culprit. *
Sevilla FC Sevilla Fútbol Club () is a Spanish professional football club based in Seville, the capital and largest city of the autonomous community of Andalusia, Spain. It plays in Spanish football's top flight, La Liga. Sevilla have won the UEFA Euro ...
and Spanish international left wing-back
Antonio Puerta Antonio José Puerta Pérez (; 26 November 1984 – 28 August 2007) was a Spanish professional footballer who played solely for Sevilla. Mainly a left midfielder who could also operate as an attacking left-back, he died on 28 August 2007 affec ...
died from the condition, at the age of 22, on 28 August 2007, three days after suffering several cardiac arrests, while disputing a
La Liga The Campeonato Nacional de Liga de Primera División, commonly known simply as Primera División in Spain, and as La Liga in English-speaking countries and officially as LaLiga Santander for sponsorship reasons, stylized as LaLiga, is the men's ...
game against
Getafe CF Getafe Club de Fútbol (), or simply Getafe, is a professional football club based in Getafe, a city in the Community of Madrid. The team competes in La Liga, the highest tier of the Spanish football system. The club's home stadium (owned and op ...
. * Englishman Matt Gadsby also died from the condition after collapsing on the pitch on 9 September 2006, while playing for Hinckley United in a
Conference North The National League North, formerly Conference North, is a division of the National League in England, immediately below the National League division. Along with the National League South, it is at the second level of the National League Sy ...
game against
Harrogate Town Harrogate Town A.F.C. is a professional association football club in Harrogate, North Yorkshire, England, which competes in League Two, the fourth tier of the English football league system. The club is nicknamed the Sulphurites, due to the ...
. * Suzanne Crough, an American child actress best known for her role on
The Partridge Family ''The Partridge Family'' is an American musical sitcom starring Shirley Jones and featuring David Cassidy. Jones plays a widowed mother, and Cassidy plays the oldest of her five children, in a family who embarks on a music career. It ran from Se ...
, died suddenly from the condition in 2015 at age 52. *
James Taylor James Vernon Taylor (born March 12, 1948) is an American singer-songwriter and guitarist. A six-time Grammy Award winner, he was inducted into the Rock and Roll Hall of Fame in 2000. He is one of the best-selling music artists of all time, havi ...
English international cricketer, retired April 2016. *
Krissy Taylor Kristen Erin "Krissy" Taylor (May 15, 1978 – July 2, 1995) was an American model. Early life and career Taylor was born in Miami and lived in South Florida with her parents and two older sisters. Taylor’s foray into the modeling world was ...
, an American model, died at the age of 17 on July 2, 1995, in the family home in Florida. Her official cause of death was cardiac arrhythmia and severe asthma, the latter of which she had never been diagnosed with. Her family had independent experts examine tissue samples of her heart muscle and they concluded that the most likely cause of death was a missed diagnosis of ACM. * Jordan Boyd (1997-2013), Canadian junior hockey player. He was posthumously diagnosed with the ailment after passing away from a collapse from training camp in 2013.


See also

*
Woolly hair nevus Woolly hair nevus (alternatively spelled "Wooly hair nevus") is a congenital condition in which hair in a circumscribed area of the scalp is kinked or wool Wool is the textile fibre obtained from sheep and other mammals, especially goats, ...
*
List of conditions caused by problems with junctional proteins Mutations of proteins that hold the cells of the skin together can cause disease. Autoantibodies against proteins that hold the cells of the skin together can also cause disease. See also * List of keratins expressed in the human integumen ...


References


External links


GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant

OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
{{DEFAULTSORT:Arrhythmogenic Right Ventricular Dysplasia Cardiomyopathy