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{{More citations needed|date=February 2009}}
[[File:Arrhythmogenic right ventricular cardiomyopathy - histology.jpg|Arrhythmogenic right ventricular cardiomyopathy - histology|thumb]]
{{Infobox medical condition (new)
| name            = Arrhythmogenic cardiomyopathy
| image          = Arrhythmogenic right ventricular cardiomyopathy - histology.jpg
| caption        = Photomicrograph of an ACM heart.
| pronounce      =
| field          =
| synonyms        = arrhythmogenic right ventricular cardiomyopathy (ARVC), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), right ventricular dysplasia
| symptoms        =
| complications  =
| onset          =
| duration        =
| types          =
| causes          =
| risks          =
| diagnosis      =
| differential    =
| prevention      =
| treatment      =
| medication      =
| prognosis      =
| frequency      =
| deaths          =
}}
 
'''Arrhythmogenic cardiomyopathy''' ('''ACM'''), '''arrhythmogenic right ventricular dysplasia''' ('''ARVD'''), or '''arrhythmogenic right ventricular cardiomyopathy''' ('''ARVC'''), is an inherited [[heart disease]].<ref>{{cite journal |last1=Pilichou |first1=Kalliopi |last2=Thiene |first2=Gaetano |last3=Bauce |first3=Barbara |last4=Rigato |first4=Ilaria |last5=Lazzarini |first5=Elisabetta |last6=Migliore |first6=Federico |last7=Perazzolo Marra |first7=Martina |last8=Rizzo |first8=Stefania |last9=Zorzi |first9=Alessandro |last10=Daliento |first10=Luciano |last11=Corrado |first11=Domenico |last12=Basso |first12=Cristina |title=Arrhythmogenic cardiomyopathy |journal=Orphanet Journal of Rare Diseases |date=2 April 2016 |volume=11 |issue=1 |pages=33 |doi=10.1186/s13023-016-0407-1 |pmc=4818879 |pmid=27038780 }}</ref>
 
ACM is caused by [[Genetic disorder|genetic defects]] of the parts of [[Cardiac muscle|heart muscle]] (also called ''myocardium'' or ''cardiac muscle'') known as [[desmosome]]s, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several [[protein]]s, and many of those proteins can have harmful [[mutation]]s.
 
The disease is a type of [[Ischemia|non-ischemic]] [[cardiomyopathy]] that primarily involves the [[Ventricle (heart)|right ventricle]], though cases of exclusive left ventricular disease have been reported.  It is characterized by [[hypokinesia|hypokinetic]] areas involving the free wall of the ventricle, with fibrofatty replacement of the myocardium, with associated [[Heart arrhythmia|arrhythmia]]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 lead to the abandonment of the name ARVC.
 
ACM can be found in association with [[diffuse palmoplantar keratoderma]], and [[woolly hair]], in an autosomal recessive condition called [[Naxos syndrome|Naxos disease]], because this genetic abnormality can also affect the integrity of the superficial layers of the skin most exposed to pressure stress.<ref name="Fitz2">{{cite book | first1 = Irwin M | last1 = Freedberg | first2 = Thomas B | last2 = Fitzpatrick | name-list-format = vanc | title = Fitzpatrick's Dermatology in General Medicine | date = 2003 | edition = 6th | publisher = McGraw-Hill | isbn = 978-0-07-138076-8}}</ref>{{Rp|513}}<ref name="Andrews">{{cite book | first1 = William Daniel | last1 = James | first2 = Timothy G | last2 = Berger | first3 = Dirk M | last3 = Elston | first4 = Richard B | last4 = Odom | name-list-format = vanc | title = Andrews' Diseases of the Skin: Clinical Dermatology | edition = 10th | publisher = Saunders | isbn = 978-0-7216-2921-6 | year = 2006 }}</ref>
 
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.<ref name=":0">{{Cite journal|last=Corrado|first=Domenico|last2=Basso|first2=Cristina|last3=Judge|first3=Daniel P.|date=2017-09-15|title=Arrhythmogenic Cardiomyopathy|journal=Circulation Research|volume=121|issue=7|pages=784–802|doi=10.1161/CIRCRESAHA.117.309345|issn=1524-4571|pmid=28912183|pmc=4818879}}</ref> 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.<ref>{{Cite journal|last=Corrado|first=Domenico|last2=Link|first2=Mark S.|last3=Calkins|first3=Hugh|date=2017-01-05|title=Arrhythmogenic Right Ventricular Cardiomyopathy|journal=The New England Journal of Medicine|volume=376|issue=1|pages=61–72|doi=10.1056/NEJMra1509267|issn=1533-4406|pmid=28052233}}</ref> Sudden death may be the first presentation of ACM without any preceding symptoms.<ref name=":0" />  These symptoms often occur during [[adolescence]] 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.<ref name=":0" />
 
The first clinical signs of ACM are usually during [[adolescence]] and early adulthood.  However, rarely, signs of ACM have been demonstrated in infants.
 
==Genetics==
ACM is usually inherited in an [[autosomal dominant]] pattern, with variable expression. Only 30% to 50% of individuals affected by ACM will test positive to one of the known genetic mutations in [[chromosome|chromosomal]] [[allele|loci]] associated with the disease.<ref>{{cite journal | vauthors = Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, van den Wijngaard A, Houweling AC, Jongbloed JD, Jordaens L, Cramer MJ, Doevendans PA, de Bakker JM, Wilde AA, van Tintelen JP, Hauer RN | title = Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study | journal = Circulation | volume = 123 | issue = 23 | pages = 2690–700 | date = June 2011 | pmid = 21606396 | doi = 10.1161/circulationaha.110.988287 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C, Frank R, Hainque B, Charron P | title = Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice | journal = Europace | volume = 12 | issue = 6 | pages = 861–8 | date = June 2010 | pmid = 20400443 | doi = 10.1093/europace/euq104 | url = http://www.hal.inserm.fr/inserm-00588266 }}</ref> Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see [[intercalated disc]]) are the main causatives for the development of this disease. Recently it has been shown, that mutations in the [[desmin]] DES gene could cause ACM.<ref>{{cite journal | vauthors = Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H | title = De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4595–607 | date = December 2010 | pmid = 20829228 | doi = 10.1093/hmg/ddq387 | doi-access = free }}</ref> Desmin is an intermediate filament protein, which is linked to the [[desmosomes]]. Different ''DES'' mutations cause an abnormal aggregation of desmin and associated proteins.<ref>{{cite journal | vauthors = Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H | title = Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants | journal = The Journal of Biological Chemistry | volume = 287 | issue = 19 | pages = 16047–57 | date = May 2012 | pmid = 22403400 | pmc = 3346104 | doi = 10.1074/jbc.M111.313841 }}</ref> The [[penetrance]] 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:
 
{| class="wikitable"
|-
! Type
! [[OMIM]]
! Gene
! Locus
!Reference
|-
| ARVD1lpl
| {{OMIM|107970||none}}
| ''[[TGFB3]]''
| 14q23-q24
|<ref>{{cite journal | vauthors = Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A | title = Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1 | journal = Cardiovascular Research | volume = 65 | issue = 2 | pages = 366–73 | date = February 2005 | pmid = 15639475 | doi = 10.1016/j.cardiores.2004.10.005 | doi-access = free }}</ref>
|-
| ARVD2
| {{OMIM|600996||none}}
| ''[[RYR2]]''
| 1q42-q43
|<ref>{{cite journal | vauthors = Milting H, Lukas N, Klauke B, Körfer R, Perrot A, Osterziel KJ, Vogt J, Peters S, Thieleczek R, Varsányi M | title = Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy | journal = Cardiovascular Research | volume = 71 | issue = 3 | pages = 496–505 | date = August 2006 | pmid = 16769042 | doi = 10.1016/j.cardiores.2006.04.004 }}</ref>
|-
| ARVD3
| {{OMIM|602086||none}}
| ?
| 14q12-q22
|
|-
| ARVD4
| {{OMIM|602087||none}}
| ?
| 2q32.1-q32.3
|
|-
| ARVD5
| {{OMIM|604400||none}}
| ''[[TMEM43]]''
| 3p23
|<ref>{{cite journal | vauthors = Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL | title = Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene | journal = American Journal of Human Genetics | volume = 82 | issue = 4 | pages = 809–21 | date = April 2008 | pmid = 18313022 | pmc = 2427209 | doi = 10.1016/j.ajhg.2008.01.010 }}</ref><ref>{{cite journal | vauthors = Christensen AH, Andersen CB, Tybjaerg-Hansen A, Haunso S, Svendsen JH | title = Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy | journal = Clinical Genetics | volume = 80 | issue = 3 | pages = 256–64 | date = September 2011 | pmid = 21214875 | doi = 10.1111/j.1399-0004.2011.01623.x }}</ref>
|-
| ARVD6
| {{OMIM|604401||none}}
| ?
| 10p14-p12
|
|-
| ARVD7
| {{OMIM|609160||none}}
| ''DES''
| 10q22.3
|<ref>{{cite journal | vauthors = Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H | title = De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4595–607 | date = December 2010 | pmid = 20829228 | doi = 10.1093/hmg/ddq387 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J | title = Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia | journal = Circulation | volume = 137 | issue = 15 | pages = 1595–1610 | date = April 2018 | pmid = 29212896 | doi = 10.1161/CIRCULATIONAHA.117.028719 }}</ref>
|-
| ARVD8
| {{OMIM|607450||none}}
| ''[[desmoplakin|DSP]]''
| 6p24
|<ref>{{cite journal | vauthors = Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L, Frigo G, Malacrida S, Settimo L, Danieli G, Thiene G, Nava A | title = Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations | journal = European Heart Journal | volume = 26 | issue = 16 | pages = 1666–75 | date = August 2005 | pmid = 15941723 | doi = 10.1093/eurheartj/ehi341 | doi-access = free }}</ref>
|-
| ARVD9
| {{OMIM|609040||none}}
| ''[[PKP2]]''
|  12p11
|<ref>{{cite journal | vauthors = Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L | title = Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy | journal = Nature Genetics | volume = 36 | issue = 11 | pages = 1162–4 | date = November 2004 | pmid = 15489853 | doi = 10.1038/ng1461 | doi-access = free }}</ref>
|-
| ARVD10
| {{OMIM|610193||none}}
| ''[[DSG2]]''
| 18q12.1-q12
|<ref>{{cite journal | vauthors = Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A | title = Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy | journal = Circulation | volume = 113 | issue = 9 | pages = 1171–9 | date = March 2006 | pmid = 16505173 | doi = 10.1161/CIRCULATIONAHA.105.583674 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Awad MM, Dalal D, Cho E, Amat-Alarcon N, James C, Tichnell C, Tucker A, Russell SD, Bluemke DA, Dietz HC, Calkins H, Judge DP | title = DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy | journal = American Journal of Human Genetics | volume = 79 | issue = 1 | pages = 136–42 | date = July 2006 | pmid = 16773573 | pmc = 1474134 | doi = 10.1086/504393 }}</ref>
|-
| ARVD11
| {{OMIM|610476||none}}
| ''[[DSC2]]''
| 18q12.1
|<ref>{{cite journal | vauthors = Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B | title = Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy | journal = American Journal of Human Genetics | volume = 79 | issue = 6 | pages = 1081–8 | date = December 2006 | pmid = 17186466 | pmc = 1698714 | doi = 10.1086/509044 }}</ref><ref>{{cite journal | vauthors = Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ | title = Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2 | journal = American Journal of Human Genetics | volume = 79 | issue = 5 | pages = 978–84 | date = November 2006 | pmid = 17033975 | pmc = 1698574 | doi = 10.1086/509122 }}</ref>
|-
| ARVD12
| {{OMIM|611528||none}}
| ''[[JUP (gene)|JUP]]''
| 17q21
|<ref>{{cite journal | vauthors = Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N | title = Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis | journal = European Heart Journal | volume = 27 | issue = 18 | pages = 2208–16 | date = September 2006 | pmid = 16893920 | doi = 10.1093/eurheartj/ehl184 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ | title = A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy | journal = American Journal of Human Genetics | volume = 81 | issue = 5 | pages = 964–73 | date = November 2007 | pmid = 17924338 | pmc = 2265660 | doi = 10.1086/521633 }}</ref>
|-
|
|
|''ILK''
|11p15.4
|<ref>{{cite journal | vauthors = Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJ, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, Childs SJ, Gerull B | title = Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy | journal = Translational Research | volume = 208 | pages = 15–29 | date = February 2019 | pmid = 30802431 | doi = 10.1016/j.trsl.2019.02.004 | pmc = 7412573 }}</ref>
|-
|
|
|''LMNA''
|
|<ref>{{cite journal | vauthors = Forleo C, Carmosino M, Resta N, Rampazzo A, Valecce R, Sorrentino S, Iacoviello M, Pisani F, Procino G, Gerbino A, Scardapane A, Simone C, Calore M, Torretta S, Svelto M, Favale S | title = Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy | journal = PLOS ONE | volume = 10 | issue = 4 | pages = e0121723 | date = 2015 | pmid = 25837155 | pmc = 4383583 | doi = 10.1371/journal.pone.0121723 | bibcode = 2015PLoSO..1021723F }}</ref>
|}
 
==Pathogenesis==
The [[pathogenesis]] of ACM is largely unknown.  [[Apoptosis]] (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]] (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]]s) seen on microscopy.  Myocardial atrophy is due to injury and [[apoptosis]].  This leads to thinning of the RV free wall (to < 3&nbsp;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.<ref>{{Cite journal|last=Mazzanti|first=Andrea|last2=Ng|first2=Kevin|last3=Faragli|first3=Alessandro|last4=Maragna|first4=Riccardo|last5=Chiodaroli|first5=Elena|last6=Orphanou|first6=Nicoletta|last7=Monteforte|first7=Nicola|last8=Memmi|first8=Mirella|last9=Gambelli|first9=Patrick|date=December 2016|title=Arrhythmogenic Right Ventricular Cardiomyopathy|journal=Journal of the American College of Cardiology|volume=68|issue=23|pages=2540–2550|doi=10.1016/j.jacc.2016.09.951|pmid=27931611|doi-access=free}}</ref>
 
==Ventricular arrhythmias==
[[File:RVOT Tachycardia.png|thumb|right|Monomorphic ventricular tachycardia originating from the right ventricular outflow tract]]
 
Ventricular arrhythmias due to ACM typically arise from the diseased right ventricle.  The type of arrhythmia ranges from frequent [[premature ventricular contraction|premature ventricular complexes]] (PVCs) to [[ventricular tachycardia]] (VT) to [[ventricular fibrillation]] (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]] 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]] (LBBB) morphology with an inferior axis.
 
==Diagnosis==
The [[differential diagnosis]] for the ventricular tachycardia due to ACM include:
* Congenital heart disease
** Repaired [[tetralogy of Fallot]]
** [[Ebstein's anomaly]]
** [[Uhl anomaly|Uhl's anomaly]]
** [[Atrial septal defect]]
** 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]]
 
In order to make the diagnosis of ACM, a number of clinical tests are employed, including the [[electrocardiogram]] (EKG), [[echocardiography]], right ventricular angiography, cardiac MRI, and [[genetic testing]].
 
===Electrocardiogram===
90% of individuals with ARVD have some EKG abnormality.  The most common EKG abnormality seen in ACM is T wave inversion in leads V<sub>1</sub> to V<sub>3</sub>.  However, this is a non-specific finding, and may be considered a normal variant in [[right bundle branch block]] (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.
 
[[File:ARVD-Epsilon wave.png|thumb|right|The epsilon wave (marked by red triangle), seen in ARVD.]]
[[File:ARVD-Epsilon wave.png|thumb|right|The epsilon wave (marked by red triangle), seen in ARVD.]]
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 [[Cardiac ectopy|ectopy]] seen on a surface EKG in the setting of ACM is typically of [[left bundle branch block]] (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 ([[Signal-averaged electrocardiogram|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]]. Paradoxical septal motion may also be present.
===MRI===
[[File:Arvd MRI.jpg|thumb|right|MRI in a patient affected by ARVC/D (long axis view of the right ventricle): note the transmural diffuse bright signal in the RV free wall on spin echo T1 (a) due to massive myocardial atrophy with fatty replacement (b).]][[File:Arrhythmogenic right ventricular cardiomyopathy.jpg|thumb|In vitro MRI and corresponding cross section of the heart in ARVD show RV dilatation with anterior and posterior aneurysms (17-year-old asymptomatic male athlete who died suddenly during a soccer game).]]
[[File:Arvd MRI.jpg|thumb|right|MRI in a patient affected by ARVC/D (long axis view of the right ventricle): note the transmural diffuse bright signal in the RV free wall on spin echo T1 (a) due to massive myocardial atrophy with fatty replacement (b).]][[File:Arrhythmogenic right ventricular cardiomyopathy.jpg|thumb|In vitro MRI and corresponding cross section of the heart in ARVD show RV dilatation with anterior and posterior aneurysms (17-year-old asymptomatic male athlete who died suddenly during a soccer game).]]
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.
[[File:RVOT Tachycardia.png|thumb|right|Monomorphic ventricular tachycardia originating from the right ventricular outflow tract]]
 
Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall.  However, the normal RV free wall may be about 3&nbsp;mm thick, making the test less sensitive.
 
===Angiography===
Right ventricular angiography is considered the [[gold standard (test)|gold standard]] 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 chronic alcohol abuse and Duchenne/Becker muscular dystrophy.
 
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.
​'''Arrhythmogenic Cardiomyopathy (ACM)''', also known as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia (ARVD), is an inherited heart disease characterized by the replacement of myocardial tissue with fibrofatty tissue, predominantly affecting the right ventricle. This pathological change disrupts the heart's electrical activity, leading to arrhythmias and an increased risk of sudden cardiac death.​


A post mortem histological demonstration of full thickness substitution of the RV myocardium by fatty or fibro-fatty tissue is consistent with ACM.
== Etiology and Pathogenesis ==


===Genetic testing===
ACM is primarily linked to genetic mutations affecting desmosomal proteins, which are crucial for cell-to-cell adhesion in cardiac muscle. Mutations in genes encoding desmoglein-2 (DSG2), desmocollin-2 (DSC2), plakophilin-2 (PKP2), desmoplakin (DSP), and junction plakoglobin (JUP) have been implicated in the disease. These genetic defects compromise the structural integrity of myocardial cells, leading to cell detachment, death, and subsequent replacement by fibrofatty tissue. This remodeling process creates a substrate for electrical instability and arrhythmogenesis.
ACM is an [[autosomal dominant]] trait with reduced [[penetrance]]. Approximately 40–50% of ACM patients have a mutation identified in one of several genes encoding components of the [[desmosome]], which can help confirm a diagnosis of ACM.<ref>{{cite journal | vauthors = Sen-Chowdhry S, Syrris P, McKenna WJ | title = Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy | journal = Journal of the American College of Cardiology | volume = 50 | issue = 19 | pages = 1813–21 | date = November 2007 | pmid = 17980246 | doi = 10.1016/j.jacc.2007.08.008 }}</ref> 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.<ref>[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&partid=1131#arvd Overview of ARVD/C Genetic Testing]</ref>


===Diagnostic criteria===
The pathogenesis of ACM involves progressive loss of myocardial cells due to apoptosis, inflammation, and fibrosis. The disease typically initiates in the subepicardial region and advances toward the endocardium, resulting in transmural involvement. Aneurysmal dilatation often occurs in specific regions, notably the right ventricular inflow tract, outflow tract, and apex, collectively termed the "triangle of dysplasia." While the right ventricle is predominantly affected, the left ventricle can also be involved, especially in advanced stages, leading to biventricular failure.​
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.<ref>{{Cite journal|last=Marcus|first=Frank I.|date=2010|title=Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria|url=|journal=Circulation|volume=|pages=|via=}}</ref>


Major criteria
== Clinical Presentation ==
* Right ventricular dysfunction
** Severe dilatation and reduction of RV [[ejection fraction]] 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 V<sub>1</sub> – V<sub>3</sub>
** Localized prolongation (>110 ms) of QRS in V<sub>1</sub> – V<sub>3</sub>
**Inverted T waves in V1 -V<sub>3</sub> in an individual over 12 years old, in the absence of a [[right bundle branch block]] (RBBB)
**Ventricular tachycardia with a [[left bundle branch block]] (LBBB) morphology, with superior axis
* Family history
** Familial disease confirmed either clinically or on autopsy or surgery


Minor criteria
Individuals with ACM may be asymptomatic or present with a range of symptoms, often manifesting during adolescence or early adulthood. Common clinical features include:​
* 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]] (LBBB) morphology, with inferior or unknown axis
** Frequent PVCs (> 500 PVCs / 24 hours)


==Management==
'''[[Palpitations]]''': Sensation of rapid or irregular heartbeats due to ventricular arrhythmias.​
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:
'''[[Syncope]]''': Transient loss of consciousness, often precipitated by exertion or emotional stress, resulting from hemodynamically significant arrhythmias.​
* 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]].
'''[[Sudden cardiac death]]''': ACM is a notable cause of sudden cardiac death, particularly in young athletes.​


Prior to the decision of the treatment option, [[programmed electrical stimulation]] in the [[cardiac electrophysiology|electrophysiology]] laboratory may be performed for additional prognostic information.  Goals of programmed stimulation include:
'''[[Heart failure]]''': Progressive right ventricular dysfunction can lead to symptoms such as fatigue, peripheral edema, and, in advanced cases, left ventricular involvement causing pulmonary congestion and dyspnea.​
*Assessment of the disease's arrhythmogenic potential
*Evaluate the hemodynamic consequences of sustained VT
*Determine whether the VT can be interrupted via antitachycardia pacing.


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. 
== Diagnosis ==


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.<ref>{{Cite journal|last=Pelliccia|first=A|date=2019|title=Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies,myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)|url=|journal=European Heart Journal|volume=40|pages=19-33|via=}}</ref>
Diagnosing ACM requires a comprehensive evaluation, integrating clinical findings, imaging studies, electrocardiographic features, and genetic testing. The diagnostic criteria encompass:​


===Medications===
'''[[Electrocardiogram (ECG)]]''': Common findings include T-wave inversions in leads V1 to V3, epsilon waves (distinctive low-amplitude signals at the end of the QRS complex), and ventricular arrhythmias exhibiting a left bundle branch block morphology.​
Pharmacologic management of ACM involves arrhythmia suppression and prevention of thrombus formation.


[[Sotalol]], a [[beta blocker]] and a class III [[antiarrhythmic agent]], is the most effective antiarrhythmic agent in ACM.  Other antiarrhythmic agents used include [[amiodarone]] 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.
'''[[Echocardiography]]''': May reveal right ventricular dilation, wall motion abnormalities, and reduced ejection fraction.​


While [[angiotensin converting enzyme inhibitor]]s (ACE Inhibitors) are well known for slowing progression in other cardiomyopathies, they have not been proven to be helpful in ACM.
'''[[Cardiac Magnetic Resonance Imaging (MRI)]]''': Provides detailed visualization of myocardial tissue, identifying fibrofatty infiltration and ventricular aneurysms.​


Individuals with decreased RV ejection fraction with dyskinetic portions of the right ventricle may benefit from long term anticoagulation with [[warfarin]] to prevent thrombus formation and subsequent [[pulmonary embolism]].
'''[[Endomyocardial biopsy]]''': Histological analysis can detect fibrofatty replacement of myocardium, though its sensitivity is limited due to the patchy nature of the disease.​


===Catheter ablation===
'''[[Genetic testing]]''': Identifies pathogenic mutations in desmosomal genes, aiding in diagnosis and family screening.​
Catheter ablation may be used to treat intractable ventricular tachycardia. 
It has a 60–90% success rate.<ref name="Fontaine-2000">{{cite journal | vauthors = Fontaine G, Tonet J, Gallais Y, Lascault G, Hidden-Lucet F, Aouate P, Halimi F, Poulain F, Johnson N, Charfeddine H, Frank R | title = Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience | journal = Current Cardiology Reports | volume = 2 | issue = 6 | pages = 498–506 | date = November 2000 | pmid = 11203287 | doi = 10.1007/s11886-000-0034-1 }}</ref>  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 [[implantable cardioverter-defibrillator|ICD]] placement, causing frequent discharges of the ICD.


===Implantable cardioverter-defibrillator===
== Management ==
An [[implantable cardioverter-defibrillator|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:
Management strategies for ACM focus on preventing sudden cardiac death, controlling arrhythmias, and managing heart failure. Key approaches 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.
'''[[Lifestyle modification]]''': Patients are advised to avoid strenuous physical activity, which can exacerbate the disease progression and increase arrhythmic risk.​


Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during implantation, potentially causing [[cardiac tamponade|pericardial tamponade]]. Because of this, every attempt is made at placing the defibrillator lead on the ventricular septum.
'''[[Pharmacotherapy]]''': Beta-blockers are commonly prescribed to suppress adrenergic stimulation and reduce arrhythmic events. Antiarrhythmic drugs may be used, but their efficacy varies.​


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.
'''[[Implantable cardioverter-defibrillator (ICD)]]''': Indicated for patients with a history of ventricular arrhythmias or those at high risk for sudden cardiac death. The ICD monitors heart rhythms and delivers shocks to terminate life-threatening arrhythmias.​


===Heart transplant===
'''[[Catheter ablation]]''': A minimally invasive procedure targeting and destroying arrhythmogenic foci to prevent recurrent ventricular tachycardia.​
[[Heart transplant]] 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===
'''[[Heart transplantation]]''': Considered in cases of refractory heart failure or incessant ventricular arrhythmias unresponsive to other treatments.​
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]]
*[[EKG]]
*[[Signal-averaged electrocardiogram|Signal averaged EKG]]
*[[Holter monitor]]ing
*[[Cardiovascular Magnetic Resonance|Cardiac MRI]]
*[[Exercise stress test]]


==Prognosis==
== 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.
The clinical course of ACM is variable, with some individuals remaining asymptomatic while others experience rapid disease progression. Factors associated with a poorer prognosis include extensive right ventricular involvement, left ventricular dysfunction, frequent ventricular arrhythmias, and a history of syncope or sudden cardiac arrest. Regular follow-up with a multidisciplinary team is essential to monitor disease progression and adjust management strategies accordingly.​


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 ==


==Epidemiology==
ACM is estimated to affect approximately 1 in 5,000 individuals, though the prevalence may be higher due to underdiagnosis. It accounts for up to 20% of sudden cardiac deaths in individuals under 35 years old. The disease exhibits a male predominance and shows considerable geographic variation, with higher prevalence reported in certain regions, such as Italy and Greece.​
The prevalence of ACM is about 1/10,000 in the general population in the [[United States]], 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.<ref>{{cite journal | vauthors = Lahtinen AM, Lehtonen E, Marjamaa A, Kaartinen M, Heliö T, Porthan K, Oikarinen L, Toivonen L, Swan H, Jula A, Peltonen L, Palotie A, Salomaa V, Kontula K | title = Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy | journal = Heart Rhythm | volume = 8 | issue = 8 | pages = 1214–21 | date = August 2011 | pmid = 21397041 | doi = 10.1016/j.hrthm.2011.03.015 }}</ref> 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.<ref>Jain R. Athletic status and arrhythmogenic right ventricular dysplasia/cardiomyopathy: From physiological observations to pathological explanation. Hypothesis 2010, 8(1): e2. – See more at: http://www.hypothesisjournal.com/?p=844#sthash.aB859Jm2.dpuf</ref>  It accounts for up to 17% of all sudden cardiac deaths in the young. In [[Italy]], the prevalence is 40/10,000, making it the most common cause of sudden cardiac death in the young population.<ref>Corrado D, Fontaine G, Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Need for an International Registry. Circulation.
2000; 101: e101-e106</ref>


==Notable cases==
== Research Directions ==
*[[Columbus Crew]] midfielder [[Kirk Urso]] 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.<ref>{{cite web|last=Jardy|first=Adam | name-list-format = vanc |title=Crew midfielder Kirk Urso, 22, dies after being rushed to hospital from bar|url=http://www.dispatch.com/content/stories/sports/2012/08/05/05-urso-obit.html|work=The Columbus Dispatch|publisher=The Dispatch Printing Company|access-date=21 September 2012}}</ref><ref>{{cite web|last=Jardy|first=Adam| name-list-format = vanc |title=Coroner: Crew's Urso died of a preexisting heart condition|url=http://www.dispatch.com/content/stories/sports/2012/09/21/crews-urso-died-of-preexisting-heart-condition.html|work=The Columbus Dispatch|publisher=The Dispatch Printing Company|access-date=21 September 2012}}</ref>
*[[Sevilla FC]] and Spanish international left wing-back [[Antonio Puerta]] 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]] game against [[Getafe CF]].<ref>{{cite news |title=Sevilla star suffers heart attack |url=http://news.bbc.co.uk/sport1/hi/football/europe/6964586.stm |publisher=BBC Sport |date=2007-08-25 |access-date=2007-08-25 }}</ref><ref>[http://edition.cnn.com/2007/SPORT/football/08/28/spain.critical/index.html Sevilla star dies after collapse]</ref>
*Englishman [[Matt Gadsby]] also died from the condition after collapsing on the pitch on 9 September 2006, while playing for [[Hinckley United F.C.|Hinckley United]] in a [[Conference North]] game against [[Harrogate Town A.F.C.|Harrogate Town]].<ref>{{cite news|url=http://www.cidg.org/webcontent/default.aspx?tabid=173 |title=Cause of Death |publisher=Cardiac Inherited Disease Group |access-date=2006-10-31 |archive-url=https://web.archive.org/web/20060818015706/http://www.cidg.org/webcontent/Default.aspx?tabid=173 |archive-date=2006-08-18 |url-status=dead }}</ref><ref>{{Cite web| url = http://icbirmingham.icnetwork.co.uk/0100news/0100localnews/tm_objectid=17723437&method=full&siteid=50002&headline=shock-at-star-player-s-death-name_page.html| title = Shock at star player's death| date = 11 September 2006| access-date = 2007-11-26| publisher = icBirmingham.co.uk}}</ref>
*[[Suzanne Crough]], an American child actress best known for her role on [[The Partridge Family]], died suddenly from the condition in 2015 at age 52.<ref>[https://www.msn.com/en-us/tv/news/%e2%80%98partridge-family%e2%80%99-star-suzanne-crough-died-of-rare-heart-ailment-coroner-says/ar-BBlHdRZ?ocid=ASUDHP Suzanne Crough died of rare heart ailment, coroner says], msn.com; accessed October 27, 2015.</ref>
*[[James Taylor (cricketer, born 1990)|James Taylor]] English international cricketer, retired April 2016.<ref name="bbc._Jame">{{Cite news| title = James Taylor: England & Nottinghamshire batsman forced to retire| newspaper = BBC Sport| date = 2016-04-12| access-date = 2016-05-15| url = https://www.bbc.co.uk/sport/cricket/36024253| quote = }}</ref>
*[[Krissy Taylor]], an American model, died 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.<ref>{{Citation|title=The life and career of Jordan Boyd {{!}} NHL Home Team Heroes|url=https://www.youtube.com/watch?v=G85ffVGnA3k|language=en|access-date=2019-10-14}}</ref>


Ongoing research in ACM aims to elucidate the molecular mechanisms underlying the disease, identify novel genetic mutations, and develop targeted therapies. Advancements in imaging techniques and the discovery of biomarkers hold promise for earlier diagnosis and better risk stratification. Gene therapy and pharmacological interventions targeting specific molecular pathways are being explored as potential future treatments.
== See also ==
== See also ==
* [[Woolly hair nevus]]
* [[Woolly hair nevus]]
* [[List of conditions caused by problems with junctional proteins]]
== References ==
{{Reflist}}
== External links ==
== External links ==
{{Medical resources
{{Medical resources
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|  MeshID          = D019571  
}}
}}
{{Commons category|Arrhythmogenic right ventricular cardiomyopathy|Arrhythmogenic right ventricular dysplasia}}
*[https://www.ncbi.nlm.nih.gov/books/NBK1131/  GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant]
*[https://www.ncbi.nlm.nih.gov/omim/604772,605676,601214,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048  OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant]
{{Circulatory system pathology}}
{{Circulatory system pathology}}
{{Cytoskeletal defects}}
{{Cytoskeletal defects}}
{{Other cell membrane protein disorders}}
{{Other cell membrane protein disorders}}
{{Channelopathy}}
{{Channelopathy}}
{{DEFAULTSORT:Arrhythmogenic Right Ventricular Dysplasia}}
{{DEFAULTSORT:Arrhythmogenic Right Ventricular Dysplasia}}
[[Category:Cardiomyopathy]]
[[Category:Cardiomyopathy]]
{{dictionary-stub1}}
{{stub}}

Revision as of 12:41, 19 March 2025

Arrhythmogenic right ventricular cardiomyopathy - histology
The epsilon wave (marked by red triangle), seen in ARVD.
MRI in a patient affected by ARVC/D (long axis view of the right ventricle): note the transmural diffuse bright signal in the RV free wall on spin echo T1 (a) due to massive myocardial atrophy with fatty replacement (b).
In vitro MRI and corresponding cross section of the heart in ARVD show RV dilatation with anterior and posterior aneurysms (17-year-old asymptomatic male athlete who died suddenly during a soccer game).
Monomorphic ventricular tachycardia originating from the right ventricular outflow tract

​Arrhythmogenic Cardiomyopathy (ACM), also known as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia (ARVD), is an inherited heart disease characterized by the replacement of myocardial tissue with fibrofatty tissue, predominantly affecting the right ventricle. This pathological change disrupts the heart's electrical activity, leading to arrhythmias and an increased risk of sudden cardiac death.​

Etiology and Pathogenesis

ACM is primarily linked to genetic mutations affecting desmosomal proteins, which are crucial for cell-to-cell adhesion in cardiac muscle. Mutations in genes encoding desmoglein-2 (DSG2), desmocollin-2 (DSC2), plakophilin-2 (PKP2), desmoplakin (DSP), and junction plakoglobin (JUP) have been implicated in the disease. These genetic defects compromise the structural integrity of myocardial cells, leading to cell detachment, death, and subsequent replacement by fibrofatty tissue. This remodeling process creates a substrate for electrical instability and arrhythmogenesis.

The pathogenesis of ACM involves progressive loss of myocardial cells due to apoptosis, inflammation, and fibrosis. The disease typically initiates in the subepicardial region and advances toward the endocardium, resulting in transmural involvement. Aneurysmal dilatation often occurs in specific regions, notably the right ventricular inflow tract, outflow tract, and apex, collectively termed the "triangle of dysplasia." While the right ventricle is predominantly affected, the left ventricle can also be involved, especially in advanced stages, leading to biventricular failure.​

Clinical Presentation

Individuals with ACM may be asymptomatic or present with a range of symptoms, often manifesting during adolescence or early adulthood. Common clinical features include:​

Palpitations: Sensation of rapid or irregular heartbeats due to ventricular arrhythmias.​

Syncope: Transient loss of consciousness, often precipitated by exertion or emotional stress, resulting from hemodynamically significant arrhythmias.​

Sudden cardiac death: ACM is a notable cause of sudden cardiac death, particularly in young athletes.​

Heart failure: Progressive right ventricular dysfunction can lead to symptoms such as fatigue, peripheral edema, and, in advanced cases, left ventricular involvement causing pulmonary congestion and dyspnea.​

Diagnosis

Diagnosing ACM requires a comprehensive evaluation, integrating clinical findings, imaging studies, electrocardiographic features, and genetic testing. The diagnostic criteria encompass:​

Electrocardiogram (ECG): Common findings include T-wave inversions in leads V1 to V3, epsilon waves (distinctive low-amplitude signals at the end of the QRS complex), and ventricular arrhythmias exhibiting a left bundle branch block morphology.​

Echocardiography: May reveal right ventricular dilation, wall motion abnormalities, and reduced ejection fraction.​

Cardiac Magnetic Resonance Imaging (MRI): Provides detailed visualization of myocardial tissue, identifying fibrofatty infiltration and ventricular aneurysms.​

Endomyocardial biopsy: Histological analysis can detect fibrofatty replacement of myocardium, though its sensitivity is limited due to the patchy nature of the disease.​

Genetic testing: Identifies pathogenic mutations in desmosomal genes, aiding in diagnosis and family screening.​

Management

Management strategies for ACM focus on preventing sudden cardiac death, controlling arrhythmias, and managing heart failure. Key approaches include:​

Lifestyle modification: Patients are advised to avoid strenuous physical activity, which can exacerbate the disease progression and increase arrhythmic risk.​

Pharmacotherapy: Beta-blockers are commonly prescribed to suppress adrenergic stimulation and reduce arrhythmic events. Antiarrhythmic drugs may be used, but their efficacy varies.​

Implantable cardioverter-defibrillator (ICD): Indicated for patients with a history of ventricular arrhythmias or those at high risk for sudden cardiac death. The ICD monitors heart rhythms and delivers shocks to terminate life-threatening arrhythmias.​

Catheter ablation: A minimally invasive procedure targeting and destroying arrhythmogenic foci to prevent recurrent ventricular tachycardia.​

Heart transplantation: Considered in cases of refractory heart failure or incessant ventricular arrhythmias unresponsive to other treatments.​

Prognosis

The clinical course of ACM is variable, with some individuals remaining asymptomatic while others experience rapid disease progression. Factors associated with a poorer prognosis include extensive right ventricular involvement, left ventricular dysfunction, frequent ventricular arrhythmias, and a history of syncope or sudden cardiac arrest. Regular follow-up with a multidisciplinary team is essential to monitor disease progression and adjust management strategies accordingly.​

Epidemiology

ACM is estimated to affect approximately 1 in 5,000 individuals, though the prevalence may be higher due to underdiagnosis. It accounts for up to 20% of sudden cardiac deaths in individuals under 35 years old. The disease exhibits a male predominance and shows considerable geographic variation, with higher prevalence reported in certain regions, such as Italy and Greece.​

Research Directions

Ongoing research in ACM aims to elucidate the molecular mechanisms underlying the disease, identify novel genetic mutations, and develop targeted therapies. Advancements in imaging techniques and the discovery of biomarkers hold promise for earlier diagnosis and better risk stratification. Gene therapy and pharmacological interventions targeting specific molecular pathways are being explored as potential future treatments.

See also

External links

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