Goal 1.

Describe the clinical characteristics of ARVC.

Goal 2.

Review the genetic causes of ARVC.

Goal 3.

Provide an evaluation strategy to identify the genetic cause of ARVC in a proband.

Goal 4.

Inform genetic risk assessment in family members of a proband.

Goal 5.

Review management of ARVC.

Clinical Description

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary cardiomyopathy that is often diagnosed after an individual presents with arrhythmia findings. Presenting manifestations include heart palpitations, syncope, or even sudden death. ARVC typically presents in adults (mean age of first presentation in one large cohort study was 36 ± 14 years [Groeneweg et al 2015]), although it may less commonly be seen in children, most often during the late second decade.

ARVC typically affects the right ventricular apex, the base of the right ventricle, and the right ventricle outflow tract. The arrhythmias in ARVC most frequently arise from the right ventricle and have left bundle branch block morphology. The disease is progressive and is characterized by fibrofatty replacement of the myocardium. Pathology in ARVC may also extend to involve the left ventricle, resulting in regional left ventricular dysfunction.

Note: There is a movement within clinical cardiology to merge ARVC with other arrhythmogenic cardiomyopathies because the left ventricle can become involved, or even become predominantly involved, especially in individuals with DSP pathogenic variants; left ventricular involvement has also been reported in individuals with variants in genes encoding other desmosomal proteins (e.g., DSC2) that were previously associated with ARVC. The 2010 Task Force Criteria (see Diagnosis) are still used to establish a clinical diagnosis of ARVC [Marcus et al 2010], and these criteria do not incorporate other arrhythmogenic cardiomyopathies, leading to potential underdiagnosis. An international expert panel convened to reevaluate the diagnostic approach to arrhythmogenic cardiomyopathies and developed new criteria, the Padua Criteria [Corrado et al 2020]. There are ongoing studies to evaluate the proposed Padua Criteria in larger cohorts. Readers should be aware of the potential overlap/differentiation between ARVC and other arrhythmogenic cardiomyopathies.

Progression. The four described stages of ARVC are the following [Te Riele et al 2021, Wallace & Calkins 2021]:

1.

The concealed phase is the earliest phase and is without electrical, structural, or histologic changes as typically seen in ARVC. If scar formation is present, it can be so minimal that it goes undetected by cardiac MRI. However, affected individuals might experience sustained ventricular arrhythmias, and there is a potential risk of sudden cardiac death.

2.

An overt electrical disorder characterized by symptomatic arrhythmias including palpitations, syncope, and presyncope attributable to ventricular ectopy or sustained or nonsustained ventricular tachycardia

3.

Right ventricular failure

4.

A biventricular pump failure (resembling dilated cardiomyopathy) [Dalal et al 2006]

Cardiomyopathy in ARVC is not always isolatedto right ventricular involvement. There is evidence that the left ventricle can often become involved as well. The cohort of individuals with ARVC followed by Bhonsale et al [2015] had an overall incidence of left ventricular dysfunction of 14% over the follow-up interval, with 5% experiencing heart failure. In a separate cohort, 55% of individuals with DSP pathogenic variants experienced left ventricular predominant cardiomyopathy [Smith et al 2020].

Arrhythmia. The principal characteristic of arrhythmogenic cardiomyopathies is the tendency for ventricular arrhythmia in the absence of overt ventricular dysfunction. Arrhythmias in ARVC include ventricular tachycardia and ventricular fibrillation. Atrial fibrillation has also been described in ARVC. One recent study identified atrial fibrillation occurring in one in seven individuals with a diagnosis of definite ARVC (by 2010 Task Force Criteria), with atrial fibrillation onset at a median age of 51 years [Baturova et al 2020]. The risk of atrial fibrillation increases with severity of the ARVC phenotype compared to individuals who have an ARVC-related pathogenic variant but do not have clinical manifestations of ARVC (and thus do not meet 2010 Task Force Criteria).

Prognosis. Two long-term studies of individuals with ARVC suggested that survival was greater than 72% at six years following diagnosis. In individuals with ARVC, cardiac mortality and need for transplant are less than 5% [Bhonsale et al 2015, Groeneweg et al 2015]. An individual with a prior history of sustained ventricular tachycardia or fibrillation is at increased risk for subsequent ventricular arrhythmias and sudden cardiac death. Prognosis is worse for individuals with more than one ARVC-related pathogenic variant, with an increased propensity to arrhythmias and progression to cardiomyopathy [Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015].

Prevalence. The prevalence of clinical ARVC is estimated at 1:1,000-1,250 in the general population, although most of this data derives from cohorts of European ancestry [Wallace & Calkins 2021]. The prevalence of ARVC is greater in certain regions; in Italy and Greece (island of Naxos), it can be as high as 0.4%-0.8% [Thiene & Basso 2001].

Diagnosis

Diagnostic criteria for ARVC, initially proposed by an international task force [McKenna et al 1994], were revised by Marcus et al [2010] (full text) to incorporate new knowledge and technology to improve diagnostic sensitivity while maintaining diagnostic specificity. Diagnostic criteria rely on a combination of EKG and signal averaged EKGs, imaging studies that include 2D echocardiography, cardiac MRI or right ventricular (RV) angiography, presence of arrhythmia documented by telemetric monitoring, genetic testing, and family history. Individuals are classified as having a definite, borderline, or possible diagnosis of ARVC based on the number of major and/or minor diagnostic criteria present.

A definite diagnosis of ARVC is established in a proband with the following findings from different categories:

• Two major criteria; OR
• One major AND two minor criteria; OR
• Four minor criteria

A borderline diagnosis of ARVC is considered in a proband with:

• One major AND one minor criterion; OR
• Three minor criteria from different categories

A possible diagnosis of ARVC is considered in a proband with:

• One major criterion; OR
• Two minor criteria from different categories

Medical Evaluation

Medical history and physical examination are directed at identifying physical features associated with specific genetic causes of ARVC (Table 1).

Cardiology evaluation includes imaging to visualize the right ventricle, stress testing, and telemetric cardiac rhythm monitoring, as dictated by personal and family history.

Family history should include a three-generation family history with attention to heart palpitations, syncope, and sudden death in relatives; and documentation of relevant findings through direct examination or review of medical records, including results of molecular genetic testing, cardiovascular and physical examinations, and postmortem examination. Founder variants associated with ARVC have been reported in individuals of Dutch and Hutterite ancestry as well as in individuals from East Asia and Newfoundland, Canada (see Table 1).

Molecular Genetic Testing

The molecular cause of ARVC is established in a proband by identification of a heterozygous pathogenic (or likely pathogenic) variant in one of the known ARVC genes (see Table 1). Note: DSC2 and DSG2 are most often associated with autosomal dominant ARVC; in rare instances biallelic DSC2 or DSG2 pathogenic variants cause autosomal recessive ARVC [Wong et al 2014, Qadri et al 2017, Chen et al 2019].

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a heterozygous variant of uncertain significance does not establish or rule out the diagnosis or ARVC.

Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.

Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. In individuals with a clinical diagnosis of ARVC consider a multigene panel (see Option 1), whereas those with a phenotype indistinguishable from many other disorders with arrhythmia and/or cardiomyopathy may be more likely to be diagnosed using genomic testing (see Option 2).

Genetic Risk Assessment

DES, DSC2, DSG2, DSP, JUP, PKP2, PLN, and TMEM43 are associated with autosomal dominant ARVC, with the exception of DSC2 and DSG2, which are associated with both autosomal dominant and (rarely) autosomal recessive ARVC.

Both DSC2-related ARVC and DSG2-related ARVC are typically inherited in an autosomal dominant manner.

• Autosomal recessive DSC2-related ARVC has been reported in the Hutterite population in association with the founder variant c.1660C>T (p.Gln554Ter) [Wong et al 2014]. It is not known if heterozygosity for this founder variant is associated with an increased risk for ARVC.
• Autosomal recessive DSG2-related ARVC has been reported in two families to date [Qadri et al 2017].

Approximately 2%-4% of individuals with ARVC have more than one pathogenic variant. These individuals have either biallelic pathogenic variants in one gene (compound heterozygous or homozygous pathogenic variants) or double heterozygosity* for pathogenic variants in more than one ARVC-related gene [Xu et al 2010, Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015, Lin et al 2018, Chen et al 2019, Murray et al 2020, Brodehl et al 2021, Te Riele et al 2021]. Individuals with more than one ARVC-related pathogenic variant have a propensity to more severe disease, including a younger age of onset, arrhythmias, and progression to cardiomyopathy [Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015, Chen et al 2019, Brodehl et al 2021].

* The presence of pathogenic variants in two different ARVC-related genes may be referred to in cardiology literature as "digenic ARVC." In genetics literature, the term "digenic" more typically refers to expression of a phenotype that requires the presence of pathogenic variants in two different genes. While additional genetic variants may modify outcome and result in more specific disease, nonsyndromic ARVC can be caused by the presence of one pathogenic variant in one ARVC-related gene.

Risk to Family Members (Autosomal Dominant Inheritance)

Parents of a proband

• The majority of individuals diagnosed with autosomal dominant ARVC inherited a pathogenic variant from a heterozygous parent [van Lint et al 2019]. A parent who is heterozygous for an ARVC-related pathogenic variant may or may not have ARVC-related clinical findings.
• If a proband has two pathogenic variants in the same ARVC-related gene, both parents may be heterozygous. If a proband has pathogenic variants in two different ARVC-related genes, both parents may be heterozygous or, less commonly, one parent may have two pathogenic variants.
• Rarely, a proband with autosomal dominant ARVC may have the disorder as the result of a de novo pathogenic variant. In one study, 1.4% of affected individuals had the disorder as the result of a de novo pathogenic variant [van Lint et al 2019].
• If the status of the parents is unknown:
  • And a molecular diagnosis has been confirmed in the proband, targeted molecular genetic testing is recommended for the parents of the proband to confirm their genetic status, clarify their need for cardiac surveillance, and allow reliable recurrence risk assessment;
  • And a molecular diagnosis has not been confirmed in the proband, recommendations for the evaluation of parents include cardiac MRI or echocardiogram, EKG, and Holter monitoring.
  Because ARVC may be asymptomatic, both the maternal and paternal lineages should be considered as possibly contributing to familial ARVC.
• If the proband has a known pathogenic variant that cannot be identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The proband has a de novo pathogenic variant.
  • The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ cells only.

Sibs of a proband. The risk to the sibs of the proband depends on the genetic status of the proband's parents:

• If one parent of the proband is heterozygous for an ARVC-related pathogenic variant, the risk to the sibs of inheriting the pathogenic variant is 50%.
• If one parent of the proband has biallelic ARVC-related pathogenic variants, all sibs will inherit an ARVC-related pathogenic variant.
• If both parents of a proband are heterozygous for an ARVC-related pathogenic variant, sibs have a 75% chance of inheriting one or two ARVC-related pathogenic variants and a 25% chance of inheriting neither pathogenic variant.
• Sibs who inherit an ARVC-related pathogenic variant are at increased risk for ARVC and should undergo surveillance for cardiac involvement. Risk is further increased in sibs who inherit more than one ARVC-related pathogenic variant. Individuals with more than one ARVC-related pathogenic variant have an increased propensity to arrhythmias and progression to cardiomyopathy [Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015].
• If the parents are clinically unaffected but their genetic status is unknown, sibs are still presumed to be at increased risk for ARVC (and surveillance for cardiac involvement is recommended) because of the possibility of reduced penetrance in a heterozygous parent or parental germline mosaicism.

Offspring of a proband

• Each child of an individual with one ARVC-related pathogenic variant has a 50% chance of inheriting the pathogenic variant.
• Each child of an individual with biallelic pathogenic variants in one ARVC-related gene will inherit one pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if one or both parents are affected or have a pathogenic variant, family members are at risk.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Evaluation of Relatives at Risk

It is appropriate to clarify the status of apparently asymptomatic relatives of an individual with ARVC in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures to reduce the risk of syncope, cardiac arrest, and sudden death. Clinical evaluation, genetic counseling, and targeted genetic testing of at-risk relatives (if the proband has a known ARVC-related pathogenic variant) constitute a class I recommendation in the American College of Cardiology / American Heart Association / Heart Rhythm Society (AHA/ACC/HRS) guideline for management of individuals with ventricular arrhythmias and the prevention of sudden cardiac death [Al-Khatib et al 2018].

Note: Predictive testing should be offered in the context of formal genetic counseling.

In order to appropriately assess the risk status of asymptomatic relatives of an individual with ARVC, it is important to ensure that:

• The proband has a clinical diagnosis of ARVC meeting the 2010 Task Force Criteria [Marcus et al 2010]; and
• The pathogenic variant (or pathogenic variants) identified in the proband (if applicable) is in a known ARVC-related gene and represents the full genetic etiology of ARVC in the proband.

If the proband meets 2010 ARVC Task Force Criteria and is identified as having a pathogenic variant in a gene not known to be associated with ARVC, then cascade genetic testing in family members is not reliable for ARVC risk assessment because the identified pathogenic variant may not represent the underlying cause of ARVC in the proband or may only partially account for the genetic risk of ARVC in the family. Cascade genetic testing can still be offered for the pathogenic variant identified in the proband, but a complete ARVC evaluation and risk assessment should still occur for all at-risk family members regardless of the results of genetic testing for the pathogenic variant identified in the proband.

Family members of an individual with a clinical diagnosis of ARVC meeting 2010 Task Force Criteria who has a known pathogenic variant(s) in an ARVC-related gene(s). Molecular genetic testing is recommended for parents, sibs, offspring, and other at-risk family members (even those age <18 years) in order to clarify their genetic status, allowing for the following:

• Identification of those individuals with a familial ARVC-related pathogenic variant(s) who have an increased lifetime risk for ARVC and should undergo surveillance for cardiac involvement. Guidelines exist for screening for cardiac involvement in asymptomatic first-degree relatives at risk for ARVC [Hershberger et al 2018].
• Identification of individuals without the familial ARVC-related pathogenic variant(s) to be discharged from high-risk cardiac surveillance. Individuals without the familial ARVC-related pathogenic variant(s) can be discharged from high-risk cardiac surveillance ONLY when their ARVC-affected relative has had a detailed discussion with a cardiologist with expertise in ARVC genetics and when this cardiogenetic expert has deemed that the pathogenic gene variant identified in the affected relative is fully causative of their ARVC disease. If the pathogenic gene variant does not fully explain the proband's phenotype, then family members should continue cardiac screening (see Surveillance for Cardiac Involvement).

Family members of an individual with a clinical diagnosis of ARVC meeting 2010 Task Force Criteria in whom the specific genetic cause of ARVC has not been identified. Screening for cardiac involvement is recommended for asymptomatic at-risk first-degree relatives (see Surveillance for Cardiac Involvement).

Risk Assessment for ARVC

To establish the extent of disease and needs of an individual diagnosed with ARVC the following evaluations are recommended if not performed at the time of diagnosis:

• EKG
• Cardiac imaging. Cardiac MRI has improved yield compared to echocardiography, because cardiac MRI is superior in its ability to image the right ventricle and its ability to discern fibrofatty infiltration.
• Noninvasive monitoring. Cardiac rhythm can be monitored noninvasively through patch recorders that can record heart rate/rhythm data for up to 14 days. Event monitors can gather information for 30 days. Implantable loop recorders are useful for longer-term (three to five years) monitoring. These monitors can detect irregular atrial or ventricular rhythms including nonsustained ventricular tachycardia.
• Signal-averaged EKGs may also be useful [Philips & Cheng 2016].
• Electrophysiology study to assess the risk for ventricular arrhythmias and determine if an implantable cardioverter-defibrillator may be indicated. Cardiac catheter ablation of tissue causing abnormal rhythms can be performed during the electrophysiology study (see Recommendations for Medical and Surgical Management of ARVC).

Surveillance for Cardiac Involvement

Proband. Screening for degree of cardiac involvement in persons diagnosed with ARVC is essential to ascertain severity and disease progression over time. Screening recommendations include the following:

• EKG, annually or more frequently depending on symptoms
• Holter monitoring, event monitoring, implantable loop recorder
• Exercise stress testing
• Cardiac MRI, with frequency depending on symptoms and findings
• Echocardiogram, with frequency depending on symptoms and findings and degree of left ventricular involvement (and with knowledge that echocardiogram is insufficient for evaluating the right ventricle)

Family members who have tested positive for the ARVC-related pathogenic variant(s) identified in an affected relative. Surveillance is similar as for ARVC in a proband.

First-degree relatives (i.e., parents, sibs, offspring) of an affected individual in whom the specific genetic cause of ARVC has not been identified. If genetic testing has not been performed or did not identify a pathogenic variant in an affected family member, screening for cardiac involvement is recommended for asymptomatic at-risk first-degree relatives every one to three years after age ten years [Towbin et al 2019].

Screening for cardiac involvement comprises the following [Towbin et al 2019, Wilde et al 2022]:

• Medical history, with attention to symptoms of arrhythmia, presyncope, syncope, and heart failure
• EKG, with consideration of signal-averaged EKG
• Holter monitoring
• Cardiac MRI
• Echocardiogram

At-risk first-degree relatives with any abnormal clinical screening tests for cardiac involvement should be considered for repeat clinical screening in one year [Towbin et al 2019].

Children younger than age ten years are not usually screened, as manifestations of ARVC are not usually seen in children prior to age ten years. See Hamilton & Fidler [2009] for a review of screening for ARVC in younger individuals. A study in younger individuals suggested that cardiac MRI was more sensitive than echocardiogram but that it was still unusual, even with cardiac MRI, to identify ARVC in children before age ten years [Etoom et al 2015].

In children younger than age 18 years. The 2010 Task Force Criteria [Marcus et al 2010] should be used with caution, as many of the EKG diagnostic criteria are a normal finding in children, such as inverted T waves in right precordial leads (V1, V2, and V3) [Te Riele et al 2021]. Cardiac MRI has been shown to have a better positive predictive value (and especially data from echocardiogram and cardiac MRI combined) [Steinmetz et al 2018, Te Riele et al 2021].

Recommendations for Medical and Surgical Management of ARVC

Affected individuals should be monitored by a cardiologist who is knowledgeable about ARVC. Management of individuals with ARVC is complicated by its variable course and the limited specificity of clinical findings to predict arrhythmia risk. Management should be individualized and based on the specific results of detailed clinical and genetic investigation.

Prevention of Primary Manifestations

Prospective randomized trials have not been conducted in individuals with ARVC for the prevention of arrhythmias. Management relies on personalized recommendations based on clinical assessment.

Implantable cardioverter-defibrillators (ICDs). Observational studies support that ICD placement is effective in reducing the risk for sudden cardiac death in individuals with ARVC. ICD placement should be considered in anyone with a clinical diagnosis of ARVC; scoring systems have been developed to ascertain risk and guide device management [Jordà et al 2022]. Wallace & Calkins [2021] describe risk factors for ventricular arrhythmias or sudden cardiac death. Risk for ventricular tachycardia or sudden cardiac death include the following [Towbin et al 2019]:

• Prior history of sustained ventricular tachycardia or ventricular fibrillation
• Elevated burden of premature ventricular contractions (more than 1,000 in 24 hours)
• Nonsustained ventricular tachycardia
• A prior history of syncope
• Male sex. Males are more likely to be diagnosed and are 1.6 times more likely to have ventricular arrhythmias and to receive an appropriate shock from their ICD for ventricular arrhythmias than females [Akdis et al 2017].
• Intense exercise [James et al 2013, Gasperetti et al 2020]
• Degree of myocardial involvement, defined as right ventricular ejection fraction ≤45% or >2 areas of regional dysfunction [Wichter et al 2004]
• PKP2 or DSP pathogenic variants. ARVC due to PKP2 or DSP pathogenic variants was correlated with increased risk for a life-threatening arrhythmic event; this was greatest between ages 21 and 40 years [Al-Khatib et al 2018].

The AHA/ACC/HRS and Heart Rhythm Society (HRS) guidelines, which are based on experience and previously published reports, recommend ICD placement as a class I indication (i.e., procedure/treatment should be performed) for prevention of sudden cardiac death in individuals with resuscitated sudden cardiac arrest, documented sustained ventricular tachycardia or ventricular fibrillation, or significant ventricular dysfunction with right ventricular ejection fraction or left ventricular ejection fraction ≤35% who have a reasonable expectation of survival with good functional status for more than one year. Class II indications for ICD placement (i.e., it is reasonable to perform procedure/treatment) include syncope presumed due to ventricular arrhythmias; an ICD can be useful if meaningful survival greater than one year is expected [Al-Khatib et al 2018, Towbin et al 2019].

Agents/Circumstances to Avoid

Individuals with ARVC are discouraged from participating in frequent, intense physical exercise and intense competitive athletic activity because of the strain caused on the right heart [Corrado et al 2015, Al-Khatib et al 2018].

Pregnancy Management

The majority of individuals with ARVC tolerate pregnancy well with no additional complications [Hodes et al 2016, Platonov et al 2020]. One study found 13% of individuals with ARVC had ventricular arrhythmias and 5% had heart failure [Hodes et al 2016], and a separate study found an elevated risk of ventricular arrhythmias during the two years postpartum in women diagnosed with ARVC prior to conception, with only two events occurring during pregnancy [Platonov et al 2020]. Specific guidelines for managing ARVC in pregnancy have not been developed, but individuals with ARVC should be managed by a multidisciplinary team.

Revision History

• 11 May 2023 (sw) Comprehensive update posted live
• 25 May 2017 (ha) Comprehensive update posted live
• 9 January 2014 (me) Comprehensive update posted live
• 13 October 2009 (cd) Revision: sequence analysis available clinically for TGFB3 mutations
• 15 December 2008 (cd) Revision: clinical testing for JUP mutations (ARVD12); prenatal testing for ARVD/C 5 (TMEM43)
• 10 July 2008 (cd) Revision: sequence analysis available clinically for TMEM43 mutations (ARVD5)
• 12 December 2007 (me) Comprehensive update posted live
• 5 April 2006 (cd) Revision: Clinical testing for DSP and PKP2 available; prenatal diagnosis for PKP2 available
• 18 April 2005 (me) Review posted live
• 6 July 2004 (em) Original submission

Published Guidelines / Consensus Statements

• Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2018;15:e73-e189. [PubMed]
• Corrado D, van Tintelen PJ, McKenna WJ, Hauer RNW, Anastastakis A, Asimaki A, Basso C, Bauce B, Brunckhorst C, Bucciarelli-Ducci C, Duru F, Elliott P, Hamilton RM, Haugaa KH, James CA, Judge D, Link MS, Marchlinski FE, Mazzanti A, Mestroni L, Pantazis A, Pelliccia A, Marra MP, Pilichou K, Platonov PGA, Protonotarios A, Rampazzo A, Saffitz JE, Saguner AM, Schmied C, Sharma S, Tandri H, Te Riele ASJM, Thiene G, Tsatsopoulou A, Zareba W, Zorzi A, Wichter T, Marcus FI, Calkins H; International Experts. Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis. Eur Heart J. 2020;41:1414-29. [PubMed]
• Hershberger RE, Givertz MM, Ho CY, Judge DP, Kantor PF, McBride KL, Morales A, Taylor MRG, Vatta M, Ware SM. Genetic evaluation of cardiomyopathy-a Heart Failure Society of America practice guideline. J Card Fail. 2018;24:281-302. [PubMed]
• Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MGPJ, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Safitz JE, Yoeger Sanborn DM, Steinberg JS, Tandri H, Theine G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J. 2010;31:806-14. [PubMed]
• Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, Daubert JP, de Chillou C, DePasquale EC, Desai MY, Estes NAM 3rd, Hua W, Indik JH, Ingles J, James CA, John RM, Judge DP, Keegan R, Krahn AD, Link MS, Marcus FI, McLeod CJ, Mestroni L, Priori SG, Saffitz JE, Sanatani S, Shimizu W, van Tintelen JP, Wilde AAM, Zareba W. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019;16:e301-e372. [PubMed]
• Wallace R, Calkins H. Risk stratification in arrhythmogenic right ventricular cardiomyopathy. Arrhythm Electrophysiol Rev. 2021;10:26-32. [PubMed]

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