Arrhythmogenic Right Ventricular Cardiomyopathy Saeed Oraii MD, - - PowerPoint PPT Presentation

Arrhythmogenic Right Ventricular Cardiomyopathy

Saeed Oraii MD, Cardiologist Interventional Electrophysiologist Tehran Arrhythmia Clinic April 2016

Introduction

• The name Arrhythmogenic Right Ventricular Dysplasia

(ARVD) was introduced for the first time in 1977 by Frank and Fontaine:

– “Total or partial replacement of right ventricular (RV) muscle by adipose and fibrous tissue associated with arrhythmias of LBBB configuration.”

• In 1996, WHO and the ISFC decided that ARVD had to

be considered as a manifestation of a cardiomyopathy (ARVC).

Fontaine G, Guiraudon G, Frank R, Vedel J, Grosgogeat Y, Cabrol C, Facquet J. Stimulation studies and epicardial mapping in ventricular tachycardia: study of mechanisms and selection for surgery. In: Kulbertus HE, ed. Reentrant Arrhythmias: Mechanisms and

• Treatment. Lancaster: MTP Press Limited; 1977:334–350.

ARVC

• ARVC is an inherited

desmosomal cardiomyopathy characterized pathologically by fibrofatty replacement of the RV myocardium and clinically by electrical instability resulting in ventricular arrhythmias.

Ventricular Involvement

• RV abnormalities classically include the triangle
• f dysplasia: RV inflow tract, outflow tract, and

apex.

• Although RV disease

predominates, early and predominant LV disease has been recognized, hence the term Arrhythmogenic cardiomyopathy.

Prevalence

• The prevalence of the disease in the general

population is estimated at 1 in 2000 to 1 in 5000.

• A higher prevalence is reported in certain regions of

Italy (Padua, Venice) and Greece (Island of Naxos).

• ARVC occurs in young adults with a male/female

ratio of 2.7/1.0.

• 80% of the disease is diagnosed in patients younger

than 40 years.

• It is exceedingly rare to manifest clinical signs or

symptoms of ARVC before the age of 12 or after the age of 60.

Binu Philipsa and Alan Cheng. 2015 update on the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy. Curr Opin Cardiol 2016, 31:46–56h

Presentation

• Unlike other cardiomyopathies, ventricular

arrhythmias and sudden cardiac death (SCD)

• ften are the presenting symptoms before the

development of any overt myocardial dysfunction.

• Early detection and management of ARVC are,

therefore, of utmost importance.

• ARVC should be suspected in all young patients

presenting with syncope, ventricular tachycardia,

• r cardiac arrest.

Diagnosis

• The broad spectrum of phenotypic variation,

age-related penetrance, and lack of a definitive diagnostic test makes the clinical diagnosis challenging.

• The diagnosis is, therefore, based on fulfilling

a set of major and minor criteria proposed by an International Task Force.

Task Force Criteria

• The initial 1994 set of Task Force criteria

were highly specific but lacked sensitivity for early forms of ARVC.

• These criteria were revised in 2010.
• Current criteria are based on findings from the

ECG, signal-averaged ECG, Holter monitoring, endomyocardial biopsy, family history, and advanced cardiac imaging.

Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 2010; 121:1533–1541.

2010 Task Force Criteria for ARVC

• I. Global or regional dysfunction and structural

alterations

• II. Tissue characterization of wall
• III. Repolarization abnormalities
• IV. Depolarization/conduction abnormalities
• V. Arrhythmias
• VI. Family history

• I. Global or regional dysfunction and structural alterations

Echocardiography

• A severely dilated RV with a localized aneurysm of the RVOT.

Echocardiography

Angiography

Prominent trabeculations and akinetic aneurysmal bulges of the RVOT

RV Angiography

CMR

Dilation and extensive transmural fatty replacement of the RV

• II. Tissue characterization of wall

• III. Repolarization abnormalities

• IV. Depolarization/conduction abnormalities

Epsilon Waves

Epsilon waves are uncommon and vary considerably in prevalence from 7% to 30%.

ECG Findings of ARVC

Ventricular Arrhythmias

Ventricular Arrhythmias

• VI. Family history

Genetics

• To date, mutations in seven genes associated

with ARVC have been described, five of which encode the cardiac desmosome.

• Pathogenic mutations can be seen in up to 60%
• f clinically diagnosed ARVC patients.
• A familial occurrence is reported in 30% to

60% but with autosomal dominant inheritance, various degrees of penetrance, and polymorphic phenotypic expression.

Groeneweg JA, Bhonsale A, James CA, et al. Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members. Circulation Cardiovascular genetics 2015; 8:437–446.

Genetic Testing

• Genetic testing is generally recommended of

the proband who has met the criteria for definite or borderline ARVC to allow cascade screening of family members.

• Genetic testing is not

recommended for patients suspected of ARVC with just a single minor criterion.

Genetic Testing

• Asymptomatic gene carriers require life-long

monitoring because of age-dependent penetrance, whereas non-carriers are unlikely to have the disease.

• A major criterion requires the identification of

a pathogenic mutation, which is associated or probably associated with ARVC.

Clinical Presentations

• Asymptomatic form with transient or sustained

VT of LBBB configuration, although RBBB configuration also can be observed.

• An asymptomatic form consisting of

ventricular ectopic beats.

• RV failure with or without arrhythmias.
• A masked form in which sudden death, usually

during exercise, is the first clinical presentation.

Practical Tips

• 40% -80% of ARVC patients may have a normal ECG
• n initial presentation, although they will develop

pathological ECG changes within six years.

• Interpretation of CMR for ARVD should be performed

at experienced centers. An abnormal CMR in isolation is not diagnostic for ARVC.

• Endomyocardial biopsy of the RV free wall should be

performed with extreme caution and at an experienced centers due to the high risk of myocardial perforation and cardiac tamponade. There may be patchy involvement.

Howlett JG, McKelvie RS, Arnold JMO et al. Can J Cardiol 2009;25(2):85-105.

Differential Diagnosis of ARVD

Anatomic Atrial septal defect Biventricular dysplasia Isolated myocarditis Naxos disease (ARVD associated with palmoplantar keratosis) Right ventricular infarct Right-sided valve insufficiency Uhl’s anomaly (congenital absence of right ventricular myocardium) Arrhythmias Benign extrasystoles Bundle branch reentry Dilated cardiomyopathy VT Idiopathic right ventricular arrhythmia Ischemic heart disease VT Right ventricular outflow tract VT Supraventricular tachycardia

Risk Stratification

• Patients with a prior history of sustained

ventricular tachycardia/ventricular fibrillation are at highest risk of arrhythmic events.

• Reports on whether syncope is predictive of

arrhythmic risk are conflicting.

• Family history of SCD is not a risk factor for

adverse prognosis in ARVC.

Risk Stratification

• There are conflicting data regarding the role of

an electrophysiology study in risk stratification

• f SCD in ARVC.
• Other markers of risk include: severe RV

dilation, extensive RV involvement, LV involvement and certain genotypes.

High Risk Patients

• Prior sustained ventricular arrhythmias
• Severe dysfunction of RV, LV, or both

(EF35%)

• Aborted sudden cardiac death

Corrado D, Wichter T, Link MS, et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement. Circulation 2015; 132:441–453.

Intermediate-risk Patients

Major risk factors

• Syncope
• NSVT
• Moderate dysfunction of RV, LV, or both (RV

fractional area change between 24 and 17% or RV EF between 40 and 36% and/or LV EF between 45 and 36%)

Intermediate-risk Patients

Minor risk factors

– Young age – Male gender – Complex genotype – Presence of more than one mutation – Compound or digenic heterozygosity of desmosomal-gene mutations – Desmoplakin mutation – Proband status – Inducible VT/VF

Intermediate-risk Patients

Minor risk factors

– Extent of RV scar on electroanatomical mapping – Fragmented electrograms on electroanatomical mapping – Extent of TWI across precordial leads or in inferior leads – QRS fragmentation – Precordial QRS amplitude ratio – CMR abnormalities – Heart failure/transplantation

Exercise Restriction

• The RV is more distensible, particularly during

exercise, than the LV, and may be more prone to injury resulting in inflammation, subsequent fibrosis and arrhythmogenesis.

• Participation in competitive sports was

associated with a two-fold increase in risk.

• Patients with suspected or confirmed ARVC

should avoid physical activity, particularly competitive sports and strenuous exertion.

Kirchhof P, et al. Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation 2006; 114:1799–1806

Medical Therapy

• In ARVC, ventricular arrhythmias often arise in

the setting of adrenergic stimulation.

• The current consensus is that they should be used

empirically in all patients diagnosed with ARVC.

• In patients with recurrent ventricular tachycardia,

class III antiarrhythmic medications, particularly sotalol and amiodarone, may be effective in addition to ICDs.

Wichter T, et al. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Circulation 1992; 86:29–37.

ICD Therapy

• There are no prospective randomized studies.
• Between 48–78% of individuals receive

appropriate therapies during long-term follow- up.

• Inappropriate ICD therapy occurs in 10–15%
• f ARVC patients.

Indications for ICD Implant

• There is a consensus that individuals in the

high-risk group should undergo ICD implantation.

• Among patients in the intermediate-risk group,

the presence of syncope, non-sustained ventricular tachycardia, or moderate ventricular dysfunction has conventionally been cited as a reason for ICD implantation

Catheter Ablation

• The initial results of endocardial catheter

ablation in ARVC showed limited efficacy.

• Epicardial catheter ablation, however, has

demonstrated better outcomes and is often the treatment of choice in patients with recurrent VT.

– It is associated with freedom from ventricular arrhythmia recurrence that varied from 70% to 85%.

Garcia FC, et al. Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation 2009; 120:366–375.

• 21 yrs. old man
• Recurrent VT, previously failed RFA at

another center followed by ICD implantation

• Repeated ICD shocks refractory to multiple

anti-arrhythmic drugs

A representative case

Surface ECG

Chest X Ray

Echocardiogram

VT

VT

Surface ECG

Induction of VT

VT

• VT at CL 370ms with mostly 1:1 VA

conduction was repeatedly induced by RV pacing studies

• Mapping was performed by entrainment

mapping at RVOT. The closest signals were found at RVOT free wall.

Entrainment

Entrainment

Pace mapping

Entrainment

Concealed Entrainment

• RF ablation at this area accelerated the

tachycardia and stopped it promptly

• Non-sustained runs of VT were still

inducible during Isuprel infusion.

3D Mapping

Termination of VT

Isuprel Infusion

Epicardial Access

Epicardial Access

3D Mapping

Non-inducible

Non-inducible

Final Remarks

• ARVC is a significant cause of sudden death in

the young.

• Early detection and management of ARVC are
• f utmost importance.
• ARVC should be suspected in any patient with

– Benign looking outflow tract ectopies with ECG abnormalities or syncope – Multifocal ventricular arrhythmias

• RF ablation has still a significant role in the

palliative care of these patients.

Tehran Arrhythmia Center WWW.IranEP.org info@IranEP.org Full version of this lecture is available at TAC website.