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

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 of 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