Arrhythmogenic Right Ventricular Dysplasia Georgia Giakoumis Spear, M.D. April 10, 2007

What is ARVD? Myocardial disorder of primarily the RV Characterized histologically by gradual replacement of myocytes by adipose and fibrous tissue

Epidemiology Uncertain cause and prevalence Idiopathic cardiomyopathy Idiopathic cardiomyopathy Some report prevalence as 0.4% (Van der Wall EE et al.) or 1 in 5000 (Gemayel et al.) Some report prevalence as 0.4% (Van der Wall EE et al.) or 1 in 5000 (Gemayel et al.) Familial (30%) Autosomal dominant inheritance with variable penetrance and incomplete expression Autosomal dominant inheritance with variable penetrance and incomplete expression Recently, several genes have been implicated Recently, several genes have been implicated

Etiology Many theories have been described These include: Apoptosis leading to progressive myocardial muscle loss followed by fibrofatty replacement Apoptosis leading to progressive myocardial muscle loss followed by fibrofatty replacement This results in electrical vulnerability of the RV which may lead to life threatening arrythmias CHD-abnormal development of RV leading to dysplasia CHD-abnormal development of RV leading to dysplasia Metabolic disorder affects the RV and fatty and fibrous replacement occurs Metabolic disorder affects the RV and fatty and fibrous replacement occurs Healing process in context of myocarditis Healing process in context of myocarditis

Pathologic features of ARVD Two variants: fatty and fibrofatty Fatty Replacement of myocardium without thinning of ventricular wall Replacement of myocardium without thinning of ventricular wall Involves only the RV Involves only the RVFibrofatty Thinning of RV Thinning of RV May involve LV as well May involve LV as well Specifically, the septum, LV free wall with a predilection for the posteroseptal and posterolateral areas.

Anatomic findings Mild to severe global dilitation of the ventricle Mild to severe global dilitation of the ventricle Ventricular aneurysms at the site of the “Triangle of Dysplasia” can be considered pathognomonic for ARVD Ventricular aneurysms at the site of the “Triangle of Dysplasia” can be considered pathognomonic for ARVD TRIANGLE OF DYSPLASIA RV subtricuspid areas RV subtricuspid areas Apex Apex infundibulum infundibulum Segmental hypokinesia Segmental hypokinesia

Clinical Picture Predominantly young adults M:F ratio is 2.7:1 M:F ratio is 2.7:1 May result in sudden death 20% of sudden deaths in <35yo 20% of sudden deaths in <35yo 22% of sudden deaths in young athletes 22% of sudden deaths in young athletes

Clinical Picture 80% of cases are diagnosed <40 yo Patient presentation Syncope Syncope VT VT Cardiac arrest Cardiac arrest Adult patients with CHF Adult patients with CHF

Clinical Picture Spectrum of disease Asymptomatic form: ventricular ectopic beats Asymptomatic form: ventricular ectopic beats Biventricular heart failure Biventricular heart failure +/- arrythmias +/- arrythmias (ie. Ventricular arrythmias with LBBB (originates from RV) High incidence of inducible supraventricular arrythmias High incidence of inducible supraventricular arrythmias Possible sudden death Possible sudden death Temporal progression

EKG findings Regular sinus rhythm QRS>110msec in V1 Epsilon wave beyond the QRS in V1 (30%) Inversion of T waves in precordial leads V1-V3 (50%)

Manifestations of ARVD Electrocardiographic repolarization and depolarization changes Structural abnormalities ranging from subtle wall aneurysms within the “triangle of dysplasia” Biventricular regional or global dysfunction Localized or widespread fibrofatty infiltration of the RV myocardium

Diagnosis Major and minor criteria which include: Genetics Genetics Electrocardiographic findings Electrocardiographic findings Pathophysiologic phenomena Pathophysiologic phenomena Histopathologic factors Histopathologic factors Imaging, especially MR should be used as an important additional criteria (Kayser et al. Radiographics 2002; 22: ) Imaging, especially MR should be used as an important additional criteria (Kayser et al. Radiographics 2002; 22: ) Patients must have 2 major, 1 major and 2 minor or 4 minor to fulfill the appropriate criteria for ARVD

Van der Wall EE et al. MRI Findings in ARVD

DDX Idiopathic dilated cardiomyopathy Dilated CM vs ARVD Dilated CM vs ARVD Generalized CM manifests as progressive decline in LV fxn ARVD progressive decline in RV fxn Uhl anomaly (paper-thin RV due to near complete absence of myocardial muscle fibers Uhl anomaly vs ARVD. Uhl anomaly vs ARVD. Uhl anomaly has no gender predilection or familial occurrence Usually presents in infancy with CHF

Imaging modalities which aid in the evaluation of the RV Conventional angiography Echocardiography Radionuclide angiography Ultrafast CT MR—allows the clearest visualization of the heart

Imaging Evaluation RV angiography is the standard of reference for diagnosis Discerns abnormalities such as akinetic or dyskinetic bulging in infundibular, apical and subtricuspid regions Discerns abnormalities such as akinetic or dyskinetic bulging in infundibular, apical and subtricuspid regionsEcho Used to exclude other anatomic abnormalities Used to exclude other anatomic abnormalities However, these traditional methods lack sensitivity and specificity for detecting structural and functional abnormalities of the RV myocardium

MR 3D evaluation of ventricular anatomy and volumes Excellent spatial resolution Unlimited FOV

MR Findings T1- high signal intensity of fat in the RV myocardium Fibrofatty replacement leading to diffuse thinning of the RV myocardium (major criteria) RV and RVOT aneurysms (major criteria) Dilation of the RV and RVOT (major criteria when severe; minor criteria when mild) *These findings should be considered a major criteria in the diagnosis of ARVD

Fatty replacement of the myocardium

Diffuse thinning and fatty replacement of the myocardium

More MR findings Can also assess both systolic and diastolic function RV diastolic dysfunction is an early marker of disease even with LV fxn is preserved RV diastolic dysfunction is an early marker of disease even with LV fxn is preserved Regional contraction abnormalities (minor) Global systolic dysfunction (major) Global diastolic dysfunction (minor)

Therapy Options include: Antiarrythmic medication Antiarrythmic medication Sotalol, Amiodarone or combination therapy Goal to prevent recurrent ventricular tachycardia Catheter ablation Catheter ablation Using RF or DC energy Reserved for patients who are unresponsive or intolerant to the drugs Patients may have new ventricular arrythmias Implantable AICD Implantable AICD Surgery Surgery Total disconnection of the RV

References: Gemayel, C. et al. “Arrythmogenic Right Ventricular Cardiomyopathy.” Journal of the Americal College of Cardiology. 38 (2001) Marcus et. Al. “Arrhymogenic right ventricular dysplasia/cardiomyopathy:a review.” Pacing Clinical Electrophysiology. 18 (1995) Auffermann et al. “Arrhythmogenic Right Ventricular disease: MR Imaging vs Angiography.” AJR. 161 (1993) Kayser et al. “Diagnosis of Arrhythmogenic Right Ventricular Dysplasia: A Review.” Radiographics. 22 (2002) Van der Wall et al. “Arrythmogenic Right Ventricular Dysplasia: MRI Findings.” Herz Cardiovascular Disease. 25 (2000)