Arrhythmogenic Right Arrhythmogenic Right Ventricular DysplasiaVentricular Dysplasia

Georgia Giakoumis Spear, M.D.Georgia Giakoumis Spear, M.D.

April 10, 2007April 10, 2007

What is ARVD?What is ARVD?

Myocardial disorder of primarily the RVMyocardial disorder of primarily the RV

Characterized histologically by gradual Characterized histologically by gradual replacement of myocytes by adipose and replacement of myocytes by adipose and fibrous tissuefibrous tissue

EpidemiologyEpidemiology

Uncertain cause and prevalenceUncertain cause and prevalence Idiopathic cardiomyopathyIdiopathic cardiomyopathy Some report prevalence as 0.4% (Van der Some report prevalence as 0.4% (Van der

Wall EE et al.) or 1 in 5000 (Gemayel et al.)Wall EE et al.) or 1 in 5000 (Gemayel et al.)

Familial (30%) Familial (30%) Autosomal dominant inheritance with variable Autosomal dominant inheritance with variable

penetrance and incomplete expressionpenetrance and incomplete expression Recently, several genes have been implicatedRecently, several genes have been implicated

EtiologyEtiology

Many theories have been described Many theories have been described These include:These include: Apoptosis leading to progressive myocardial muscle Apoptosis leading to progressive myocardial muscle

loss followed by fibrofatty replacement loss followed by fibrofatty replacement This results in electrical vulnerability of the RV which may This results in electrical vulnerability of the RV which may lead to life threatening arrythmiaslead to life threatening arrythmias

CHD-abnormal development of RV leading to CHD-abnormal development of RV leading to dysplasiadysplasia

Metabolic disorder affects the RV and fatty and Metabolic disorder affects the RV and fatty and fibrous replacement occursfibrous replacement occurs

Healing process in context of myocarditisHealing process in context of myocarditis

Pathologic features of ARVDPathologic features of ARVD

Two variants: fatty and fibrofattyTwo variants: fatty and fibrofatty

FattyFatty Replacement of myocardium without thinning of Replacement of myocardium without thinning of

ventricular wallventricular wall Involves only the RVInvolves only the RV

FibrofattyFibrofatty Thinning of RVThinning of RV May involve LV as wellMay involve LV as well

Specifically, the septum, LV free wall with a predilection for Specifically, the septum, LV free wall with a predilection for the posteroseptal and posterolateral areas.the posteroseptal and posterolateral areas.

Anatomic findingsAnatomic findings

Mild to severe global dilitation of the ventricleMild to severe global dilitation of the ventricle Ventricular aneurysms at the site of the Ventricular aneurysms at the site of the

“Triangle of Dysplasia” can be considered “Triangle of Dysplasia” can be considered pathognomonic for ARVDpathognomonic for ARVD

TRIANGLE OF DYSPLASIATRIANGLE OF DYSPLASIA RV subtricuspid areasRV subtricuspid areas Apex Apex infundibuluminfundibulum

Segmental hypokinesiaSegmental hypokinesia

Clinical PictureClinical Picture

Predominantly young adultsPredominantly young adults M:F ratio is 2.7:1M:F ratio is 2.7:1

May result in sudden deathMay result in sudden death 20% of sudden deaths in <35yo20% of sudden deaths in <35yo 22% of sudden deaths in young athletes22% of sudden deaths in young athletes

Clinical PictureClinical Picture

80% of cases are diagnosed <40 yo80% of cases are diagnosed <40 yo

Patient presentationPatient presentation SyncopeSyncope VTVT Cardiac arrestCardiac arrest Adult patients with CHFAdult patients with CHF

Clinical PictureClinical Picture

Spectrum of diseaseSpectrum of disease Asymptomatic form: ventricular ectopic beatsAsymptomatic form: ventricular ectopic beats Biventricular heart failure Biventricular heart failure +/- arrythmias +/- arrythmias

(ie. Ventricular arrythmias with LBBB (originates (ie. Ventricular arrythmias with LBBB (originates from RV)from RV)

High incidence of inducible supraventricular High incidence of inducible supraventricular arrythmiasarrythmias

Possible sudden deathPossible sudden death

Temporal progressionTemporal progression

EKG findingsEKG findings

Regular sinus rhythmRegular sinus rhythm

QRS>110msec in V1QRS>110msec in V1

Epsilon wave beyond the QRS in V1 Epsilon wave beyond the QRS in V1 (30%)(30%)

Inversion of T waves in precordial leads Inversion of T waves in precordial leads V1-V3 (50%)V1-V3 (50%)

Manifestations of ARVDManifestations of ARVD

Electrocardiographic repolarization and Electrocardiographic repolarization and depolarization changesdepolarization changes

Structural abnormalities ranging from Structural abnormalities ranging from subtle wall aneurysms within the “triangle subtle wall aneurysms within the “triangle of dysplasia” of dysplasia”

Biventricular regional or global dysfunctionBiventricular regional or global dysfunction

Localized or widespread fibrofatty Localized or widespread fibrofatty infiltration of the RV myocardiuminfiltration of the RV myocardium

DiagnosisDiagnosis

Major and minor criteria which include:Major and minor criteria which include: GeneticsGenetics Electrocardiographic findingsElectrocardiographic findings Pathophysiologic phenomenaPathophysiologic phenomena Histopathologic factorsHistopathologic factors Imaging, especially MR should be used as an Imaging, especially MR should be used as an

important additional criteria (Kayser et al. important additional criteria (Kayser et al. Radiographics 2002; 22: 639-650)Radiographics 2002; 22: 639-650)

Patients must have 2 major, 1 major and 2 minor Patients must have 2 major, 1 major and 2 minor or 4 minor to fulfill the appropriate criteria for or 4 minor to fulfill the appropriate criteria for ARVDARVD

Van der Wall EE et al. Van der Wall EE et al.

MRI Findings in ARVDMRI Findings in ARVD

DDXDDX

Idiopathic dilated cardiomyopathy Idiopathic dilated cardiomyopathy Dilated CM vs ARVDDilated CM vs ARVD

Generalized CM manifests as progressive decline in LV fxnGeneralized CM manifests as progressive decline in LV fxn

ARVD progressive decline in RV fxnARVD progressive decline in RV fxn

Uhl anomaly (paper-thin RV due to near Uhl anomaly (paper-thin RV due to near complete absence of myocardial muscle fiberscomplete absence of myocardial muscle fibers Uhl anomaly vs ARVD. Uhl anomaly vs ARVD.

Uhl anomaly has no gender predilection or familial Uhl anomaly has no gender predilection or familial occurrenceoccurrence

Usually presents in infancy with CHFUsually presents in infancy with CHF

Imaging modalities which aid in the Imaging modalities which aid in the evaluation of the RVevaluation of the RV

Conventional angiographyConventional angiography

EchocardiographyEchocardiography

Radionuclide angiographyRadionuclide angiography

Ultrafast CTUltrafast CT

MR—allows the clearest visualization of MR—allows the clearest visualization of the heartthe heart

Imaging EvaluationImaging Evaluation

RV angiography is the standard of reference for RV angiography is the standard of reference for diagnosisdiagnosis Discerns abnormalities such as akinetic or dyskinetic Discerns abnormalities such as akinetic or dyskinetic

bulging in infundibular, apical and subtricuspid bulging in infundibular, apical and subtricuspid regionsregions

EchoEcho Used to exclude other anatomic abnormalitiesUsed to exclude other anatomic abnormalities

However, these traditional methods lack However, these traditional methods lack sensitivity and specificity for detecting structural sensitivity and specificity for detecting structural and functional abnormalities of the RV and functional abnormalities of the RV myocardiummyocardium

MRMR

3D evaluation of ventricular anatomy and 3D evaluation of ventricular anatomy and volumesvolumes

Excellent spatial resolutionExcellent spatial resolution

Unlimited FOVUnlimited FOV

MR FindingsMR Findings

T1- high signal intensity of fat in the RV T1- high signal intensity of fat in the RV myocardiummyocardiumFibrofatty replacement leading to diffuse thinning Fibrofatty replacement leading to diffuse thinning of the RV myocardium (major criteria)of the RV myocardium (major criteria)RV and RVOT aneurysms (major criteria)RV and RVOT aneurysms (major criteria)Dilation of the RV and RVOT (major criteria Dilation of the RV and RVOT (major criteria when severe; minor criteria when mild)when severe; minor criteria when mild)

*These findings should be considered a major *These findings should be considered a major criteria in the diagnosis of ARVDcriteria in the diagnosis of ARVD

Fatty replacement of the Fatty replacement of the myocardiummyocardium

Diffuse thinning and fatty Diffuse thinning and fatty replacement of the myocardiumreplacement of the myocardium

More MR findingsMore MR findings

Can also assess both systolic and diastolic Can also assess both systolic and diastolic functionfunction RV diastolic dysfunction is an early marker of RV diastolic dysfunction is an early marker of

disease even with LV fxn is preserveddisease even with LV fxn is preserved

Regional contraction abnormalities (minor)Regional contraction abnormalities (minor)

Global systolic dysfunction (major)Global systolic dysfunction (major)

Global diastolic dysfunction (minor) Global diastolic dysfunction (minor)

TherapyTherapy

Options include:Options include: Antiarrythmic medicationAntiarrythmic medication

Sotalol, Amiodarone or combination therapySotalol, Amiodarone or combination therapyGoal to prevent recurrent ventricular tachycardiaGoal to prevent recurrent ventricular tachycardia

Catheter ablationCatheter ablationUsing RF or DC energyUsing RF or DC energyReserved for patients who are unresponsive or intolerant to Reserved for patients who are unresponsive or intolerant to the drugsthe drugsPatients may have new ventricular arrythmiasPatients may have new ventricular arrythmias

Implantable AICDImplantable AICD SurgerySurgery

Total disconnection of the RVTotal disconnection of the RV

References:References:

Gemayel, C. et al. “Arrythmogenic Right Ventricular Cardiomyopathy.” Journal of the Americal College of Cardiology. 38 (2001)1773-1781

Marcus et. Al. “Arrhymogenic right ventricular dysplasia/cardiomyopathy:a review.” Pacing Clinical Electrophysiology. 18 (1995) 1298-314

Auffermann et al. “Arrhythmogenic Right Ventricular disease: MR Imaging vs Angiography.” AJR. 161 (1993) 549-555

Kayser et al. “Diagnosis of Arrhythmogenic Right Ventricular Dysplasia: A Review.” Radiographics. 22 (2002) 639-650.

Van der Wall et al. “Arrythmogenic Right Ventricular Dysplasia: MRI Findings.” Herz Cardiovascular Disease. 25 (2000) 356-364.