Review of a rare but important cardiac dysplasia causing high mortality and morbidity in mostly young patients. In this presentation, the epidemiology, pathophysiology, diagnosis and treatment of said disease is examines.

1. ARRHYTHMOGENIC RIGHT
VENTRICULAR DYSPLASIA
(ARVD)
BY: KHALED GHANEYM
DEPARTMENT OF INTERNAL MEDICINE G’, HAEMEK MEDICAL CENTER
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2. OVERVIEW
• Genetics
• Natural history
• Diagnosis
• Management
• Recommendations
• Conclusion
(42 slides)
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3. ARVD - INTRO
• Genetic form of cardiomyopathy
• Familial occurrence of 30% to 50%
• Genetic screening
- Early detection of healthy carriers
- Prognostic role in patients
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4. GENITICS
• Dominant mutations:
o Desmoplakin
o cardiac ryanodine receptor
o plakophilin 2 (PKP2) – younger age / malignant arrhythmias
o transforming growth factor-β3
o desmoglein – 2
o desmocollin – 2
o TMEM43 (most recent – non desmosomal)
• Recessive mutations:
o junctional plakoglobin (JUP) – Naxos/Carvajal Syndrome
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5. ARVD – Molecular mechanism
• Mutations render desmosomes inappropriately sensitive to mechanical stresses,
resulting in myocyte death
• Signal transduction processes induced by mutant desmosome proteins can lead to
reprogrammed myocyte cell biology so that these cells adopt a fibrofatty lineage
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6. ARVC – Natural History
• Typically present between the teenage years and the forties
• Prevalence – 1:2000/1:5000
• Male : Female = 1:3
• Natural history characterized by four phases:
• Concealed phase (asymptomatic, but at risk of SCD)
• Overt clinical expression of an electrical system disturbance
• Signs and symptoms of right ventricular failure
• Frank biventricular congestive heart failure
• Common symptoms: Palpitations (27%-67%), syncope (26%-32%), SCD (10%-26%), atypical
chest pain (27%, dyspnea (11%)
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7. SUDDEN CARDIAC DEATH (SCD)
• ARVD accounts for 22% of sudden cardiac death cases among young athletes in
northern Italy.
• In the United States, hypertrophic cardiomyopathy was the most common cause,
and ARVD was reported in only 4% cases
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8. ARVC – DIAGNOSIS
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9. Framework of New Task Force Criteria 2010
• Global or regional dysfunction and structural alteration
• Tissue characterization of walls
• Repolarization abnormalities
• Depolarization and conduction abnormalities
• Arrhythmias
• Family history
Each category has major and minor criteria
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10. Diagnostic Terminology
• Definite diagnosis (from different categories):
- 2 major or
- 1 major and 2 minor criteria or
- 4 minor
• Borderline (from different categories):
- 1 major and 1 minor or
- 3 minor criteria
• Possible (from different categories):
- 1 major or
- 2 minor criteria
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11. CATEGORY -I – “global or regional
dysfunction and structural alteration”
Major Criteria Minor Criteria
Echo Regional RV akinesia, dyskinesia, or
aneurysm : + 1 of the following:
Regional RV akinesia /dyskinesia
+ 1 of the following:
- PLAX RVOT ≥32 mm (≥19 mm/m2) - PLAX RVOT ≥29 to <32 mm
- PSAX RVOT ≥36 mm (≥21 mm/m2) corrected (≥16 to <19 mm/m2)
- Fractional area change ≤ 33% - PSAX RVOT ≥32 to <36 mm
corrected (≥18 to <21 mm/m2)
MRI Regional RV akinesia, dyskinesia or dyssynchrony: + 1 of the following:
- RVEDV index: - RVEDVi :
≥110 mL/m2 (male)
≥100 mL/m2 (female)
100 - 110 mL/m2 (male)
90 - 100 mL/m2 (female)
- RV EF ≤ 40% - RV EF >40% to ≤45%
RV Angio Regional RV akinesia, dyskinesia, or aneurysm
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12. Echocardiography in ARVC
• The most conspicuous findings:
- RV dilation
- Enlargement of the RA
- Isolated dilatation of the RVOT
- Increased reflectivity of the moderator band
- Localized aneurysms, fractional area change, & akinesis/ dyskinesis of the inferior wall
and the RV apex
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13. ECHO FINDINGS
PLAX PSAX
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14. Focal RV apical aneurysm-EchoMajor Criteria
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15. ECHO FEATURES OF ARVC
Hyperreactive
band
Excessive trabeculations
moderator
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16. Contrast Echo of the RV
Dilated RV clearly showing enhanced border delineation with a localized aneurysm of the RVOT.
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17. Cardiac MR in ARVC
• five criteria for diagnosis of ARVC:
(1) High signal intensity (substitution of myocardium by fat)
(2) Ectasia of RVOT
(3) Dyskinetic bulges
(4) Right ventricular dilation
(5) RA enlargement
• Fibrosis is more specific than myocardial fat – detected by increased
delayed enhancement in contrast CMR signal
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18. End-diastolic and end-systolic frames of a short-axis cine magnetic resonance image
showing an area of dyskinesia on free wall of a dilated RV
characterizing a focal ventricular aneurysm
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19. Axial T1-weighted black blood spin-
cardiovascular MRI showing
extensive transmural fatty
replacement of the RV myocardium
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20. 30-80% of (advanced) cases have LV, as well as RV
late GAD enhancement indicating focal fibrosis
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21. RV ANGIO
(Anterior oblique view, systolic frame). Dilation of RV with
apical dyskinesia and bulging of the inferior wall (lower
arrows) and infundibular tract (upper arrow)
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22. CATEGORY - II – “Tissue characterization
of walls”
Endomyocardial
biopsy
Major Criteria Minor Criteria
New TFC
Residual myocytes <60% by
morphometric analysis (or
<50% if estimated), with fibrous
replacement of the RV free wall
myocardium in ≥1 sample, with
or without fatty replacement of
tissue
Residual myocytes 60%–75% by
morphometric analysis (or 50%–
65% if estimated), with fibrous
replacement of the RV free wall
myocardium in ≥1 sample, with or
without fatty replacement of tissue
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23. 23

24. Endomyocardial biopsy - role in
ARVD
• Definitive Dx - histologic demonstration of transmural fibrofatty replacement of RV
myocardium at biopsy/surgery
• Dx based on RV endomyocardial biopsy specimens is limited because segmental
nature of the disease causes false neg.
• Use of electroanatomic voltage mapping to identify pathological areas for biopsy
sampling may improve yield
• RV free wall biopsy has a slight risk of perforation
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25. CATEGORY - III – “Repolarization
abnormalities”
Electrocardiography Major Criteria Minor Criteria
New TFC
• Inverted T waves in
right precordial leads
(V1, V2, and V3) or
beyond in individuals
>14 yrs of age (in the
absence of complete
RBBB QRS ≥120 ms)
• Inverted T waves in leads
V1 & V2 or V4, V5, V6 in
individuals >14 yrs age (in
the absence of complete
RBBB)
• Inverted T waves in leads
V1, V2, V3, and V4 in
individuals >14 years of age
in the presence of complete
RBBB
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26. Major / Minor Criteria?
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27. Repolarization Abnormalities
 Repolarization abnormalities are early and sensitive markers of disease
expression in ARVC/D
 T-wave inversion in V1, V2, and V3 and beyond in individuals >14 years of
age who are otherwise healthy is observed in only 4% of healthy women and
1% of men.
it is reasonably specific in this population and considered a major diagnostic
abnormality in ARVC
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28. CATEGORY -IV – “Depolarization and
Conduction Abnormalities”
ECG Major Criteria Minor Criteria
NEW TFC
Epsilon wave in the right
precordial leads (V1 to V3)
• Late potentials by SAECG in ≥1 of 3
parameters (absence of a QRS ≥110 ms
on standard ECG):
o Filtered QRS duration ≥114 ms
o Duration of terminal QRS <40 μV
(low- amplitude signal duration)
≥38 ms
o Root-mean-square voltage of
terminal 40ms ≤20 μV
• Terminal activation duration of QRS ≥55
ms from the nadir of the S to the end of
QRS, incl. R´, in V1, V2, or V3, in the
absence of complete RBBB
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29. (Reproducible low-amplitude signals between end of QRS
complex to onset of the T wave)
during regular sinus rhythm, with an epsilon wave (arrow) in leads
V1–V. The ECG shows a RBBB pattern.
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30. ECG from proband with T-wave inversion in V1 through V4 and prolongation of the
terminal activation duration ≥55 ms measured from the nadir of the S wave to the end of
the QRS complex in V1.
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31. CATEGORY - V – “Arrhythmias”
ECG/Holter/
Exercise
Major Criteria Minor Criteria
NEW TFC
Nonsustained or sustained VT
of LBBB morphology with
superior axis
• Nonsustained or sustained VT of
RV outflow configuration, LBBB
morphology with inferior axis or
of unknown axis
• >500 VES per 24 h (Holter)
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32. MAJOR/MINOR CRITERIA??
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33. AXIS?
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34. Exercise and ventricular arrhythmias
• Usually occurrence of symptomatic RV arrhythmias during exercise
• Fibrofat form arrhythmic substrate induced by adrenergic stimulation
• During exercise testing, 50% to 60% of patients with ARVD show ventricular
arrhythmias: monomorphic LBBB pattern in 96%
• The occurrence of arrhythmic cardiac arrest due to ARVD is significantly increased in athletes.
Particularly in certain regions in Italy, ARVD has been shown to be the most frequent disease
(22%) leading to exercise-induced cardiac death in athletes.
• Diagnosis of ARVD is considered incompatible with competitive sports and/or moderate-to-
high intensity level recreational activities.
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35. CATEGORY -VI – Family history
Major Criteria Minor Criteria
NEW TFC
• ARVC confirmed in a first degree
relative
• ARVC confirmed pathologically at
autopsy or surgery in a first-degree
relative
• Identification of a pathogenic
mutation categorized as associated
or probably associated with ARVC
in the patient under evaluation
• History of ARVC in a first- degree
relative in whom it is not possible
or practical to determine whether
the family member meets current
task force criteria
• Premature sudden death (<35
years of age) due to suspected
ARVC in a first- degree relative
• ARVC confirmed pathologically or
by current task force criteria in
second- degree relative
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36. Diagnosis of Familial ARVD
documentation of one of the following in a family member:
• T-wave inversion V1, V2, and V3 in individuals ≥ 14 years.
• Late potentials by SAECG
• VT of LBBB morphology on ECG, Holter, or during exercise testing or >200 PVCs in
24 hours
• Either mild global dilatation or reduction in RVEF with normal LV or mild segmental
dilatation of the RV or regional RV hypokinesis.
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37. MANAGEMENT
There are five therapeutic options in patients with ARVD/C:
• ICD therapy
• Antiarrhythmic agents
• Radiofrequency ablation
• HF treatment
• Surgical treatment / cardiac transplantation
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38. Recommendations for ICD in ARVD
ACC/AHA 2006/2008 guidelines
• Recommend ICD implantation for secondary prevention in all patients of
ARVD with prior sustained VT or ventricular fibrillation
• ICD implantation is reasonable for the prevention of SCD in patients with ARVD who
have 1 or more risk factors for SCD
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39. RISK STRATIFICATION & ICD USE
ACC/AHA 2006/2008 guidelines
• Induction of VT during electrophysiological testing
• Detection of non-sustained VT on noninvasive monitoring
• Male gender
• Severe RV dilation, and extensive RV involvement
• Young age at presentation (less than 5 years)
• LV involvement
• Prior cardiac arrest, and unexplained syncope serve as markers of risk
• Patients with genotypes of ARVD associated with a high risk for SCD should be considered
for ICD therapy
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40. Subgroups
Risk
markers
Recommend-
ations Follow-up
ICD
indication
DefiniteARVD
High risk
Aborted SCD
Sustained VT
Unexplained
syncope
Reduce physical
exercise
Avoid competitive sport
β-blockers
Annualy:
ECG,
ECHO vs
CMR
Holter
Exercise
stress
Recommended
Definite ARVD
Moderate risk
Extensive disease
(severe RV
dysfunction, large LV
involvement)
Nonsustained VT
Remaining
SAME SAME Consider
Definite ARVD
Low risk
patients with
definite
diagnosis of
ARVD
SAME SAME
Not
recommended
RECOMMENDATIONS
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41. CONCLUSIONS
• SCD is the 3rd most common presenting symptom (behind syncope and palpitations)
& the initial symptom in 23% cases
• An increased awareness and prompt recognition of ARVD has considerable life-saving
potential (ICD/transplant)
• Revised TFC is more sensitive than the original TFC
• A quick diagnosis can be made with only history, ECG & Echo
• Electrical/arrhythmic abnormalities precede morphological changes on echo/MRI:
ECG has highest diag. sensitivity.
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42. THANK YOU!
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