Arrhythmogenic right ventricular dysplasia/ cardiomyopathy

1. ARRHYTHMOGENIC RIGHT VENTRICULAR
DYSPLASIA
(ARVD)
DR. Prithvi
Puwar
DNB Cardio
Vijaya hospital Chennai

2. ARVD - GENETICS
“ARRYTHMOGENIC RIGHT
VENTRICULAR CARD
IOM
YOPATHY”
• Genetic form of cardiomyopathy
• Familial occurrence of 30% to 50%
• Genetic screening –
- early detection of healthy carriers
- prognostic role in patients

3. • Dominant mutations –
- desmoplakin
- cardiac ryanodine receptor
- plakophilin 2 (PKP2) – younger age /
malignant arrhythmias
- transforming growth factor-β3
- desmoglein - 2
- desmocollin – 2
- TMEM43 (most recent – non desmosomal)
• Recessive mutations –
- junctional plakoglobin (JUP) – Naxos/Carvajal
Syndrome

4. ARVD – Molecular mechanism
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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

5. ARVC – Natural History
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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

6. History
Common symptoms reported in different series include the
following:
Palpitatio
n (27%-
67%)
Syncope
(26%-
32%)
Sudden
cardiac
death
(10%-
26%)
Atypical
chest
pain
(27%)
Dyspnea
(11%)
It has wide range of presentations, ranging from being
asymptomatic to biventricular failure and/or sudden cardiac
death.

7. Palpitation
• It is the most frequent symptom and is caused by
ventricular arrhythmias.
• Supraventricular arrhythmias, including atrial flutter and
fibrillation, may be seen in about 25% of cases
• Depending on the disease severity, ventricular ectopics
may be isolated or may result in nonsustained/sustained
ventricular tachycardia, ventricular fibrillation
Progressive RV
and LV
dysfunction
• Results In Dyspnea And Leg Swelling.
• In more severe cases with LV involvement,
patients may present with biventricular congestive
heart failure that may mimic DCM

8. SUDDEN
CARDIAC
DEATH
• 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

9. ARVC – DIAGNOSIS
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”

10. The Need To Change The 1994 Criteria
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 1994 criteria were highly specific, but lacked sensitivity for early and
familial disease
• Additional ECG markers have been proposed in last 15 yrs
• Genetic basis recognized - potential for mutation analysis
• Experience in quantification of imaging criteria of ARVC ↑
• Newer imaging techniques –
- contrast echo, 3D Echo , CMR, SAECG
• Recognition that LV involvement may occur early

11. Framework of New Task Force Criteria
2010
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
The approach
• 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

12. Diagnostic Terminology
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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

13. CATEGORY -I – “global or regional dysfunction and
structural alteration”
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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)
PSAX RVOT ≥36 mm (≥21
mm/m2)
PLAX RVOT ≥29 to <32 mm
(≥16 to <19 mm/m2)
PSAX RVOT ≥32 to <36 mm
(≥18 to <21 mm/m2)
MRI Regional RV akinesia,
dyskinesia or dyssynchrony: +
1 of the following -
RVEDV index: ≥110 mL/m2
(male)
≥100 mL/m2
(female)
RV EF ≤ 40%
RVEDVi : 100 - 110 mL/m2
(male)
90 - 100 mL/m2
(female)
RV EF >40% to ≤45%
RV Angio Regional RV akinesia,

14. Echocardiography in ARVC
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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

15. major/minor criteria?
PLAX PSAX
Echo Criteria

16. Focal RV apical aneurysm –Echo Major Criteria

17. ECHO FEATURES OF ARVC
Excessive trabeculations Hyperreactive
moderator

18. Contrast Echo of the RV
Dilated RV clearly showing enhanced border delineation with a localized aneurysm of the
RVOT.

19. Cardiac MR in ARVC
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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

20. 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

21. Axial T1-weighted
black blood spin-
cardiovascular MRI
showing extensive
transmural fatty
replacement of the
RV myocardium

22. 30-80% of (advanced) cases have LV, as well as RV
late GAD enhancement indicating focal fibrosis

23. RV ANGIOGRAPHY

24. CATEGORY - II – “Tissue characterization of walls”
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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

25. Endomyocardial biopsy - role in ARVD
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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 –ve
• 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,
• More accessible IVS rarely exhibits histological changes

26. CATEGORY - III – “Repolarization abnormalities”
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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 & in V4, V5, or 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

27. Major / Minor Criteria ?

28. 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/D
Marcus FI. Prevalence of T-wave inversion beyond V1 in young normal individuals and usefulness for the
diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia.
Am J Cardiol. 2005; 95: 1070–1071.

29. CATEGORY -IV – “Depolarization and Conduction
Abnormalities”
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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):
- Filtered QRS duration ≥114 ms
- Duration of terminal QRS <40 μV
(low-
amplitude signal duration) ≥38 ms
- 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

30. during regular sinus rhythm, with an epsilon wave
(arrow) in leads V1–V. The ECG shows a RBBB
pattern.
(Reproducible low-amplitude signals between
end of QRS complex to onset of the T wave)

31. 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.
Marcus F I et al. Circulation 2010;121:1533-1541

32. CATEGORY - V – “Arrhythmias”
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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)

33. AXIS? MAJOR/MINOR CRITERIA??

35. 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.

36. CATEGORY -VI – Family history
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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

37. Diagnosis of Familial ARVD
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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.

38. Uhl’s Anomaly VS ARVD/C
 The mechanism operating in ARVD/C should be
essentially different from the apoptosis triggered in Uhl’s
anomaly
 As in Uhl’s anomaly there is complete loss of RV
myocardium unlike in ARVD/C , where some myocardium
is still present.
 Further, there is no fibrofatty replacement of myocytes
observed in Uhl’s anomaly in contrast, which is the main
pathological feature observed in ARVD/C.

39. ARVD/C VS RVOT-VT
RVOT VT ARVD/C
AGE OF ONSET 3RD TO 4TH DECADE 3RD TO 4TH DECADE
SEX FEMALES PREDOM MALES PREDOM
FAMILY HISTORY ----- +++
SCD ------- +++
12 LEAD ECG NORMAL T WAVE
ABNORMALITIES ,
EPSILON WAVES
SAECG NORMAL LATE POTENTIALS
ECHO NORMAL WALL MOTION
ABNORMALITY OR
DILATATION OF RV
ARRHYTHMIAS REPETATIVE
MONOMORPHIC VT
SVT,NSVT,VF
ORIGIN OF
ARRHYTHMIAS
SEPTUM PARIETAL WALL OF RV

40. MANAGEMENT
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
There are five therapeutic options in patients with ARVD/C:
• ICD therapy
• Antiarrhythmic agents,
• Radiofrequency ablation,
• HF treatment,
• Surgical treatment / cardiac transplantation

41. Recommendations for ICD in ARVD
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
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

42. RISK STRATIFICATION & ICD USE
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
ACC/AHA 2006/2008 guidelines
• Induction of VT during electrophysiological testing,
• Detection of nonsustained 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

43. Proposed recommendations for clinical management and
prevention of sudden cardiac death in patients with ARVD
Arrhythmogenic right ventricular dyplasia
An article from the ESC Council for Cardiology Practice
Fernández-Armenta J., Brugada J.
Vol10 N°26 16 Apr 2012

44. Subgroups
Risk
markers
Recommend-
ations
Follow-up
ICD
indication
Definite ARVD
High risk
Aborted SCD
Sustained VT
Unexplained
syncope
Reduce physical
exercise
Avoid competitive
sport
β-blockers
Annually :
ECG,
ECHO vs
CMR
Holter
Exercise
stress
Recommended
Definite ARVD
Moderate risk
Extensive
disease (severe
RV dysfunction,
large LV
involvement)
Nonsustained
VT
SAME SAME Consider
Definite ARVD
Low risk
Remaining
patients with
definite
diagnosis of
ARVD
SAME SAME
Not
recommended

45. ROLE OF CATHETER ABLATION
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• RFA has proven largely palliative due to patchy and progressive nature of
the disease
• RFA currently reserved for patients who experience frequent ventricular
arrhythmias (and ICD shocks) despite optimal therapy with both ICDs
and antiarrhythmic medication
• Role of RFA may continue to increase in the future, as mapping
techniques continue to evolve

46. Combined endocardial and epicardial
substrate guided catheter ablation
 Epicardial scar is wider than the endocardial scar
in ARVD
 Combined endocardial & epicardial substrate
guided ablation resulted in a very good short-
and mid-term success rate.
 The high recurrence rate published in earlier
series may be due to the conventional only-[Combined endocardial and epicardial catheter ablation in arvc. Brugada J.; Circulation: Arrhythmia and EP.
2012;5:111-121]

47. ARVD - CONCLUSIONS
“ARRYTHMOGENIC RIGHT
VENTRICULAR
CARDIOMYOPATHY”
• 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 -“this will have practical
significance for the serial assessment of family members at risk of disease
development”
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