ARVD is one of important coardiomyopathy in our clinical practice,early diagnosis, risk stratification and early diagnosis of CHF, management of VT will make big difference in patient life

1. ARVD/C – a short review
DR.R SASINTHAR
SR, CARDIOLOGY
JIPMER

2. ARVC
Inherited progressive CMP characterized by fibro-fatty
replacement of RV +/- LV myocardium that predisposes
patients to life threatening arrhythmia and heart failure
• Prevalence: 1/5000 to 1/2000
• M:F = 3:1
• Leading cause of SCD in young athletes, 10% of death
from it
• Median age of onset of symptom 29
• First presentation can be SCD

3. 1. Clinical presentations of ARVC – diverse
• Syncope
• Progressive heart failure (HF)
• Ventricular tachyarrhythmias
• Sudden cardiac death (SCD)
2. Predominantly affects the RV with fibrofatty replacement
pathologically
3. LV involvement usually late (typically the posterior lateral
wall) - 10% of patients

4. Genetics of ARVC
• Family hx +ve in 30-50% of cases
• AD inheritance but highly variable penetrance and
expressivity
• AR form in Naxos disease
• “Defective desmosome hypothesis”
Marcus et al. JACC 2013
DSP
DSC2
DSG2
PKP
JUP

5. Clinical impact of genotyping
• Genotyping in Preclinical phase
• Possibility to identify genetically affected
relatives before a malignant clinical
phenotype manifests
• Focussed prevention strategy and Timely
therapy with b-blockers and/or ICD is highly
effective in prevention of SCD

6. Clinical course : 4 phases
1. Concealed phase (Mild or absence of RV structural
abnormalities but SCD can still occur)
2. Overt electrical disorder (Palpitation syncope PVC VT
with LBBB)
3. RV failure (RV pump failure due to progressive loss of
RV myocardium)
4. Bi-ventricular failure (LV involvement similar to DCM)

7. Diagnosis of ARVC: from past to
present
McKenna et al initially proposed international TF
criteria for the diagnosis of ARVC in 1994
Marcus et al revised them in 2010
• Major criteria : 2 TFC points
• Minor criteria : 1 TFC point.
• ≥4 TFC points  Definite ARVD
• 3 TFC points  Borderline ARVD
• 2 TFC points  Possible ARVD

8. Incorporation of quantitative parameters by echo or
MRI yields high specificity (90–98% for major criteria)
Non-invasive
1. ECG
2. Signal averaged ECG
3. Echocardiogram
4. MRI
5. Holter monitoring
6. Genetic analysis
Invasive
1. RV angiography
2. RV endomyocardial
biopsy

9. Epsilon wave in V1–3 and diffuse T wave inversion in V1–6.
The morphology of clinical VT - LBBB and superior axis

10. ECG screening and pre-symptomatic
diagnosis
• The annual incidence of SCD in athletes
decreased approximately by 90%, from
3.6/100 000 personyears in the pre-screening
period to 0.4/100 000 person-years in the late
screening period

11. Signal-averaged electrocardiogram (SAECG)
depicting 3+ according to Task Force criteria.

12. Imaging in ARVC
• Diagnostic challenge
• Overemphasis to Imaging may be problematic
• RV Imaging – not the gold standard

13. Predilection areas
1. Subtricuspid region
2. Basal RV free wall
3. LV posterior wall

14. TRANSTHORACIC
ECHOCARDIOGRAPHY
• 1st line imaging modality
• Ideal screening tool
• Follow-up
• Should be performed using current ASE
guidelines
• North american multidisciplinary study :
enlarged RVOT – 100% of probands

15. RV dilatation
• Not specific to ARVC
• Physiologic adaptation to high-intensity
exercise
• RV enlargement in ARVC - a/w increased risk
of SCD and ventricular arrhythmias in athletes
• ARVC vs Normal adaptaion
RV function
• Challenging by TTE
• A4C FAC – useful correlate of global RV
function
• FAC <33% - sensitivity 55% and specificity 95%

16. Other morphologic abnormalities
• Trabecular prominence
Most frequently noted morphologic abnormality (54%)

17. NEWER ECHOCARDIOGRAPHIC
TECHNIQUES IN ARVC
1. RV myocardial performance index
• Independent of geometric assumptions
• Reduced RV MPI in ARVC probands, even
when global RV function as assessed by FAC
was normal
Yoerger DM, Marcus F, Sherrill D, et al.
Right ventricular myocardial performance index in probands from the multicenter
study of arrhythmogenic right ventricular dysplasia (abstr).
J Am Coll Cardiol 2005;45:147A.

18. 2. Intravenous TTE contrast
3. TAPSE with M mode or
tissue doppler
4. 3D TTE
5. RV free wall myocardial
velocity, strain, and strain rate
By a. TDI
b. Speckle tracking

19. CMR
• RV wall thinning
• RV outflow tract enlargement,
• Trabecular disarray
• Fibrofatty replacement
• Ventricular dilation and
• Global or regional systolic dysfunction

20. LGE – indicative of fibrosis (prevalence : 88%)Intramyocardial hyperintense signal in T1W
spin echo imaging in 22-100%

21. ROLE OF CMR IN ARVC DIAGNOSIS
Emphasis on functional abnormalities.
(95% specificity)
(79% to 89% sensitivity)

22. ROLE OF CMR IN EARLY DIAGNOSIS AND RISK
STRATIFICATION
• Wall motion abnormalities in the RV
subtricuspid region - 94% of subjects with
CMR structural involvement
• Fatty infiltration of LV posterior wall – in ARVD
mutation carriers
te Riele AS, James CA, Philips B, et al. Mutationpositive ARVD:
the triangle of dysplasia displaced.
J Cardiovasc Electrophysiol 2013;24:1311–20
Rastegar et al

23. ROLE OF CMR IN RISK STRATIFICATION
OF ARRHYTHMIAS
• Previous studies : severe RV dysfunction and LV
involvement predict adverse outcome in ARVC
• Sustained arrhythmias during follow-up coincide with
structural abnormalities on CMR
• CMR - independent predictor of ventricular
arrhythmia among 369 consecutive patients
undergoing evaluation for ARVD/C.
• Normal CMR  No events in 6 yr f/u
te Riele AS, Bhonsale A, James CA, et al.
Incremental value of CMR in arrhythmic risk stratification of ARVD-
associated desmosomal mutation carriers. J Am Coll Cardiol 2013;62:1761–9.
Deac et al

24. COMPUTED TOMOGRAPHY
• Tissue characterizationPossible use of CT
• Evaluation of claustrophobic patients
• Subjects with frequent ventricular
extrasystoles leading to severe arrhythmia
artifacts on CMR
• Serial evaluation of ICD carriers

25. RV angiography
• May depict sacculation, segmental contraction
impairment, and variable trabecular patterns
• Remains the gold standard for structural
assessment in some laboratories

26. Endomyocardial Biopsy
• Assessment of transmural fibrofatty
infiltration by EMB
• Potential risk of free wall perforation
• Possibility of false negative results owing to
the nature of segmental involvement.
• Guiding EMB based on the low voltage area
identifiable on electroanatomic mapping -
yield higher diagnostic sensitivity

27. Voltage mapping
3D electroanatomic bipolar voltage maps.
Marcus et al
Normal ARVC

28. EP studies by programmed stimulation (PVS)
• Pivotal role in evaluating the vulnerability of
ventricular tachyarrhythmias
• Also provide clues for the diagnosis of ARVC
1) Presence of PVCs with ≥ 1 couplet
2) VT or NSVT with LBBB after excluding RVOT VT
by high dose isoproterenol (45 mg/min) infusion
help in making the diagnosis of ARVC in the early
stage of disease (sensitivity 91.4% ; specificity
88.9%) Denis et al

29. • Incidence of appropriate ICD discharge did not
differ between patients who were and were not
inducible at PVS for either 1° and 2° prevention
of arrhythmic sudden death, regardless of
indication for ICD implant
•Inducibility of VT or VF at pre-implant
electrophysiologic study demonstrated a trend
toward statistical significance for subsequent
appropriate device intervention
Corrado et al
Witchter et al
•VT induction was the most significant
independent predictor of appropriate ICD firing
Roguin et al

30. DDRisk stratification in patients with ARVC
Corrado et al Bhonsale et al

31. Major determinants in predicting
sudden death and worse outcome
• Young age
• Prior cardiac arrest
• Fast and poorly tolerated VT with different
morphologies
• Syncope
• Severe RV dysfunction, heart failure with LV
involvement
• Familial occurrence of juvenile sudden death

32. Factors influence disease progression and
the arrhythmic episodes
Progressive nature of ARVD, incomplete genetic
penetrance and variable manifestations
• Endurance training – induce RV enlargement
and/or VT
• Summer season [Chung et al]

33. MANAGEMENT OF ARVC
Aim : to prevent the occurrence of ventricular
tachyarrhythmias and SCD
1. Antiarrhythmic drugs (AADs)
2. AICD
3. Radiofrequency catheter ablation
4. Heart transplantation

34. Asymptomatic and healthy gene
carriers
• To refrain from participating in physical
exercise and sport activity
• Prophylactic B blockers ?
Patients with well tolerated and not
life threatening ventricular arrhythmias
•Either sotalol or amiodarone (alone or in
combination with Beta-blockers)
•Catheter ablation

35. ICD implantation
• 28% reduction in 5 year mortality in males with an ICD
[Hodgkinson et al ]
• Average incidence of ICD therapies for VF/VFL-4%/year in 84
patients with definite or probable ARVD [Bhonsale et al. ]
• Current guidelines -- Class I indication
Family members :
• It is unknown whether and when the family members should
receive an ICD implantation for 1̊ prevention
• ICD implantation for family members with SCD, or
undiagnosed syncope when ventricular tachyarrhythmias
cannot be excluded as cause of syncope after OMT -- Class II
indication

37. Antiarrhythmic medication
• Empirical AADs should be considered for patients with a propensity
to the occurrences of VT/VF
• No prospective study elucidating and comparing the efficacy of
individual AADs
• Wichter et al :
Sotalol- effective ; Class I AADs – ineffective
• North American ARVC Registry, Marcus et al:
1. Amiodarone significantly reduced the risk of clinically relevant
ventricular arrhythmias
2. Sotalol increased the risk of ventricular tachyarrhythmias
3. Beta-blockers did not influence the risk

38. EAM & Catheter ablation of ventricular
tachyarrhythmias
• Characteristics of re-entrant VT similar to
ischemic VT
• Acute success rate- 50 to 90%
• Induced by iso/PVS
• Morphology compared to clinically-
documented VT
• Stable VT – both activation and entrainment
mapping done

40. Pathogenesis of arrhythmogenic
substrates and VT isthmuses
•Fibrofatty replacement : Epicardium gradually toward the
endocardium
•Extent of fibrofatty infiltration epicardium > endocardium
•Longer and delayed epicardial activation sequence
•Layered activation of epicardial scar in ARVD/C rather than
transmural activation of RV
•Arrhythmogenicity of epicardial VT circuits dominantly

41. Substrate mapping of endocardium
and epicardium
• 3D navigation systems – more reliable method
• 3D color-coded voltage mapping - tricuspid
valve region and the RV outflow tract
• Endocardial substrate bipolar voltage cutoff -
0.5- 1 mV
• Epicardial substrate bipolar voltage cutoff - 1
mV
• Distribution of epicardial scar is more
extensive than scar identified endocardially

42. Epicardial bipolar voltage mapping and the distribution of
abnormal electrograms, consisting of isolated and fractionated
late potentials

43. • Pacing maneuver -facilitate recognition of
delayed components of electrograms through
different direction of wavelet propagation
• Nonmappable VTs  unstable VT, multiple
reentrant circuit, and nonsustained VT
• Endocardial – initial strategy
• Endocardial - prevention of VT recurrence
could be achieved in only 25–53% of cases
• Endo+Epi – freedom from VT in 45–84.6%

44. Heart transplantation
• Pts with extensive HF or drug-refractory
ventricular tachyarrhythmias unresponsive to
other invasive interventions
Load-reducing therapy

45. Conclusion
• Early investigation and risk stratification essential
for successful Mx
• Accurate diagnosis based on cardiac imaging,
ECG, histopathology, family history, EP study, and
genetic screening
• With understanding of the underlying substrate
properties, and improvement of navigation
system, mapping, and epicardial ablation
techniques, the prognosis of VT ablation in
ARVD/C has improved tremendously