cardiopyopathy rvot tachycardia naxos disease greek italy

1. Uhl’s Anomaly Vs Arrhythmogenic Right
Ventricular Dysplasia/Cardiomyopathy
(ARVD/C)
DR.NILESH TAWADE
JHRC MUMBAI

2. CASE SCENARIO
• 50 yr old Nigerian hypertensive gentleman
• Came with complaints of on and off
palpitations since 3 yrs (2 -3 episodes per
week) .
– Sometimes related to exertion and many a times at
rest
– Palpitations were sudden in onset and offset used
to relieve in few seconds .
– No history of post palpitation syncope
/diuresis/blackout .
– No Family history of palpitation Or Sudden Cardiac
Death

3. CASE SCENARIO
• Gen exam/ systemic examination were
un -remarkable except for high blood pressure
• Patient was evaluated in Nigeria with 2 D Echo and
Holter monitoring
• 2-d Echo revealed the normal left ventricle with mild
hypertrophy , normal ejection fraction of LV and
dilated right ventricle .
• Holter revealed 6993 ventricular ectopic beats with
several episodes of nonsustained VT

4. BASE LINE ECG
NORMAL SINUS
RHYTHM
NORMAL QRS
AXIS
NO
ABNORMALITIES
OF QRS OR ST –T
SEGMENTS

5. Exercise Stress Testing
STAGE 2 AT 3’ MIN STARTED
DEVELOPING VPCS OF LBBB
MORPHOLOGY
TILL LATE RECOVERY STAGE
VPBS KEPT COMING AT
REGULAR INTERVALS

6. HOLTER MONITORING

7. ECHO CARDIOGRAPHY
RV THICKNESS
2 mm

8. RV FUNCTION
21.2 mm
10.3cm/s
TAPSE
TASE

9. MRI

10. MRI
Marked thinning of right ventricular
myocardium with mild dilatation of the right
ventricle and normal tricuspid valve
No evidence of fat deposition suggestive of
UHL’S ANOMALY

11. DIFFRENTIAL DIAGNOSTIC CONSIDERATIONS
• ARRHYTHMOGENIC RIGHT VENTRICLE
/CARDIOMYOPATHY (ARVD/C)
• UHL’S ANOMALY
• IDIOPATHIC RIGHT VENTRICULAR OUTFLOW
TRACT TACHYCARDIA (RVOT-VT)
• DILATED CRDIOMYOPATHY

12. DIFFRENTIAL DIAGNOSTIC CONSIDERATIONS
• Uhl anomaly
– This is a rare congenital disorder characterized by total
lack of RV myocardium and results in a very thin-walled RV
(parchment RV).
• ARVD/C
– is an inherited cardiomyopathy characterized by structural
and functional abnormalities in the right ventricle (RV)
resulting in ventricular arrhythmias.
– result from the fatty infiltration and fibrosis of the RV
myocardium.

13. DIFFRENTIAL DIAGNOSTIC CONSIDERATIONS
• Idiopathic right ventricular outflow tract
tachycardia
– This is a benign disorder that may mimic
arrhythmogenic right ventricular dysplasia (ARVD)
– the occurrence of exercise-induced left bundle branch
block (LBBB) morphology ventricular tachycardia.
– The heart is structurally normal, and there is no
history of ARVD or sudden cardiac death in the family.
– Electrocardiography (ECG) in RV tachycardia shows
upright T waves in V2 -V5, and epsilon waves are
absent.

14. DIFFRENTIAL DIAGNOSTIC CONSIDERATIONS
• Dilated cardiomyopathy
– Biventricular dilatation and congestive heart
failure may mimic advanced ARVD with LV
involvement.
– Characteristic ECG and cardiac MRI (CMRI)
abnormalities in ARVD help to distinguish the two
entities.

15. ARVD VS UHL’S ANOMALY
SOMETHING ABOUT ARVD/C

16. Background
ARVD was first described in 1977 and was included in the WHO classification
of cardiomyopathies in 1996.
Its is an inherited cardiomyopathy characterized by structural and functional
abnormalities of RV mainly which causes ventricular arrhythmias.
It is an important cause of sudden cardiac death (SCD) in young adults,
accounting for 11% of all cases and 22% of cases among athletes.
there have been significant advances in the understanding of its
etiopathogenesis, diagnosis, and management

17. Pathophysiology
The structural abnormalities in ARVD result from the fatty infiltration and fibrosis of the RV
myocardium. This leads to progressive RV dilatation and dysfunction.
The left ventricle (LV) is less commonly involved, and the septum is relatively spared.
However, in a cohort of 200 probands, Sen-Chowdhry et al 1 found that LV involvement
may even precede the onset of significant RV dysfunction.
The prognosis is worse in patients with LV involvement.
The mechanisms for myocardial loss include the following:
•Apoptosis (programmed cell death)
•Fatty replacement of myocardium
•Inflammation, enhanced fibrosis, and loss of function1.Circulation. 2007; 115(13):1710-20

18. ETIOLOGY
• it is an inherited disorder and 30%-90% of cases are familial .
• OTHER cases, it may result from an acquired etiology such as viral
infection (myocarditis) or unidentified inheritance.
Genetics
• The most common pattern of inheritance is autosomal dominance, with a
variable penetrance ranging from 20%-35% of family members.People
living in the Veneto region of Italy have a higher penetrance.
• The autosomal-recessive (Naxos disease) pattern of inheritance is localized
to the Greek island of Naxos and is associated with palmoplantar keratosis
and wooly hair.
• Genetic abnormalities in ARVD are located on chromosomes 1, 2, 3, 6, 7,
10, 12, and 14.

19. ARVD Genes
The responsible genes include :
Plakoglobin (JUP),
Desmoplakin (DSP),
Plakophilin-2 (PKP2),
Desmoglein-2 (DSG2),
Desmocollin-2 (Dsc2), and others.

20. Molecular mechanism
The probable molecular
mechanism hypothesized was
that by mutating desmosomal
protein impairs the desmosomal
assembly by releasing free
plakoglobin from the
desmosomes
Provokes Adipogenesis,
Fibrogenesis, And
Apoptosis, The
characteristic Hallmark Of
ARVD.

21. Epidemiology
• As clinically silent cases may go unrecognized ,the exact
incidence and prevalence of ARVD remains unknown,
• It is estimated incidence is 1 case per 1000-5000 population
and is more common in individuals of Greek and Italian origin.
• In a cohort of 100 patients from the United States, the median
age at presentation was 26 years, and 51% were males.
• The median time to diagnosis was one year from the initial
presentation, and median survival in the entire cohort was 60
years.

22. 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.

23. 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 dilated cardiomyopathy.

24. 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

25. Clinical Phases Of ARVD/C
From Concealed Phase ,Overt Phase To Biventricular Pump Failure
Phase
In The Early Concealed Phase :-
• Individuals are often asymptomatic but may be at a risk of sudden cardiac
death, notably during extreme exertion.
• Structural changes are absent or subtle
• Structural changes are frequently confined to one region of the ‘triangle
of dysplasia’: the inflow, outflow, and apical portions of the RV.

26. Overt Phase
• The second phase marks the onset of the overt electrical disorder,
with symptomatic arrhythmia of RV origin
• More prominent RV morphological abnormalities readily identified
by conventional imaging .
Biventricular failure
• In the third phase, diffuse RV disease results in an isolated right
heart failure.
• LV involvement with biventricular pump failure occur in the final
stage, leading to a phenotype that may resemble dilated
cardiomyopathy

27. LABORATORY STUDIES
• The diagnosis of (ARVD) poses a great challenge because of its
variable presentation.
• In 1994, an International task force first proposed the major
and minor diagnostic criteria of ARVD based on family history,
arrhythmias ,ECG abnormalities, tissue characterization, and
structural and functional RV abnormalities.
• In 2010, the task force criteria were revised to include
quantitative data in criteria.
• The proposed terminology for the diagnosis of ARVD include
major or minor criteria from 6 different categories

28. Global or regional
dysfunction and structural
alterations on
echocardiography, CMRI,
and/or RV angiography
Tissue
characterization of
RV wall as shown
on endomyocardial
biopsy
Repolarization
abnormalities
on ECG
conduction
abnormalities on ECG
and/or signal-averaged
ECG (SAECG)
Arrhythmias
on Holter
monitoring
Family
history

29. CRITERIA FOR DIAGNOSIS
• A definite diagnosis is defined as the presence
of 2 major criteria, 1 major and 2 minor
criteria, or 4 minor criteria.
• A borderline diagnosis is defined as the
presence of 1 major and 1 minor criteria or 3
minor criteria.
• A possible diagnosis is defined as the presence
of 1 major criterion or 2 minor criteria.

30. FAMILY HISTORY
Major :
1. confirmed diagnosis of ARVD based on task force
criteria/autopsy or surgery in a first-degree relative.
2. or identification of a pathogenic mutation categorized as
associated or probably associated with ARVD/C
Minor :
1. history of ARVD (not confirmed based on task force criteria)
or premature sudden death (< 35 years) from suspected
ARVD in a first-degree relative .
2. confirmed diagnosis of ARVD in a second-degree relative.

31. ECG
• ECG findings may be normal in the latent phase of
ARVD, but abnormalities
(depolarization/repolarization and/or conduction)
are seen in most patients upon progression of the
disease .
1. Intraventricular conduction abnormality.
2. T wave abnormalities in presence of right bundle
branch block
3. Anteroseptal T wave inversion.

32. MAJOR ECG CRITERIA :
• Inverted T waves in right Precordial leads (V1 -V4) or
beyond
– in individuals older than 14 years
– in the absence of complete right bundle branch
block (RBBB);
– this feature is seen in 87% cases
• Epsilon waves
– low-amplitude signals between end of QRS
complex to the onset of T wave) in leads V1 -V3
– (33% of cases)

33. MINOR ECG CRITERIA
1. Inverted T waves in leads V1 and V2 in individuals older than
14 years in the absence of complete RBBB or in V4, V5, or V6
2. Terminal activation of QRS ≥55 ms measured from the nadir
of the S wave to the end of the QRS, including R', in V1, V2, or
V3, in the absence of complete RBBB

34. SIGNAL-AVERAGED
ELECTROCARDIOGRAPHY
• Abnormalities on SAECG are common and have fair
sensitivity and specificity but do not reliably predict
spontaneous or inducible ventricular tachycardia.
– Filtered ECG that is able to detect low amplitude potentials
filtered out of standard ECGs.
– Myocardial scar (infarction, ARVD) creates zones of slow
conduction that appear as low amplitude late potentials
on SAECG.
– Areas of slow conduction are necessary components for
reentry

35. SAECG
• SAECG abnormalities are included as minor criteria and
should have at least 1 of 3 parameters. These parameters
include the following:
1. Filtered QRS duration ≥114 ms
2. Duration of terminal QRS < 40 μV (low-amplitude signal
duration)is more than ≥38 ms
3. Root mean squared voltage of the terminal 40
msecs of QRS complex is less than 20 microvolts

36. Twenty-four–hour Holter Monitoring
• This is very helpful in detecting arrhythmias.
• Ventricular Tachycardia of LBBB morphology with superior axis
is a major criterion,
• Ventricular Tachycardia with inferior axis and/or more than
500 ventricular extra systoles per 24 hours are considered
minor criteria per the revised task force.

37. ECHOCARDIOGRAPHY
• Echocardiography serves as a good screening tool to evaluate
patients with suspected ARVC.

38. ECHOCARDIOGRAPHY
• Major criteria are defined as regional RV akinesia or
dyskinesia or aneurysm and one of the following (end-
diastole):
1. PSAX RVOT >36 mm (≥21 mm/m2 BSA corrected)
2. Fractional area change ≤33%
•Minor criteria are defined as regional RV akinesia or dyskinesia and one of
the following:
1. PSAX RVOT ≥32 to < 36 mm (≥18 to < 21 mm/m2 BSA corrected)
2. Fractional area change >33 to ≤40%

39. CMRI is used to evaluate
RV size, function, wall motion
abnormalities,
Intramyocardial Fat (using fat
suppression sequence), and
Late Gadolinium Enhancement to
assess areas of fibrosis.
RV wall thickening or thinning and
prominent trabeculations are also
seen in ARVC

40. Revised task force criteria for RV
abnormalities
• Major criteria are defined as regional RV akinesia or dyskinesia or
dyschronous RV contraction and one of the following:
1. Ratio of RV end-diastolic volume to BSA in males ≥110 mL/m2 or
BSA ≥100 mL/m2 in females
2. RV ejection fraction (RVEF) ≤40%
MINOR :
1. Ratio of RV end-diastolic volume to BSA ≥100 to < 110 mL/m2 in
males or BSA ≥90 to < 100 mL/m2 in females
2. RVEF >40% to ≤45%

41. • RV angiography may show RV enlargement, hypertrophic
trabeculae, and wall motion abnormalities.
• However, since this method is invasive, it is rarely used.
• RV regional akinesia, dyskinesia, or aneurysm on angiography
is a major diagnostic criterion.
• The transversally arranged hypertrophic trabeculae, separated
by deep fissures, were associated with the highest probability
of ARVC
RIGHT VENTRICULOGRAPHY

42. Anatomy and histology
• The most classic feature of ARVD is fatty infiltration of the RV
free wall.
• The typical sites of involvement include the RV apex, inflow,
and outflow.
• This results in variable areas of fibrosis and scarring, causing
aneurysm formation or generalized dilatation and loss of
function. The RV wall may be thickened or thinned out
• There is variable involvement of the LV, and trabeculae at the
the apex and septum are hypertrophied

43. Gross specimen
Right side of the heart is
opened laterally to show
the normal atrial wall and
atrophic ventricular wall
and small papillary muscle

44. Gross Specimen
Right Ventricle has been opened from the
front and is illuminated from behind
showing very thin and translucent free wall.
Apical trabeculations and papillary muscle
are thin

45. The top left demonstrates an area of
fat in the right ventricle, with
fibrous tissue highlighted by the
Masson trichrome stain.
(top right)
the areas of involvement in the left
ventricle often show fat and more
fibrous tissue
bottom left). A higher magnification
demonstrates altered myocyte with
vacuoles, which are seen in all areas of
fibrofatty infiltration.
Inflammation with myocyte necrosis is
seen in over 25% of cases (bottom
right).

46. Endomyocardial Biopsy
• Endomyocardial biopsy is not routinely performed owing to
patchy distribution of the abnormalities, resulting in a poor
diagnostic yield.
• RV free wall biopsy carries a small risk of perforation.
• Histological demonstration of fibrofatty infiltration is not
pathognomonic of ARVC, as fatty infiltration may be a normal
finding in elderly persons.

47. Endomyocardial Biopsy
• Major criteria include residual myocytes < 60% by
morphometric analysis, with fibrous replacement of the RV
free wall myocardium in ≥1 sample, with or without fatty
replacement of tissue.
• Minor criteria include residual myocytes 60%-75% by
morphometric analysis, with fibrous replacement of the RV
free wall myocardium in ≥1 sample, with or without fatty
replacement of tissue.

48. Genetic Testing
• Family studies have suggested that ARVC is caused by genetic
alterations in desmosomal proteins, especially plakoglobin
and desmoplakin , mutation of desmosomes is seen in 40%-
50% cases.
• Genetic testing is indicated for symptomatic patients with
ARVC/ARVD and family members of a patient with a positive
mutation.
• At present, genetic testing is available for 7 types of
abnormalities (DSC2, DSG2, DSP, JUP, PKP2, RYR2, TMEM43).

49. UHL’S ANOMALY
• In 1952, Uhl described a case in which the wall of the right ventricle
was said to be paper thin and almost devoid of muscle fibers, an
appearance akin to ‘parchment heart’.
• In Uhl’s anomaly, with no fatty tissue interposed between layers of
myocardium.
• Uhl’s anomaly has been associated with other disorders like dysplasia
of the tricuspid valve, pulmonary atresia and persistent ductus
arteriosus
• Uhl’s malformation is usually diagnosed in neonatal or infant life
• The clinical presentation of Uhl’s anomaly includes cyanosis, dypnea
and right-sided failure and less commonly arrhythmias.

50. 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.

51. 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
BNP LEVEL NORMAL ELEVATED

52. Treatment And Management
• As the natural history of arrhythmogenic right ventricular
cardiomyopathy (ARVC) is poorly understood, it is difficult to
define a definite therapeutic algorithm.
• The treatment is essentially empirical and based on
presentation
Prevention of Sudden Cardiac Death
• Major Goal of treatment
• An implantable cardioverter-defibrillator (ICD) is
recommended for secondary prevention of SCD in patients
with sustained VT/VF and for primary prevention in high-risk
patients

53. Markers To Predict Sudden Cardiac Death
 Induction of ventricular tachycardia during electrophysiology testing
 Nonsustained ventricular tachycardia during noninvasive
evaluation/monitoring
 Male sex
 Early disease onset (< 5 years)
 Severe RV dilatation
 Extensive RV involvement
 LV involvement
 Prior cardiac arrest
 Unexplained syncope

54. Suppression of Symptomatic Cardiac
Arrhythmias
• Beta-blockers are generally considered the first line of drug
therapy.
• Sotalol is the most effective drug for inducible or
noninducible ventricular tachycardia.
• Amiodarone may not be useful because of side effects
associated with long-term use in young patients.
• Pharmacotherapy is also used as an adjunct to ICD in selected
patients with frequent life-threatening arrhythmias.

55. Radiofrequency Ablation
• Radiofrequency ablation has limited utility in treating
arrhythmogenic foci in ARVC owing to the patchy and
progressive nature of the disease.
• However, it has been used with some success in
limited cases as an alternative or adjunct to ICD to
reduce the burden of ventricular tachycardia

56. Lifestyle Modification
• In general, vigorous exercise should be avoided in
persons with ARVD, as it can trigger arrhythmias.
• Patients should be advised against participation
in competitive sports.
• It is also best to avoid cardiac stimulants such as
caffeine/pseudoephedrine.