Arvd - dr prithvi puwar

ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA

(ARVD)

DR. Prithvi Puwar

DNB Cardio Vijaya hospital

Chennai

ARVD - GENETICS

“ARRYTHMOGENIC RIGHT VENTRICULAR CARD

IOMYOPATHY”

• Genetic form of cardiomyopathy

• Familial occurrence of 30% to 50%

• Genetic screening –

- early detection of healthy carriers - prognostic role in patients

• 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

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

ARVC – Natural History


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

History

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

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

ARVC – DIAGNOSIS


CARDIOMYOPATHY”

The Need To Change The 1994 Criteria


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

Framework of New Task Force Criteria 2010


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

Diagnostic Terminology


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

CATEGORY -I – “global or regional dysfunction and structural alteration”


CARDIOMYOPATHY”

Major Criteria Minor CriteriaEcho 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, dyskinesia, or aneurysm

Echocardiography in ARVC


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

major/minor criteria?

PLAX PSAXEcho Criteria

Focal RV apical aneurysm –Echo Major Criteria

ECHO FEATURES OF ARVC

Excessive trabeculations Hyperreactive moderator band

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

Cardiac MR in ARVC


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

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

Axial T1-weighted black

blood spin- cardiovascular MRI showing extensive

transmural fatty

replacement of the RV

myocardium

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

fibrosis

RV ANGIOGRAPHY

CATEGORY - II – “Tissue characterization of walls”


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

Endomyocardial biopsy - role in ARVD


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

CATEGORY - III – “Repolarization abnormalities”


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

Major / Minor Criteria ?

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.

CATEGORY -IV – “Depolarization and Conduction Abnormalities”


CARDIOMYOPATHY”

ECG Major Criteria Minor Criteria

NEW TFCEpsilon 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

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)

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

CATEGORY - V – “Arrhythmias”


CARDIOMYOPATHY”

ECG/Holter/Exercise Major Criteria Minor Criteria

NEW TFCNonsustained 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)

AXIS? MAJOR/MINOR CRITERIA??

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.

CATEGORY -VI – Family history


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

Diagnosis of Familial ARVD


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.

Uhl’s Anomaly VS ARVD/CThe 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.

ARVD/C VS RVOT-VTRVOT VT ARVD/C

AGE OF ONSET 3RD TO 4TH DECADE 3RD TO 4TH DECADESEX FEMALES PREDOM MALES PREDOMFAMILY HISTORY ----- +++SCD ------- +++12 LEAD ECG NORMAL T WAVE

ABNORMALITIES , EPSILON WAVES

SAECG NORMAL LATE POTENTIALSECHO 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

MANAGEMENT


CARDIOMYOPATHY”

There are five therapeutic options in patients with ARVD/C:

• ICD therapy

• Antiarrhythmic agents,

• Radiofrequency ablation,

• HF treatment,

• Surgical treatment / cardiac transplantation

Recommendations for ICD in ARVD


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

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

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

Subgroups

Risk markers

Recommend-

ationsFollow-

upICD

indication

Definite ARVD

High risk

Aborted SCDSustained VTUnexplained

syncope

Reduce physical exercise

Avoid competitive

sportβ-blockers

Annually :ECG,

ECHO vs CMR

HolterExercise 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

ARVDSAME SAME Not

recommended

Asymptomatic

mutation carriers

Asymptomatic mutation-carrying

relatives of ARVD

Reduce physical exercise

Avoid competitive

sport

SAME Not recommended

ROLE OF CATHETER ABLATION


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

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-endocardial approach

[Combined endocardial and epicardial catheter ablation in arvc. Brugada J.; Circulation: Arrhythmia and EP. 2012;5:111-121]

ARVD - CONCLUSIONS


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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Arvd - dr prithvi puwar

Healthcare

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