+

Ambulatory: Case based study

LT. S.T. Anthony Kaviratne MD

28 January 2015

+Case presentation

19 year old female nonsmoker with no significant past medical

history presented today to discuss the sudden death of her sister.

The patient’s sister passes away suddenly at the age of 21.

Subsequent autopsy showed fatty infiltration of the right

ventricular wall consistent with ARVD.

The patient wish to discuss the implication of this diagnosis on

her and her family.

+ Arrhythmogenic right ventricular

cardiomyopathy/dysplasia

Identify what ARVD is in order to raise clinical suspicion

Basic of Pathology and natural clinical course

Be aware of diagnosis using 2010 revised task force criteria

Components of Treatment

Who to screen, screening interval and what tests consider

Objectives

+ Arrhythmogenic right ventricular

cardiomyopathy

What is it?

ARVC is a genetic form of cardiomyopathy that primarily affects the

right ventricle (RV)but can involve the LV with relative sparring of the

septum

ARVC is characterized macroscopically by fibrofatty replacement of

the right ventricle (RV) myocardium, which initially produces regional

wall motion abnormalities that later become global, producing RV

dilation

Culminates in life-threatening ventricular arrhythmias, prompting

sudden cardiac death (SCD) and/or biventricular heart failure

The prevalence in the general population is estimated to be 1:1000 to

1:2000

Male : Female = 1:3

+ARVD

Autosomal dominant encode desmosomal proteins

(plakoglobin, desmoplakin, plakophilin-2, desmoglein, and

desmocollin.

Autosomal recessive autosomal dominant disease and

plakoglobin and desmoplakin disease

Impaired desmosome function when subjected to

mechanical stress causes myocyte detachment and cell

death

Autosomal dominance most common with a variable

penetrance ranging from 20%-35%

Mutations render desmosomes inappropriately sensitive to mechanical stresses, resulting in myocyte death

Reprogrammed myocyte cell biology so that these cells adopt a fibrofatty lineage

Pathology

+ARVDNatural History

ARVC is a genetic form of cardiomyopathy that primarily affects

the right ventricle (RV)but can involve the LV

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

ARVD is an important cause of sudden cardiac death in young

adults, accounting for 11% of all cases and 22% of cases

among athletes.

The prognosis is worse in patients with LV involvement

Annual mortality rate of 2.3% (Fontain et al)

+ARVD

The diagnosis of ARVC should be considered in a variety of clinical

situations:

Patients who present with symptomatic or asymptomatic VT of LBBB configuration in

the absence of apparent heart disease

Patients with multiple QRS morphologies when VT is induced during electrophysiology

testing

Survivors of SCD, particularly SCD occurring during exercise

Presenting symptoms varies

syncope (26%-32%)

Palpitations (26%-67%)

sudden cardiac death (10%-26%)

Atypical chest pain (27%)

Dyspnea (11%)

heart failure - occurs in a minority, but is the predominant mode of death in those protected from SCD by an ICD

ARVC accounts for 20% of cases of sudden cardiac death (among young athletes dying suddenly, the prevalence is higher)

Clinical Presentation

+ARVDDiagnosis

Definite diagnosis of ARVC using the 2010 revised Task Force

criteria requires the presence of:

Two major criteria OR

One major and two minor criteria OR

Four minor criteria from different categories

Borderline diagnosis of ARVC using the 2010 revised Task

Force criteria requires the presence of:

One major and one minor criteria OR

Three minor criteria from different categories

Possible diagnosis of ARVC using the 2010 revised Task

Force criteria requires the presence of:

One major criteria OR

Two minor criteria from different categories

+ECHO FEATURES OF ARVC

Dilated RV

+ECHO FEATURES OF ARVCFocal RV apical aneurysm

+ECHO FEATURES OF ARVCExcessive trabeculations Hyperreactive

moderator

+Cardiac MRI in ARVC

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

(arrows)

+Cardiac MRI in ARVCFatty infiltration

Axial T1-weighted black

blood spin-echo

cardiovascular MRI

showing extensive

transmural fatty

replacement of the RV

myocardium (arrow)

+Cardiac MRI in ARVCLate GAD enhancement indicating focal fibrosis

Copyright © American Heart Association

Endomyocardial biopsy findings in a proband affected by a diffuse form of

ARVC/D. All 3 biopsy samples are from different regions of the RV free wall.

There is extensive fibrofatty tissue replacement with myocardial atrophy, which

is a major criterion (ie, residual myocytes <60% by morphometric analysis or

<50% if estimated).

Contributed by C. Basso, Padua, Italy.

+ARVDEKG features

The ECG shows a RBBB pattern. with an epsilon wave

(arrow) in leads V1–V3. Reproducible low-amplitude

signals between end of QRS complex to onset of the T

wave

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.

+ARVDTherapy

Activity restriction: No competitive sports

Conservative measure: Betablocker therapy

Antiarrhythmic agents:

Radiofrequency ablation,

ICD therapy

HF treatment

Surgical treatment

+Antiarrhythmic agents

Reduce the frequency and suppress inducibility of sustained and nonsustained ventricular arrhythmias

The effects are difficult to assess:

small series of patients.

limited time to follow-up.

006 ACC/AHA/ESC guidelines for the management of ventricular arrhythmias and sudden cardiac death suggested that sotalol or amiodarone

Wichter et al: sotalol was more effective than BBs or amiodarone both in inducible and noninducible VT.

It is not known whether sotalol is able to prevent SD, even in patients tested by programmed electrical stimulation.

+ARVC in ICD

Recommend ICD implantation for secondary prevention in all patients of ARVD/C with prior sustained VT or ventricular fibrillation

ICD implantation is reasonable for the prevention of SCD in patients with ARVD/C who have 1 or more risk factors for SCD

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/C associated with a high risk for SCD should be considered for ICD therapy

2008 Guidelines (No changes in 2012)

+Role Catheter ablation

Radiofrequency ablation 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 (CARTO) continue to evolve

+HF treatment

When the disease has progressed to RV or biventricular failure,

treatment consists of the current therapy for HF, including

diuretics, BBs, ACEIs and anticoagulants.

In case of intractable RV failure, cardiac transplantation may be

the only remaining alternative.

+Surgical treatment

More than 20 years ago, surgical treatment was

introduced, initially consisting of right ventriculotomy.

Total disconnection of the right free wall then was tried.

This approach was abandoned because of

The risk of developing RV failure,

The increased availability of cardiac transplantation,

The improvement in the technology of ICD.

Occasionally, disconnection surgery or RV

cardiomyoplasty is a useful therapeutic option

Transplant: When all else fails

+ARVD

All of their first-degree relatives of that person

need to be screened. Incomplete penetrance

noted

Screening interval of 2-5 year (most 2-3y)

Suggested screening tools

Standard 12 lead ECG

Signal averaged ECG with 40mHz filter

Holter monitor for 24 hours

Echocardiogram

Exercise stress test

Cardiac MRI

Identification of pathogenic mutations in

affected patients with cascade screening of

relatives

Screening of asymptomatic relatives

Time to Disease Progression Among 37 Subjects

With Complete Re-Evaluation

Anneline et al. JACC. 2014 Jul 22

+Diagnosis of Familial ARVC

In the context of proven ARVC/D in a first-degree relative, the diagnosis of familial ARVC/D is based on the documentation of one of the following in a family member:

T-wave inversion V1, V2, and V3 in individuals ≥ 14 years

Late potentials by signal-averaged ECG (SAECG).

Ventricular tachycardia of LBBB morphology on ECG, Holter, or during exercise testing or >200 PVCs in 24 hours

Either mild global dilatation or reduction in RV ejection fraction with normal LV or mild segmental dilatation of the RV or regional RV hypokinesis.

+

QUESTIONS?

+SUMMERY

Disorder of unknown course that is characterized pathologically by fibrofatty

replacement of the RV myocardium and electrical instability

High suspicion is needed when family member SCD, syncope, abnormal RV,

or EKG findings (epsilon wave, delayed potentials)

Diagnosis needs a combination imaging (echo and MRI), tissue biopsy, EKG

findings (repol and depol abnormalities), arrhythmia, or FH

Treatment includes antiarrhythmic therapy, HF therapy, early ICD.

Screen in stepwise fashion all fist degree relatives.

Don’t forget to restrict activity not only in proband but at risk family members

Role of genetic screening is helpful but incompletely understood