Transcript
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
“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
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
“ARRYTHMOGENIC RIGHT VENTRICULAR
CARDIOMYOPATHY”
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
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
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
CATEGORY -I – “global or regional dysfunction and structural alteration”
“ARRYTHMOGENIC RIGHT VENTRICULAR
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
“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
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
“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
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”
“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
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
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
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”
“ARRYTHMOGENIC RIGHT VENTRICULAR
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”
“ARRYTHMOGENIC RIGHT VENTRICULAR
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
“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
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.
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
“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
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
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
“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
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
“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”
THANK YOU
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