Arrhythmogenic Right Ventricular Cardiomyopathy. Europace June 28,2011
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1 Arrhythmogenic Right Ventricular Cardiomyopathy Europace June 28,2011
2 Right Ventricular Cardiomyopathy Classical ARVC is defined as a cardiac disease mainly involving the right ventricle, characterized by variable replacement of myocardium with fibrous and fatty tissue, and associated with ventricular arrhythmias and a risk of sudden cardiac death.
3 Clinical Presentation in 108 Probands With Newly Diagnosed ARVC. (NIH) Palpitations 56% Sustained Clinical VT 35% Syncope 21%
4 Diagnosis of ARVC 1994 Task Force Criteria There is no gold standard Diagnosis is based on multiple criteria Electrical abnormalities ECG, SAECG, VT morphology RV structural and functional abnormalities RV function, segmental wall motion Family history McKenna WJ et al. Br. Heart J. 1994; 71;215
5 The problem The diagnosis of ARVC is a clinical challenge, especially in the early stages of disease Differentiation from other disease entities can be difficult (e.g., RVOT tachycardia)
6
7 RG
8 Incidence of T wave inversion beyond V1 and V2 In ages <4% in women <1% in men Marcus F Am J Card 2005:95:1070
9 T wave inversion in V1-V3 ARVC 35/94 37% RVOT 5/121 4% Sensitivity = 37%; specificity = 96% for diagnosis of ARVC using these criteria Morin D.P. et al. Am. J Cardiol. 2010;105:
10
11 T wave inversion 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% N = 68 N = 68 V 3 N = 32; 59% N = 32; V 4 59% N = 27 N = 30; 12% N = 27 N = 30; 12% ARVC/D Normals ARVC/D + RBBB Normals + RBBB Jain R, et al. Circulation 2009;120;
12 Prolonged RV Endocardial Activation Duration (EAD) in ARVC (Surface QRS Duration) 14 Patients with ARVC 11 Patients with Idiopathic V.T. from RVOT Surface QRS Durations were similar Harikrishna T, et al., Heart Rhythm, 2009; 6:
13 RV Endocardial Activation Duration (EAD) Measured by 3-D Electroanatomic Mapping (earliest onset to latest RV activation) Idiopathic V.T. ARVC 50.8 ± 7msec 83.9 ± 10 msec P= <0.001 All RVOT had EAD 65 msec Harikrishna T, et al., Heart Rhythm, 2009; 6:
14 MP Age 59 Recurrent VT RV markedly enlarged with tricuspid regurgitation
15 MP 12 LEAD
16 MP V1 V3
17
18 RG 24 year old man Palpitations since age 23 Rapid heart beat 1/2 hour Several hours of nausea and vomiting Cardiac arrest resuscitated VT after jogging 5-6 miles age 32
19 RG VT
20 Patients with ARVC as well as those with RVOT tachycardia the PVCs typically have a left bundle branch block morphology If the PVCs have a inferior QRS axis (+in 2,3, and AVF) and are negative in AVL: They originate from the RVOT If the left bundle branch block PVCs have a superior QRS axis (- in 2,3 and AVF ) and are positive in AVL: They do not originate from the RVOT
21 ECG continued PVC axis originating from the right ventricular outflow tract may be common to RVOT and ARVC: -AVL + I or + III + AVF + II
22 ECG continued PVCs of LBBB superior axis originating from the right ventricular apex: - AVF - III - II + AVL + I or
23
24 LM
25 TASK FORCE CRITERIA REQUIRED REVISION ECG CRITERIA NEEDED UPDATING RIGHT VENTRICULAR IMAGING STUDIES REQUIRED QUANTIFICATION INCLUDE CRITERIA FOR LV AND BIVENTRICULAR DISEASE INCLUDE GENETIC ABNORMALITIES DIAGNOSIS OF ARVC REQUIRES ASSESSMENT OF ALL TASK FORCE CRITERIA.
26 Conference to Modify Task Force Criteria May 12 14, 2007 Denver, Colorado Dr. Frank Marcus and Dr. William McKenna, Cochairmen Cristina Basso Guy Fontaine Michael H Picard Barbara Bauce Kathleen Gear Jeffrey Saffitz David A Bluemke Richard Hauer Danita Sanborn Hugh Calkins Cindy James Jonathan Steinberg Domenico Corrado Katsuya Kajimoto Gaetano Thiene Moniek Cox Frank Marcus Jeffrey A Towbin James Daubert William McKenna Thomas Wichter Sergio Dubner Scott McNitt Wojciech Zareba
27 Methods to Modify Task Force Criteria Data from 108 Probands from ARVC registry was compared with that from large number of normals. Sensitivity and Specificity for each test was then determined
28 Publications New Task Force Criteria Circulation 2010; 121; European Heart Journal 2010; 31;
29 New Task Force Criteria Original (1994) Revised (2010) T V2 and V3(>age 12) (Minor) (Major) Epsilon Waves (Major) (Major) >1000 PVCs /24 hrs. (Minor) (Minor) >500 PVCs/24 hrs. Late Potentials SAECG (Minor) (Minor) Need only 1 of 3 Criteria (duration of filtered QRS; or amplitude or duration of terminal 40 msec. Ventricular Tachycardia (Minor) (Major) if QRS axis is LBBB if QRS is LBBB and inferior and superior
30 ARVD.org
31 Arrhythmogenic Right Ventricular Cardiomyopathy 2010 Task Force Criteria Calculator Developed By Vuk Vuksanovic And Andrew Krahn based on: Marcus et al, Circulation ;121(13): STEP 1 Click on the button below to input relevant source data from the tests (ECG, echocardiogram, MRI, etc.). A data entry screen will appear for you to complete once done, press "auto score TFC". STEP 2 Fill out the checklist directly. Once you are satisfied the checklist has been correctly filled in, press "calculate summary" for the final calculation of major and minor criteria.
32 patient unspecified ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 2010 TASK FORCE CRITERIA CALCULATOR DEVELOPED BY VUK VUKSANOVIC AND ANDREW KRAHN based on: Marcus et al, Circulation Apr 6;121(13): patient name MAJOR CRITERIA: 2 MINOR CRITERIA: 0 definite diagnosis of ARVC I. Global or regional dysfunction and structural alterations MAJOR By 2D echo: Regional RV akinesia, dyskinesia, or aneurysm ++ PLAX RVOT 32 mm (corrected for body size [PLAX/BSA] 19 mm/m²) II. Tissue characterization of wall MAJOR 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 on endomyocardial biopsy
33 Validation of Task Force Criteria 103 probands or family members, all with desmosomal mutations 102 age/gender matched healthy relatives, none gene positive Original and revised criteria were evaluated, including family history/genetics Sensitivity increased from 92 to 99% (p = 0.016) Specificity unchanged Protonotarios N. et al Eur Ht J. 2011;32;
34 Classification after core lab analysis of 108 probands by original (1994) criteria and modified task force criteria, not including genetic results Original 1994 Criteria Modified 2010 Criteria 73 Affected (23)* 87 Affected (27) 28 borderline (9) 10 Borderline (3) 7 Unaffected (1) 11 Unaffected (3) Affected = 2 major or 1 major +2 minor or 4 minor criteria from different groups Borderline = 1 major + 1minor, or 3 minor criteria from different groups. Suspected = 1 major or 2 minor from different groups *(Number of gene positive probands)
35 What s New for Treatment of ARVC Epicardial Ablation for Treatment of V.T. in ARVC Four patients with ARVC and Rapid V.T. had open chest endocardial and epicardial mapping using multiple electrode arrays from epicardium (sock) and endocardial balloon. In every V.T., the earliest activation point was located on the epicardial surface Doig JC, et al., (ABS) Pace, 1996; 19:590
36 Successful Ablation of V.T. by Epicardial Mapping and Ablation After Failure of Endocardial Ablation 1) Bazan V, et al., Heart Rhythm, 2006; 3:1132 2) Reddy V, et al., (ABS) Heart Rhythm, 2007; 4:S329 3) Isaba MM, et al., (ABS) Heart Rhythm, 2007; 4:S331 4) Pokushalov E, et al., Heart Rhythm, 2010; 7:1406 5) Sacher F, et al., J Am. Coll. Cardiol, 2010; 55:2366 6) Grimard C, et al., J Cardiovasc Electrophysiol, 2010; 21:56
37
38
39 50 Year Old Man Syncope During Bicycle Ride Injured Shoulder And Hip
40 ECG T wave inverted in V1 - V5 PVC s LBBB, superior QRS axis SAECG Markedly positive all 3 criteria ARVD suspected MRI performed at a University Hospital
41
42 MRI Interpretation Normal RV anatomy and function Slight hypokinesis at apex; normal variant No fatty infiltration
43 Based on MRI results the physician had a lower index of suspicion for ARVC/D Beta blockers suggested refused Resumed long bicycling trips
44 2 years later he died while on long bicycling trip Autopsy: RV wall diffusely replaced fibrofatty tissue Subepicardial fat in lateral and posterior walls of LV
45
46 Organization of Family Screening Charron P et al. European Heart Journal 2010; 31:
47 Clinical family screening indicated in first-degree relatives of a patient with ARVC (situation in which genetic results are not available within the family) b only ECG and echocardiography Charron P et al. European Heart Journal 2010; 31:
48 Organization of Family Screening Charron P et al. European Heart Journal 2010; 31:
49 Clinical family screening indicated in first-degree relatives of a patient with ARVC (situation in which genetic results are not available within the family) b only ECG and echocardiography Charron P et al. European Heart Journal 2010; 31:
50 The genetic defect is due to altered proteins that provide mechanical coupling between myocardial cells and bind the myocardial cells to each other These include plakoglobin,plakophilin-2, desmoplakin, desmoglein, and desmocollin. A disease of the desmosomes Defective glue
51 There are seven pathogenic desmosomal abnormalities reported in patients with ARVC/D. The most common is plakophilin-2 30% of probands have these genetic abnormalities.
52 Genetics of ARVC/D Complex 1. Variable Penetrance 2. May have more than one genetic abnormality in same or related genes 3. Genotype phenotype relation still undetermined
53 father mother 73 years 70 years Plakophilin 2 brother 39 years Plakophilin 2 40 years Plakophilin 2 Desmoplakin kin
54
55
56 Implications of Misdiagnosis of ARVC/D Improper Therapy Economically costly Psychologically damaging Genetic implications
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