1.ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Dr. Imran Ahmed DM. (Cardiology)

2. SPOT THE DIAGNOSIS ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ARVC NAXOS DISEASE 3. ARVC - GENETICS ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Genetic form of cardiomyopathy Dominant mutations - desmoplakin - cardiac ryanodine receptor - plakophilin 2 (PKP2) younger age / malignant arrhythmias - transforming growth factor-3 - desmoglein - 2 - desmocollin 2 - TMEM43 (most recent non desmosomal) Recessive mutations - junctional plakoglobin (JUP) Naxos/Carvajal Syndrome Familial occurrence of 30% to 50% Genetic screening - early detection of healthy carriers - prognostic role in patients 4. ARVC Genetic 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 5. 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 6. ARVC Clinical Presentation ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Presenting symptoms varied - syncope - palpitations - sudden cardiac death - 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) 7. ARVC DIAGNOSIS ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 8. The Need To Change The 1994 Criteria ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 1994 criteria were highly specific, but lacked sensitivity for early and familial disease (clinical experience dominated by symptomatic index cases & SCD victims) 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 - cardiovascular magnetic resonance with late enhancement - electroanatomic voltage mapping Recognition that LV involvement may occur early 9. Framework of New Task Force Criteria ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY The approach of classifying structural, histological, ECG, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained 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 10. Diagnostic Terminology for Revised Criteria 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 11. CATEGORY I global or regional dysfunction and structural alteration ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Major Criteria Minor Criteria Echo 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) Fractional area change 33% PLAX RVOT 29 to 1000 per 24 hr) 34. AXIS? MAJOR/MINOR CRITERIA?? 12 lead ECG from a 25 y.o. man recorded during VT with a LBBB morphology and a slight-to-moderate right axis, typically originating from the RVOT. INFERIOR AXISMINOR CRITERIA 35. LBBB-VT LEFT AXIS MAJOR CRITERIA 36. Exercise and ventricular arrhythmias ARVD/C usually is characterized by the 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/C show ventricular arrhythmias: monomorphic LBBB pattern in 96% The occurrence of arrhythmic cardiac arrest due to ARVD/C is significantly increased in athletes. Particularly in certain regions in Italy, ARVD/C has been shown to be the most frequent disease (22%) leading to exercise-induced cardiac death in athletes. Diagnosis of ARVD/C is considered incompatible with competitive sports and/or moderate-to-high intensity level recreational activities. 37. CATEGORY VI Family history ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Major Criteria Minor Criteria NEW TFC ARVC confirmed in a first- degree relative who meets current task force criteria 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 (