FANS ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) Investigation Protocol
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1 Clinical Features FANS ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) Investigation Protocol History: Progressive disease, characterised by the following clinical stages: o Early concealed phase (asymptomatic, risk of sudden cardiac death) o Electrical phase (arrhythmias, structurally normal heart) o Structural phase (abnormal ventricular morphology) Symptoms develop usually in 2 nd to 4 th decade of life Symptoms are usually due to ventricular arrhythmias and include palpitations, lightheadedness, syncope and sudden cardiac death. Advanced disease may present as heart failure (right, left or biventricular). Competitive sport is associated with earlier ARVC presentation and an increased risk of fatal arrhythmias. Left ventricular involvement was thought to develop at a late stage of disease, but with cardiac MRI and genetic testing this is now recognized to occur early in some patients (particularly those with desmoplakin mutations). Diagnosis: There is no single gold standard investigation for ARVC. Diagnosis is made according to the 2010 International Task Force criteria (1) using histological, genetic, ECG, Holter and imaging parameters to classify into the following categories: definite diagnosis, borderline diagnosis and possible diagnosis (see Diagnostic tool, Appendix 1) Investigations: 12 lead ECG Signal averaged ECG (SAECG) Ambulatory Holter monitoring Exercise tolerance test Echocardiography Cardiac MRI ECG characteristics: Most ECG abnormalities have low specificity for ARVC and many patients /mutation carriers may have a normal ECGs in the early disease phase. Progressive ECG changes are common and indicate progression of the disease, abnormalities include: Epsilon wave (most specific finding, but only seen in 8-30% of patients with advanced disease) (see arrow) T wave inversions in V1-3 (85% of patients) Prolonged S-wave upstroke of 55ms in V1-3 (95% of patients) Localised QRS widening of 110ms in V1-3 Paroxysmal episodes of ventricular tachycardia with a LBBB morphology
2 Arrhythmia: Ventricular ectopicc beats or sustained ventricular tachycardia (with LBBB morphology) precipitated by exercise. Genetics: Inheritance is commonly autosomal dominant. In most cases, ARVC is associated with mutations in genes encoding desmosomal proteins. Counselling and consent is mandatory before testing noting the complexities that arise if a variant of unknown significance (VUS) is found. All patients should be discussed with colleagues in Clinical Genetics, within an MDT meeting if possible, prior to testing. Risk Stratification The prognosis for patients with ARVC depends largely on the severity of arrhythmias and ventricular dysfunction. Prior cardiac arrest due to ventricular fibrillation and sustained ventricular tachycardia are the most important predictors of SCD [2, 3]. References: 1. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. Eur Heart J 2010;31: Corrado D et al, Arrhythmogenic Right Ventricular Cardiomyopathy. N Engl J Med 2017;376: ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, European Heart Journal (2015) 36, S.A. Jaoude, J.F. Leclercq, P. CoumelProgressive ECG changes in arrhythmogenic right ventricular disease: Evidence for an evolving disease Eur Heart J, 17 (1996), pp Moniek G.P.J. Cox, Jasper J. van der Smagt, et al.new ECG Criteria in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Circulation: Arrhythmia and Electrophysiology. 2009;2: , 6. Nasir K, Bomma C, Tandri H, et al. Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to ARVC February 2018 For review February 2021
3 disease severity: a need to broaden diagnostic criteria. Circulation. 2004;110: ,
4 Appendix 1 PATIENT NAME: CHI: Patient Results 1. Global and / or regional dysfunction and structural alterations (seen on imaging). 2-D echo: Regional right ventricular akinesia, dyskinesia or aneurysm plus one of the following: PLAX RVOT 19 mm/m 2 PSAX RVOT 21mm/m 2 Fractional area change (FAC) 33% Regional right ventricular akinesia or dyskinesia plus one of the following: PLAX RVOT 16 19mm/m 2 PSAX RVOT mm/m 2 FAC > 33% 40% MRI: Regional right ventricular akinesia, dyskinesia or dyssynchronous right ventricular contraction plus one of the following: RVEDV / BSA 110ml/m 2 (male) RVEDV / BSA 100ml/m 2 (female) RVEF 40% Wall motion abnormality as above plus one of the following: RVEDV / BSA ml/m 2 (male) RVEDV / BSA ml/m 2 (female) RVEF > 40% 45% RV angiogram: Regional right ventricular akinesia or dyskinesia.
5 2. Tissue characterisation of wall (seen at histology). Residual myocytes < 60% by morphometric analysis (or < 50% if estimated) with fibrous replacement of the right ventricular free wall in at least one 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 right ventricular free wall in at least one sample, with or without fatty replacement of tissue. 3. Depolarisation/Cond uction abnormalities (seen on ECG) Epsilon wave in V 1-3. Late potentials by signal averaged ECG in at least 1 of 3 parameters in the absence of a QRS duration of 110msec on standard ECG: Filtered QRS duration 114ms Duration of terminal QRS<40µV 38ms RMS voltage of terminal 40msec 20µV Terminal activation duration of QRS 55ms in V 1-3 in the absence of complete RBBB 4. Repolarisation abnormalities (seen on ECG). Inverted T waves in V 1-3 or beyond, in individuals > 14 years of age in the absence of complete right bundle branch block (RBBB). Inverted T waves in V 1-2 in individuals > 14 years of age in the absence of complete RBBB, or in V 4, V 5 or V 6. Inverted T waves in leads V 1-4 in individuals > 14 years of age in the presence of complete RBBB. 5. Arrhythmias (seen on ECG). Non-sustained or sustained ventricular tachycardia of left bundle branch morphology with superior axis (negative or indeterminate QRS in II, III, avf and positive in avl). Non-sustained or sustained ventricular tachycardia of RVOT configuration, left bundle branch block morphology with inferior axis (positive QRS in II, III, avf and negative in avl) or of unknown axis. Greater than 500 ventricular extrasystoles over twenty four hours on Holter monitoring.
6 6. Family history (from oral history or genetic screening). Arrhythmogenic right ventricular cardiomyopathy (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 categorised as associated with ARVC in the patient under evaluation. ARVC confirmed pathologically or by current Task Force criteria in a second degree, or more distant, relative. History of ARVC in a first degree relative in whom it is not possible or practical to determine whether current Task Force criteria are met. Premature sudden death (< 35 years of age) due to suspected ARVC in a first degree relative. Diagnostic terminology for proposed modified criteria: Definite ARVC: two major OR one major and two minor OR four minor criteria from different diagnostic categories. Borderline ARVC: one major and one minor OR three minor criteria from different diagnostic categories. Possible ARVC: one major OR two minor criteria from different categories.
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