Arrythmogenic rv dysplasia (ARVD)

Intended for Echocardiographers /cardiac Technology students

1. Arrythmogenic RV Dysplasia DR.Sruthi Meenaxshi

2. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC) is an inherited cardiomyopathy characterized by structural and functional abnormalities in the right ventricle (RV) resulting in ventricular arrhythmias.  [1]  It is an important cause of  sudden cardiac Death(SCD ) in young adults, accounting for 11% of all cases and 22% of cases among athletes

3. Autosomal dominant genetic disorder of myocardium in which there is fatty infiltration of the right ventricular free wall, predisposing to paroxysmal ventricular arrhythmias, sudden cardiac death, and biventricular failure

4. Second most common cause of sudden cardiac death in young people (after HOCM), accounting for   up to 10% of sudden cardiac deaths in patients < 65 yrs of age Prevalence ~ 1 in 5000 Diagnosis is difficult and relies on a combination of clinical, electrocardiographic and radiological features ARVD was first described in 1977 and was included in the World Health Organization (WHO) classification of cardiomyopathies in 1996.  [4]  Since then, there have been significant advances in the understanding of its etiopathogenesis , diagnosis, and management.  [

5. The structural abnormalities in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC) result from the fatty infiltration and fibrosis of the RV myocardium. This leads to progressive RV dilatation and dysfunction. The left ventricle (LV) is less commonly involved, and the septum is relatively spared.  [6 ]   However, in a cohort of 200 probands , Sen- Chowdhry et al found that LV involvement may even precede the onset of significant RV dysfunction.  [7]  The prognosis is worse in patients with LV involvement.  [8] The mechanisms for myocardial loss include the following: Apoptosis (programmed cell death) Inflammation, enhanced fibrosis, and loss of function Fatty replacement of myocardium

6. Etiology Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC) is an inherited disorder, as it is already present in the fetus . Familial cases account for 30%-90% of cases.  [9]  In other cases, it may result from an acquired etiology such as viral infection myocarditis or unidentified inheritance. It is also likely that patients with a genetic predisposition are more likely to develop myocarditis. The disease manifests more frequently in active individuals, when mechanical sheer stress can cause cell membrane damage, inflammation, and fibrosis in genetically predisposed RV.

7. Genetics ARVD is considered a genetic disorder, as most cases are familial, and there is geographical clustering. The most common pattern of inheritance is autosomal dominance, with a variable penetrance ranging from 20%-35% of family members.  [10, 11]   People living in the Veneto region of Italy have a higher penetrance. The autosomal-recessive (Naxos disease) pattern of inheritance is localized to the Greek island of Naxos and is associated with palmoplantar keratosis and wooly hair. The genetic mutation occurs on chromosome 17q21, and penetrance is almost 100%.  [12, 13] Genetic abnormalities in ARVD are located on chromosomes 1, 2, 3, 6, 7, 10, 12, and 14. There is no single unique genetic abnormality, posing a challenge in evaluation of patients and families with suspected ARVD.

8. The responsible genes include plakoglobin ( JUP ), desmoplakin ( DSP ), plakophilin-2 ( PKP2 ), desmoglein-2 ( DSG2 ), desmocollin-2 ( DSC2 ), and others.  [14, 15, 16]    In some cases, mutation in the  SCN5A  gene may cause dysfunction in the cardiac voltage-gated sodium channel (Na v 1.5), resulting in cardiomyopathy.  [17] The Heart Rhythm Society and the European Heart Rhythm Association published a consensus statement on genetic testing for cardiomyopathies

9. Genetic abnormalities in ARVD are located on chromosomes 1, 2, 3, 6, 7, 10, 12, and 14. There is no single unique genetic abnormality, posing a challenge in evaluation of patients and families with suspected ARVD. The responsible genes include plakoglobin ( JUP ), desmoplakin ( DSP ), plakophilin-2 ( PKP2 ), desmoglein-2 ( DSG2 ), desmocollin-2 ( DSC2 ), and others.  [14, 15, 16]    In some cases, mutation in the  SCN5A  gene may cause dysfunction in the cardiac voltage-gated sodium channel (Na v 1.5), resulting in cardiomyopathy.  [17] The Heart Rhythm Society and the European Heart Rhythm Association published a consensus statement on genetic testing for cardiomyopathies

10. Clinical Presentation Common symptoms reported in different series  [21, 26]  include the following: Palpitation (27%-67%) Syncope (26%-32%) Sudden cardiac death (10%-26%) Atypical chest pain (27%) Dyspnea (11%)

11. Palpitation is the most frequent symptom and is caused by ventricular arrhythmias. Depending on the disease severity, ventricular ectopics may be isolated or may result in nonsustained /sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. Progressive RV dysfunction results in dyspnea and leg swelling . In more severe cases with left ventricular involvement, patients may present with biventricular congestive heart failure that may mimic dilated cardiomyopathy . Supraventricular arrhythmias, including atrial flutter and fibrillation, may be seen in about 25% of cases.  [27]

12. Exercise can induce ventricular arrhythmias and sudden cardiac death. ARVD accounts for 22% of sudden cardiac death cases among young athletes in northern Italy.  [2, 28]  In the United States, in a series of 286 cases of sudden cardiac death in athletes, hypertrophic cardiomyopathy was the most common cause, and ARVD was reported in only 4% cases. Extracardiac manifestations include palmoplantar keratosis and curly hair seen in individuals with autosomal-recessive inheritance.

13. T wave inversion in right precordial leads V1-3, in absence of RBBB (85% of patients) Epislon wave (most specific finding, seen in 50% of patients) Localised QRS widening in V1-3 (> 110ms) Prolonged S wave upstroke of 55ms in V1-3 Ventricular ectopy of LBBB morphology, with frequent PVCs > 1000 per 24 hours Paroxysmal episodes of ventricular tachycardia (VT) with LBBB morphology (RVOT tachycardia)

14. Echo Echocardiography serves as a screening tool to evaluate patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC).  [39, 40] RV dilatation and wall motion abnormalities constitute diagnostic criteria for ARVC . The abnormalities of the RV posterior wall underneath the tricuspid valve are most common . RV outflow dilatation was seen with increasing frequency upon progression of disease severity.  [41]    Left ventricular (LV) involvement was seen in 16% of cases in this series. The RV morphologic abnormalities include trabecular derangement (most common), hyperreflective moderator band, and sacculations seen in the probands , but not in controls.  

15. Revised task force criteria using two-dimensional echocardiography are discussed below. Major criteria are defined as regional RV akinesia or dyskinesia or aneurysm and one of the following (end-diastole): Parasternal long-axis view (PLAX) right ventricular outflow tract (RVOT) = 32 mm (= 19 mm/m 2  body surface area [BSA] corrected) Parasternal short-axis view (PSAX) RVOT >36 mm (= 21 mm/m 2  BSA corrected) Fractional area change = 33% Minor criteria are defined as regional RV akinesia or dyskinesia and one of the following: PLAX RVOT =29 to < 32 mm (= 16 to < 19 mm/m 2  BSA corrected) PSAX RVOT =32 to < 36 mm (= 18 to < 21 mm/m 2  BSA corrected) Fractional area change >33 to = 40%

16. Epislon wave

17. Prolonged S wave upstroke in V2 with QRS widening

18. Baseline ECG of a patient with  Arrhythmogenic Right Ventricular Dysplasia (ARVD) , demonstrating: T-wave inversion in precordial and inferior leads, without RBBB pattern Epsilon wave in V1 Localised widening of QRS in V1-2

19. ARVC