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  Introduction

Arrhythmogenicright ventricular cardiomyopathy/dysplasia (ARVC/ARVD) is a rare familial cardiomyopathy characterized by progressive fibrofatty replacement of myocardium mainly involving right ventricle, rarely involving left ventricle. Clinically, it presents with life-threatening malignant ventricular arrhythmias arising from RV apex, which may lead to sudden death, most often in young people and athletes. ARVC/ARVD is difficult to diagnose.A previous Task Forcecriteriawas highly specific but lacked sensitivity for early & familial disease.The present Task Force criteria 2010,incorporated imaging modalities like MRI, thus improving sensitivity & specificity for early diagnosis of ARVD. The therapeutic options at present are focused on the prevention of life-threatening cardiac arrhythmia, by using antiarrhythmic drugs, catheter ablation, and/or an implantable cardioverter defibrillator (ICD). A rare case of ARVD in young patient who presented with sudden onset of loss of consciousness with documented RV apical VT on ECG is discussed here. The diagnosis was made on the basis of history, electrocardiography,2D echocardiography [1, 2], and cardiac MRI [3, 4].

Case report

A 38-year-old male, farmer from Nalgonda district, Telangana, came to hospitalwith history of recurrent episodes of syncope preceded by palpitations and chest discomfort since one year. There was no family history of heart disease or sudden death.ECG revealed Broad QRS complex,tachycardia with superior axis (Figure 1)which was DC verted to sinus rhythm at a local hospital in Nalgonda. However, no specific etiology of this patient's arrhythmia was identified. At the time of admissionatKIMS hospital,Secunderabad, patient had episodes of chest discomfort and light headedness.ECG showed an incomplete RBBB with T waves inverted in V1- V5 & II, III, aVF& epsilon waves in V1 & V2 (Figures 2,3,4). CK MB was normal & troponin-T was mildly elevated (? secondary to DC Shock). Chest X ray revealed mild cardiomegaly (Figure 5).2D echocardiogram done at KIMS Hospital showed normally functioning left ventricle, dilated RVOT & RVcavity with good RVsystolic function&mild tricuspid regurgitation(Figure 6). Patient was suspected to be a case of ARVD, based on abnormal ECG & 2D Echo (Dilated RV) & RV apical VT.

Figure 1:ECG during episode of syncope: LBBB morphology VT with superior axis.

Figure 2:ECG- Post DC version showing nonspecific T wave changes.

Figure 3: Line diagram showing epsilon wave in anterior, inferior precordial leads and epsilon wave,lead V1.

Figure 4:Enlarged image of the patients ECG showing epsilon wave in lead V1.

Figure 5:Chest radiograph showing mild cardiomegaly.

Figure 6:2D echo a 4chamber view showingdilated RV.

With the above history & investigations, cardiac MRI was done which showed Dilated, akinetic right ventricle with thinning of right ventricular wall & fatty infiltration of right ventricular free wall (Figures 7,8,9,10). Provisional diagnosis of arrhythmogenic RV dysplasia was made and was discharged on oral drug therapy (Beta blockers/Cardarone). He was advised to have ICD implantation for secondary prevention of ventricular dysrhythmia.

Figure 7:MRI 4 chamber showing dilated RV.

Figure 8: MRI suggestive of RV scarring.

Figure 9: MRI 2 chamber showing dilated RVOT.

Figure 10: MRI showing T1 hyperintensity of RV free wall.

Discussion

Arrhythmogenicright ventricular cardiomyopathy (also called arrhythmogenic RV dysplasia [ARVD]) is a heterogeneous inherited disease that results in fibrofatty infiltration of the right ventriclepredominantly, although the disease can also affect the left ventricle (typically the posterior portion) [5].This fatty and fibrous tissue replacement of myocardium initially affects epicardium and then endocardium. This loss of muscle results in thinning and focal dilation of RV free wall and leads to systolic dysfunction. The IVS(Interventricular septum) is generally spared involving RV free wall. Endomyocardial biopsy generally obtained from IVS may be non-diagnostic. The predominant site of RV involvement is often the “triangle of dysplasia”, an area involving the RV outflow tract, an area below the tricuspid valve, and the RV apex; this is the most common area of RV thinning, and aneurysm formation[6].

ARVD is a common cause of sudden death in young adult. It can affect any age group but the typical patient is a male patient in the third decade of life [7].ARVD is characterized by progressive structural abnormalities of RV, associated with arrhythmia.

ARVD can exist in sporadic and familial forms (30-50% of cases). The inheritance of ARVD is primarily by autosomal dominant mode with variable expression and penetrance [8].However, an autosomal recessive pattern has been reported in Naxos disease and in Carvajal syndrome [9, 10].Mutations in genes that encode various proteins of the desmosome (plakoglobin, desmoplakin, plakophilin, desmoglein, and desmocollin) have been found to cause the disease but are present in only approximately 50% of patients [11-13].Ten genes for ARVD have been identified on chromosomes 1, 2, 3, 6, 10, 14 and 17. Major candidate genes identified are involved in encoding for desmoplakin (ARVD8) and plakoglobin (Naxos disease), a protein for cell to cell adhesion and ryanodine receptor, RYR2 (ARVD2), involved in ion channels [7, 10, 14, 15]. Desmosomaldysfunction should be considered as final pathway of ARVD pathogenesis[16].

Clinical presentation of ARVD varies from asymptomatic to Palpitations, syncope, arrhythmias, sudden cardiac death&heart failure. Typically the ventricular tachycardia in ARVD has LBBB morphology and superior QRS axis, indicating origin of arrhythmia from Right ventricle and Inflow tract.RVOT Ventricular tachycardia also presents with LBBB morphologybut it is benign & has inferior axis or normal axis. ARVD forms about 3-4% of SCD in athletes. Heart failure is mainly right heart failure, although occasionally biventricular failure can occur due to concomitant left ventricular involvement.

ECG abnormalities in ARVD, usually show regular NSR with QRS duration >110msec in V1 and T inversion in right precordial leads beyond V1, (in absence of RBBB). RV late potentials,in the form of epsilon waves in V1–V3. ‘T’ waveinversion beyond V1, is normal in children up to 12years and is present in 1-3% healthy population of age group 19–45 years and 87% patients with ARVD. Epsilon waves are seen onlyin 33% ofpatients [17].

Mechanism of VT in ARVD is twofold, with enhanced automaticity early in natural history of disease and scarmediated reentry in established disease,with recurrent sustained VT.The VT of enhanced automaticity is rapid, self-terminating, occurs at the beginning of exercise and beta blockade is highly effective. The VT that occurs due to reentry is often recurrent and sustained VT and needs more aggressive therapy like catheter ablation, in addition to antiarrhythmic drug therapy.

Provocative isoproterenol infusion – High dose of 45mcg/min x 3minutes – resulting in polymorphic PVC’s/NSVT, is highly reliable for ARVD with sensitivity of 91.4% and specificity of 88.7%, early in the course of disease where it can be mistaken for RVOT tachycardia[18].

Diagnosis

Diagnosis of ARVD is based upon the presence of two or more abnormalities of RV structural, electrical abnormality (depolarisation and repolarization abnormality of RV, typical ventricular arrhythmias of RV inflow),tissue characteristics of RV free wall and family history.

A limitation of the previous Task Force criteria1994,was the reliance on subjective criteria for assessing ventricular structure and function and for evaluation of myocardial histology which was highly specific but lacked sensitivity for early and familial disease[19].Technical advances in MRI [3, 4] and 2-dimensional echocardiography [1, 2] have improved the capability to image the RV with reproducible measurements of volume and systolic function, which permits classification of severity and differentiation from normality& thus has improved the sensitivity & specificity in diagnosis of ARVD (Tables 1 and 2).

Table 1:Task Force criteria 2010 for diagnosis of ARVD [20, 21].

Table 2: Criteria.

Finally as per latest Task Force criteria,KIMS hospitalpatient fits into diagnosis of definite ARVD, where he satisfies 4 major criteria from 4 different categories: (i) 2D echocardiogram showing dilated RVOT, RV cavity; (ii) Repolarization abnormalities in ECG; (iii) Depolarization/ Conduction abnormalities in ECG; (iv) LBBB morphology with superior axis.

Emerging data suggest [22], increasing role for endocardial voltage mapping, in identifying scarring of RV,early diagnosis of disease, presence, location and extent of scar in RV by electroanatomic mapping and is useful in differential diagnosis of RVOT tachycardia. It also has prognostic implications, as scar related RVOT tachycardiahas higher recurrence.

Treatment

1. Drugs:In asymptomatic patients or those with non-lethal arrhythmias, beta-blockers are agents of choice. Sotalol has been reported to be the most effective drug in suppressing ventricular arrhythmias in patients with ARVD. Amiodarone is also effective[23]. Drug therapy may be continued as an adjunct to an implantable cardioverterdefibrillator (ICD)or as primarytherapy for sustained arrhythmias.

2. Radiofrequency ablation:It has variable success rates and recurrence rates. It is used in patients not responding to drug therapy or those patients who received ICD but continues to have arrhythmias [24].

3. ICD implantation: Patients presenting with either hemodynamically unstable ventriculartachycardia or SCD should be considered for ICD implantation. ICD implantation is technically challenging in patients with ARVD due to thinning of RV wall with increased risk of RV perforation. Further as disease progresses, replacing more cardiac muscle with fibrous tissue, may lead to loss of sensing function in RV defibrillation lead, consequently lead revision may be necessary [25, 26].

4. Surgery: surgical resection of ventricular focus or cardiac transplantation in patients with refractory heart failure [27].

Conclusion

It is important to consider ARVD as one of the possible causes for RVOT VT in young patients who present with syncope or VT and high suspicion should be exercised by the clinician, so that the diagnosis can be clinched.

Acknowledgement

The Department of Radiology &Imageology, Krishna Institute of Medical Sciences (KIMS), Secunderabad.

Conflicts of interest

Authors declare no conflicts of interest.