Arrhythmogenic Right Ventricular Dysplasia

Arrhythmogenic Right Ventricular Dysplasia

In arrhythmogenic right ventricular dysplasia (ARVD), myocardium of right ventricular free wall is replaced by fibrofatty tissue. Regional wall motion/function is reduced and there is a propensity for ventricular arrhythmias originating from the right ventricle. Sudden cardiac death (SCD) can occur in the young with ARVD. This disorder is also called as arrhythmogenic right ventricular cardiomyopathy (ARVC).

Pathological features of ARVD namely the replacement of right ventricular wall myocardium by fat and fibrous tissue and aneurysms are seen at right ventricular apex, inferior or diaphragmatic aspect and outflow tract. These regions together constitute the triangle of dysplasia [1]. ARVD is a disease of desmosomal dysfunction and is genetically mediated. Important mutations are in PKP2, DSG2, DSP and DSC2. A rare recessive form is called Naxos disease, associated with palmoplantar keratoderma and woolly hair [2]

Triangle of dysplasia in ARVD
Triangle of dysplasia in ARVD

The initial report by Frank Marcus, Guy Fontaine and colleagues had 24 cases. Twenty two patients had recurrent ventricular tachycardia. There was a male preponderance with male/female ratio of 2.7:1. All but one of the patients had ventricular tachycardia of left bundle branch block morphology. T waves were inverted in right precordial leads in most patients. Two patients without arrhythmia were diagnosed by right and left heart angiography. All patients had undergone right ventriculography and six had echocardiography. 12 patients had confirmation of findings at surgery and one at autopsy [1].

Seven patients had incomplete right bundle branch block pattern and one had complete RBBB. Ventricular postexcitation waves (Epsilon wave) were suspected on the resting ECG in seven patients. High-amplification and signal averaged techniques showed ventricular postexcitation in 13 of the 16 patients in whom it was performed.

Diagrammatic representation of Epsilon wave in ARVD
Diagrammatic representation of Epsilon wave in ARVD

Initial diagnostic criteria for ARVD were proposed by an international task force in 1994 [3]. Important modifications were proposed in 2010 which included quantitative criteria [4]. Both sets of criteria are quite extensive, including many parameters. The six domains in which major and minor criteria were proposed are global or regional dysfunction and structural alterations, tissue characterization of wall, repolarization abnormalities, depolarization/conduction abnormalities, arrhythmias and family history.

Global or regional dysfunction can be documented by echocardiography, cardiac magnetic resonance imaging or right ventricular angiography. Main features are right ventricular akinesia, dyskinesia or aneurysm formation. Right ventricular outflow tract measurement of 32 mm or more in parasternal long axis view by echo is a major criterion if present along with the wall motion abnormality. Corresponding figure in parasternal short axis view is 36 mm or more.

Major criteria on tissue characterization is residual myocytes less than 60% by morphometric analysis with fibrous replacement of right ventricular free wall of myocardium in one or more samples. This could be with or without fatty replacement of tissue on endomyocardial biopsy. Residual myocytes of 60-75% will be a minor criteria.

Major repolarization criteria is the presence of inverted T waves in right precordial leads V1-V3 or beyond in individuals more than 14 years of age, in the absence of complete right bundle branch block. Inverted T waves in the presence of RBBB, inverted T waves in V1 and V2 or in V4-V6 are minor criteria.

Epsilon wave between the end of QRS complex and the onset of T wave in leads V1 to V3 is a major depolarization criteria. Minor criteria are based on signal averaged ECG parameters which indicate postexcitation. Major arrhythmia criterion is  sustained or nonsustained ventricular tachycardia with left bundle branch morphology and superior axis. NSVT and sustained VT of RV outflow configuration with LBBB pattern and inferior axis is a minor criterion. More than 500 ventricular ectopics on 24 hour Holter is also a minor criterion.

In family history major criteria are confirmed ARVD in a first degree relative by 2010 Task Force criteria, confirmed ARVD in first degree relative at autopsy or surgery and identification of a pathogenic mutation in the patient under evaluation. History of ARVD in first degree relative which is not confirmed, premature sudden death before 35 years in first degree relative due to suspected ARVD and ARVD confirmed in second degree relative pathologically or by 2010 Task Force criteria are taken as minor criteria.

Another set of diagnostic criteria known as Padua criteria has been published in 2020 [5]. They mention that autopsy investigations, genotype-phenotype correlation studies and contrast MRI have shown that fibro-fatty replacement affects both ventricles, with left ventricular involvement which may parallel or exceed right ventricular involvement. Hence a new designation as “Arrhythmogenic Cardiomyopathy” (ACM) has been suggested.

In the Padua criteria, left ventricular systolic dysfunction and wall motion abnormalities have been added as minor criteria. Left ventricular late gadolinium enhancement on CMR of certain regions of the free wall and septum have been included as a major criterion. Inverted T waves in left precordial leads in the absence of left bundle branch block is a minor criterion. Low QRS voltage of less than 5 mm in limb leads in the absence of obesity, emphysema or pericardial effusion is another minor criterion.

VT and NSVT of RBBB morphology excluding the fascicular pattern have also been included among the minor features in Padua criteria. Family history/genetics criteria have been modified to include the proposed new name ‘Arrhythmogenic Cardiomyopathy” instead of “ARVD”.

References

  1. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, Grosgogeat Y. Right ventricular dysplasia: a report of 24 adult cases. Circulation. 1982 Feb;65(2):384-98. doi: 10.1161/01.cir.65.2.384. PMID: 7053899.
  2. Sajeev CG, Francis J, Sankar V, Vasudev B, Venugopal K. Images in cardiovascular medicine. Ventricular tachycardia: the spectrum continues to broaden: report of Naxos disease. Circulation. 2006 Jul 25;114(4):e60-1. doi: 10.1161/CIRCULATIONAHA.105.562835. PMID: 16864732.
  3. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, Camerini F. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J. 1994 Mar;71(3):215-8. doi: 10.1136/hrt.71.3.215. PMID: 8142187; PMCID: PMC483655.
  4. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010 Apr 6;121(13):1533-41. doi: 10.1161/CIRCULATIONAHA.108.840827. Epub 2010 Feb 19. PMID: 20172911; PMCID: PMC2860804.
  5. Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Anastasakis A, Asimaki A, Bucciarelli-Ducci C, Haugaa KH, Marchlinski FE, Mazzanti A, McKenna WJ, Pantazis A, Pelliccia A, Schmied C, Sharma S, Wichter T, Bauce B, Basso C. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. Int J Cardiol. 2020 Nov 15;319:106-114. doi: 10.1016/j.ijcard.2020.06.005. Epub 2020 Jun 16. PMID: 32561223.