BrHeart3' 1994;71:215-218

CRITERIA

Diagnosis of arrhythmogenic right ventriculardysplasia/cardiomyopathy

William J McKenna, Gaetano Thiene, Andrea Nava, Fabrice Fontaliran,Carina Blomstrom-Lundqvist, Guy Fontaine, Fulvio Camerini on behalf of the TaskForce of the \Working Group Myocardial and Pericardial Disease of the European Societyof Cardiology and of the Scientific Council on Cardiomyopathies of the InternationalSociety and Federation of Cardiology, supported by the Schoepfer Association

Correspondence to:Prof William J McKenna,Department of CardiologicalSciences, St George'sHospital Medical School,Cranmer Terrace, LondonSW17 ORE.Accepted for publication1 December 1993

Appendix: Members oftheARVD task force include:Saroja Bharati, 11745 SWHighway, Palos Heights,Illinois 60463, USA.Carina Blomstrom-Lundqvist,Department of Cardiology,University ofLund Hospital,S-221 85 Lund, Sweden.Fulvio Camerini, Departmentof Cardiology, OspedaleMaggiore, Piazza Ospedale 1,34100 Trieste, Italy.Domenico Corrado, Istituto diAnatomia Patologica,Universita di Padova, 61 via AGabelli, 35121 Padova, Italy.Guy Fontaine, Service deCardiologie, H6pital Jean-Rostand, 39-41 rue Jean LeGalleu, 94200 Ivry-sur-Seine,Paris, France.Fabrice Fontaliran, Service deCardiologie, H6pital Jean-Rostand, 39-41 rue Jean LeGalleu, 94200 Ivry-sur-Seine,Paris, France.Toru Iwa, ClinicalElectrophysiology, InternalMedicine 3, Aichi MedicalCollege, Yazako, Nagajute-cho, Aichigun 480-11, Japan.Francesca Lobo, Departmentof Laboratory Medicine,Hamilton Civic Hospital, 237Barton Street East, Hamilton,Ontario L8L 2X2, Canada.Robert Loire H6pital LouisPradel, 28 avenue du DoyenLapine, 69500 Bron, France.William McKenna,Department of CardiologicalSciences, St George's HospitalMedical School, CranmerTerrace, London SW17 ORE.Andrea Nava, Istituto diAnatomia Patologica,Universita di Padova, 61 via AGabelli, 35121 Padova, Italy.Ryoso Okada, ResearchLaboratory for CardiovascularPathology, JuntendoUniversity, 2-1-1 Hongo,Bunkyo-Ku, Tokyo 113,Japan.N Protonotarios, MedicalCenter of Naxos, Hora Naxos84300, Greece.Peter Richardson, CardiacDepartment, King's CollegeHospital, Denmark Hill,London SE5 9RS.

Right ventricular dysplasia or cardiomyopathyis a heart muscle disorder of unknown causethat is characterised pathologically by fibro-fatty replacement of the right ventricularmyocardium.1-5 Segmental right ventriculardisease is usual, but evolution to more diffuseright ventricular involvement and left ventric-ular abnormalities with heart failure havebeen described.6l0 The incidence is unknown.Clinical manifestations of the disease includestructural and functional abnormalities of theright ventricle, electrocardiographic depolari-sation/repolarisation changes, and presenta-tion with sudden death or arrhythmias ofright ventricular origin. The disease is oftenfamilial (about 30%) with an autosomal dom-inant inheritance.11 12 It remains unclearwhether this genetic background predisposesto a degenerative disease with atrophy andfibrofatty replacement of the right ventricularmyocardium, or whether the inflammatorycells seen in approximately 25% of cases indi-cate an infectious or possibly geneticallydetermined immune pathogenesis."3

Uncertainty concerning the pathogenesis ofright ventricular dysplasia leads to the as yet

unresolved question of whether it is a singleentity or the common end point of several dis-ease processes. The familial nature of manycases has led to recognition that in any partic-ular family the phenotypic expression of thedisease can be very variable. In turn this leadsto the need for criteria to delineate the spec-trum of disease that justifiably can be calledright ventricular dysplasia in clinical practice.A definitive (gold standard) diagnosis of

right ventricular dysplasia is based on histo-logical demonstration of transmural fibrofattyreplacement of right ventricular myocardiumat either necropsy (figs 1 and 2) or surgery.'4 15In most patients, however, assessment oftransmural myocardium is not possible.

Diagnosis based on right ventricular endo-myocardial biopsy specimens is inherently dif-ficult because the segmental nature of thedisease causes false negatives and because theinterventricular septum is rarely involved.Biopsy specimens cannot reflect transmuralchanges and not infrequently in normal sub-jects there are islands of adipose tissuebetween myocytes in the right ventricle.Nevertheless the positive finding of fibrofatty

Criteria for diagnosis of right ventricular dysplasia

I Global and/or regional dysfunction and structuralalterations"7-2 *

MAJORSevere dilatation and reduction of right ventricular ejectionfraction with no (or only mild) LV impairmentLocalised right ventricular aneurysms (akinetic or dyskineticareas with diastolic bulging)Severe segmental dilatation of the right ventricle

MINORMild global right ventricular dilatation and/or ejection fractionreduction with normal left ventricleMild segmental dilatation of the right ventricleRegional right ventricular hypokinesia

II Tissue characterisation ofwallsMAJORFibrofatty replacement of myocardium on endomyocardialbiopsy

m Repolarisation abnormalitiesMINORInverted T waves in right precordial leads (V2 and V3)(people aged more than 12 yr; in absence of right bundlebranch block)

IV Depolarisation/conduction abnormalitiesMAJOREpsilon waves or localised prolongation (> 1 10 ms) of theQRS complex in right precordial leads (V1-V3)

MINORLate potentials (signal averaged ECG)

V ArrhythmiasMINORLeft bundle branch block type ventricular tachycardia(sustained and non-sustained) (ECG, Holter, exercisetesting).Frequent ventricular extrasystoles (more than 1000/24 h)(Holter)

VI Family historyMAJORFamilial disease confirmed at necropsy or surgery

MINORFamilial history of premature sudden death (<35 yr) due tosuspected right ventricular dysplasia.Familial history (clinical diagnosis based on present criteria)

*Detected by echocardiography, angiography, magnetic resonance imaging, or radionuclide scintigraphy. ECG, electrocardio-gram; LV, left ventricle.

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McKenna, Thiene, Nava, Blomstrom-Lundqvist, Fontaine, Camenini

Ketty Schwartz, UniteINSERM 153, PavillonRambuteau, H6pital de laSaltpetriere, 47 boulevard del'H6pital, 75013 Paris, France.Morie Sekiguchi, Departmentof Internal Medicine andCardiology, ShinshuUniversity School ofMedicine, Matsumoto City390, Japan.Furio Silvestri, Department ofMorbid Anatomy, Universityof Trieste, Italy.Gaetano Thiene, Istituto diAnatomia Patologica,Universita di Padova, 61 via AGabelli, 35121 Padova, Italy.A Tsatsopoulou, MedicalCenter of Naxos, Hora Naxos84300, Greece.

replacement of myocytes on biopsy can bea valuable diagnostic pointer. Diagnosis,however, relies heavily on the clinical demon-stration of structural, functional, and electro-physiological abnormalities that are causedby or reflect the underlying histologicalchanges.

Problems in the assessment of right ven-tricular structure and function, the multiplepotential aetiologies of arrhythmias of rightventricular origin, and difficulties in the inter-pretation of the right ventricular endomyocar-dial biopsy have all made the establishment ofdefinitive diagnostic criteria necessary.16 Theimportance of a common approach to diagno-sis led to the development of the task force

and the following proposals for the establish-ment of diagnostic criteria. These are basedon the identification of structural abnormali-ties, fatty or fibrofatty replacement of theright ventricular myQcardium, electrocardio-graphic changes, arrhythmias of right ventric-ular origin, and familial disease.

It is proposed that the diagnosis of rightventricular dysplasia would be fulfilled by thepresence from different groups (table) of:

Two major criteriaor

One major plus two minor criteriaor

Four minor criteria

ordF:

B,.,

Figure 1 Necropsyfindings in a 39year old man with afamily history ofsudden death (two brothers) who had complexarrhythmia and died suddenly. (A) Cross section of the heart showing pronounced adipose infiltration of the rightventricularfree wall and nearly normal left ventricle and ventricular septum. (B) Histological view of the right ventricularfree wall showing myocardial atrophy and massive fibrofatty replacement. (Azan; original magnification, x 1.)

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Diagnosis of arrhyth ig

S "'s"z~~~.j-- f''IFigure 2 Histological view of the nght ventricularfree wall at high magnification, showingfibrofatty replacement.(Azan; original magnification, x 25.)

Dilatation of the right ventricle or seg-ments of the right ventricle is defined byechocardiographic or angiographic dimen-sions that are two to three (mild) or >,threestandard deviations from normal.'7-23Problematic areas of interpretation are thosewhere a subjective assessment is required,such as regional right ventricular dysfunctionand structural alterations. Right ventricularendomyocardial biopsy on its own must beregarded as non-diagnostic, although whenfibrofatty replacement is shown24 biopsy mayhelp with in vivo histological validation of theclinical diagnosis. Experience with magneticresonance imaging and ultra-fast computedtomography in the diagnosis of right ventric-ular dysplasia is limited and requires furtherevaluation.25 26; preliminary studies suggestthat it may be possible to distinguish betweenfat and myocardium. Conventional defini-tions are used for epsilon waves, an abnormalsignal averaged electrocardiogram based ontime analysis, and ventricular arrhythmias.27-29The diagnosis of arrhythmogenic right

ventricular dysplasia based on the presence ofmajor and minor criteria encompassingstructural, histological, electrocardiographic,arrhythmic, and genetic factors is presentedas a working framework to improve under-standing of this condition. We expect thatwith increased pedigree ascertainment thepotential identification of the gene(s) respon-sible, and a more detailed understanding ofthe natural history our concepts will evolve toeither a more succinct clinico-pathologicaldiagnosis or ideally a diagnosis based on a spe-cific gene abnormality. At present, however, acommon approach to diagnostic criteria for aphenotypic expression of right ventriculardysplasia will be essential, both to clinicalmanagement and to scientific progress.

1 Marcus FI, Fontaine GH, Guiraudon G, Frank R,Laurenceau JL, Malergue S, Grosgogeat Y. Right ven-tricular dysplasia. A report of 24 adult cases. Circulation1982;65:384-98.

2 Fontaine G, Tereau Y, Frank R, Guiraudon G, Fillette F,Chomette G, Grosgogeat Y. Dysplasie ventriculairedroite arhythmogene et maladie de Uhl. Arch Mal CoeurVaiss 1982;4:361-70.

3 Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Rightventricular cardiomyopathy and sudden death in youngpeople. N EnglJMed 1988;318:129-33.

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