[MIM 107 970]

(Arrhythmogenic right ventricular dysplasia, ARVD - acronym for Arrhythmogenic Right Ventricular Dysplasia)

Prevalence 1/2500 to 1/5,000, 3 times more frequent in men than in women. Autosomal dominant transmission, with variable penetrance  in most cases; some cases are due to a complex heterozygosity. There are two forms of autosomal recessive transmission: Naxos disease and Carvajal syndrome (see these terms).

From the genetics point of view, one can distinguish:

-        ARVD1: mutation of the TGFB3 gene (14q24.3) [MIM 107 970]

-        ARVD2: mutation of the RYR2 gene (1q42-q43) [604 772], causing ventricular tachycardia induced by stress and catecholamines

-        ARVD3: mutation on 14q12-q22 [MIM 602 086]

-        ARVD4: mutation on 2q32.1-q32.3 [MIM 602 807]

-        ARVD5: mutation of the TMEM43 gene (23p23) [MIM 604 400]

-        ARVD6: mutation on 10p14-p12 [MIM 604 401]

-        ARVD7 : mutation of the DES gene (2q35) [MIM 601 419] : it is in fact a myofibrillar myopathy

-        ARVD8 : mutation of the DSP gene (6p24) [MIM 607 450] : other mutations of this gene (recessive transmission) cause the Carvajal syndrome

-        ARVD9 : mutation of the PKP2 gene (2p11) [MIM 609 040]

-        ARVD10 : mutation of the DSG2 gene (18q12.1) [MIM 610 193]

-        ARVD11 : mutation of the DSC2 gene [18q12.1) [MIM  610 476] : autosomal dominant or recessive transmission; it can present as  Carvajal syndrome

-        ARVD12 : mutation of the JUP gene (17q21) [MIM 611 528] ; other mutations of this gene (recessive transmission) cause Naxos disease

-        ARVD13 : mutation of the CTNNA3 gene (10q21) [MIM 615 616]

-        ARVD14: mutation of the CDH2 gene (18q12) [MIM 618 920]

The mutations of the JUP, DSP, pKP2, DSG2, DSC2 genes are responsible for the synthesis of the proteins of the five intermyocytic desmosomes and are implied in more than 50 % of cases.

It is a hereditary cardiomyopathy where myocytes are gradually replaced by fibroadipose tissue in the intramural zone of the RV (the LV is affected later), and associated with ventricular arrhythmias. There is a risk of sudden  death during or just after the exercice. This could be the cause of unexplained  perioperative deaths in young asymptomatic subjects (10-30 years of age) . Clinical manifestations usually occur between the 2nd and 4th decade.

There are 4 phases:

-        asymptomatic: discovered by chance (family screening) or following sudden death linked to an effort (athletes)

-        arrhythmias: chest pain, syncope, ventricular arrhythmia

-        right ventricular failure

-        biventricular failure: clinical picture of dilated cardiomyopathy.

ECG:        abnormal in 90 % of cases: complete or incomplete right bundle block, T wave inversion in V1-V4, QRS widening without bundle block (epsilon wave in 50 %).

Diagnosis:        based on the personal and familial history, ECG (Holter), RV scanner or cardiac MRI. A diagnosis score is used with major  (2 points) and minor (1 point) criterias: the diagnosis is considered as certain when the score is ≥ 4 and possible if it is  ≤ 2

Treatment:        restriction of the strenuous sport activities,  anti-arrhythmics (cordarone, sotalol,  β-blockers), ablation by catheterization, implanted automatic defibrillator, cardiac failure, heart transplant

Indication of the implantation of an automatic defibrillator:

-        absolute:  history of sudden death with ventricular tachycardia, sustained VT, severe dysfunction of the RV and/or the LV

-        to be considered:  1 major risk factor (syncope, unsustained VT, RV and/or LV dysfunction ) or 1 minor risk factor (complex genotype, male gender,  ≥  1000 VES/24h, positive ECG diagnosis, negative T waves in  ≥ 3 precordial derivations)

-        negative:  'healthy' carrier of a mutation without risk factors (but regular cardiologic monitoring)

               

Anesthetic implications: 

keep that diagnosis in mind in presence of a family history of sudden death or ventricular tachycardia during or following exercice. Major risk of sudden death in the perioperative period. Avoid all the factors likely to cause rhythm disorders: hypoxia, hypercarbia, hypovolemia, too light anesthesia, insertion of a Swan-Ganz catheter. It seems prudent to avoid agents that prolong myocardial depolarization: metoclopramide, ondansetron. Epidural anesthesia has been used without problems for a cesarean section. ARVD2 caused by a mutation of the RYR2 gene (receptor in the cardiac level) does not increase the risk of malignant hyperthermia (generaly caused by a mutation of the RYR1 gene coding for the RYR1 receptor in the striated muscle).

References : 

• Fontaine G, Gallais Y, Fornes P, Hebert JL, Frank R. 
  Arrhythmogenic right ventricular dysplasia/cardiomyopathy. 
  Anesthesiology 2001; 95: 250-4.
• Houfani B, Meyer P, Merckx J, Roure P, Padovani JP, Fontaine G et al. 
  Postoperative sudden death in two adolescents with myelomeningocele and unrecognized arrhythmogenic right ventricular dysplasia. 
  Anesthesiology 2001; 95:257-9. 
• Swan H, Laitinen PJ, Toivonen L.
  Volatile anesthetics and succinylcholine in cardiac ryanodine receptor defects.
  Anesth Analg 2004; 99: 435-7.

• Alexoudis AK, Spyridonidou AG, Vogiatzaki TD, Iatrou CA. 
  Anaesthetic implications of arrhythmogenic right ventricular dysplasia/cardiomyopathy. 
  Anaesthesia 2009; 64: 73-8.
• Staikou C, Chondrogiannis K, Mani A. 
  Perioperative management of hereditary arrhythmogenic syndromes. 
  Br J Anaesth 2012; 108: 730-44. 

• Corrado D, Wichter T, Linl MS et al.
  Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia.
  Circulation 2015; 132: 441-53.
• Riad Z, Fellahi J-L.
  La cardiomyopathie arythmogène du ventricule droit.
  Le Praticien en Anesthésie-Réanimation 2020 ; 24 :269-74

Updated: April 2023