Phenotypic expression is a prerequisite for malignant arrhythmic events and sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy

Europace. 2016 Jul;18(7):1086-94. doi: 10.1093/europace/euv205. Epub 2015 Jul 2.


Aims: Whether a desmosomal (DS)-gene defect may in itself induce life-threatening ventricular arrhythmias regardless of phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) is still debated. This prospective study evaluated the long-term outcome of DS-gene mutation carriers in relation to the ARVC phenotypic expression.

Methods and results: The study population included 116 DS-gene mutation carriers [49% males; median age 33 years (16-48 years)] without prior sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The incidence of the arrhythmic endpoint, including sudden cardiac death (SCD), aborted SCD, sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) intervention was evaluated prospectively and stratified by the presence of ARVC phenotype and risk factors (syncope, ventricular dysfunction, and non-sustained VT). At enrolment, 40 of 116 (34%) subjects fulfilled the criteria for definite ARVC while the remaining were either borderline or phenotype negatives. During a median follow-up of 8.5 (5-12) years, 10 patients (9%) had arrhythmic events (0.9%/year). The event rate was 2.3%/year among patients with definite ARVC and 0.2%/year among borderline or phenotype negative patients (P = 0.002). In patients with definite ARVC, the incidence of arrhythmias was higher in those with ≥1 risk factors (4.1%/year) than in those with no risk factors (0.4%/year, P = 0.02). Mortality was 0.2%/year (1 heart failure death and 1 SCD).

Conclusions: The ARVC phenotypic expression is a prerequisite for the occurrence of life-threatening arrhythmias in DS-gene mutation carriers. The vast majority of malignant arrhythmic events occurred in patients with an overt disease phenotype and major risk factors suggesting that this subgroup most benefits from ICD therapy.

Keywords: Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathy; Genetics; Implantable cardioverter-defibrillator; Primary prevention; Sudden cardiac death; Ventricular arrhythmias.

MeSH terms

  • Adolescent
  • Adult
  • Arrhythmias, Cardiac / epidemiology*
  • Arrhythmogenic Right Ventricular Dysplasia / complications*
  • Arrhythmogenic Right Ventricular Dysplasia / genetics*
  • Arrhythmogenic Right Ventricular Dysplasia / mortality
  • Cicatrix / pathology*
  • Death, Sudden, Cardiac / epidemiology*
  • Defibrillators, Implantable / adverse effects*
  • Desmoglein 2 / genetics
  • Desmoplakins / genetics
  • Female
  • Heterozygote
  • Humans
  • Italy
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Plakophilins / genetics
  • Primary Prevention
  • Prospective Studies
  • Risk Factors
  • Young Adult


  • DSG2 protein, human
  • Desmoglein 2
  • Desmoplakins
  • PKP2 protein, human
  • Plakophilins