The impact of implantable cardioverter-defibrillator therapy on survival in autosomal-dominant arrhythmogenic right ventricular cardiomyopathy (ARVD5)

Abstract

Objectives: We sought to determine the impact of implantable cardioverter-defibrillator (ICD) therapy in patients with familial arrhythmogenic right ventricular cardiomyopathy (ARVC).

Background: Arrhythmogenic right ventricular cardiomyopathy is a cause of sudden cardiac death, which may be prevented by ICD.

Methods: We studied 11 families in which a 3p25 deoxyribonucleic acid (DNA) haplotype at locus ARVD5 segregated with disease and compared mortality in subjects who received an ICD with that in control subjects who were matched for age, gender, ARVC status, and family. Subjects (n = 367) at 50% a priori risk of inheriting ARVC were classified as high risk (HR) (n = 197), low risk (n = 92), or unknown (n = 78) on the basis of clinical events, DNA haplotyping, and/or pedigree position. Forty-eight HR subjects (30 males, [median age 32 years] and 18 females [median age 41 years]) were followed after ICD (secondary to ventricular tachycardia [VT] in 27%). Survival was compared with 58 HR control subjects who were alive at the same age to-the-day at which the ICD subject received the device.

Results: In the HR group, 50% of males were dead by 39 years and females by 71 years: relative risk of death was 5.1 (95% confidence interval 3 to 8.5) for males. The five-year mortality rate after ICD in males was zero compared with 28% in control subjects (p = 0.009). Within five years, the ICD fired for VT in 70% and for VT >240 beats/min in 30%, with no difference in discharge rate when analyzed by ICD indication.

Conclusions: The unknown mutation at the ARVD5 locus causing ARVC results in high mortality. Risk stratification using genetic haplotyping and ICD therapy produced improved survival for males.

Figure 1

Part of one of 11 autosomal-dominant families with arrhythmogenic right ventricular cardiomyopathy linked to 3p25 showing family members at high risk (n = 197), low risk (n = 92), and unknown (n = 78) status.

Figure 2

Time to death or last follow-up (censored) in high-risk males and females with arrhythmogenic right ventricular cardiomyopathy linked to 3p25.

Figure 3

(A) Time to death or last follow-up (censored) in 30 male subjects at high-risk for arrhythmogenic right ventricular cardiomyopathy linked to 3p25 who received implantable cardioverter-defibrillators (ICDs) and 36 matched control subjects. (B) Time to death or last follow-up (censored) in 18 female subjects at high risk for arrhythmogenic right ventricular cardiomyopathy linked to 3p25 who received ICDs and 22 matched control subjects.

Figure 4

Time to first appropriate discharge or last follow-up (censored) for sustained ventricular tachycardia (VT) and for VT >240 beats/min in males who received an implantable cardioverter-defibrillator and time to death or last follow-up (censored) in matched controls with arrhythmogenic right ventricular cardiomyopathy linked to 3p25.