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CLINICAL RESEARCH: HEART RHYTHM DISORDERS

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

Kathy A. Hodgkinson, MSc^*,, Patrick S. Parfrey, MD, FRCPC, FACP^*,*, Anne S. Bassett, MD, FRCPC^,, Christine Kupprion, MD, Jörg Drenckhahn, MD, Mark W. Norman, MD, MRCP, Ludwig Thierfelder, MD, Susan N. Stuckless, MSc^*, Elizabeth L. Dicks, MSc^*, William J. McKenna, MD, FRCP^|| and Sean P. Connors, MD, DPhil, FRCPC^¶

^* Clinical Epidemiology Unit
Discipline of Genetics, Memorial University, Health Sciences Centre, St. John's, Newfoundland, Canada
Clinical Genetics Research Program, Centre for Addiction & Mental Health, University of Toronto, Toronto, Ontario, Canada
Max-Delbrück Centrum fur Molekulare Medizin, Berlin, Germany
^|| The Heart Hospital, London, England
^¶ Division of Cardiology, Memorial University, St. John's, Newfoundland, Canada

Manuscript received May 17, 2004; revised manuscript received July 28, 2004, accepted August 9, 2004.

^* Reprint requests and correspondence: Dr. Patrick Parfrey, Clinical Epidemiology Unit, Memorial University Health Sciences Centre, St. John's, Newfoundland, Canada A1B 3V6 (Email: pparfrey{at}mun.ca).

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.

Abbreviations and Acronyms   ARVC = arrhythmogenic right ventricular cardiomyopathy   ARVD = arrhythmogenic right ventricular dysplasia   ARVD5 = the locus for the mutation causing ARVC on chromosome 3p25   ECG = electrocardiogram   HM = Holter monitoring   HR = high risk   ICD = implantable cardioverter-defibrillator   LR = low risk   LVE = left ventricular enlargement   MRI = magnetic resonance imaging   SAECG = signal-averaged electrocardiogram   SCD = sudden cardiac death   UK = unknown   VT = ventricular tachycardia

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