Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy

Abstract

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) is an uncommon but increasingly recognized inherited cardiomyopathy that is associated with malignant ventricular arrhythmias and sudden cardiac death, particularly in young individuals. The implantable cardioverter-defibrillator (ICD) is widely regarded as the only treatment modality with evidence to support improved survival in patients with ARVC and secondary prevention indications. In contrast, there is no universally accepted risk stratification scheme to guide ICD therapy for primary prevention against sudden cardiac death. Potential benefits must be weighed against the considerable risks of complications and inappropriate shocks in this young patient population. This article tackles the challenges of risk stratification for sudden cardiac death in ARVC and critically appraises available evidence for various proposed risk factors. The authors’ over-arching objective is to provide the clinician with evidence-based guidance to inform decisions regarding the selection of appropriate candidates with ARVC for ICD therapy.

Keywords:

• arrhythmogenic right ventricular cardiomyopathy/dysplasia
• cardiac genetics
• implantable cardioverter-defibrillators
• sudden cardiac death
• therapy
• ventricular arrhythmias

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an uncommon genetic disease and important cause of sudden cardiac death in young individuals and athletes.

• Management of ARVC is primarily geared toward prevention of sudden cardiac death, the most common cause of mortality.

• Implantable cardioverter-defibrillator (ICD) therapy implantation is the only therapeutic intervention with evidence to suggest improved survival in selected patients with ARVC.

• Judicious patient selection for ICD implantation is of paramount importance considering the well-characterized drawbacks of lifelong ICD therapy in young individuals, including cumulative risks of inappropriate shocks and device and lead-related complications.

• ICD therapy is currently recommended for secondary prevention and in patients with recent unexplained syncope.

• Beyond these indications, prophylactic ICD implantation remains a major challenge and is individualized.

• Notwithstanding limitations of the current literature, potential risk factors supported by strongest evidence include: RV dysfunction, LV dysfunction, p.S358L mutation of TMEM43 gene in males, T-wave inversion beyond V3 and non-sustained ventricular tachycardia.

• Considering the low event rate, ICDs should not be routinely implanted in low-risk family members without other risk factors, even if the proband died suddenly.

• Due to the progressive nature of the disease, the decision to implant an ICD should be reassessed periodically in patients who do not initially receive such therapy.

Notes

ARVC: Arrhythmogenic right ventricular cardiomyopathy; LV: Left ventricular; PVC: Premature ventricular complexes; RV: Right ventricular; SAECG: Signal averaged ECG; VT: Ventricular tachycardia.