UNLABELLED Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) typically present with ventricular tachyarrhythmias preferentially triggered by an elevated sympathetic tone. Previous studies demonstrated an impairment of the presynaptic catecholamine reuptake as assessed by (123)I-labeled norepinephrine analog on metaiodobenzylguanidine ((123)I-MIBG) SPECT. Mutations in the gene encoding for plakophilin-2 (PKP-2) are the most common cause of autosomal dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients with ARVC and correlated these findings with the causative genotype. METHODS (123)I-MIBG SPECT was performed for 42 patients with definite ARVC (10 women, 32 men; mean age ± SD, 43 ± 14 y). Images were acquired at 4 h after injection and analyzed for regional (123)I-MIBG uptake in a standardized 33-segment polar map. Results were compared with those obtained from 10 control subjects (5 women, 5 men; mean age ± SD, 43 ± 12 y). RESULTS An abnormal tracer uptake was detected in 25 patients with ARVC (59%). The extents of right ventricular dilation and regional wall motion abnormalities as well as electrocardiographic markers of de- or repolarization were not significantly different between patients with normal and abnormal (123)I-MIBG SPECT findings. However, during long-term follow-up of 11.9 ± 4.1 y, patients with abnormal (123)I-MIBG SPECT findings experienced life-threatening ventricular tachyarrhythmias significantly more often (22/25 patients [88%]) and independent of the extent of right ventricular dysfunction than those with a normal sympathetic innervation (6/17 patients [35%]; P < 0.0005). Mutations in PKP-2 were identified in 17 patients (40%) but were not correlated with the degree of adrenergic dysfunction. CONCLUSION In patients with ARVC, an impairment of adrenergic innervation independent of the underlying genotype is associated with a higher incidence for future recurrences of ventricular tachyarrhythmias. This finding may suggest a potential role of (123)I-MIBG SPECT for individualized risk stratification in ARVC patients and asymptomatic PKP-2 mutation carriers alike.
Cardiac sympathetic dysfunction in genotyped patients with arrhythmogenic right ventricular cardiomyopathy and risk of recurrent ventricular tachyarrhythmias.