Impaired cardiac sympathetic innervation in symptomatic patients with long QT syndrome

Increased sympathetic activation is a key modifier for arrhythmogenesis in patients with long QT syndrome (LQTS), a congenital channelopathy. Therefore, we investigated cardiac sympathetic function using (123)I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) in a cohort of symptomatic LQTS patients and correlated these findings with the underlying genotype. [(123)I]MIBG SPECT was performed in 28 LQTS patients. Among these, 18 patients (64%) had a previous syncope and 10 patients (36%) survived sudden cardiac arrest. Patients were characterized in terms of genetic subtypes and QTc interval on surface ECGs. SPECT images were analysed for regional [(123)I]MIBG uptake in a 33-segment bullseye scheme and compared to those obtained from 10 age-matched healthy control subjects (43 +/- 12 years). An abnormal (123)I-MIBG scan was found in 17 of 28 LQTS patients (61%) with a tracer reduction mainly located in the anteroseptal segments of the left ventricle. This finding was independent of the genetic LQTS subtype. In addition, no differences were found between LQTS patients with a QTc > 500 ms vs < 500 ms or those suffering from syncope vs VF (p > 0.05). A distinct regional pattern of impaired cardiac sympathetic function was identified in the majority of symptomatic LQTS patients. This innervation defect was independent of the underlying genotype and clinical disease expression.