T-Cell Mediated Inflammatory Activity in the Stellate Ganglia of Patients with Ion Channel Disease and Severe Ventricular Arrhythmias.

BACKGROUND: -Long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are electrical diseases characterized by catecholamine-induced ventricular arrhythmias. Unbalanced autonomic innervation of the heart may trigger arrhythmic events and stellectomy is a treatment option for patients who are resistant to pharmacological drugs. We analysed left stellectomy specimens of LQTS and CPVT patients for signs of inflammatory activity. METHODS AND RESULTS: -Stellate ganglia were retrieved from 12 consecutive patients (8F, 4M, mean age 23.4±17 yrs) with either LQTS (n=8) or CVPT (n=4) and serious arrhythmias. Control stellate ganglia were obtained from 10 accidently deceased patients (6F, 4M, mean age 35±17.6 yrs). Sections were immunostained with antibodies against T cells (CD3, CD4, CD8, CD20, Granzyme B), CD68 (macrophages) and HLA-DR antigens (activation marker). Immunopositive cells were quantified as cells/mm2. PCR and RT-PCR were performed to screen for herpes virus DNA. Stellate ganglia of all 12 LQTS/CVPT patients revealed mild but distinct inflammatory infiltrates composed of T-lymphocytes and macrophages, which were diffusely spread, but also clustered in small foci apposed to ganglion cells, interpreted as T cell-mediated ganglionitis. Morphometrical analysis showed that CD3+ and CD8+ T cells/mm2 were significantly higher in the ganglia of LQTS/CVPT cases than in healthy controls (p=0.0018 and p=0.0009, respectively). Molecular analyses were negative for neurotropic viruses. CONCLUSIONS: -T-cell mediated cytotoxicity towards ganglion cells may boost adrenergic activity as to trigger or enhance electrical instability in LQTS/CVPT patients who are already genetically predisposed to arrhythmias.