Abstract 816: Surgical Bilateral Stellate Ganglionectomy Reduces Mitochondrial Reactive Oxygen Species (mROS) and Prevents Sudden Cardiac Death (SCD) in Non-ischemic Heart Failure (HF)

Abstract

Introduction: Current therapies for SCD are limited. Bilateral sympathetic stellate ganglionectomy ( BSG ) is a promising new adjunctive therapy in patients with ischemic HF who have incessant ventricular tachyarrhythmias ( VT/VF ) despite optimal medical management. The underlying mechanisms are unknown. The effect of BSG in non-ischemic HF is unclear. Hypothesis: BSG prevents VT/VF and SCD in non-ischemic HF by restoring sympathovagal balance and reducing mROS. Methods: We used a unique pressure-overload guinea pig model that closely mimics human non-ischemic HF, including a high incidence of spontaneous VT/VF/SCD. We randomized the animals to non-failing controls, HF+Sham, or HF+BSG surgery. We used intention to treat analysis to evaluate VT/VF-free survival. We analyzed continuous ECG (VT/VF burden, heart rate variability, QT variability) and echo (cardiac function). In isolated left ventricular (LV) myocytes, we measured Ca 2+ transients and mitochondrial reactive oxygen species (mROS) using targeted ratiometric probes. Results: Half of the HF+Sham animals experienced SCD in 4 weeks. In contrast, BSG abolished SCD, reduced VT/VF, and increased parasympathetic tone (beyond corresponding reductions in sympathetic tone). Fractional shortening of the LV was markedly reduced in HF+Sham (0.28±0.02) vs. control (0.50±0.01), but preserved by BSG (0.45±0.02). Whereas HF+Sham increased mROS levels in LV myocytes (fractional oxidation, F ox : 0.53±0.015) compared to control (0.29±0.020), BSG reduced mROS (0.38±0.035). Mitochondrial antioxidant capacity, as indexed by H 2 O 2 challenge of LV myocytes, was compromised in HF+Sham (F ox : 0.81±0.040) compared to control (0.44±0.061), but preserved by BSG (0.48±0.023). Conclusions: Surgical BSG prevents SCD in non-ischemic HF by reducing mROS, decreasing sympathetic tone, and by increasing parasympathetic tone (possibly by facilitating cholinergic transdifferentiation). This promising new minimally-invasive surgical therapy may be particularly useful in patients with non-ischemic HF on optimal medical therapy who require recurrent ICD shocks to prevent SCD. Patients in the early stages of HF who are not eligible for ICDs but remain at higher SCD risk may also benefit from BSG surgery.