Tafamidis and Incidence of Atrial Fibrillation in Transthyretin Amyloid Cardiomyopathy.

The sympathetic nervous system plays an integral role in cardiac physiology. Nerve fibers innervating the left ventricle are amenable to transvenous catheter stimulation along the coronary sinus (CS).The aim of the present study was to modulate left ventricular control by selective intracardiac sympathetic denervation.First, the impact of epicardial CS ablation on cardiac electrophysiology was studied in a Langendorff model of decentralized murine hearts (n = 10 each, ablation and control groups). Second, the impact of transvenous, anatomically driven axotomy by catheter-based radiofrequency ablation via the CS was evaluated in healthy sheep (n = 8) before and during stellate ganglion stimulation.CS ablation prolonged epicardial ventricular refractory period without (41.8 ± 8.4 ms vs 53.0 ± 13.5 ms; P = 0.049) and with β1-2-adrenergic receptor blockade (47.8 ± 7.8 ms vs 73.1 ± 13.2 ms; P < 0.001) in mice. Supported by neuromorphological studies illustrating a circumferential CS neural network, intracardiac axotomy by catheter ablation via the CS in healthy sheep diminished the blood pressure increase during stellate ganglion stimulation (Δ systolic blood pressure 21.9 ± 10.9 mm Hg vs 10.5 ± 12.0 mm Hg; P = 0.023; Δ diastolic blood pressure 9.0 ± 5.5 mm Hg vs 3.0 ± 3.5 mm Hg; P = 0.039).Transvenous, anatomically driven axotomy targeting nerve fibers along the CS enables acute modulation of left ventricular control by selective intracardiac sympathetic denervation.