Acute Modulation of Left Ventricular Control by Selective Intracardiac Sympathetic Denervation

BACKGROUND 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). OBJECTIVES The aim of the present study was to modulate left ventricular control by selective intracardiac sympathetic denervation. METHODS 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 1/4 8) before and during stellate ganglion stimulation. RESULTS CS ablation prolonged epicardial ventricular refractory period without (41.8 +/- 8.4 ms vs 53.0 +/- 13.5 ms; P = 0.049) and with b1-2-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 (D systolic blood pressure 21.9 +/- 10.9 mm Hg vs 10.5 +/- 12.0 mm Hg; P = 0.023; D diastolic blood pressure 9.0 +/- 5.5 mm Hg vs 3.0 +/- 3.5 mm Hg; P = 0.039). CONCLUSIONS Transvenous, anatomically driven axotomy targeting nerve fibers along the CS enables acute modulation of left ventricular control by selective intracardiac sympathetic denervation. (J Am Coll Cardiol EP 2023;9:371-384) (c) 2023 by the American College of Cardiology Foundation.

Automated summary

Selective intracardiac sympathetic denervation can modulate left ventricular control by transvenous catheter stimulation along the coronary sinus. Epicardial coronary sinus ablation prolongs ventricular refractory period in mice, while intracardiac axotomy via the coronary sinus attenuates the blood pressure increase in healthy sheep during sympathetic stimulation. Therefore, nerve fiber targeting along the coronary sinus enables acute modulation of left ventricular control by selective sympathetic denervation.