Abstract
Background
Transcatheter renal denervation procedures often produces incomplete renal denervation and inconsistent antihypertensive effect. The lack of an intraprocedural method for renal sympathetic nerve function assessment has precluded a rational and physiologically based approach to ensure adequate denervation has been achieved at the time of the procedure.
Purpose
To demonstrate that it is possible to localise aorticorenal ganglia via transvascular pacing to provide: 1) a testable procedural endpoint for transcatheter renal denervation and, 2) a novel ablation target for renal denervation.
Methods
High frequency pacing in the inferior vena cava and aorta, invasive blood pressure measurements and renal angiography was performed in sheep (N=19) to identify ARG pace-capture sites by concurrent hypertensive and renal vasoconstrictive responses. Group A (N=5) underwent ink injection labelling at the ARG pace-capture site for histological verification; Group B (N=6) received unilateral irrigated radiofrequency ablation of ARG pace-capture sites and assessment of renal innervation at 1week post-procedure; and Group C (N=8) had ARG pacing performed prior to and 2–3 weeks after unilateral transcatheter microwave renal denervation.
Results
ARG pace-capture responses were observed at paired discrete sites in the posterior IVC and anterolateral aorta approximately 40mm above the ipsilateral renal artery. Pacing elicited a mean arterial blood pressure change of 22.2 [IQR 15.5–34.3] mmHg, p<0.001, together with ipsilateral renal vasoconstriction with main renal artery calibre change of −0.42mm [IQR −0.64mm to −0.24mm] measured with quantitative coronary analysis (QCA), p<0.0001, and branch renal artery median pixel density index change −10.4% [IQR −22.7% to −3.0%], p=0.003. Contralateral renal arterial vasoconstriction was not observed consistently at either the main or branch renal artery level. Sympathetic ganglionic tissue was observed at ARG pace-capture sites, and ganglion ablation caused significant ipsilateral renal denervation with a median hilar functional sympathetic nerve area reduction of 51% [IQR 24%–52%], p=0.043, and renal cortical norepinephrine reduction of 54% [IQR 36%–59%], p=0.043. Circumferential renal denervation resulted in immediate and sustained abolition of ARP pacing induced renal vasoconstriction and significant ipsilateral renal denervation.
Conclusion
Localisation of ARG using transvascular pacing is feasible with pace-capture demonstrated by concurrent hypertensive and ipsilateral renal arterial vasoconstrictive responses. Abolition of ARG pacing induced renal arterial vasoconstriction may indicate successful renal sympathetic denervation, providing a physiological procedural endpoint to guide transcatheter renal denervation. Additionally, ablation of ARG could provide an alternative or adjunctive method for renal denervation.
Acknowledgement/Funding
University of Sydney; Western Sydney Local health District; National Health and Medical Research Council of Australia; National Heart Foundation (Au)
Chronic Stress Facilitates the Development of Deep Venous Thrombosis
