Renal Denervation Update From the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review

Abstract

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.

Keywords: blood pressure; cardiovascular disease; hypertension; renal denervation; sympathetic nervous system.

FIGURE 1. Results From Recent Renal Denervation Randomized, Sham-Controlled Clinical Trials

Comparison of changes in 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) in renal denervation versus sham-control groups in 3 recent randomized, sham-controlled clinical trials. Reprinted with permission from Kandzari et al. (13), Townsend et al. (15), and Azizi et al (16). ABPM = ambulatory blood pressure monitoring; BP = blood pressure; CI = confidence interval; SPYRAL HTN-ON MED = Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomized trial; SPYRAL HTN-OFF MED = Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomized, sham-controlled, proof-of-concept trial; RADIANCE-HTN SOLO = Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicenter, international, single-blind, randomized, sham-controlled trial.

FIGURE 2. Schematic of Possible Connections Among Different Neural Structures

There are multiple pathways through which renal denervation can directly and indirectly result in brain stem and stellate ganglion remodeling and reduced nerve activity. These include inhibition of afferent nerve signaling (green lines) and retrograde trans-synaptic degeneration (blue lines) (28).

FIGURE 3. Modalities of Procedural Monitoring

The promising 3 modalities of procedural monitoring (direct neural stimulation, reflex elicitation, and passive monitoring) evaluated by new technologies, providing intraprocedural validation of renal denervation.

FIGURE 4. Theoretical Framework for Selective Versus Nonselective Renal Denervation

(Top) The right renal artery sympathetic innervation in (A) anterior and (B) posterior views divided in 3 segments: proximal (green squares), middle (green diamonds), and distal (green triangles). (Bottom) A schematic concept for selective versus global renal denervation: red dots represent “hot spots”—pressor spots. These are nerves that when stimulated increase BP. They are the ideal target for renal denervation. Blue dots represent “cold spots”—inhibitory spots, which lower BP when stimulated. The yellow dots represent the majority of nerve fibers, which are neutral in their contribution to BP control and do not show hemodynamic effects when stimulated. *Connection between ganglia. Adapted with permission from Fudim et al. (39) Mompeo et al. (68). Ag = adrenal gland; Arg = aorticorenal ganglion; Coe = coeliac ganglion; CoT = coeliac trunk; Ig = renal inferior ganglion; LC = contribution of the lumbar chain to the renal plexus; Pg = renal posterior ganglion; RK = right kidney; SMg = superior mesenteric ganglion; SP = thoracic splanchnic nerves.

CENTRAL ILLUSTRATION. Areas of Ongoing Research in the Field of Renal Denervation

BP = blood pressure; NE = norepinephrine; RADIANCE-HTN SOLO = Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicenter, international, single-blind, randomized, sham-controlled trial; SPYRAL HTN-ON MED = Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomized trial; SPYRAL HTN-OFF MED = Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomized, sham-controlled, proof-of-concept trial.