BEST IN PHYSICS (THERAPY) - Stereotactic Radiotherapy for Renal Sympathetic Ablation for the Treatment of Refractory Hypertension
P Maxim1*, M Wheeler1 , P Maguire2 , B Loo1 , (1) Stanford University, Stanford, CA, (2) Cyberheart, Inc., Sunnyvale, CA,
PresentationsWE-E-BRE-2 Wednesday 1:45PM - 3:45PM Room: Ballroom E
Purpose: To determine the safety and efficacy of stereotactic radiotherapy as a novel treatment for patients with refractory hypertension in a swine model. Uncontrolled hypertension is a significant contributor to morbidity and mortality, substantially increasing the risk of ischemic stroke, ischemic heart disease, and kidney failure.
Methods: High-resolution computed tomography (CT) images of anesthetized pigs were acquired and treatment plans for each renal artery and nerve were developed using our clinically implemented treatment planning system. Stereotactic radiotherapy, 40Gy in single fraction was delivered bilaterally to the renal nerves using a state-of-the-art medical linear accelerator under image guidance utilizing dynamic conformal arcs. Dose to nearby critical organs was evaluated by dose-volume histogram analysis and correlated to toxicity data obtained through follow up pathology analysis. The animals were observed for six months with serial measurements of blood pressure, urine analysis, serum laboratories, and overall clinical and behavioral status.
Results: All animals survived to the follow-up point without evidence of renal dysfunction (stable serum creatinine), skin changes, or behavioral changes that might suggest animal discomfort. Plasma norepinephrine levels (ng/ml) were followed monthly for 6 months. The average reduction observed was 63%, with the median reduction at 73.5%. Microscopic evaluation 4-6 weeks after treatment showed evidence of damage to the nerves around treated renal arteries. Considerable attenuation in pan neurofilament expression by immunohistochemistry was observed with some vacuolar changes indicative of injury. There was no histological or immunohistochemical evidence of damage to nearby spinal cord or spinal nerve root structures.
Conclusion: Our preclinical studies have shown stereotactic radiotherapy to the renal sympathetic plexus to be safe and effective in reducing blood pressure, thus this approach holds great promise as a novel treatment modality for patients with refractory hypertension.
Funding Support, Disclosures, and Conflict of Interest: This study was funded by the Stanford University Cardiovascular Institute. B. Loo and P. Maxim have received funding from RaySearch Laboratories.