Ample data exists to support the concept of renal sympathetic nerve RF ablation for the treatment of resistant hypertension [1, 2]. Despite these results, an unmet need for alternative approaches still exists, mainly due to the fact that RF renal nerve ablation requires strategically placed ablations separated both longitudinally and rotationally within each renal artery to avoid adverse vascular events, particularly renal artery stenosis, and offer ‘complete’ denervation.

While safety results from pilot studies suggest safety with RF ablation [1], recent findings suggest that a degree of vascular injury exists that may not have initially been appreciated. Using a very sensitive tool for detection of vascular injury, Templin et al. assessed the morphological features of endothelial and vascular injury induced by RF renal nerve ablation using optical coherence tomography [3]. The authors were able to demonstrate local tissue damage that was not apparent with angiography, particularly local and diffuse vasospasm and thrombus formation following endothelial injury. Safety concerns notwithstanding, it has also been difficult to ascertain why as many as 16 % of patients undergoing RDN do not respond. While the precise failure mechanism is not entirely clear, a possible explanation may be missed ablation spots, which are the result of ‘patchy’ ablations or inability of the RF catheter to cause permanent nerve damage. Indeed, next generation RDN RF catheters are now being designed with this in mind. Brachytherapy for RDN may offer a method which is either as safe or perhaps improves on vascular safety, and may prove more efficacious given its large, homogenous effect.

The concept of radiation-mediated nerve injury has been studied in the animal model as well as implemented in current daily clinical practice. In 1985, after discovering that a number of their patients developed clinical signs of lumbosacral or sciatic neuropathy following wide surgical excision plus intraoperative radiotherapy at doses of 20–25 Gy, Kinsella et al. used the canine model to investigate this clinical observation. Loss of nerve fibers, particularly large myelinated fibers, were observed after treatment with 20–75 Gy of intraoperative radiation therapy to the sciatic nerve [4]. No vascular thrombosis or occlusion was observed. A few years later, LeCouteur et al. evaluated radiotherapy on the peripheral nerves in canines and found a graded effect of radiation-induced nerve damage at doses beginning at 15 Gy [5]. Irreversible peripheral neuropathies were seen beginning around 6 months. Histopathological studies of nerves up to 2 years following irradiation demonstrated loss of axons and myelin, with a corresponding increase in endoneurial, perineurial, and epineurial connective tissue. Percentage of axon and myelin decreased to about 60 % of normal at 15 Gy and additionally at higher doses. Sindelar et al. studied pathological changes at autopsy (1–18 months after radiation therapy) for 22 patients who had been treated with intraoperative radiotherapy resulting in perineural fibrosis in the areas that were radiated [6]. Importantly, significant radiation related changes were generally not observed in major blood vessels. Clinically, stereotactic radiosurgery causes focal axonal degeneration of the trigeminal nerve. Gamma knife radiosurgery is now standard treatment for trigeminal neuralgia, showing safety and positive long-term results [7].

For many years, VBT has demonstrated to be a safe method for the treatment of coronary and renal artery in-stent restenosis [8–12]. The theoretical advantage of this approach is one of both safety and efficacy. Available histology data show that the degree of arterial damage may be smaller as compared with other reported methods, and VBT offers the ability to cover a more diffuse vascular segment, allowing, in theory, a more ‘complete’ denervation. This theory was tested by Waksman et al. who initially assessed the safety and feasibility of beta radiation for RDN in the animal model [13].

A total of 10 normotensive domestic swine underwent bilateral renal artery brachytherapy via the Beta-Cath™ 3.5F System (Fig. 12.1) at doses of 25 Gy (n = 8) or 50 Gy (n = 8) at 2 mm from the source center. Compared with untreated arteries serving as controls (n = 4), the VBT procedure proved safe at both the clinical and microscopic levels with no apparent angiographic or intravascular ultrasound injuries to the vessel evident at follow up, (Figs. 12.2 and 12.3) and no thrombus or microscopic evidence of stenosis in any of the larger artery sections. Varying degrees of arteriolar changes were present in the examined sections, with most showing a 2–20 % degree of endothelial cell loss. Importantly, there was no damage to adjacent body tissue or organs.