1. Renal Artery Brachytherapy for Sympathetic Renal Denervation for the Treatment of Resistant Hypertension: Preclinical safety study
Ron Waksman, Issi Barbash, Renu Virmani
MedStar Washington Hospital Center

2. I/we have no real or apparent conflicts of interest to report.
Israel M. Barbash, MD
I/we have no real or apparent conflicts of interest to report.

3. Background
Renal sympathetic efferent and afferent nerves lie immediately adjacent to the wall of the renal arteries
Historical experience of radical surgical approaches for sympathetic denervation were successful in lowering BP with the cost of high rates of morbidity and mortality
Renal sympathetic denervation was achieved more recently with a percutaneous catheter based approach utilizing radio frequency ablation
And play significant role in pathophysiology of HTN

4. SYMPLICITY HTN-2: Office BP was reduced in resistant HTN patients
In patients with RHTN, Data from
Showed
At 6 mo f/u
SYMPLICITY HTN-2, Lancet 2010

5. SYMPLICITY HTN-1, 2 year follow-up: In patients with resistant hypertension, catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to 2 years
2 yr f/u from
Showed paersistent decrease
Up to 24 mo
And data from other RF systems continue to accumulate showing comparable efficacy
SYMPLICITY HTN-1, Hypertension 2011

6. Limitations of RF-ablation mediated-renal denervation
Potential damage to vascular endothelium with late vascular stenosis
Pain associated with the ablation
Need for multiple ablations resulting in long procedure time
RF energy

7. A novel approach for renal denervation by β-radiation using Beta-Cath™ 3.5F System (Novoste)
Potential “sparing” of endothelial injury
Limited perivascular effect
Small sheath size
Short procedure time
Our purpose was to test a ..
No pain

8. Clinical and histologic (arrows) neuropathies were
Radiation-mediated nerve damage was initially identified after intraoperative radiotherapy.
Clinical and histologic (arrows)
neuropathies were
documented after a dose
of only 35 Gy
Theoretical support for this approach comes from studies like this, showing that
LeCouteur et al. Int J Rad Oncol Biol Phys 1989

9. Gamma knife radiosurgery is used routinely for nerve ablation in trigeminal neuralgia
Radiation dosages of Gy in a 4-mm isocenter.
Long term effects of up to 3 years f/u.
Animal histology indicates that gamma knife radiosurgery creates localized, irreversible nerve damage.
Similarly,
Delayed enhancement by MRI indicates fibrosis of the trigeminal nerves
Park et al. J Clinical Neuro 2011, Kondziolka et al. Neurosurg 2000

10. β-radiation induces linear myocardial lesions
The isthmus was irradiated by Beta-Cath catheter ([Sr/Y]-90, Novoste) in 8 dogs.
High dose radiation created effective bidirectional block:
High dose radiation was safe:
Did not damage the endothelium
Created localized transmural lesion
25 Gy
50 Gy n 2 6
Conduction block
Immediate
None
Late (>1 week)
1/2
6/6
With regards to safety
lesion
Guerra & Bonan, Circulation 2004

11. β-radiation has been used to treat ISR in the renal arteries
Patient
Age
Dose (Gy)
F/U (mo)
Adverse events 1 65
20.7 7
None 2 5 3 71
16.9 4 70
22.15 62
21.00
We have a lot of experience with brachytherapy in the coronaries
Jahraus et al. Southern Med J 2003

12. Methods 10 naïve Yorkshire swine
β -emitting radiation dose of 25 or 50 Gy was delivered to the main renal artery
Follow-up of 1-2 months:
Angiography
IVUS
Histology*
* Data available for 1 month follow up

13. Renal artery angiography showed no angiographic stenosis up to 2 months follow-up
Baseline angio
BetaCath location
2 mo f/u

14. IVUS showed no endothelial or adventitial damage
Baseline
1 month
2 months

15. Nerve injury assessment
Perivascular nerve fascicles with mild cellular degeneration, inflammation
and fibrosis
Hypocellular fascicles with cellular degeneration and perineural inflammation
In terms of efficacy, these are 2 H&E slides
2nd: High power mag showing

16. Nerve injury assessment
This slide summarize the histolgy quantification of the
Dose response effect

17. Vascular injury assessment
Focal adventitial fibrosis with myxoid change
Arteriolar fibrinoid necrosis periarteriolar chronic inflammation
In terms of
And damage only to
With sparing of the endothelium of the main vessel

18. Vascular injury assessment
This slide summarize the histolgy quantification of the

19. Conclusions Renal denervation using β-emitting radiation is feasible
In the tested dosages (25-50 Gy) there is minimal vascular damage
β-emitting radiation can cause renal nerve damage
Further clinical studies are required to assess efficacy
If proven effective, dedicated device should be developed
Our preliminary results indicate