Percutaneous Radiofrequency Renal Sympathetic Denervation- Evaluation of results

Introduction:
In Western countries approximately 30-40% of the population exhibits
hypertension. Despite availibility of multiple farmacological therapies,
treatment of hypertension often remains suboptimal. Treatment goals are often
not achieved.
New therapeutical options are warranted for patients with treatmentresistent
hypertension. Recently, a new treatment has become available, namely
Percutaneous Radiofrequency Renal Sympathetic Denervation. The renal
sympathetic nerves are denervated by local ablation. In a recently published
proof-of-principle study, this new treatment resulted in a long persistent
blood pressure lowering effect. And in a decrease in sympathetic tone.

Percutaneous Radiofrequency Renal Sympathetic Denervation:
Renal afferent and efferent nerves play an important role in the development
and maintenance of hypertension. It is already known that sympathetic
denervation results is an effective decrease in blood pressure. But surgical
intervention resulted in a high number of morbidity and mortality. Now a local
treatment is available.

Procedure:
Renal sympathetic denervation is a local ablation of the renal nerves via a
catheter (Ardian Inc®) without effect on surrounding nerves.
Renal sympathetic denervation is achieved by insertion of the catheter through
the renal artery, and then applying radiofrequent ablation while pulling the
catheter from kidney through origo of the artery.
Ablations are applied with a maximum duration of 2 minutes a time and with a
maximum of 8 watt. Median treatment time is 38 minutes (both kidneys). Due to
treatment, pain can occur for which pain medication can be given.

Long term results:
Post procedure blood pressure decreased by 20/11, 24/10, 24/12, 25/12, 29/17,
and 33/14 mmHg at 1, 3, 6, 12, 18, and 24 months respectively. A failure rate
of 10% is reported now. A randomised controlled, recently published, also
showed a significantly lower office blood pressure (32/12 mmHg) after the
procedure in comparison with optimal medical therpay (1/0 mmHg) after 6 months.

Complications:
4 acute complications are reported durng the proof-of-principle study: 3
pseudoaneurysms and 1 renal artery dissection. All of these complications could
be treated during the procedure without further consequences. These
complications are related to the catherisation and not to the treatment itself.
In theory bradycardia could occur, bot none were observed. No late
complications are described.

Safety:
Besides the known complications of arterial catherisation no short and long
term adverse events have been reported so far.

Re-innervation:
So far, no re-innervation has been reported, as has been described in kidney
transplant literature.

Renal sympathetic denervation is currently introduced in the Erasmus Medical
Center. Th objective of the current study is to
1) study the effectiveness and safety of renal sympathetic denervation in
patient with treatment resistent hypertension.
2) study to what extent sympathetic tone is decreased by renal sympathetic
denervation

Since renal sympathetic denervation is only recently available and little
clinical experience is obtained, we aim to start with 10 patients for this
study.

Prior to the procedure standardised 1 hour automated blood pressure is taken.
Basal characteristics are obtained (medical history, comorbidity, medication,
height, length, ECG). Blood withdrawals are performed for CBC, kidney function,
elektrolytes, lipids en blood glucose. Additionally catecholamines, renin,
aldosteron and endothelin-1 are deteremined. All blood withdrawals are taken in
1 procedure through a venous catheter.
Furthermore, 24-hour ambulatory blood pressure monitoring and 24 -hour urine
collection for kreatinine and protein are performed. Prior (and 6 months after)
the procedure, exercise testing is performed with monitoring of ECG and
fingerbloodpressure (Finometer®) and with withdrawal of catecholamines as
determinant for sympathetic tone.

At t=0 renal sympathetic denervation is performed at the intervention radiology
department. Adverse events are noted. Use of aspirine is to be withdrawn 5-7
days prior to procedure. Observation after procedure of 24 hour at the short
stay department.

After renal sympathetic denervation patients are seen at fixed timepoints: 1
week after the procedure and 1, 3, 6, 9 and 12 months after denervation.
Follow-up (FU) takes place at the research department of vascular medicine by
NAJ van der Linde (internist i.o.) and /or. AH van den Meiracker (internist).
During FU at every visit 1 hour automated bood pressure is taken and blood for
catecholamines, renin, aldosteron and endothelin-1 is taken. Furthermore,
adverse advents and actual medication are noted. At 6 months a second
exercisetest is performed. During the other visits 24-h ABPM and collection of
24 h urine are performed at fixed moments.
The study is observational.

- minimum of 1 visit before and 6 visits after the procedure to our research
center within 12 months
- visits app. last: 1.5- 2 h
- visits contain of 1 hour automated blood pressure monitoring, dokters visit,
blood withdrawal
- 3 times collection of 24 hour urine < 12 months
-3 times 24 hour ambulatory blood pressure monitoring < 12 months
- 2 times exercise testing < 3 months
- home bloodpressure measurements