This document discusses various interventional therapies for resistant hypertension and renal artery stenosis, including renal sympathetic nerve ablation (RDN), baroreceptor activation therapy (BAT), and arteriovenous shunt creation. It provides details on techniques such as radiofrequency ablation and ultrasound ablation for RDN. It outlines trial results showing reductions in blood pressure from RDN, BAT, and arteriovenous shunts. It also discusses limitations of renal artery stenting based on recent trials. In summary, the document reviews novel interventional approaches for treating difficult cases of high blood pressure.

1. Dr. Osama El-Shahat
Head of Nephrology Department
New Mansoura General Hospital (international)
Vice president of Dakahlia Nephrology Group
ISN Educational Ambassador

2.  Interventional therapies in:-
◦ Resistant hypertension
◦ Renal Artery Stenosis
 Conclusions

3.  Blood pressure that remains above target despite
concurrent use of at least three antihypertensive agents
from different classes at optimal doses, one of which
should be a diuretic

4.  We should exclude pseudoresistance and evaluate of
potential secondary causes of hypertension
 The ability to diagnose true treatment-resistant
hypertension is important for selection of patients who
may be appropriately treated with an invasive therapy.

5. There are three interventional approaches
(1) reduction of the activity of the sympathetic
nervous system by renal nerve ablation
(2) stimulation of baroreceptors
(3) creation of a peripheral arterial venous
anastomosis

8.  In the era preceding the emergence of modern
antihypertensive pharmacotherapy , surgical
denervation was perhaps the only effective approach to
treating patients with significant elevations in blood
pressure.

9.  These crude approaches to unselected sympathetic
denervation were accompanied by significant adverse
events , patients experienced impotence, incontinence
and, almost invariably and orthostatic hypotension.

10.  A number of newer approaches have been developed to
achieve specifically renal sympathetic denervation, but
to avoid the complications of the earlier surgical
approaches.
 Most of these approaches focus on the sympathetic
nerve plexus that surrounds the main trunk of each
renal artery.

11.  These novel approaches include various approaches to
radiofrequency (RF) energy application, use of
ultrasound waves and direct injection of neurotoxins
such as guanethidine .

12.  Anatomic variations are also an issue for successful
RDN, as anatomy must be favorable for the
procedure.
 Typically, the renal artery must be ≥4 mm in
diameter, ≥20 mm in length, with absence of
significant atherosclerosis, previous angioplasty,
fibromuscular dysplasia or accessory arteries.

13.  There are a number of different catheters designed
and in development for RDN.
 The ideal catheter should be safe, easily delivered to
the renal artery, effective in a reproducible fashion
with minimal operator variability, cause little local
trauma to the tissue and facilitate as short a procedure
time as possible.

14.  The most advanced and best investigated of these
strategies is that of percutaneous RF ablation such that
4–6 on average (often more) are applied to the
individual renal artery.

16.  Imaging studies including (MRA) and (CTA) have
indicated absence of atherosclerotic responses to the
RF energy application in denervated arteries.
 This imaging was undertaken both early (1–2 weeks
post-procedure) and late (approximately 6 months
post-procedure) in these early studies.

17.  It was noted that diffuse visceral pain .
 These findings suggest that somatic afferent C-fibres
travel with the sympathetic nerves which were the
targets of the ablation .
 Subsequent to this observation, patients now routinely
receive prophylactic intravenous analgesia and/or
sedation.

18.  One episode of renal artery dissection during the
catheter procedure (but before application of RF
energy) which was subsequently successfully stented.
 There have also been a number of cases of impaired
haemostasis in the groin but at a rate consistent with
other arterial cannulation procedures involving the
femoral artery.

20.  Patients who meet blood pressure criteria then
underwent anatomical screening via MRA, CTA or
duplex scanning and if the renal arteries were found to
be appropriate for intervention they were then
randomized to a control or treatment group with a 6
month primary end point assessment of safety and
efficacy.

21.  The initial 6 month results demonstrated acceptable
safety and a 32/12 mmHg reduction from baseline in
the denervation group (n = 49) compared with a 1/0
mmHg increase in blood pressure in the control group
(n = 51).
 This was achieved despite more patients decreasing
their medication in the denervation group compared
with the control group

23. This is a radiofrequency-based catheter, compatible with
6 Fr and 8 Fr introducer sheaths via the femoral artery,
passed over-the-wire, with a single unipolar electrode at
the tip to create spot lesions using radiofrequency
ablation.
April 26, 2017

24.  Negative outcomes from SYMPLICITY-3 but there are
lessons to be learned.
 A first-generation device was used with significant operator
and procedure variability.
 More recent devices with multiple electrodes may increase
procedure success from a complete denervation perspective
and subsequently clinical outcomes.

25.  A new concept in the field of RDN being the first ultrasound-
based catheter, instead of radiofrequency ablation.
 This design consists of a circumferential balloon catheter,
available in 6 mm or 8 mm, delivered to the renal artery over-
the-wire via a 6 Fr guiding catheter.

26.  The balloon has a cylindrical piezoelectric ultrasound
transducer, which emits circumferential high
frequency sound waves over 30 seconds, generating
heat to induce nerve injury.
 It is recommended to target three different spots per
artery.

27.  Baroreceptor activation therapy (BAT) is another
exciting investigational area for an interventional role
in treatment of hypertension
 Baroreceptors are located at the carotid sinus, at the
level of the bifurcation of the carotid artery and the
aortic arch

29.  First implantation was in 2005.
 Tis requires surgical insertion with bilateral electrodes being
tested intra-operatively to ensure correct positioning and
activation of the right and left carotid sinus with leads
connecting the electrodes to a generator device, placed usually
in the right infraclavicular area.
 It is activated one month after implantation

30.  Two feasibility trials initially assessed the Rheos system, the
Device Based Therapy of Hypertension Trial (DEBUT) in
Europe and US Feasibility trial enrolling 61 patients.
 Two-year follow-up showed :
A sustained reduction in baseline blood pressure of systolic 30
mmHg and diastolic 15 mmHg, with reduced use of
antihypertensive medications.

31.  PIVOTAL trial was a follow-on double-blind study
with 181 patients having device activation one month
after surgery
and 84 having activation at month 7 months after
surgery).
 It confirmed BAT efficacy and long-term device
safety

32.  Patients with advanced chronic obstructive pulmonary
disease underwent studies of arteriovenous (AV) shunt
creation with the theory to improve oxygenation, cardiac
output and functional capacity.
 Large and unexpected blood pressure reductions were
noted suggesting that this may be a treatment option for
resistant hypertension.

33.  Creating a shunt reduces total systemic vascular
resistance by moving blood into the high capacity
venous system, thus reducing blood pressure.

34.  Rox Medical developed The Coupler, a paperclip size
device inserted angiographically between the iliac
artery and vein, creating a 4-mm shunt.

35. (ROX CONTROL HTN)
 Trial published in the Lancet in 2015 evaluated 83 patients
with resistant hypertension.
 Of the 83 patients, 44 underwent implantation of a Coupler
device alongside medication and 39 continued on medical
treatment.
 Patients who received the Coupler device had significant
blood pressure reductions comparing to the control arm
 Ten patients in the active arm had prior unsuccessful RDN,
with good response to AV shunt treatment
Catheterization and Cardiovascular
Interventions 85:880–886 (2015)

36.  Reports from recent trials indicate little additional benefit from
stent supported revascularization in patients with atherosclerotic
renal artery stenosis.
 These data have been questioned and moved the pendulum away
from renal revascularization as a primary maneuver to one
reserved for refractory hypertension and/or progressive loss of
renal function and circulatory congestion.

38. Conclusions
In RADAR, the outcomes of renal artery stenting
were similar to BMT.

39. Doppler ultrasonography was used as the screening tool, and
angiography was the diagnostic method for TRAS. The indications
for PI were
(1) a reduction in lumen diameter of >50% or
(2) a mean pressure gradient of >15 mm Hg.

40.  From October 2009 to July 2015, a total of 660 patients had
kidney transplantation and 22 cases underwent PI. The
technical success was 100%.
Conclusions:
 Percutaneous intervention for TRAS is safe and results in
significant improvement both in allograft function and in BP.

41.  Hypertension is a major risk factor for increased
cardiovascular events .
 Blood pressure is not adequately controlled in many
patients, despite the availability of effective
pharmacotherapy.
 Novel procedure- as well as device-based strategies can be
used in treatment of resistant hypertension.
 RDN initially appeared to be a very successful adjuvant to
medication in the treatment of resistant hypertension, but
this excitement was tempered with SYMPLICITY-3.

42.  Baroreceptor activation therapy may also have a future
role for these patients, however the current device is too
invasive.
 Arteriovenous Shunt is promising in treatment of resistant
hypertension.
 Stenting of renal artery has good results in transplant
kidney but not in native kidney in controlling hypertension

44.  Concerns also exist regarding the potential for high
output cardiac failure and lack of a sham procedure in
this trial. However, further studies need to be
undertaken to fully evaluate the role AV shunt creation
may play in the treatment of resistant hypertension, and
to elucidate the patients that would benefit most from
this procedure in the future

45. Renal artery stenosis: medical versus interventional
therapy.
Textor SC1, Lerman LO.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA. textor.stephen@mayo.edu
 Reports from recent trials indicate little additional benefit from stent
supported revascularization in patients with atherosclerotic renal
artery stenosis.
 These data have been questioned, particularly on the basis of
including subjects with modest occlusive disease and reports of
clinical benefits to patients with episodic congestive heart failure.
Nonetheless, these data have moved the pendulum away from renal
revascularization as a primary maneuver to one reserved for
refractory hypertension and/or progressive loss of renal function and
circulatory congestion.

46.  Recent data emphasize the limits of the kidney
adaptation to reduced blood flow, the eventual
development of widespread renal hypoxia with
activation of inflammatory and fibrogenic pathways.
Experimental data now support developing
adjunctive measures to support angiogenesis and anti-
inflammatory renal repair mechanisms, such as those
observed with cell-based therapy with mesenchymal
stem/stromal cells.

47.  A randomized, multi-center, prospective study
comparing best medical treatment versus best medical
treatment plus renal artery stenting in patients with
hemodynamically relevant atherosclerotic renal artery
stenosis (RADAR) - one-year results of a pre-maturely
terminated study.
Zeller T1, Krankenberg H2, Erglis A3, Blessing E4, Fuss T5,6, Scheinert D7, Weser
R8, Doerr BB9, Yollo WD10, Radermacher J11; RADAR Investigators. 2107

48.  In the diagnosis of treatment-resistant hypertension
include the exclusion of pseudoresistance and the
evaluation of potential secondary causes of
hypertension and of concomitant conditions that
maintain high blood pressure

49.  Short-term procedural adverse effects :
 sustaining nerve injury 9.2 %
 surgical complications 4.4 %
 respiratory complications 2.6 %
 Long-term data suggests favorable regression of left
ventricular hypertrophy and significant reductions in
cardiac dimensions following BAT

50.  There were some complications related procedure or
device,
 two were serious and all resolved without
consequences.
 However, 28.6 % of patients experienced issues with
lower limb edema 2–9 months following the procedure
and were diagnosed with iliac vein stenosis proximal to
the anastomosis.
 Eleven patients required venoplasty and stenting and
one required just venoplasty.

51. Blood pressure was also improved at 1 month postintervention,
as assessed by systolic (157.0 ± 13.0 vs 131.0 ± 11.0 mm
Hg, P < .001), diastolic (95.0 ± 5.0 vs 77.0 ± 9.0 mm Hg, P <
.001), . There was no significant deterioration in graft function
or BP (P > .05) postintervention when compared to
posttransplantation
Conclusions:
 Percutaneous intervention for TRAS is safe and results in
significant improvement both in allograft function and in BP.

52.  Hypertension is a major risk factor for increased
cardiovascular events with accelerated sympathetic
nerve activity implicated in the pathogenesis and
progression of disease. Blood pressure is not
adequately controlled in many patients, despite the
availability of effective pharmacotherapy. Novel
procedure- as well as device-based strategies, such as
percutaneous renal sympathetic nerve denervation,
have been developed to improve blood pressure in
these refractory patients. Renal sympathetic
denervation not only reduces blood pressure but also
renal as well as systemic sympathetic nerve activity in
such patients. The reduction in blood pressure appears

54.  Baroreceptor activation therapy (BAT) is another
exciting investigational area for an interventional role
in treatment of hypertension
 Baroreceptors are located at the carotid sinus, at the
level of the bifurcation of the carotid artery and the
aortic arch
 Stretch mechanoreceptors are activated by pressure in
the arterial wall and information transmitted via the
glossopharyngeal nerve to the nucleus tractus solitarus
in the medulla of the central nervous system