1. Renal Denervation
Current evidence and new
technical developments
OA Dr. med Massimiliano Fusaro
fusaro@dhm.mhn.de
Deutsches Herzzentrum and 1. Medizinische Klinik, Klinikum rechts der Isar
Technische Universität - Munich, GERMANY
SITE 2013
Barcelona, 9 May 2013

3. US Patients with HTN 75M
Diagnosed HTN 78%
75M
Patients with HTN
Treated HTN 68%
Uncontrolled HTN 38%
Diagnosed HTN
Treated HTN
Uncontrolled HTN
Lloyd-Jones D: Circulation 2010;121:e46 – e215
Persell SD: Hypertension 2011;57:1076-1080
Resistant HTN 9%

4.
•
•
•
Blood pressure >140/90 mmHg
Diabetes mellitus >130-139/85
Chronic renal disease >130/80
In the presence of three or more antihypertensive
drugs of different classes (including diuretic) at
maximal or highest tolerated dose
(European society of hypertension and ESC Guidelines)

5. 1Chobanian
2Lancet
et al. Hypertension 2003;42:1206-1252
2002;360:1903-1913

7. Effec&veness
0
Side
Effects
1940s
1950s
1960s
Direct
Vasodilators
Peripheral
Sympatholytics
Ganglion
Blockers
Veratrum
Alkaloids
Thiazide
Diuretics
1970s
Alpha
Blockers
Central
Alpha2
Agonists
Beta Blockers
1980s
1990s
ACE
Inhibitors
ARBs
2000s
DRIs
DHP CCBs
38% of HTN population remain
Uncontrolled
9% of HTN population remain
resistant

8. Denerva&on
Sites
• Catheter-­‐based
delivery
of
low-­‐power
RF
energy
administered
at
mul&ple
site,
ensures
denerva&on
• Bilateral
denerva&on
required
• Asa
required
during
and
aKer
4
weeks
• Seda&on
and
analgesia
mandatory
90.5%
of
all
nerves
existed
within
2.0
mm
of
the
renal
artery
lumen

10. BP change (mm Hg)
-9
-10
-10
-13
-15
-19
-19
-21
-22
Systolic BP
-26
Diastolic BP
-33
1M (n=143)
3M (n=148)
6M (n=144)
12M (n=130)
24M (n=59)
-33
36M (n=24)

11. Lancet. 2010. published electronically on November 17, 2010
• Purpose: To demonstrate the effectiveness of catheter-based renal
denervation for reducing blood pressure in patients with uncontrolled
hypertension in a prospective, randomized, controlled, clinical trial
• Patients: 106 patients randomized 1:1 to treatment with renal
denervation vs. control
• Clinical Sites: 24 centers in Europe, Australia, & New Zealand
(67% were designated hypertension centers of excellence)
Symplicity HTN-2 Investigators. The Lancet. 2010.
11

12. Inclusion Criteria:
– Office SBP ≥ 160 mmHg (≥ 150 mmHg with type II diabetes mellitus)
– Stable drug regimen of 3+ more anti-HTN medications
– Age 18-85 years
Exclusion Criteria:
– Hemodynamically or anatomically significant renal artery abnormalities or prior renal
artery intervention
– eGFR < 45 mL/min/1.73m2 (MDRD formula)
– Type 1 diabetes mellitus
– Contraindication to MRI
– Stenotic valvular heart disease for which reduction of BP would be hazardous
– MI, unstable angina, or CVA in the prior 6 months
Symplicity HTN-2 Investigators. The Lancet. 2010.
12

13. RDN (n=49)
Control (n=51)
10
∆ from
Baseline
to
6 Months
(mmHg)
1
0
Systolic
Diastolic
0
-10
-12
-20
Diastolic
-30
-40
-32
Systolic
-50
•
•
33/11 mmHg
difference between RDN and Control
(p<0.0001)
84% of RDN patients had ≥ 10 mmHg reduction in SBP
10% of RDN patients had no reduction in SBP
Symplicity HTN-2 Investigators. The Lancet. 2010.
13

14. • No serious device or procedure related adverse events (n=52)
• Minor adverse events
•
1 femoral artery pseudoaneurysm treated with manual compression
•
1 post-procedural drop in BP resulting in a reduction in medication
•
1 urinary tract infection
•
1 prolonged hospitalization for evaluation of paraesthesias
•
1 back pain treated with pain medications & resolved after one month
• 6-month renal imaging (n=43)
•
No vascular abnormality at any RF treatment site
•
1 MRA indicates possible progression of a pre-existing stenosis unrelated to
RF treatment (no further therapy warranted)
Symplicity HTN-2 Investigators. The Lancet. 2010.
14

15. Mahfoud F et al. Eur Heart J 2013

16. 1. Office-based systolic BP ≥ 160 mmHg (≥150 mmHg diabetes type 2)
2. ≥3 antihypertensive drugs in adequate dosage and combination
(incl. diuretic)
3. Lifestyle modification
4. Exclusion of secondary hypertension
5. Exclusion of pseudo-resistance using ABPM (average BP > 130
mmHg or mean daytime BP > 135 mmHg)
6. Preserved renal function (GFR ≥45 ml/min/1.73 m2)
7. Eligible renal arteries: no polar or accessory arteries, no renal artery
stenosis, no prior revascularization
BP, blood pressure;
ABPM, ambulatory blood pressure monitoring;
GFR, glomerular filtration rate.

17. Baseline 3 Mo 6 Mo 12 Mo 24 Mo 36 Mo 48 Mo 60 Mo
Office BP
ABPM
Heart rate
Body weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review medications
X
X
X
X
X
X
X
X
Blood tests, including GFR determination
X
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
X
Renal artery imaging
(duplex ultrasound, MRI/CT with contrast or
angiogram)
X
X
X
X
X
X
X
Oral glucose tolerance test (where appropriate)
X
X
X
X
X
X
X
Echocardiography in patients with heart failure or
left ventricular hypertrophy
X
X
X
X
X
X
X
UACR in patients with albuminuria
X
X
X
X
X
X
X
X
BP, blood pressure;
ABPM, ambulatory blood pressure monitoring;
GFR, glomerular filtration rate
UACR, urine albumin to creatinine ratio.

18. • Long-lasting effect of renal denervation beyond currently
documented 36 months is uncertain
• Repeated intervention for patients with inadequate response
to a first RDN procedure has been raised. with present
knowledge, this could not be recommended.
• In contrast to some antihypertensive drug regimen, renal
denervation has not been shown to affect cardiovascular
morbidity and mortality. The multicentre, prospective, singleblinded, randomized, placebo-controlled
(NCT01418261) is recruiting patients in
the USA, which will hopefully answer the question.

19. •
Diabetes mellitus and insulin resistance
In a pilot study renal denervation positively influenced glucose metabolism in patients with
resistant hypertension (Mahfoud F et al. Circulation 2011;123:1940-1946)
•
Cardiac effects
One published study investigated the effects of renal denervation on left ventricular mass and
diastolic filling pattern in 46 patients with resistant hypertension. Renal denervation was
associated with substantial reductions in blood pressure and significantly reduced left
ventricular mass. Diastolic function was also improved (Brandt MC et al. J Am Coll Cardiol
2012;59:901-909)
•
Chronic kidney disease
In 15 patients with moderate-to-severe chronic kidney renal denervation was effective in terms
of blood pressure lowering and there was no evidence of a further decline in GFR or effective
renal plasma flow 6 months after the procedure. (Hering D et al J Am Soc Nephrol
2012;23:1250-1257)
•
Antiarrhythmic effects
27 patients were randomized to pulmonary vein isolation alone or pulmonary vein isolation plus
renal denervation. Besides significant reductions in blood pressure, patients in the pulmonary
vein isolation plus renal denervation group experienced significantly fewer episodes of atrial
fibrillation at follow-up. (Pokushalov E. et al. J Am Coll Cardiol 2012;60:1163-1170)

20. • Catheter-based radiofrequency ablation of renal nerves
reduces blood pressure and improves blood pressure
control in patients with drug-treated resistant
hypertension, with data now extending out to 36 months
• In patients with resistant hypertension, whose blood
pressure cannot be controlled by a combination of
lifestyle modification and pharmacological therapy
according to current Guidelines
• Renal denervation may also be beneficial in other clinical
states characterized by sympathetic nervous system
activation