Renal Denervation

in Resistant Hypertension

« a Belgian Experience »

Jean Renkin

Alexandre Persu

Cardiology and Interventional Cardiology Units

UCL St Luc University Hospital

Brussels

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Tips and Tricks

for a

Successful Renal Denervation Procedure

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Renal Angiogram

Eligible Anatomy

•Absence of flow-limiting

obstructions and significant

disease

•Vessel Length >= 20 mm

•Diameter ≥4 mm

in targeted area

•Absence of prior

renal angioplasty,

indwelling renal stents,

or aortic grafts

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Non challenging

anatomy

Aortography

Challenging

anatomy

CA6711A DV

01-08-2012

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Appropriate Views/Projections for Selective Angiography

Right Renal Artery: RAO 10-20°

Left Renal Artery : LAO 20-30°

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6 6

Assessing Eligible Anatomy

Accessory Vessel

Partially Supplies

Lower Portions of

the Kidney

Lower Pole Not

Completely Filling

on Selective Injection

Data on file. Medtronic, Inc.

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Triple Right Renal Artery

D69380R

13-07-2011

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Double Left Renal Artery

D69380R

13-07-2011

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Assessing Eligible Anatomy 13-07-2011

BR1823T

Moderately large artery with

acceptable segment proximal

to 1st major bifurcation

QCA : diam 3.51 - 5.86 mm

lenght 56 mm

Marker wire allowing :

- Better support to the guiding cath

- More accurate lenght measurement

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Guide Catheter Selection

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Guide Catheter Selection

Alternate: IMA or LIMA Typical: RDND1 or RDC-1

RDND1 and RDC = renal double curve; IMA = internal mammary artery; LIMA = left internal mammary artery.

Data on file. Medtronic, Inc.

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Use of «Extra-Supportive»

0.014/0.018 Guidewire

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Areas to Avoid

• Avoid treating areas of visible disease

– For example: atherosclerosis, major calcification,

or fibromuscular dysplasia

Atherosclerosis (Ostial Stenosis)

Avoid treating in segment

with stenosis

Calcification

Avoid energy delivery to area with visible calcification

Fibromuscular Dysplasia (FMD)

Avoid treating in segment with FMD

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Dysplastic Right Renal Artery

Long and diffusely

diseased vessel

QCA : diameter 3.51 – 5.51 mm

lenght 60 mm

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Dysplastic Left Renal Artery

Long and diffusely

diseased vessel

QCA : diameter 3.70 – 5.45 mm

lenght 62 mm

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Minor Focal Arterial Wall Changes

First angio

Before ablations

Final angio

after ablations

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Minor Diffuse Arterial Wall Changes

L50914Z

23-03-2011

7 Ablations

(2 incomplete)

Final angio

after ablations

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Our Results in Line

with

Symplicity Trials

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Efficacy – SBP at 6 Months in Symplicity Trials

SBP: Systolic Blood Pressure

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10

0

10%

47%

84%

35%

20

50

30

70

60

40

No decrease

in SBP

39%

6%

>10 mm Hg

decrease in SBP

SBP < 140 mm Hg

at 6 months

%

80

90

Renal Denervation Group (n=52)

Control Group (n=54)

p value for all between-group comparison < 0.0001

Efficacy – SBP at 6 Months in SymplicityHTN2

Esler M. et al. Lancet 2010

SBP: Systolic Blood Pressure

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Change in Office Blood Pressure

Through 36 Months in SymplicityHTN1

BP

ch

an

ge

(mm

Hg

)

P<0.01 for ∆ from BL

for all time points

Sobotka P. ACC 2012

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Efficacy – SBP at 6 Months in SymplicityHTN1 Percentage Responders Over Time

Responder was defined as an office SBP reduction ≥10 mm Hg

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Sobotka P. ACC 2012

DENERVATION RENALE

SymplicityHTN-2 Trial – UCL St Luc

1er Patient Belge traité par Dénervation Rénale

06/11/2009

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Traitement Pharmacologique

5 Nov 2009

• Irbesartan (AprovelR) 300 mg/j

• Bisoprolol (EmconcorR) 5 mg/j

• Prazosine (MinipressR) 5 mg 3x/j

• Amlodipine (AmlorR) 10 mg/j

• Spironolactone (AldactoneR) 100 mg/j

• Furosemide (LasixR) 40 mg/j

• Cardioaspirine 100 mg/j

• Simvastatine 40 mg/j

• + CPAP nocturne

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Resultats Cliniques – TA en Consultation (pt 01)

120

110

174

190

179

128 130

160

140

180

170

150

200

190

TA syst

(mm Hg)

PRESSION

ARTERIELLE

(mm Hg)

Basal 1 Mois 3 Mois 6 Mois

12-Mois

Assis (Moy 3 mesures)

(174 / 108 ) (190 /107.7)

(179.3 / 104)

(128.3/ 77.7)

(130/80 )

Debout (193 /110 ) (204 / 119)

(185 / 107)

(121 / 70)

( / )

Couché (186 / 101 ) (185 / 103 )

(170 / 106)

(126 / 79)

( / )

D

E

N

E

R

V

A

T

I

O

N

Rénale

130 Valeur cible

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Monitoring Ambulatoire de Pression Artérielle à 6 Mois

May 6, 2010

La Tension Artérielle diurne et nocturne est strictement normale

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Traitement Pharmacologique

5 Nov 2009

5 May 2010

• Nisoldipine (SularR ) 10 mg/j

• Cardioaspirine 100 mg/j

• Simvastatine 40 mg/j

• + CPAP nocturne

• Irbesartan (AprovelR) 300 mg/j

• Bisoprolol (EmconcorR) 5 mg/j

• Prazosine (MinipressR) 5 mg 3x/j

• Amlodipine (AmlorR) 10 mg/j

• Spironolactone (AldactoneR) 100 mg/j

• Furosemide (LasixR) 40 mg/j

• Cardioaspirine 100 mg/j

• Simvastatine 40 mg/j

• + CPAP nocturne

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Monitoring Ambulatoire de Pression Artérielle à 1 an

Nov 12, 2010

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Resultats Cliniques – TA en Consultation (pt 02)

120

110

218 204

192

204

130

160

140

180

170

150

200

190

TA syst

(mm Hg)

PRESSION

ARTERIELLE

(mm Hg

Basal 1 Mois 3 Mois 6 Mois

12 Mois

Assis (Moy 3 mesures)

(218 / 88) (204 / 86)

(192 / 72)

(204 / 73)

(183/68)

Debout

(--- /--- ) (184 / 84)

(197 / 79)

(213 / 76)

(189/82)

Couché (222 / 102 ) (203 / 83 )

(184 / 77)

(197 / 73)

(--/--)

D

E

N

E

R

V

A

T

I

O

N

Rénale

183

Target

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Impact of Renal Denervation on Office SBP at 6 Months

128

174

181

152

204

218

186187

175

208

145

161

150

180

141

191

110

120

130

140

150

160

170

180

190

200

210

220

230

1 2

BEFORE 6 MONTHS

Off

ice

Sy

sto

lic

Blo

od

Pre

ss

ure

(m

m H

g)

Treatment Group patients (n=6)

Control Group patients eventually treated 7 months after randomization (n = 2 cross over)

188 ± 18

160 ± 26

Impact of Renal Denervation on office SBP at 6 months

BP ~ 28mmHg

A. Persu, J. Renkin et al. Société Belge de Cardiologie, Brussels, 11-12 February 2011

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120

140

160

180

200

220

240

1 2 3 4

Baseline 1 Month 3 Months 6 Months

Sy

sto

lic

Blo

od

Pre

ss

ure

(m

mH

g)

176 ± 19

165 ± 23

Impact of Renal Denervation on Office Systolic BP at 6 months

n=20

BP ~ 11mmHg

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Clinical Results in Treated Patients Office Systolic Blood Pressure

Symplicity HTN-2 Cohort (n=49) vs. Real World ??

10

0

10%

15-25%

84% 75-80%

20

50

30

70

60

40

No decrease

in SBP

Symplicity HTN-2

Real

Life

39%

15-20%

>10 mm Hg

decrease

in SBP

SBP < 140 mm Hg

at 6 months

%

80

Symplicity HTN-2

Real

Life

Symplicity HTN-2

Real

Life

90

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Safety Profile (1) – data from Homburg/Saar

• 44 minutes mean procedure time

Treatment delivered without complication : 98 % (337/343)

- 5 access site complications

- 1 contrast medium reaction

Vascular complications

- 3 progressions of pre-existing renal artery stenosis

(30-50% up to 80%) possibly related to catheter

manipulation, successfully stented

Mahfoud F. ESC 2012

Vonend O. et al. Lancet. 2012 Aug 25;380(9843):778

Secondary Rise in Blood Pressure after Renal Denervation

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Safety Profile (2)

• No negative impact on:

- Renal function

- GFR in moderate to severe CKD

- Microalbuminuria

- Renal hemodynamics

- Cardiorespiratory response to exercise

- Chronotropic competence

- Orthostatic function

• Positive impact on:

- LV Hypertrophy

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Who are the Good Responders ??

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Blood Pressure Reduction Correlates

to Baseline Systolic Blood Pressure

But no predictor of non response available…

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Limitations of the Evidence Supporting Renal Denervation

in Resistant Hypertension from Symplicity Trials

Treated pts

Control pts

Registry

SYMPLICITY HTN1 153 5

Randomized

SYMPLICITY HTN2 52 54

>35 «crossover»

Total number in

Trials

+/- 250

Total number

Worldwide

(Medtronic files)

+/- 5000

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• True size of significant BP effect in Real World?

• Duration of the effect? (compensatory mechanisms?re-innervation?)

• Determinants of response? (patient vs technique?)

• Mechanisms of (remote) BP decrease? (S. fibrosis vs V. remodeling?)

• Early markers of technical success? (MSNA?)

• Long-term adverse effects (Renal Artery Stenosis, eGFR?)

• Effect on cardio-vascular morbi-mortality?

Limitations of the Evidence Supporting Renal Denervation

in Resistant Hypertension from Symplicity Trials

Open Questions

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Limitations of the Evidence Supporting Renal Denervation

in Resistant Hypertension from Symplicity Trials

Perspectives

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Resistant Hypertension

Electric Rhythmic

Storm

Chronic Kidney Disease

Essential Hypertension

Stage 1-2

Obstructive Sleep Apnea

Syndrome

Insulin Resistance Type 2 Diabetes

Polycystic Ovary

Syndrome

Heart Failure

LV Hypertrophy

Atrial Fibrillation

The Guyton Model

Describing Circulation Regulation

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Renal denervation: for whom? Personal view

– < 80 yo

– Refractory HTN confirmed by ABPM

– At least 3 antihypertensive drugs including a diuretic

– The 5 main classes of antihypertensive drugs (bb, diu, CA,

ACEI, AT1RA) have been tested

– Spironolactone has been considered

– GFR> 40 ml/min/1.73 m2 (30-40 tbd)

– The main causes of secondary HTN have been excluded

(angioscan or abdominal MRI, 24h-urine catecholamines

and cortisol)

– Compliance? (questionnaire, hospitalisation…)

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Renal denervation: for whom? Anatomic criteria (SYMPLICITY HTN-2)

– No significant renal artery stenosis

– No previous PTA

– Diameter 4 mm

– Lenght 20 mm

– No surnumerary renal artery (tbd)

All patients treated by renal denervation should benefit from a

long-term follow-up and be included in an (inter)national registry.

We need new randomized trials to confirm SymplicityHTN2.

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