Renal Denervation in Resistant...
Transcript of Renal Denervation in Resistant...
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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2 Lenght 45-55 cm
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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