N = 21

Baroreflex Stimulation:
Emerging Treatment for
Hypertension and Heart Failure
William C. Little, MD
Wake Forest University School of Medicine
Winston-Salem, NC
Disclosures
I have financial relationships to disclose:
Employee of: Wake Forest University Health
Sciences
Consultant for: ABIM, Amylin, BMS,
BioControl Medical, CorAssist,CVRx
Gilead, Medtronic
The Baroreflex as a Therapeutic Target
3
Floras, et al. JACC Vol. 54, No. 5, 2009
Baroreflex Stimulation:
CVRX BaroStimTM
Wireless Programming
System
Baroreflex
Activation Lead
Implantable
Pulse Generator
Baroreflex Stimulation
Continuously Modulates the Autonomic Nervous System
Carotid Baroreceptor Stimulation
Brain
Autonomic Nervous System
Inhibited Sympathetic Activity
Enhanced Parasympathetic Activity
Heart
↓ HR
Vessels
↑ Vasodilation
↓ Stiffness
Kidneys
↑ Diuresis
↓ Renin
secretion
Barostim™: Mechanism of Action for HTN and HF
Programmable Baroreceptor
Stimulation
Brain
Autonomic Nervous System
Reduces Sympathetic Activity
Enhances Parasympathetic Activity
Heart
- Heart rate
- Irritability
Vessels
Kidneys
+ Diuresis
+ Vasodilation
+ Natriuresis
- Stiffness
+ Venous capacitance - RAAS activity
Reduces excessive blood pressure
Reduces myocardial work and oxygen consumption
Reduces neurohormonal stimulus
Reduces arrhythmogenesis
Rheos Baroreflex Activation Therapy
7
Stimulating Carotid Sinus Slows Heart Rate
and Reduces Blood Pressure
63 yo awake female
~ 4 min
MSNA (%)
Blood Pressure (mmHg)
Baroreflex Stimulation Decrease Blood Pressure
and Sympathetic Activity
Heusser et al, HTN 2010
Sustained Blood Pressure Reduction at 1, 2 and 3 Years
Systolic
Diastolic
(Baseline = 192 mmHg)
(Baseline= 108 mmHg)
0
Change in mmHg
-5
-10
N=17
-15
-18
-21
-21
-20
-25
-30
-35
-40
-35
-37
-38
1 Year
2 Years
Anti-hypertensive
Medications
Baseline
5.1  1.2
1 Year
4.5  1.1
2 Years
4.4  2.0
3 Years
4.4  1.5
3 Years
Scheffers et al, J Hypertension 2009
Reduction in Left Ventricular Mass Index at
3 and 12 Months
100%
80%
132
132
60%
116
40%
108
116
108
Severely Abnormal
20%
Mildly or Moderately Abnormal
P < 0.01
P < 0.01
Reference Range
0%
* Based on current ASE guidelines and classifications
Baseline
3 Months
(N=21)
11
12 Months
(N=21)
Bisognano et al, J Clinical Hypertension 2009
Reduction in Left Ventricular Mass Index at
3 and 12 Months
100%
80%
132
132
60%
116
40%
108
116
108
Severely Abnormal
20%
Mildly or Moderately Abnormal
P < 0.01
P < 0.01
Reference Range
0%
* Based on current ASE guidelines and classifications
Baseline
3 Months
(N=21)
12
12 Months
(N=21)
Bisognano et al, J Clinical Hypertension 2009
Heart Rate Variability and Systolic Blood
Pressure After 3 Months
30
N = 21
190
3.5
185
3
175
15
10
SBP (mm Hg)
20
2
1.5
1
5
OFF
ON
RMSSD
165
160
155
145
140
p<0.001
0
0
170
150
0.5
p<0.001
13
180
2.5
Ratio LF:HF
RMSSD (ms)
25
p<0.001
135
OFF
ON
Ratio LF:HF
OFF
ON
SBP
Wustmann K, et al. Hypertension 2009;54;530-536.
Change in Plasma Renin
Plasma Renin (ng/L)
11
10
p < 0.05
9
8
7
6
5
N=12
4
OFF
14
ON
Hiasser K, et al. Hypertension 2010;55:619-626
53 yo Man with Hypertension on 5 Meds
Meds Stopped After Neo BaroStim
53 year old male
639
220
202
200
Pre-Implant
3-Month
184
600
180
No significant change in
BMI was observed in
the patient
500
160
140
127
116
120
100
24-Hr PVC Count
144
142
400
300
80
200
60
44
40
100
20
6
6
0
Patient had all anti-HTN
meds, except a diuretic,
removed over the 3
month period
0
Office SBP
15
Pre-implant medications
included:
• ACE-inhibitor
• ARB
• Beta-blocker
• Calcium channel
blocker
• Diuretic
ABPM SBP
ATI
LVMi
PVC Count
Bisognano J, et al. Heart Rhythm 2009;625:S327
Rheos Pivotal Trial
322 Pts with Resistant Hypertension
183
180
Barostim
168 169 169
170
160
160
N=322
N=322
Screening
Pre-Implant
181
54
Group A
N=84
Group B
Goal – 140
Roll-in
150
Group A
152
Group B
SBP using BpTRU
(mmHg)
No Barostim
178
146
N=80 170
Pre-Activation
(1 month post-
145
143
52
142
N=78
50
166
-20
-30
-10
-32
-32
-10
-16
-26
-32
-32
-36
-36
-40
Bakris et al, J Hypertens 2012
Roll-in
-32
Group A
Group B
-8
Roll-in
Group B
Change in SBP using BpTRU
(mmHg, +/- SE)
-10
Group A
Implant)
0
N=271
Most Recent
(22 – 53 months)
Month 12
Month 6
143
-33
Pre-specified Echo Sub-Study
LV Mass Index (kg/m2)
Long Term Regression in LVH
120
117
p-value < 0.01
115
110
105
102
100
95
90
Bisognano et al, J Am Coll Cardiol 2011
N = 60
N = 60
Baseline
12 Months
Barostim HF Studies
MEDICAL MANAGEMENT (N=70)
Study Objectives
• Ejection fraction
• NYHA Class
• 6 minute hall walk
• NTproBNP
• Minnesota Living with HF Questionnaire
• Evaluate safety
IMPLANT
DEVICE (N=70)
0
1
2
3
LONG-TERM
12 FOLLOW-UP
4 5
8
6
Months Post Activation
OPTIMIZE
MEDS
AND
STABILE ≥
1 MONTH
1:1 RANDOMIZATION
US Barostim HFrEF Feasibility Study
MEDICAL MANAGEMENT (N=30)
IMPLANT
2)
1:1 RANDOMIZATION
OPTIMIZE
MEDS
AND
STABILE ≥
1 MONTH
BASELINE
International Barostim HFrEF Study
BASELINE
1)
DEVICE (N=30)
LONG-TERM
0
1
2
3
12 FOLLOW-UP
4 5
8
6
Months Post Activation
Key Inclusion Criteria
Key Exclusion Criteria
EF ≤ 35%
Known or suspected baroreflex failure or autonomic
neuropathy
NYHA Class III
Body mass index >40
Six-minute hall walk test performance: 150m ≤ 6MW ≤ 450m
Significant, uncontrolled, symptomatic bradyarrhythmias
Heart rate is between 60 and 110 b/min via a clinic
measurement
Asthma, severe COPD (e.g. FEV1<1.5 liter), or severe
restrictive lung disease
No ulcerative carotid plaques or carotid stenosis ≥ 50%
CONFIDENTIAL
21
Summary
• Baroreflex Stimulation (BaroStimTM) in Resistant
Hypertension
– Programmable device with ability to personalize therapy
– Sustained BP reduction with regression of LV Hypertrophy
• Potential Therapy for HF
–
–
–
–
Reduced sympathetic activity
Increased parasympathetic activity
Studies in HFrEF underway
Studies in HFpEF being planned