Transcript Therapy of CHF, Outline Slides

Robert C. Bourge, M.D., Ph.D.
Director
Division of Cardiovascular Disease
University of Alabama
The Clinical & Investigational Potential
of Implanted Remotely Monitored
Hemodynamic Monitoring Devices
Robert C. Bourge, MD
Professor of Medicine, Radiology and Surgery
M. G. Waters Chair of Cardiovascular Medicine
Director, Division of Cardiovascular Disease
The University of Alabama at Birmingham
<[email protected]>
Congestive Heart Failure:
Definition
“Heart failure occurs when an
abnormality of cardiac function
causes the heart to fail to pump
blood at a rate required by the
metabolizing tissues or when the
heart can do so only with an
elevated filling pressure.”
Report of the Task Force on Research in Heart Failure. National Heart, Lung and Blood Institute, 1994.
Acute Exacerbations Contribute to the
Progression of the Disease
Clinical Status
With each event, hemodynamic
alterations/myocardial injury
contribute to progressive
ventricular dysfunction
Acute event
Heart failure progression
may be accelerated by the
aggressive therapies
initiated during hospitalization
Time
Jain P et al. Am Heart J. 2003;145:S3-S17.
Congestive Heart Failure
Congestion
(as measured by increased intracardiac
end diastolic pressures)

 Symptoms and  Survival
Physiological Premise of IHM Guided
Care (1)
Heart Failure Event
Symptoms
Pressure Changes
-21
-14
-7
Proactive
0
Days
Reactive
Physiological Premise of IHM Guided Care
(2)
Medical Intervention
Averted
Heart Failure Event
Pressure Changes
-21
-14
Proactive
-7
0
Days
Chronicle® Implantable Hemodynamic
Monitor (Medtronic, Inc.)




Implantable Hemodynamic Monitor (IHM), RV lead
4+ year battery life (SVO-Lithium)
Internal memory 512k RAM, 96k ROM
Programable “resolution” from 2 sec - 52 min (mean,
range) and trend data storage from 3.5 hr – 3 months
 Parameters Measured/Calculated/Stored Include:







PA systolic (RV systolic) pressure
PA diastolic (ePAD from RV pressure at +dP/dtmax)
RV diastolic pressure (RA)
Maximum positive and negative RV dP/dt (calculated)
Heart Rate, Temperature, Patient Activity
Pressure and Electrogram Waveforms
Programmable and Patient Initiated Trigger for high-res.
data store
 Additional System Components:
 External Pressure Reference (EPR) – size of “pager”
 Telemetry data download-upload (office/phone)
 Chronicle web site data review via internet browser
Chronicle® Implantable Hemodynamic
Monitor (Medtronic, Inc.)
25g, 14cc
Chronicle IHM - Lead Positioning
Pressure
Sensor
Capsule
Chronicle Pressure Measurements
EGM
1 = RVDP at QRS detection
2
2 = RVSP at peak of waveform
3
3 = ePAD at maximal dP/dt
1
RVP
dP/dt
Accuracy of Intracardiac
Pressure Monitoring
20
40
60
80
100
120
Swan-Ganz RV Systolic Pressure (mmHg)
80
40
60
r = 0.84
0
20
40
60
Chronicle PAD Pressure (mmHg)
r = 0.87
20
60
40
20
0
ePAD
0
Chronicle RV Diastolic Pressure (mmHg)
r = 0.95
80
100 120
Diastolic
0
Chronicle RV Systolic Pressure (mmHg)
Systolic
0
20
40
60
Swan-Ganz RV Diastolic Pressure (mmHg)
0
20
40
60
80
Swan-Ganz PAD Pressure (mmHg)
N = 32 patients, 217 measurements at rest (supine, siting), Valsalva, exercise)
Magalski, A, et al. Continuous Ambulatory Right Heart Pressure Measurements with an Implantable Hemodynamic
Monitor: a Multi-center, 12 Month Follow-up Study of Patients with Chronic Heart Failure, J Card Failure. 2002;8(2):63-70.
120
r = 0.94
20
40
60
80
100 120
6 Months
0
20
40
60
80
100
120
Swan-Ganz RV Systolic Pressure (mmHg)
100 120
80
60
40
20
0
20
40
60
80
100
120
Swan-Ganz RV Systolic Pressure (mmHg)
Chronicle RV Systolic Pressure (mmHg)
Swan-Ganz RV Systolic Pressure (mmHg)
0
Chronicle RV Systolic Pressure (mmHg)
100
12 Months
100 120
80
r = 0.94
80
60
60
40
40
20
r = 0.95
20
60
40
20
0
0
3 Months
0
r = 0.96
80
100 120
Implant
0
Chronicle RV Systolic Pressure (mmHg)
Chronicle RV Systolic Pressure (mmHg)
Chronicle Phase I Validation
0
20
40
60
80
100
120
Swan-Ganz RV Systolic Pressure (mmHg)
Magalsky A. et al., J Card Failure 2002;vol.8 n.2:63-70
Chronicle System & Information Flow
Chronicle IHM
Remote Monitor
Secure
Network
Clinician
Access
Chronicle IHM System
Web Site
94th percentile
Median
6th percentile
Bourge, RC et al. J Am Coll Cardiol 2008;51:1073-9
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
UAB
E011
68y/o male
DM, IHD, EF 45%, severe
diastolic dysfunction, renal
insufficiency, morbidly
obese; peripheral
neuropathy, LE venous
insufficiency, intermittently
non-compliant with salt and
fluid restriction.
CHF/IHD Rx:
torsemide 200 bid
metolazone 5mg bid
spironolactone 50 bid
atenolol 25 qDay
C/o progressive weight gain
(19lbs) over prior weeks,
orthopnea, PND, despite
massive oral diuretic use.
Review of Chronicle IHM
pressures revealed only
modestly increased RV
pressures and no significant
change in serum bNP.
Admitted from clinic with
severe edema for IV therapy.
Heart Rate
Heart Rate
UAB
E011
After admission, treated with
IV diuretics, IV nesiritide, and
strict salt and fluid restriction
with a 16kg diuresis. With
this, he had a significant
improvement in his
symptoms and a modest
reduction in his daytime
filling pressures.
Serum BNP:
99
119
75
112 100
126 54
UAB
E011
Chronicle Nightly Minimum Pressures
Retrospective review of
nightly minimums from
Chronicle:
Note: On April 17th,
metolazone dose was
increased to 5mg bid due to
12 lb weight gain.
After admission, treated with
IV diuretics, IV nesiritide, and
strict salt and fluid restriction
with a 16kg diuresis. With
this, he had a significant
improvement in his
symptoms and a modest
reduction in his daytime
filling pressures.
54
126
75
112
Serum BNP
106
Clinical Explanation ?
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
81yo female – BMI 39.1, BP 108/68, HR 80; Hx of HF (2007), HTN (1995),
PAH and Rt renal artery aneurysm (2006), and diastolic dysfunction CHF
(Jan 2007), hypercholesterolemia, stress incontinence, Atrial Fibrillation; h/o
renal dysfunction when treated with loop diuretics; Referred to UAB for
therapy of pulmonary hypertension, class III+ on presentation.
Study device implanted 8/28/07
Baseline meds (daily) – Carvedilol (50mg), Coumadin (2.5mg), Atorvastatin
(20mg), Triamterene (50mg), Hydrochlorothiazide (50mg)
No changes to medical regimen - patient treated only with changes to diet
Implanted Monitor Derived Hemodynamics
in Pulmonary Arterial Hypertension
 N=8, a sub-study of a pilot implanted hemodynamic
monitor (Chronicle® Device) study in PAH
 RV pressure waveforms recorded utilizing the
implantable monitor and SG catheter
 Breath-by-breath cardiac output was recorded
during acute IV epoprostenol infusion at 3, 6 and 9
ng/kg/min.
 Late systolic pressure augmentation and the
cardiac output were estimated using the right
ventricular pressure waveforms and correlated with
direct measurement of cardiac output (Fick)
Karamanoglu, M, et al, Chest 2007, 132:37-43
CO= 30 x(P1st-PES)x(STI-PEI)/RR
AP=PSYS-P1st
Implanted Monitor Derived
Hemodynamics in PAH
Psys
P1st
40
Qmax
ePAD
mmHg
The basic features of the RV pressure
waveform and the identification of these
feature points using the first derivative of
the RV pressure waveform. Three of
these points identify the turning points
of the PA flow waveform (in mmHg), PEI,
T1st and STI, where PEI = time of
dP/dtmax, T1st = time of the early
shoulder of the RV pressure waveform,
and STI = time of dP/dtmin. The area of
the triangle (shaded area) = (P1st-Pes)x
ED/2 corresponds to estimated stroke
volume (SV). RR = R-R interval
PES
SV
SV
ED
T1st
0
PEI
STI
RR
dP/dtmax
0
mmHg/s
The augmented pressure (AP) caused by
the presence of wave reflection is the
difference between the late systolic
pressure (Psys) and the early systolic
shoulder (P1st).
dP/dtmin
Fig 1, Karamanoglu, M, et al,
Chest 2007, 132:37-43
-1000
500 ms
Implanted Monitor Derived Hemodynamics
in Pulmonary Arterial Hypertension
90
90
mmHg
120
mmHg
120
60
30
0
60
30
0
200
400
600
t (ms)
800 1000
0
0
200
400
600
800 1000
t (ms)
The estimated PA flow waveforms inscribed within the RV pressure
waveforms before (Left) and after (Right) the infusion of IV epoprostenol.
Note that the increase in the estimated stroke volume following the infusion.
Fig 3, Karamanoglu, M, et al, Chest 2007, 132:37-43
6
500
4
300
200
2
mmHg
L/min/m2
400
100
0
0
Measured (L/min/m2)
Implanted Monitor Derived Hemodynamics in
Pulmonary Arterial Hypertension
Cardiac Index
6
5
4
Y=X, r2=0.95
3
2
1
0
0
1
2
3
4
5
6
Estimated
Measured
Dose
L/min/m2
6
4
2
0
01
03
05
06
07
09
31
34
Difference (L/min/m2)
Estimated (L/min/m2)
1.0
+95% CI=0.37 L/min/m2
0.5
Mean=0.0 L/min/m2
0.0
-95% CI=0.37 L/min/m2
-0.5
Bland - Altman Plot
-1.0
0
1
2
3
4
5
2
Average (L/min/m )
Fig 6 & 7, Karamanoglu, M, et al, Chest 2007, 132:37-43
6
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
Heart Rate
UAB E11
Chronically
Implanted
Hemodynamic
Monitor
68y/o male
DM, IHD, EF 45%, severe
diastolic dysfunction,
renal insufficiency,
morbidly obese;
intermittently noncompliant with salt and
fluid restriction.
Rx:
torsemide 150 bid
metolazone
spironolactone 50 bid
atenolol 25 qDay
RV Systolic Pressure (mmHg)
40
RV Diastolic Pressure (mmHg)
20
ePAD (estimated PA diastolic) Pressure (mmHg)
Nesiritide
+ IV
diuretics
Heart Rate
UAB E11
68y/o male
DM, IHD, EF 45%, severe
diastolic dysfunction,
renal insufficiency,
morbidly obese;
intermittently noncompliant with salt and
fluid restriction.
Rx:
torsemide 150 bid
metolazone
spironolactone 50 bid
atenolol 25 qDay
After episode of nausea
and diarrhea, consumed
beef and chicken
bouillon (high in salt).
Admitted with
hyperkalemia (7.7mm/l)
and class IV CHF, 3 lb
weight gain.
RV Systolic Pressure (mmHg)
40
RV Diastolic Pressure (mmHg)
20
ePAD (estimated PA diastolic) Pressure (mmHg)
Nesiritide
+ IV
diuretics
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
Chronicle™ Implantable Hemodynamic Monitor: Patient Example
UAB Pt E1: Systolic and Diastolic
80
70
Implant
60
RVsys
mmHg
50
40
30
20
RVdiast
10
0
-10
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
days
19-Oct
20-Oct
Clinic Visit
21-Oct
22-Oct
Chronicle™ Implantable Hemodynamic Monitor: Patient Example
UAB Pt E1: Temperature
40.0
39.5
39.0
degrees C
Implant
38.5
38.0
37.5
37.0
36.5
36.0
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
19-Oct
20-Oct
days
Clinic Visit
21-Oct
22-Oct
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
COMPASS-HF Study Design / Enrollment
Baseline Evaluation
Withdrew prior to implant = 24
n = 301
Implant Attempted
Unsuccessful implant = 3
n = 277
Total Clinician
Access Group = 134
CHRONICLE
Randomization - 274
(stratified by LVEF  or  50%)
Blocked Clinician
Access Group =140
CONTROL
1 Month Follow-up
1 Month Follow-up
3 Month Follow-up
3 Month Follow-up
6 Month Follow-up
6 Month Follow-up
At 6 months Chronicle guided care enabled in all patients
Study timeline: First implant  March 18, 2003;
Database closed  June 3, 2005
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Study Clinical Care Guidelines
Pressure
State
•
•
(RV systolic, RV diastolic,
Estimated PAD)
Treatment strategy
Hypervolemic
• Medication titration
• Modify dietary restrictions
• ? Hospitalize, ? IV therapy
Optivolemic
• Ongoing management &
assessment
Hypovolemic
• Medication titration
• Modify dietary restrictions
• ? hospitalize, ? fluid
administration
Ranges were determined for each patient at baseline and assessed over time
Guidelines were followed in 96% of patient state assessments
COMPASS Patient Baseline
Characteristics
Chronicle
n=134
Control
n=140
p-value
58  14
58  13
0.75
Gender (% female)
34
36
0.80
Ethnicity (% Caucasian)
47
53
0.71
Etiology (% Ischemic)
47
44
0.72
NYHA (% Class III)
84
87
0.49
2.2  1.9
2.4  1.7
0.29
Concomitant Devices (%)
43
37
0.39
Diuretic Use (%)
93
99
0.02
ACE-I or ARB Use (%)
83
80
0.64
Beta Blockade Use (%)
81
79
0.88
Age, years (mean ± sd)
Prior HF Events (mean ± sd)*
*Six months prior to implantation
RESULTS:
All Safety Objectives Exceeded
Number of
patients at
risk
Number of
complications
(patients)
Complication-free
survival at 6 months
(95% CI)
System
277*
24 (23)
91.5% (88.7%-94.3%)
Sensor
274
0 (0)
100% (98.9%-100%)
* 3 patients had unsuccessful implant
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Comparison of Observed Call
Rates During Randomized Period
Call Type
Group
Mean Call Rate
(Calls/Patient)
CHRONICLE
20.7
Clinician-Initiated
0.88
CONTROL
21.2
CHRONICLE
3.0
Patient-Initiated
0.51
CONTROL
2.8
CHRONICLE
23.7
Overall Call Rate
0.94
CONTROL
CHRONICLE (n=134)
CONTROL (n=140)
p-value
24.0
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Efficacy Objective
Control
(n = 140)
# of Pts with
Events
44
60
Total HF Related
Events
84
113
Hospitalizations
72
99
Emergency
Department Visits
10
11
2
3
0. 67
0.85
Urgent Clinic Visits
Event Rate /
6months*
% Reduction in
Event Rate
1.
2.
Cumulative Events
120
Chronicle
Control
100
Events
Chronicle
(n =134)
(p=0.091;
21%
p=0.332)
80
60
40
20
0
1
2
4
Months
Poisson model - Scaled Deviance = 1.8
Negative Binomial model - Scaled Deviance = 0.8
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
6
Major Component of Primary
Endpoint: HF-related Hospitalization
Time to Event Analysis
Freedom from HF-related
hospitalization
100%
80%
Chronicle
Control
60%
40%
RR = 0.64 (95%CI = 0.42 - 0.96)
p=0.03
20%
0%
0
50
100
150
200
Days
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Efficacy in NYHA Class III Patients
Control
(n = 122)
# of Pts with
Events
35
51
Total HF Related
Events
58
99
50
86
Emergency
Department Visits
6
11
Urgent Clinic Visits
2
3
0. 54
0.85
Hospitalizations
Event Rate /
6months
1
% Reduction in
Event Rate
1.
2.
Cumulative Events
120
100
Events
Chronicle
(n =112)
Chronicle
Control
80
60
40
20
0
2
(p=0.0061;
36%
p=0.0582)
4
6
Months
Poisson model - Scaled Deviance = 1.7
Negative Binomial model - Scaled Deviance = 0.8
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Body Weight and RV Diastolic
Pressure Before Hospitalization
Body Weight
Lbs
RV Diastolic
Pressure
mmHg
300
25
250
20
200
*
*
Chronicle
Control
150
15
*
*
100
7 weeks 4 weeks 2 weeks 1 day
prior
5 days
post
10
7 weeks 4 weeks
* = p<0.05 vs 1 day prior hospitalization
2 weeks
1 day
prior
5 days
post
™
®
Savacor HeartPOD
Heart Failure Therapy System
 Senses:
 Left Atrial Pressure
 Temperature
 IEGM
 ‘Chip’ in tip
 RF power / telemetry
 Personalized-realtime:
LASIX®
(Furosemide)
40 mg
1 white tablet
 Drug management
 CRM programming
RA
LA
LASIX®
40
Recheck in 12h
CardioMEMS Wireless Heart Failure Sensor
HF Sensor technology based on clinically proved commercially
available system for abdominal aneurysms repair monitoring
AAA Sensor
HF Sensor
Externally powered – no battery
Remon Tech (Boston Scientific):
Acoustic-Non Data Recording
 Miniature pressure transducer, attached to
self expanding anchor device, inserted
into pulmonary artery via percutaneous
venous approach
 Implant activated, measurements taken,
data transmitted via ultrasound
 External unit operated by patient, displays
Anchoring device
and records data
 Implant may communicate with other
implanted devices using acoustic
telemetry
 Micro battery, life > 5 years; may be
recharged using acoustic energy
The Implantable Hemodynamic Monitor:
Potential Clinical Applications
 Improve our understanding of the hemodynamic
alterations that occur with heart failure and the
hemodynamic response to therapy
 Allow more precise titration and tailoring of heart failure
and pulmonary vascular disease (PH) therapy
 Provide “early warning” of hemodynamic deterioration
 Aid in the diagnosis of symptomatic events in the
outpatient setting (home or clinic)
 Provide method by which to develop, refine, and
optimize the use of chronic hemodynamic data for longterm patient management
 Possibly affect the intermediate and long term morbidity
and mortality in patients with heart failure
END
Robert C Bourge MD
The University of Alabama at Birmingham
< [email protected] >