Transcript Therapy of CHF, Outline Slides

Implanted Hemodynamic Monitoring:
Realized & Potential Applications
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]>
I will discuss off label use and/or investigational use of the following
drugs/devices in my presentation: Chronicle® Implanted Hemodynamic Monitor
I have the following relationships to disclose:
Medtronic, Cardiomems, Remon Techonologies: (Grant Support, Advisory
Board, Consultant, Honoraria)
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.
U.S. Population > 65 Years
100
75.6
80
60
40
20
0
16.6
9.2
60
34.9
31.
25.6
1
11.3 12.5 12.7
53.6
Millions
16.6
20.7
% of total
70 80 90 00 10 20 30 40
Year
Courtesy of R. Rodeheffer, Mayo
Congestive Heart Failure
Heart Failure Signs and Symptoms
are Insensitive and Non-specific
Symptoms Include:
 Dyspnea
 Fatigue
 Peripheral Edema
 Orthopnea
 Weight gain
 Rales
 Shortness of breath
 Feeling of tiredness
 Swelling of legs and ankles
 Pulmonary congestion
 Due to fluid retention
 Abnormal lung sounds
Diagnosis and Evaluation of of CHF:
Clinical Challenge
 The symptoms and signs of heart failure like shortness of
breath and edema have a broad differential diagnosis
 The physical exam is neither sensitive nor specific for
volume overload and, even in good hands, there are often
errors.
 Chest X-Ray findings have limited accuracy for CHF
 One-third to one-half of patients with CHF have normal
systolic function
 The needed routine estimate of left sided filling pressures in
the medical management of heart failure is difficult and
fraught with error.
 Even with frequent clinic visits, the average patient with CHF
is usually seen less than once a month.
Adapted and Expanded from Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85
Weight and Edema are
Unreliable over Time
 Weight may stay stable
when fluid increases, if
appetite decreases.
 Weight may increase
despite stable fluid
status over longer period
when patients eat better
 Edema usually indicates
> 2 L of fluid retention
 Many patients never get
edema despite severe
volume overload
Edema and Weight are Unreliable Indices of
Congestion; Especially At Home (Remotely)
 Edema usually indicates >2 L of fluid retention
 Many patients never exhibit edema despite severe
volume overload
 Edema in older populations is more sensitive,
less specific
 Weight may stay stable when fluid increases,
if appetite falls
 Weight may increase over time when patients eat
better
 With chronic heart failure, significant increases in
pressure may occur with little symptoms,
especially at rest.
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
Changes in BNP Levels and Pulmonary Wedge
Pressure During 24 Hours of Treatment
1300
33
PAW
BNP
29
1200
1100
27
25
1000
23
900
21
800
19
700
17
600
15
baseline
4
8
12
16
Hours
15 Heart failure patients responding to vasodilators and diuretics
20
24
BNP (pg/ml)
PAW (mm Hg)
31
Clinical Utility of Serum BNP Levels
 Serum BNP < 100 pg/ml
 Normal or well compensated heart failure
 Serum BNP = 100-200 pg/ml





Well compensated heart failure
Normal (elderly, female, BB use)
Cor pulmonale (right heart failure),
Hypertension, Diastolic Dysfunction
Ischemic Heart Disease,normal resting LVEDP
 Serum BNP = 200 – 400 pg/ml
 Mild - Moderate Decompensated Acute Heart Failure;
moderate to severe HF in obese patient
 Compensated Chronic Heart Failure
 Serum BNP > 400 pg/ml
 Severe Congestive Heart Failure (hypervolemia)
Adapted & expanded from W. Miller, MD, Mayo Clinic and A. Maisel, UCSD.
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
Chronicle Data
ECG
Variables collection
RVSP
 RV Diastolic Pressure
(RVDP)
ePAD (PAD=RVP)
PA press
 RV Systolic Pressure
(RVSP)
 Estimated Pulmonary
Artery Diastolic Pressure
(ePAD)
RV press
RVDP
RV dP/dt
1. Ohlsson A et al.J Cardiac Failure 1995; 1:161-168
2. Chuang PP et al., Journal of Cardiac Failure Vol. 2 No.1 1996:41-46
3. Reynolds DW et al., J Am Coll Cardiol 1995;25:1176-1182.
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
Daily e-PAD Mean and Variability
in pts with or without events
Daily Mean
Daily Variability
mmHg
mmHg
35
6
With events
30.5+6.6
No events
With events
4.2+3.1
30.1+8.2
30
No events
4.0+2.2
4
3.2+2.1
2.7+1.7
25.3+6.1
25.4+5.9
25
2
P<0.001
P<0.001
20
P=0.031
P<0.001
Chronicle
Control
0
Chronicle
Control
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
Sys / Dia
RVP
(mmHg)
Chronicle Patient E4
100
90
80
70
60
50
40
30
20
10
0
-10
-20
0
18-Nov-99
7
14
Time (days)
6-Dec-99
See speaker notes.


Median
No
activity
08-Dec
07-Dec
06-Dec
05-Dec
04-Dec
03-Dec
02-Dec
01-Dec
30-Nov
29-Nov
28-Nov
27-Nov
26-Nov
25-Nov
24-Nov
23-Nov
22-Nov
21-Nov
20-Nov
19-Nov
Data
points:
18-Nov
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
-10.0
17-Nov
mmHg
UAB E4: Systolic / Diastolic, Days 0-18; Lo
days
See speaker notes.

Median

No
days
20-Jun
19-Jun
18-Jun
17-Jun
16-Jun
15-Jun
14-Jun
Data
points:
13-Jun
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
-10.0
12-Jun
mmHg
E4: Systolic / Diastolic, 6/13-6/19
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
Heart Rate
UAB
E19
RV systolic
RV diastolic
RV pulse pressure
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: Heart Rate and Activity
120
10.0
Implant
9.0
8.0
100
7.0
90
6.0
5.0
80
4.0
70
3.0
2.0
60
activity counts (blue)
bpm
110
1.0
50
0.0
13-Oct 14-Oct 15-Oct 16-Oct 17-Oct 18-Oct 19-Oct 20-Oct 21-Oct 22-Oct
days
All data, mean of 2 min resolution
Clinic Visit
See speaker notes.
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: ePAD
45
Implant
40
mmHg
35
30
25
20
15
10
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
19-Oct
20-Oct
days
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
Things are not always as they seem!
Chronicle® Offers Management to Patients
with Advanced Signs & Symptoms of
Heart Failure (COMPASS-HF):
Ambulatory Hemodynamic Guided
Management of Heart Failure
Robert C. Bourge, MD
Mark F. Aaron , MD
Anthony Magalski , MD
Lynne W. Stevenson , MD
Andrew L. Smith , MD
Mark A. O'Shaughnessy , MD
William T. Abraham, MD
Juan M. Aranda, Jr., MD
Philip B. Adamson , MD
Michael R. Zile , MD
Frank W. Smart , MD
Mariell L. Jessup , MD
For the COMPASS-HF Investigators and Coordinators
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
COMPASS-HF Study Hypothesis
A management strategy based on
continuously monitored intra-cardiac
pressures in patients with heart failure
already on optimal medical care improves
patient morbidity
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
COMPASS-HF
Primary Study Endpoints
 Primary Efficacy Endpoint
 HF-related hospitalizations
 HF-related Emergency Department visits requiring
IV therapy
 HF-related urgent clinic visits requiring IV therapy
 Safety Endpoints
 Freedom from system-related complications at 6
months is  80%
 Freedom from pressure sensor lead failure at 6
months is  90%
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Patient Selection
 Diagnosed with chronic NYHA class III-IV
heart failure and on standard medical therapy
for at least 3 months
 At least one prior heart failure related
hospitalization or a heart failure related
Emergency Department visit necessitating
intravenous treatment within 6 months prior
to baseline evaluation
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Methodology
 Subjects were blinded to their randomization
assignment through their 6 month follow-up visit a randomized single-blind study
 All patients transmitted data at least once weekly
via a home-based remote monitor
 Standardized communication scripts were used to
maintain subject blind
 Scheduled surveillance calls were made to the
Control (blocked clinician access) group to
minimize bias
 All major events: primarily hospitalizations,
emergency department and urgent clinic visits
were adjudicated by an Independent Physician
Review Committee blinded to randomization
assignment
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Statistical Methodology
 Hypothesized heart failure event rate was 1.2 for 6
months resulting in a minimum sample size of 274
patients and cumulative, randomized follow-up of 1354
patient months
 Analyzed dataset reports results through June 3, 2005, which
was when all patients completed randomized follow-up (total of
1,620 patient months)
 Normalized HF-related event rates were analyzed using
both Poisson and negative binomial regression model
 An intention to treat principle was used for all study
endpoints
 Pre-specified sub-groups were evaluated for interaction
with outcome and for treatment effect within those prespecified sub-groups
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
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
Pre-specified Sub-group Analysis:
Interaction with Primary Endpoint
Sub-group
(patients%)
Systolic HF (74%)
Chronicle
Control
Events
Events
65
88
Diastolic HF (26%)
19
25
Ischemic (46%)
46
60
Non-Ischemic (54%)
38
53
NYHA Class III (85%)
58
99
NYHA Class IV (15%)
26
14
No Device Rx (60%)
37
64
Device Rx (40%)
47
49
Interaction p-value
Poisson
Negative
Binomial
0.95
0.95
0.95
0.86
0.01
0.08
0.15
0.31
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
Heart Failure Hospitalizations
through 12 Months Follow-up
(All Patients)
Randomized
Follow-up Period
(Implant to 6 months)
Post Randomized
Follow-up Period
(6 to 12 months)
Number of
Events
Rate / 6
months
Number of
Events
Rate / 6
months
CHRONICLE
(n=102)
57
0.56
48
0.54
CONTROL
(n=105)
95
0.90
48
0.53
INVESTIGATOR ADJUDICATED HEART FAILURE HOSPITALIZATIONS
207 patients completing 12 month follow-up visit, or died or withdrew between 6-12 months
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Pressure Changes Associated
with Volume Overload Events
(Daily e-PAD)
Chronicle Group
45
**
Daily ePAD (mmHg)
Daily ePAD (mmHg)
45
Control Group
40
35
30
*
40
**
35
30
25
25
20
20
-49
-28
-14
-1
Days from hospitalization
5
-49
-28
-14
-1
Days from hospitalization
* = p<0.05 vs pressure at 5 days after hospitalization
** =p<0.005 vs pressure at 5 days after hospitalization
5
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
Decreased Heart Failure Hospitalizations
Associated With Use of Chronicle
Information (NYHA Class III)
Randomized Follow-up
Period (Implant to 6 mos)
Post Randomized Follow-up
Period (6 to 12 mos)
Number of
Events
Rate / 6
months
Number of
Events
Rate / 6
months
CHRONICLE
(n=97)
49
0.51
38
0.45
CONTROL
(n=108)
87
0.80
48
0.51
 Investigator adjudicated heart failure hospitalizations
 205 patients with paired data after 6 months randomized period
Bourge, RC, et al. J Am Coll Cardiol 2008;51:1073-9
Mean Changes in Pressures from
Baseline to 12 Months (RVSP)
CHRONICLE
CONTROL
1st 6 months
CONTROL to IHM
2nd 6 months
Change from Baseline (mm Hg)
5
4
3
2
1
2
4
6
8
10
12
0
-1
-2
p=0.21
vs baseline
-3
-4
p=0.0012
vs baseline
-5
Months
COMPASS-HF Summary
 Chronicle IHM system is safe and reliable
 A 21% reduction in rate of heart failure events, beyond
currently available HF therapies (p=0.33)
 Nearly three times as many adjustments of
medications were made in CHRONICLE group, with no
evidence of over-diuresis
 A 36% reduction in relative risk of a HF-related
hospitalization (post-hoc, p=0.03)
 Additional trials are necessary to establish the clinical
benefit of IHM guided care
Bourge, RC J Am Coll Cardiol 2008;51:1073-9
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. Manuscript Submitted
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.
Manuscript Submitted
-1000
500 ms
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. Manuscript Submitted
6
™
®
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
CardioMEMS Wireless Heart Failure Sensor
• Miniaturized, wireless sensor implanted in the
pulmonary artery using a simple catheter-based
technique
• Clinical evaluation has demonstrated safety,
stability and excellent correlation to swan-ganz
catheter
Regression Plot of Sensor vs. SG Mean
Pressure Measurements for All Patients
Sensor reading (mm Hg)
70
60
R2 = 0.9788
50
40
30
20
10
0
0
20
40
SG reading (mm Hg)
60
80
HF Sensor
CardioMEMS Wireless Heart Failure Sensor
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
Remon (Boston Scientific):
Acoustic-Non Data Recording
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
Historical Therapy of Heart Failure: Bloodletting
"The importance of blood-letting , as a medicinal agent, in comparison with
other means of cure, is shown in various respects...it is the least equivocal of
remedies: its good effects, when properly administered, are, in most cases, so
immediate and striking as not to be mistaken...In short, blood-letting is a
remedy which, when judiciously employed, it is hardly possible to estimate too
highly."
On the Proper Administration of Blood-Letting, for the
Prevention and Cure of Disease, (London, 1840) by Henry
Clutterbuck, M.D., Member of the Royal College of
Physicians.*
Anatomical points for Bloodletting:
Castellani, Giovani Marie (1585-1655).
Filactirion della flebotomia et arteriotomia...
(Viterbo, 1619).*
Instruments used in Blood Letting; Scultetus,
Johannes (1595-1645). Armamentarium
hirurgicum...(Lugdunum Batavorum, 1693).).*
Leach Bowl: Bossche, Willem van den. Historia
Medica (Bruxellae,1639). (Image from: Lyons &
Petrucelli. Medicine, an illustrated history. (New
York, 1978).*
* From the UCLA Biomedical Library: www.library.ucla.edu/libraries/biomed
END
Robert C Bourge MD
The University of Alabama at Birmingham
< [email protected] >