Congestive Heart Failure: Definition

1
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.
2
Acute Exacerbations Contribute to the Progression
of the Disease
With each event, hemodynamic alterations/myocardi
al injury contribute to progressive ventricular
dysfunction
Heart failure progression may be accelerated by
the aggressive therapiesinitiated during
hospitalization
Time
Jain P et al. Am Heart J. 2003145S3-S17.
3
Congestive Heart Failure

• Congestion
• (as measured by increased intracardiac
• end diastolic pressures)
• ?
• ? Symptoms and ? Survival

4
Physiological Premise of IHM Guided Care (1)
Heart Failure Event
Symptoms
Pressure Changes
Days
-21
-14
- 7
0
Proactive
Reactive
5
Physiological Premise of IHM Guided Care (2)
Averted Heart Failure Event
Medical Intervention
Pressure Changes
Days
-21
-14
- 7
0
Proactive
6
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

7
Chronicle Implantable Hemodynamic Monitor
(Medtronic, Inc.)
25g, 14cc
8
Chronicle IHM - Lead Positioning
Pressure Sensor Capsule
9
Chronicle Pressure Measurements
1 RVDP at QRS detection
2 RVSP at peak of waveform
3 ePAD at maximal dP/dt
10
Accuracy of Intracardiac Pressure Monitoring
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. 20028(2)63-70.
11
Chronicle Phase I Validation
Magalsky A. et al., J Card Failure 2002vol.8
n.263-70
12
Chronicle System Information Flow
Chronicle IHM
Remote Monitor
Clinician Access
Secure Network
13
Chronicle IHM System Web Site
94th percentile
Median
6th percentile
Bourge, RC et al. J Am Coll Cardiol 2008511073-9
14
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16
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure

17
UAB E011
Heart Rate
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.
18
UAB E011
Heart Rate
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.
19
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. Clinical Explanation ?
106
126
112
54
75
Serum BNP
20
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure

21

• 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

22
Implanted Monitor Derived Hemodynamics in
Pulmonary Arterial Hypertension

• N8, 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, 13237-43
23
Implanted Monitor Derived Hemodynamics in
Pulmonary Arterial Hypertension
Karamanoglu, M, et al, Chest 2007, 13237-43
24
Implanted Monitor Derived Hemodynamics in PAH
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 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).
Fig 1, Karamanoglu, M, et al, Chest 2007,
13237-43
25
Implanted Monitor Derived Hemodynamics in
Pulmonary Arterial Hypertension
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,
13237-43
26
Implanted Monitor Derived Hemodynamics in
Pulmonary Arterial Hypertension
Fig 6 7, Karamanoglu, M, et al, Chest 2007,
13237-43
27
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure

28
UAB E11 Chronically Implanted Hemodynamic Monitor
Heart Rate
68y/o male DM, IHD, EF 45, severe diastolic
dysfunction, renal insufficiency, morbidly obese
intermittently non-compliant 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
29
UAB E11
Heart Rate
68y/o male DM, IHD, EF 45, severe diastolic
dysfunction, renal insufficiency, morbidly obese
intermittently non-compliant 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
30
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure

31
Chronicle Implantable Hemodynamic Monitor
Patient Example
Implant
RVsys
RVdiast
32
Chronicle Implantable Hemodynamic Monitor
Patient Example
Implant
33
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure

34
COMPASS-HF Study Design / Enrollment
Baseline Evaluation n 301
Withdrew prior to implant 24
Unsuccessful implant 3
Total Clinician Access Group 134 CHRONICLE
Blocked Clinician Access Group 140 CONTROL
1 Month Follow-up
1 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
2008511073-9
35
Study Clinical Care Guidelines
Pressure
State
Treatment strategy
(RV systolic, RV diastolic, Estimated PAD)

• Medication titration
• Modify dietary restrictions
• ? Hospitalize, ? IV therapy

Hypervolemic

• Ongoing management assessment

Optivolemic

• Medication titration
• Modify dietary restrictions
• ? hospitalize, ? fluid administration

Hypovolemic

• Ranges were determined for each patient at
  baseline and assessed over time
• Guidelines were followed in 96 of patient state
  assessments

36
COMPASS Patient Baseline Characteristics
Chronicle n134 Control n140 p-value
Age, years (mean sd) 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
Prior HF Events (mean sd) 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
Six months prior to implantation
37
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
2008511073-9
38
Comparison of Observed Call Rates During
Randomized Period
Call Type Group Mean Call Rate (Calls/Patient) p-value
Clinician-Initiated CHRONICLE 20.7 0.88
Clinician-Initiated CONTROL 21.2 0.88
Patient-Initiated CHRONICLE 3.0 0.51
Patient-Initiated CONTROL 2.8 0.51
Overall Call Rate CHRONICLE 23.7 0.94
Overall Call Rate CONTROL 24.0 0.94
CHRONICLE (n134)CONTROL (n140)
Bourge, RC, et al. J Am Coll Cardiol
2008511073-9
39
Efficacy Objective
Chronicle (n 134) Control (n 140)
of Pts with Events 44 60
Total HF Related Events 84 113
Hospitalizations 72 99
Emergency Department Visits 10 11
Urgent Clinic Visits 2 3
Event Rate / 6months 0. 67 0.85
Reduction in Event Rate 21 (p0.091 p0.332) 21 (p0.091 p0.332)
Chronicle
Control
6
4
2
Months

1. Poisson model - Scaled Deviance 1.8
2. Negative Binomial model - Scaled Deviance 0.8

Bourge, RC, et al. J Am Coll Cardiol
2008511073-9
40
Major Component of Primary Endpoint HF-related
HospitalizationTime to Event Analysis
Bourge, RC, et al. J Am Coll Cardiol
2008511073-9
41
Efficacy in NYHA Class III Patients
Chronicle (n 112) Control (n 122)
of Pts with Events 35 51
Total HF Related Events 58 99
Hospitalizations 50 86
Emergency Department Visits 6 11
Urgent Clinic Visits 2 3
Event Rate / 6months 0. 54 0.85
Reduction in Event Rate 36 (p0.0061 p0.0582) 36 (p0.0061 p0.0582)
Cumulative Events
120
Chronicle
100
Control
80
Events
60
40
20
0
6
4
2
Months
1

1. Poisson model - Scaled Deviance 1.7
2. Negative Binomial model - Scaled Deviance 0.8

Bourge, RC, et al. J Am Coll Cardiol
2008511073-9
42
Body Weight and RV Diastolic Pressure Before
Hospitalization
Body Weight
RV Diastolic Pressure
Lbs
mmHg




plt0.05 vs 1 day prior hospitalization
43
Savacor HeartPOD Heart Failure Therapy System

• Senses
• Left Atrial Pressure
• Temperature
• IEGM
• Chip in tip
• RF power / telemetry
• Personalized-real-time
• Drug management
• CRM programming

44
CardioMEMS Wireless Heart Failure Sensor
HF Sensor technology based on clinically proved
commercially available system for abdominal
aneurysms repair monitoring
Externally powered no battery
45
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 and
  records data
• Implant may communicate with other implanted
  devices using acoustic telemetry
• Micro battery, life gt 5 years may be recharged
  using acoustic energy

46
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
  long-term patient management
• Possibly affect the intermediate and long term
  morbidity and mortality in patients with heart
  failure