2 nd Generation

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Transcript 2 nd Generation

Brief History of Major
Advancements in Cardiac Pacing
Mark D. Carlson, MD, MA
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Pacing System Component
pulse generator
•
•
•
•
Casing (can)
• Titanium (biocompatible,
lightweight, stronger than
steel)
Connector (header)
• Leads plug into ports in the
clear epoxy header
Components
• Diodes, resistors, oscillator,
microchips
Battery
• The largest single component
inside the pulse generator
• Lithium iodide
2. Leads
3. Programmer/Remote
monitor
Path to Medical Device Innovation and
Improved Patient Care
 Problem/Opportunity
 Population
 Therapy (Current and Innovative)
 Outcomes
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Path to Medical Device Innovation and Improved
Patient Care
 Problem/Opportunity
 Etiology and Mechanism
 Therapy (Current or Innovative)
 Mechanism of action
 Population
 Risk
 Prevalence
 Incidence
 Outcomes (Clinical/Regulatory/Health Economic)
 Measurements
 Surrogates
 Short/Long Term
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Problem: Sudden Cardiac Death (1960s and Now)
 SCD: the most common cause of death in the U.S.
 Incidence: 300,000 to 400,000 each year (U.S.)
 Only 2% – 15% reach the hospital
 Half of these early survivors die before discharge
Therapy: SCD prevention the1960s, 70s, and 80s
 Frequent PVCs post MI associated with increased
mortality (SCD)
 Assumptions:
 PVCs trigger life-threatening sustained ventricular arrhythmias
 Suppression of PVCs with AAD improves survival
 SCD is increased in post-MI patients with low EF
 Assumptions:
 Induction of sustained VT during EP study identifies patientss
at increased risk
 Suppression of inducibility by AADs improves survival
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Population: Sudden Cardiac Deaths – Incidence and
Prevalence
Incidence (%/Year)
Total Events (#/Year)
Overall Incidence
in Adult Population
High Coronary
Risk Sub-Group
Any Prior
Coronary Event
EF < 30%
Heart Failure
Out-of-Hospital
Cardiac Arrest Survivors
Convalescent Phase
VT/VF After MI
0
1
2
5 10 20 30
(%)
Source: Myerburg RJ. Circulation. 1992;85(suppl I):I-2 – I-10.
0
100
200
(x 1000)
300
Innovative Therapy: Automatic Implantable Defibrillator)
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Timeline
 1966, Dr. Harry Heller died of
SCD in Israel
 1969, Michel Mirowski and
Morton Mower performed the
first canine transvenous
defibrillation at Sinai Hospital,
Baltimore
 1975, First canine implants
 February 4,1980, First human
implant at Johns Hopkins
Early AIDs
 1980-1985 clinical trial of first
ICDs
 1985 FDA approved first ICD
for human use
 First pulse generators were
140 cc (similar to a pack of
cigarettes)
 Abdominal implant
 Thoracotomy patch lead
implant
 Considered tx of last resort
 Patients had failed drugs and
survived two episodes of SCD
Landmark ICD Clinical Trials
1991: CAST
•AADs
suppressed
PVCs but
increased
mortality
1996:
MADIT
•ICDs
reduced
mortality
by 54% vs
AADs
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1997/98:
AVID, CASH,
CIDS
•ICDs
improved
mortality in
secondary
prevention
2002: DAVID I
• Dual-chamber
pacing (70ppm)
vs ventricular
back-up pacing
(40 ppm)
increased
mortality in ICD
pts.
2002:
MADIT II
•ICDs
reduced
mortality
by 31%
vs AADs
2004:
DINAMITE
•ICDs
reduced SD
but not
mortality
early after
MI
2004:
DEFINITE
• ICDs
reduced
SAD and allcause
mortality in
NICM by an
amount that
bordered
significance
2005: SCDHeFT
• ICDs
reduced
mortality vs
amiodarone
or placebo
Advances in ICD Therapy
Lead Implant
Procedure
Implanting Physician
Device size
Procedure time
Perioperative
mortality
Post-implant
hospitalization
Battery longevity
Programmability
Pacing
Monitoring
Sensors
Then
Thoracotomy
Median sternotomy
Lateral thoracotomy
Cardiac surgeon
120 - 140 cc
2 - 4 hours
2.5%
Now
Tranvenous
Skin incision
3 - 5 days
1 day
18 months
None/Defib
None
In clinic
HR
Up to 9 years
Multiple/ATP
DDDR
Remote
Multiple physilogic
EP or surgeon
< 40 cc
1 hour
< 0.5%
Advances in ICD Therapy
Then
Now
Rhythm discrimination
none
Tx Programmability
Pacing
Stored Electrograms
None/Defib
None
None
Monitoring
Sensors
In clinic
HR
MRI compatability
unproven
QRS morphology
Onset
Rate Stability
Multiple/ATP
DDDR
Atrial and Ventricular
At high rates and with therapy
Remote
Activity
Posture
Intrathoracic impedance
Intracardiac ST segment
Intravascular pressure
Validated through clinical
studies
DAVID
 Dual chamber atrial based pacing could be beneficial by
allowing for
 Optimal medical management
 Increased heart rate and cardiac output
 Reduced incidence of AF
 Hypothesis: Dual chamber pacing (70 bpm) decreases
mortality and HF hospitalization for heart failure compared
to ventricular backup pacing (40 bpm).
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DAVID – Results
Death or First Hospitalization for
New or Worsened CHF
Cumulative Probability
Dual-Chamber Rate-Responsive Pacing (DDDR)
Ventricular Backup Pacing (VVI)
0.4
Relative Hazard (95% CI), 1.61 (1.06-2.44)
0.3
0.2
0.1
0
No. at Risk
DDDR
VVI
0
6
250
256
159
158
Time, mo
12
18
76
90
21
25
The DAVID Trial Investigators. Dual-chamber pacing or ventricular backup pacing in
patients with an implantable defibrillator. JAMA. 2002;288(24):3115-3123.
SCD-HeFT Hypothesis
 Determine if amiodarone or ICD* will decrease the
risk of death from any cause in patients with mild-tomoderate heart failure
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Results
HF Prevalence
U.S.




5.8 M heart failure patients in 2006 in the US1
Prevalence: 2.6%1
670,000 people are newly diagnosed each year.1
30% will die in the first year
(US and EU)3-5
 60% will die within 5 years (US)5
 1.1M HF hospitalizations annually; readmission rate is 25% and
50% at 30 days and 6 months
 Annual Medicare costs of ~$37B for hospitalizations with
~$17.4B of costs for readmissions within 30 days
Europe
 15 M heart failure patients in the ESC 51 member countries2
 Overall 2-3% prevalence2
1.
2.
3.
4.
5.
AHA 2010 Statistics at a Glance, 2010
The European Society of Cardiology, ESC HF Guideline, 2008
Curtis et al, Arch Intern Med, 2008.
Roger et al. JAMA, 2004.
Cowie et al, EHJ, 2002.
x
Evolution of CRT Pacing
1st Generation
 Unipolar or bipolar
simultaneous BiV pacing
2nd Generation
 Unipolar or bipolar sequential
BiV pacing (V-V Timing)
25
Cumulative Patients
Cardiac Resynchronization Randomized Trials
4000
CARE HF
MIRACLE ICD
3000
2000
1000
MIRACLE
MUSTIC AF
MIRACLE ICD II
MUSTIC SR
COMPANION
PATH CHF
PATH CHF II
CONTAK CD
0
1999
2000
2001
2002
2003
Results Presented
• Actual •
Projected
Doug Smith:
2004
2005
COMPANION All-Cause Death Results
Event-Free Survival (%)
100
OPT
CRT
CRT-D
90
(CRT vs. OPT) P = 0.059
(CRT-D vs. OPT) P = 0.003
80
70
60
50
0
90
180
270
360 450 540
630
720
810 900 990 1080
Days from Randomization
No. at Risk
OPT
CRT
CRT-D
308
617
595
284
579
555
255
520
517
217
488
470
Bristow M. N Engl J Med. 2004;350:2140-2150.
186
439
420
141
355
331
94
251
219
57
164
148
45
104
95
25
60
47
4
25
21
2
5
1
CRT Challenges
 CRT pacing complications at implant and follow-up
 Phrenic nerve stimulation 1
 High pacing thresholds2
 Lead dislodgement3
 Surgical lead revision increases risks5-7
 Tradeoff: Lead stability vs optimal pacing location4
 Efficacy
1.
2.
3.
4.
5.
6.
28 7.
Biffi M, et al. CICEP, 2009.
Gurevitz O, et al. PACE, 2005.
Leon AR, et al. J Am Coll Cardiol, 2005.
Duray, et al. J of Cardio Electro, 2008.
Klug et al. Circulation, 2007.
Poole JE, et al. Circulation, 2010.
Romeyer-Bouchard et al. EHJ, 2010.
CRT Pacing Challenges: PNS
Up to 37% of CRT patients experience PNS at implant or follow-up
29
 Biffi M, et al. CICEP, 2009.
Evolution of CRT Pacing
1st Generation
 Unipolar or bipolar
simultaneous BiV pacing
2nd Generation
 Unipolar or bipolar sequential
BiV pacing (V-V Timing)
Prox 4
3rd Generation
 Quadripolar selected LV site
BiV pacing
30
Mid 3
Mid 2
Distal 1
Evolution of CRT Pacing
1st Generation
 Unipolar or bipolar simultaneous BiV
pacing
2nd Generation
 Unipolar or bipolar sequential BiV pacing
(V-V Timing)
3rd Generation
 Quadripolar selected LV site BiV pacing
4th Generation
 Quadripolar multisite LV and RV
pacing
31
P4
M3
M2
D1
The Path to Heart Failure Decompensation
Pressure Changes
Autonomic
Adaptation
Impedance
Changes
Weight Changes,
BP, HF
Symptoms
Decompensation
Stable
Time
* Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.
Hospitalization
Implanted LAP Systems
Standalone LAP and Combination CRT/D/LAP
CAUTION: Investigational Device, Limited
by Federal (or United States) Law to
Investigational Use
LAP System: Physician Directed, Patient SelfManagement Paradigm
Jack
PAM
Powers implant by RF
Atmospheric reference
Stores waveform
telemetry
Alerts patient to monitor
 DynamicRX®
 Internet connectivity
CAUTION: Investigational Device, Limited
by Federal (or United States) Law to
Investigational Use
Cardiomems Heart Failure Sensor
Verdejo, H. E. et al. J Am Coll Cardiol 2007;50:2375-2382
CAUTION: Investigational Device, Limited
by Federal (or United States) Law to
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Investigational Use
Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.
CardioMems PAP Sensor Deployment and Data
Collection
CAUTION: Investigational Device, Limited
by Federal (or United States) Law to
Investigational Use
Cumulative HF Hospitalizations Reduced
At 6 Months and Full Duration
Cumulative Number of HFR Hospitalizations
260
Treatment
240
Control
220
37% reduction
Full Duration
200
180
160
140
120
100
80
60
28% reduction
6 Months
40
20
0
0
90
180
270
360
450
540
630
720
810
900
82
67
29
25
5
10
1
0
Days from Implant
No. at Risk
Treatment 270
Control
280
262
267
244
252
210
215
169
179
131
137
108
105
Caution: Investigational Device. Limited by U.S. law to investigational use only.
St. Jude Medical – Sponsored Landmark Clinical Trial
Highlights
ADOPT-A (Atrial Dynamic Overdrive Pacing
Trial)
DAVID - (Dual-chamber
RethinQ -
(REsynchronization THerapy
In Normal QRS)
pAcing or Ventricular backup
–
CRT-D and V-V Timing
pacing in patients with an
JACC 2003
NEJM 2007
(Post AV Nodal Ablation
Implantable Defibrillator) - [DDDR
Chest 2007
Evaluation)
vs. VVIR]
JAMA 2002
JCE 2005
Manuscript published –
(Dual-chamber pAcing
JACC in 2009
or Ventricular backup pacing in patients
(DEFIbrillators in Non-Ischemic
with an Implantable Defibrillator) - [AAIR
Cardiomyopathy Treatment
vs. VVIR]
Evaluation)
- (Fractional flow
– (DefibrillatorManuscript in preparation
NEJM 2004
reserve (FFR) vs. Angiography
– (Optimal
IN Acute Myocardial Infarction
in Multivessel Evaluation)
Pharmacological Therapy in
Trial)
ANALYZE ST NEJM 2009
ICD Patients)
Intracardiac ST segment
NEJM
2004
JAMA
RHYTHM ICD
PAVE
DEFINITE
DAVID II -
FAME
DINAMIT
OPTIC
monitoring to detect ACS
Enrolling
ASSERT – (ASymptomatic
AF Stroke Evaluation in Pacemaker
Patients and the AF Reduction
Atrial Pacing Trial)
NEJM, 2011
FREEDOM - Impact of
CABANA - (Catheter ABlation
Versus ANti-Arrhythmic Drug Therapy for
AF)
Enrolling
BROADEN (BROdmann Area 25 DEep Brain Neurostim
Study)
Enrolling
Frequent QuickOpt CRT
optimization
SCD-HeFT (Sudden Cardiac Death in HEart
Failure Trial)
10-Year Follow-up Study
HRS 2012
FAME II - (Fractional flow
reserve (FFR) vs. Angiography
in Multivessel Evaluation)
LAPTOP HF -
Left Atrial
Pressure to Optimize HF
therapy
Enrolling
NEJM 2010
AF Business Area
CRM Business Area
CV Business Area
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NM Business Area
Medical Technology Innovation Cycle
Bench Testing
and Preclinical
Studies
Feasibility and
Pivotal
Clinical Trials
Therapy
Development
FDA
Post Market
Studies
Identify the
Population
Understand
Etiology
Fine tune
therapy
Device
performance
Problem or
Opportunity
to Improve
therapy
39
Thank You
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