Brief History of Major Advancements in Cardiac Pacing Mark D. Carlson, MD, MA.
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Transcript of Brief History of Major Advancements in Cardiac Pacing Mark D. Carlson, MD, MA.
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
5
Path to Medical Device Innovation and Improved Patient Care
Problem/Opportunity Population Therapy (Current and Innovative) Outcomes
6
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
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
8
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
Population: Sudden Cardiac Deaths – Incidence and Prevalence
Overall Incidencein Adult Population
High CoronaryRisk Sub-Group
Any PriorCoronary Event
EF < 30%Heart Failure
Out-of-HospitalCardiac Arrest Survivors
Convalescent PhaseVT/VF After MI
Source: Myerburg RJ. Circulation. 1992;85(suppl I):I-2 – I-10.
3020105210 3002001000(%) (x 1000)
Incidence (%/Year) Total Events (#/Year)
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
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Advances in ICD Therapy
Lead Implant Thoracotomy TranvenousProcedure Median sternotomy Skin incision
Lateral thoracotomyImplanting Physician Cardiac surgeon EP or surgeonDevice size 120 - 140 cc < 40 ccProcedure time 2 - 4 hours 1 hourPerioperative 2.5% < 0.5%mortalityPost-implant 3 - 5 days 1 dayhospitalization Battery longevity 18 months Up to 9 yearsProgrammability None/Defib Multiple/ATPPacing None DDDRMonitoring In clinic RemoteSensors HR Multiple physilogic
Then Now
Advances in ICD Therapy
Rhythm discrimination none QRS morphology Onset
Rate StabilityTx Programmability None/Defib Multiple/ATPPacing None DDDRStored Electrograms None Atrial and Ventricular At high rates and with therapyMonitoring In clinic RemoteSensors HR Activity
Posture Intrathoracic impedance Intracardiac ST segment Intravascular pressure
MRI compatability unproven Validated through clinical studies
Then Now
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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).
The DAVID Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator. JAMA. 2002;288(24):3115-3123.
Relative Hazard (95% CI), 1.61 (1.06-2.44)
Death or First Hospitalization for
New or Worsened CHF
0 6 12 18Time, mo
Cum
ulat
ive
Pro
bab
ility
0.4
0.3
0.2
0.1
0
Dual-Chamber Rate-Responsive Pacing (DDDR)
Ventricular Backup Pacing (VVI)
250
256
159
158
76
90
21
25
No. at Risk
DDDR
VVI
DAVID – Results
SCD-HeFT Hypothesis
Determine if amiodarone or ICD* will decrease the risk of death from any cause in patients with mild-to-moderate heart failure
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Results
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. AHA 2010 Statistics at a Glance, 2010
2. The European Society of Cardiology, ESC HF Guideline, 2008
3. Curtis et al, Arch Intern Med, 2008.
4. Roger et al. JAMA, 2004.
5. Cowie et al, EHJ, 2002.
HF Prevalence
x
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Evolution of CRT Pacing
1st Generation Unipolar or bipolar
simultaneous BiV pacing2nd Generation
Unipolar or bipolar sequential BiV pacing (V-V Timing)
Cardiac Resynchronization Randomized Trials
0
1000
2000
3000
4000
1999 2000 2001 2002 2003 2004 2005
Results Presented
Cum
ulat
ive
Pati
ents
PATH CHF
MUSTIC SR
MUSTIC AF
MIRACLE
CONTAK CD
MIRACLE ICD
PATH CHF II
COMPANION
MIRACLE ICD II
CARE HF
• Actual � Projected
Doug Smith:Doug Smith:
COMPANION All-Cause Death Results
Days from Randomization
Eve
nt-
Fre
e S
urv
ival
(%
)100
90
80
70
60
50
OPT
CRTCRT-D
(CRT vs. OPT) P = 0.059
(CRT-D vs. OPT) P = 0.003
Bristow M. N Engl J Med. 2004;350:2140-2150.
No. at RiskOPT 308 284 255 217 186 141 94 57 45 25 4 2CRT 617 579 520 488 439 355 251 164 104 60 25 5CRT-D 595 555 517 470 420 331 219 148 95 47 21 1
90 9008107206305403602701800 990 1080450
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. Biffi M, et al. CICEP, 2009.
2. Gurevitz O, et al. PACE, 2005.
3. Leon AR, et al. J Am Coll Cardiol, 2005.
4. Duray, et al. J of Cardio Electro, 2008.
5. Klug et al. Circulation, 2007.
6. Poole JE, et al. Circulation, 2010.
7. Romeyer-Bouchard et al. EHJ, 2010. 28
Up to 37% of CRT patients experience PNS at implant or follow-up
29 Biffi M, et al. CICEP, 2009.
CRT Pacing Challenges: PNS
30
Evolution of CRT Pacing
1st Generation Unipolar or bipolar
simultaneous BiV pacing2nd Generation
Unipolar or bipolar sequential BiV pacing (V-V Timing)
3rd Generation Quadripolar selected LV site
BiV pacing
Prox 4
Mid 3
Mid 2
Distal 1
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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 M2
M3
P4
D1
M2
M3
P4
M2
M3
P4
D1
The Path to Heart Failure Decompensation
* Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.
Decompensation
Pressure ChangesImpedance
Changes
Weight Changes, BP, HF
Symptoms Hospitalization
Time
StableDecompensation
Autonomic Adaptation
Implanted LAP SystemsStandalone LAP and Combination CRT/D/LAP
CAUTION: Investigational Device, Limited by Federal (or United States) Law to Investigational Use
Jack
LAP System: Physician Directed, Patient Self-Management Paradigm
PAMPowers implant by RFAtmospheric referenceStores waveform telemetryAlerts patient to monitorDynamicRX®
Internet connectivity
CAUTION: Investigational Device, Limited by Federal (or United States) Law to Investigational Use
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Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.
Verdejo, H. E. et al. J Am Coll Cardiol 2007;50:2375-2382
Cardiomems Heart Failure Sensor
CAUTION: Investigational Device, Limited by Federal (or United States) Law to Investigational Use
CardioMems PAP Sensor Deployment and Data Collection
CAUTION: Investigational Device, Limited by Federal (or United States) Law to Investigational Use
Cu
mu
lati
ve
Nu
mb
er
of
HF
R H
os
pit
aliz
ati
on
s
0
20
40
60
80
100
120
140
160
180
200
220
240
260
Days from Implant
0 90 180 270 360 450 540 630 720 810 900
270 262 244 210 169 131 108 82 29 5 1280 267 252 215 179 137 105 67 25 10 0
No. at RiskTreatmentControl
Treatment Control
Cumulative HF Hospitalizations Reduced At 6 Months and Full Duration
37% reductionFull Duration
37% reductionFull Duration
28% reduction6 Months
28% reduction6 Months
Caution: Investigational Device. Limited by U.S. law to investigational use only.
OPTIC – (Optimal Pharmacological Therapy in
ICD Patients)JAMA
DAVID - (Dual-chamber pAcing or Ventricular backup pacing in patients with an Implantable Defibrillator) - [DDDR vs. VVIR]JAMA 2002Manuscript published – JACC in 2009
RHYTHM ICD - CRT-D and V-V Timing
Chest 2007
FAME - (Fractional flow reserve (FFR) vs. Angiography in Multivessel Evaluation)
NEJM 2009
ASSERT – (ASymptomatic AF Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial)
NEJM, 2011
ADOPT-A - (Atrial Dynamic Overdrive Pacing Trial)
JACC 2003
DEFINITE - (DEFIbrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation) NEJM 2004 DINAMIT –
(Defibrillator IN Acute Myocardial Infarction Trial)
NEJM 2004
BROADEN - (BROdmann Area 25 DEep Brain Neurostim Study)Enrolling
CABANA - (Catheter ABlation Versus ANti-Arrhythmic Drug Therapy for AF)Enrolling
DAVID II - (Dual-chamber pAcing or Ventricular backup pacing in patients with an Implantable Defibrillator) - [AAIR vs. VVIR]Manuscript in preparation
FREEDOM - Impact of Frequent QuickOpt CRT optimization
AF Business Area
CRM Business Area
CV Business Area
NM Business Area
PAVE – (Post AV Nodal Ablation Evaluation)
JCE 2005
RethinQ - (REsynchronization THerapy In Normal QRS)
NEJM 2007
St. Jude Medical – Sponsored Landmark Clinical Trial Highlights
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)
NEJM 2010
38FOR INTERNAL USE ONLY. DO NOT DISTRIBUTE.
LAPTOP HF - Left Atrial Pressure to Optimize HF therapyEnrolling
ANALYZE ST - Intracardiac ST segment monitoring to detect ACSEnrolling
Medical Technology Innovation Cycle
39
FDA
Thank You
40