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

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)

10

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

13

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

16

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

25

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


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

31


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


CardioMems PAP Sensor Deployment and Data Collection


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

Brief History of Major Advancements in Cardiac Pacing Mark D. Carlson, MD, MA.

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