Disclosures: John D. Hummel, M.D.

1
Disclosures John D. Hummel, M.D.

• Research Grants Boston Scientific, Medtronic,
  EP Medsystems, and
• St Jude Medical
• Speakers Bureau/Honoraria Boston Scientific,
• Medtronic, and St Jude Medical
• Advisory Boards Boston Scientific, Medtronic,
  and
• St Jude Medical
• Personal Investment None

2
Prevention of Sudden Cardiac Death Increasing
Awareness In 2006
John D. Hummel, M.D. Mid-Ohio Cardiology and
Vascular Consultants Riverside Methodist
Hospital Columbus, Ohio
3
Why We Talking About This Today?

• There are patients currently in cardiology and
  primary care clinics who are at risk for Sudden
  Cardiac Arrest (SCA)
• For those who have an arrest, 95 of them will
  die (without an ICD).
• There is a simple indicator to assess who is at
  risk for SCA Ejection Fraction (EF)

4
Leading Causes of Death in the US
Septicemia
Nephritis
Only after the deaths from ALL cancers are
combined does anything cause more deaths each
year than sudden cardiac arrest .
Alzheimers Disease
Influenza/pneumonia
Diabetes
Accidents/injuries
Chronic lower respiratory diseases
Cerebrovascular disease
Other cardiac causes
Sudden cardiac arrest (SCA)
All cancers
1 National Vital Statistics Report, Vol 49
(11), Oct. 12, 2001 2 MMWR. State-specific
mortality from sudden cardiac death US
1999.Feb 15, 200251123-126.
5
Magnitude of SCA in the US

• - 450,000 per year1
• 1200 per day
• 50 every hour
• 1 every 80 seconds
• - Although SCA is the first presentation of
  cardiac disease in 20-25 of patients, most cases
  occur in patients with clinically recognized
  heart disease.2

1Circulation. 20011042158-2163. 2 Myerburg RJ,
Castellanos A. Cardiac Arrest and Sudden Cardiac
Death, in Braunwald E, Zipes DP, Libby P, Heart
Disease, A textbook of Cardiovascular Medicine.
6th ed. 2001. W.B. Saunders, Co.
6
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7
Treatments to Reduce SCA

• Improving Pump Function
• ACE inhibitor
• Beta-blocker
• Prevention of Arrhythmias
• Beta-blocker
• Amiodarone
• Terminating Arrhythmias
• ICDs
• AEDs
• Prevent Ventricular Remodeling and Collagen
  Formation
• Aldosterone receptor blockade

• Correcting Ischemia
• Revascularization
• Beta-blocker
• Preventing Plaque Rupture
• Statin
• ACE inhibitor
• Aspirin
• Stabilizing Autonomic Balance
• Beta-blocker
• ACE inhibitor

Zipes DP. Circulation. 1998982334-2351. Pitt B.
N Engl J Med. 20033481309-1321.
8
Cause of SCA
12Other CardiacCause
88ArrhythmicCause
Albert CM. Circulation. 20031072096-2101.
9
Underlying Arrhythmias of Sudden Cardiac Arrest
Torsades de Pointes13
Bradycardia17
VT62
Primary VF8
Bayés de Luna A. Am Heart J. 1989117151-159.
10
SCA Resuscitation Success vs. Time
Chance of success reduced 7 - 10 each minute
Success Non-linear DFT
Time (minutes)
Cummins RO. Annals Emerg Med. 1989181269-1275.
11
SCA Chain of Survival Statistics

• 5 estimated SCA out-of-hospital survival2,3
• Even in the best EMS/early defibrillation
  programs it is difficult to have high survival
  times due to many SCA events not being witnessed
  and the difficulty of reaching victims within 6-8
  minutes.
• 40 SCAs not witnessed or occur in sleep1
• 80 SCAs occur at home1

1 Swagemakers V. J Am Cardiol. 1997301500-1505 2
Ginsburg W. Am J Emer Med. 199816315-319. 3
Cobb LA. Circ. 199285I98-102.
12
Community Survival Rates Before and After Early
Defibrillation Programs (AEDs)
26
19
17
VF Survival
11
10
7
4
4
3
3
Ornato JP. Community experience in treating
out-of-hospital cardiac arrest. In Akhtar M.
Sudden Cardiac Death. Baltimore, Md Williams
Wilkins 1994450-462.
13
What About the High Risk Population?
14
People whove had a heart attack have a sudden
death rate thats 4-6 times that of the
general population.1
1American Heart Association. Heart Disease and
Stroke Statistics2003 Update. Dallas, Tex.
American Heart Association 2002.
15
In people diagnosed with CHF, sudden cardiac
death occurs at 6-9 times the rate of the general
population.1
1 American Heart Association. Heart and Stroke
Statistical 2003 Update. Dallas, Tex.
American Heart Association 2002.
16
Survival After Acute MI
1.0
A
0.8
B
C
0.6
Survivorship
D
0.4
N 536 113 80 37
EF ??30 ??30 ??30 ??30
VPD ??10/hr ??10/hr lt 10/hr ? 10/hr
A B C D
0.2
0
3
2
1
Year
Bigger JT. Am J Cardiology. 19865712B.
17
CAST TRIAL CONCLUSIONS
This is your Heart
This is your Heart on Drugs
18
Primary PreventionICD Trials

• MUSTT
• MADIT II
• SCD-HeFT

Post-MI
Ischemic and Non-ischemic
19
MUSTT Results, Total Mortality Pts With
EF40, NSVT EP (Inducible VT)
0.6
Best Medical Therapy
Best Medical Therapy AA drugs
0.5
Best Medical Therapy ICD
Surveillance
0.4
Event Rate
0.3
p lt 0.001
0.2
0.1
0
0
1
2
3
4
5
Time after Enrollment (Years)
20
Reduced left ventricular ejection fraction (LVEF)
remains the single most important risk factor for
overall mortality and sudden cardiac arrest.
1.00
1.00
0.98
p log-rank 0.002
0.96
0.96
0.94
0.94
Survival
Survival
0.92
0.92
p log-rank 0.0001
0.90
0.90
0.88
0.88
A
B
0.86
0.86
0
30
60
90
120
150
180
0
30
60
90
120
150
180

• Patients withoutLV Dysfunction
• (LVEF gt35)

Days
Days
Patients withLV Dysfunction (LVEF lt 35)
No PVBs1-10 PVBs/hgt 10 PVBs/h
Maggioni AP. Circulation. 199387312-322.
21
MADIT II Protocol
Inclusion Q-wave MI gt 4 weeks, LVEF lt30
ICD implant n742
No-ICD implant n490
(EPS after implant)
(Conventional Post-MI drug Rx)
20 months mean follow- up

• Avoid AAD
• Optimize ?B, ACE-I, Diuretics

Moss AJ. N Engl J Med. 2002346877-83.
22
MADIT-II Survival Results31 Relative Reduction
in MortalityStudy Stopped Early
23
MADIT II All-Cause Mortality
31 Relative Reduction
Hazard Ratio 0.69 (p 0.016)
N 742
N 490
Moss AJ. N Engl J Med. 2002346877-83.
24
Risk of Sudden Death in HF Trials
References in slide notes.
25
SCD-HeFT The Sudden Cardiac Death in Heart
Failure Trial

• Gust Bardy, MD et al, NEJM January 27, 2005
• Largest and longest follow-up ICD trial ever
  conducted
• 2521 patients
• 148 centers
• 41 month median follow-up
• Vital status known on 100 of patients
• Sponsored by NIH
• 70 of Patients were Class II NYHA (Typically
  less sick than in previous ICD trials)
• 48 of Patients were non-ischemic

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SCD-HeFT Primary Conclusions

• In class II or III CHF patients with EF lt 35 on
  good background drug therapy, the mortality rate
  for placebo-controlled patients is 7.2 per year
  over 5 years
• Simple, single lead, shock-only ICDs decrease
  mortality by 23
• Amiodarone, when used as a primary preventative
  agent, does not improve survival

Bardy G et al. NEJM 2005 3523
28
Mortality Benefit Time Dependent
29
Current Recommendations

• ICD Implantation for
• Ischemic Cardiomyopathy gt 4 post-MI with LVEF
  30
• Chronic Ischemic or Non-ischemic cardiomyopathy
  with CHF and LVEF 35
• Further EP evaluation
• Chronic Ischemic or Non-ischemic cardiomyopathy
  with LVEF gt 35 and 45

30
How Effective Are We In Getting ICD Therapy to
Eligible Patients?
1 Ruskin, N. J Cardiovascular Electrophysiologic,
20021338-43. 2 Medtronic internal estimate.
31
Why Arent These Patients Getting ICDs To
Protect Them From Sudden Cardiac Arrest?

• Can We Afford This?
• The US Pharmaceutical industry spends 10B on CV
  Drug marketing
• The predicted cost of 80 application of ICD
  therapy to eligible patients is 8.8 billion
  dollars
• Are Doctors and Patients Paying Attention To This
  Issue
• In the typical CHF clinic (Cardiology Run) 25-35
  of eligible patients have no ICD.
• Many patients will never use their ICD

32
Direct Medical Expenditures on Diseases with
High Mortality (2001 US)
Despite the higher number of SCD deaths, spending
is lower than for diseases with fewer annual
deaths.
1 Bozzette et al., 1998 2 http//www.cdc.gov/hiv/
stats.htm Accessed 2/04/2003 3
http//www.cancer.org/docroot/mit/content/mit_3_2x
_costs_of_cancer.asp Accessed 12/07/2002 4
Healthcare Financing Review, Medicare and
Medicaid Statistical Supplement, 2000
33
Comparison of Healthcare Costs
10.0
9.04
8.97
8.35
9.0
8.0
7.0
6.0
Annual Cost in Billions
5.0
4.0
2.30
3.0
2.0
1.0
0.0
ICD
PTCA
CABG
Statins
Medtronic estimations (total number of implants
x 30,000) Morgan Stanley Dean Witter Research
Report, 2001 / CMS reimbursement data. AHA 2002
/ Cowper, et al American Heart Journal.
143(1)1309.
34
Comparison of Healthcare Costs
350.0
294
300.0
11.6 Bestimated amount due to miscoding,
insufficient documentation, etc. in
Medicare (HCFA 2000 Financial Report)
250.0
Healthcare Administration1
200.0
Annual Cost in Billions
150.0
100
100.0
30
50.0
9
9
8
2
0.0
ICD
CABG
Statins
PTCA
Economic impact of over- prescribing antibiotics
Lost dollars from health care fraud, abuse and
waste
Medtronic estimations (total number of implants
x 30,000). Morgan Stanley Dean Witter Research
Report, 2001 / CMS reimbursement data. AHA 2002
/ Cowper, et al American Heart Journal.
143(1)1309. Pharmacy Times, Top 200 drugs
of 2000 2001. National Institute of Health,
Antimicrobial Resistance, NIAID Fact Sheet.
U.S. General Accounting Office 2001. 1
Woolhandler S, et al. Costs of Healthcare
Administration in the United States and Canada. N
Engl J Med 344, 2003 349 768-75.
35
Societal Spending on Other Life-Saving
Interventions 1
1. Tengs TO, et al. Five-Hundred Life-Saving
Interventions and Their Cost-Effectivenss. Risk
Analysis, Vol. 15, No. 3, 1995.
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We need to educate about EF

• EF is very easy for patients to understand
• Sudden Cardiac Arrest is a scary message
• EF is easy to understand and rally behind
• EF crosses between two at risk patient groups
• Heart Failure and Post-MI
• Research shows low patient awareness of EF
• 86 of Post-Mi and HF patients are aware of Echos
  have had one
• 14 of Post-Mi and HF patients are aware of EF
• Only 5 of patients know their EF
• Conclusions
• Getting an echo is not a key barrier
• Clinicians arent talking EF numbers to patients
• Patients dont know to ask about it

37
EF Program to Help educate and prepare patients
38
Main Heart Patient MessageGet to know your EF
number

• Continue preventive care

• Follow-up echo and clinic visit in 6 months

• Appointment to see an electrophysiologist

39
Implantable Cardioverter Defibrillators in the
Early Days
40
Are All Defibrillators Created Equal?

• Single Chamber
• Dual Chamber
• Three Chamber (Bi-Ventricular, CRT)

41
? The pathophysiology of a wide QRS is
dyssynchrony? The therapy provided by BiV
pacing is to resynchronize activation of the
heart walls so they contract in a nearly
simultaneous manner
BiVentricular PacingCorrects Dyssynchrony
42
CRT Device UtilizationRiverside Hospital

• Device 2001 2002 2003 2004
• Pacer 60 48 42 40
• BiV P 2 2 2
  2
• ICD 34 42 40 35
• BiV ICD 4 8 16
  23

Numbers Represent of Volume
43
CARE HF

• 813 pts with NYHA Class III CHF
• Randomized to Medical Treatment vs. CRT (BiV
  Pacemaker without Defib capability)
• Primary Endpoint Time to death or Unplanned
  Hospitalization for Cardiovascular Event
• Primary Endpoint Reached
• 39 CRT vs. 55 Med Rx at 30 mos (plt0.001)
• Mortality
• 20 CRT vs. 30 Med Rx (plt0.002)
• Echo Parameters of LV Fxn, CHF Class, QOL
• Better with CRT (plt0.01)

44
CRT Whos a candidate

• Standard criteria NYHA gt III, EF lt 35, QRS gt
  120ms.

45
OptiVol Fluid Trends
Sep 29 Crossed OptiVol Threshold.
Oct 7 Regular follow-up. LV Lead dislodgement
OptiVol Threshold crossing observed. No symptoms
reported. Decision made to reposition lead in
November.
Oct 28 Hospitalization for heart failure
decompensation. Patient admitted with orthopnea,
peripheral edema, crackles in lower lungs. BNP
1960 pg/ml. Weight 96 kg. Treated with IV
diuretics.
Nov 5 Lead replacement. Aldactone initiated.
Impedance stabilizes several days after
procedure. BNP 786 pg/ml. Weight 80 kg.
46
Effects of Concurrent Structural Heart Disease
and Rate Control Before Ablation on LV Function
after Ablation Among Patients with CHF
47
Improvement of CHF by Curative Ablation of Atrial
Fibrillation

• 58 consecutive patients with CHF and LVEF45
• Control group of 58 pts. without Hx/o CHF
  undergoing AF ablation,
• matched for age, sex, classification of AF
• Results
• NSR 78 of CHF, 84 non-CHF pts (p0.38)
• Increase in LVEF 21 in CHF pts. (plt0.001 vs.
  non-CHF pts)
• Improvements in LVEF occurred regardless of
  whether there was
• adequate rate control pre-procedure

48
Pulmonary Venous Anatomy
49
74 yo medically refractory AF, Echo Normal AA
Rx - Verapamil, Rythmol, Betapace, Norpace
50
Lasso Catheter
51
Circular Mapping Ablation Catheter inRight
Superior Pulmonary Vein
52
Left Atrium
53
70 y/o Male with PAF Progression of
FractionatedEgm to Organized Egm to Termination
of Arrhythmia Anteroseptal Line
5
6
3
4
I
II
V1
ABL prox
ABL dist
CS prox
CS dist
54
The Bottom Line
55
Bottom Line

• If LVEF 35 Consider Implantable Defibrillator
• If Your Patient Has CHF and a Bundle Branch
  Block Consider BiVentricular Implant or Upgrade
• If Your Patient Has CHF and AFib Consider
  restoration of NSR

56
Quality of Life