Transcript MADIT II - Primary Prevention of SCD - 2004

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
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
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)
Leading Causes of Death in the US
Septicemia
Nephritis
Alzheimer’s Disease
Influenza/pneumonia
Diabetes
Only after the deaths from ALL
cancers are combined does
anything cause more deaths each
year than sudden cardiac arrest .
Accidents/injuries
Chronic lower respiratory diseases
Cerebrovascular disease
Other cardiac causes
Sudden cardiac arrest (SCA)
All cancers
0%
1 National
2
5%
10%
15%
Vital Statistics Report, Vol 49 (11), Oct. 12, 2001
MMWR. State-specific mortality from sudden cardiac death – US 1999.Feb 15, 2002;51:123-126.
20%
25%
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.
2
2001;104:2158-2163.
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.
Treatments to Reduce SCA
Correcting Ischemia
Improving Pump Function
– Revascularization
– ACE inhibitor
– Beta-blocker
– Beta-blocker
Preventing Plaque Rupture
Prevention of Arrhythmias
– Statin
– Beta-blocker
– ACE inhibitor
– Amiodarone
– Aspirin
Stabilizing Autonomic Balance
– Beta-blocker
– ACE inhibitor
Terminating Arrhythmias
– ICDs
– AEDs
Prevent Ventricular Remodeling
and Collagen Formation
– Aldosterone receptor blockade
Zipes DP. Circulation. 1998;98:2334-2351.
Pitt B. N Engl J Med. 2003;348:1309-1321.
Cause of SCA
12%
Other Cardiac
Cause
88%
Arrhythmic
Cause
.
Albert CM. Circulation. 2003;107:2096-2101
Underlying Arrhythmias of
Sudden Cardiac Arrest
Torsades de Pointes
13%
Bradycardia
17%
VT
62%
Bayés de Luna A. Am Heart J. 1989;117:151-159.
Primary VF
8%
SCA Resuscitation Success vs. Time*
100
90
Chance of success reduced
7 - 10% each minute
80
70
60
%
Success
50
*Non-linear 40
DFT
30
20
10
0
1
2
3
4
5
6
Time (minutes)
Cummins RO. Annals Emerg Med. 1989;18:1269-1275.
7
8
9
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. 1997;30:1500-1505
2 Ginsburg W. Am J Emer Med. 1998;16:315-319.
3 Cobb LA. Circ. 1992;85:I98-102.
Community Survival Rates Before and After Early
Defibrillation Programs (AED’s)
30
26%
Before Early DF
After Early DF
VF Survival
25
19%
20
17%
15
10
11%
10%
7%
5
3%
4%
3%
4%
0
King County,
WA
Iowa
SE Minnesota NE Minnesota
Ornato JP. Community experience in treating out-of-hospital cardiac arrest. In: Akhtar M.
Sudden Cardiac Death. Baltimore, Md: Williams & Wilkins; 1994:450-462.
Wisconsin
What About the High Risk Population?
“People who’ve had
a heart attack have a
sudden death rate that’s
4-6 times
that of the general population.”1
1American
Heart Association. Heart Disease and Stroke Statistics—2003 Update. Dallas, Tex.:
American Heart Association; 2002.
In people diagnosed with CHF,
sudden cardiac death occurs at 6-9
times the rate of the general
population.1
American Heart Association. Heart and Stroke Statistical –2003 Update. Dallas, Tex.: American
Heart Association: 2002.
1
Survival After Acute MI
1.0
A
Survivorship
0.8
B
C
0.6
D
0.4
0.2
0
A
B
C
D
N
536
113
80
37
EF
30%
30%
30%
30%
VPD
10/hr
10/hr
< 10/hr
 10/hr
1
2
Year
Bigger JT. Am J Cardiology. 1986;57:12B.
3
CAST TRIAL CONCLUSIONS
This is your Heart
This is your Heart on Drugs
Primary Prevention
ICD Trials
•
MUSTT
•
MADIT – II
•
SCD-HeFT
Post-MI
Ischemic and Non-ischemic
MUSTT Results, Total Mortality:
Pts With EF≤40%, NSVT EP (Inducible VT)
0.6
Best Medical Therapy
Best Medical Therapy + AA drugs
Best Medical Therapy + ICD
Surveillance
Event Rate
0.5
0.4
0.3
p < 0.001
0.2
0.1
0
0
1
2
3
Time after Enrollment (Years)
4
5
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
Survival
Survival
0.96
0.94
0.92
0.94
0.92
0.90
0.90
0.88
0.88
p log-rank
0.0001
A
B
0.86
0.86
0
30
60
90
Patients without
LV Dysfunction
120
150
180
0
30
Days
(LVEF >35%)
60
90
120
Days
No PVBs
1-10 PVBs/h
> 10 PVBs/h
Maggioni AP.
Circulation.
1993;87:312-322.
Patients with
LV Dysfunction
(LVEF < 35%)
150
180
MADIT II Protocol
Inclusion: Q-wave MI > 4 weeks,
LVEF <30%
ICD implant n=742
No-ICD implant n=490
(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. 2002;346:877-83.
MADIT-II Survival Results
31% Relative Reduction in Mortality
Study Stopped Early
1.0
Probability of
Survival
0.9
Defibrillator
14% Mortality
0.8
0.7
p = 0.007
0.6
Conventional
Medical Therapy
20% Mortality
0.0
0
1
2
Year
3
4
MADIT II: All-Cause Mortality
19.8%
20.00%
31% Relative
Reduction
Hazard Ratio=
0.69
(p= 0.016)
14.2%
10.00%
0.00%
Conventional Therapy
N= 490
Moss AJ. N Engl J Med. 2002;346:877-83.
ICD Therapy
N= 742
Risk of Sudden Death in HF Trials
Study
HF
Class
Control
(n)
Treatment
(n)
MERIT-HF1
2-4
2001
1990
Total Mortality
Reduction
w/Treatment
Sudden Death as %
of Total Death in
Control Arm
Sudden Death- as
a % of Total Death
in Treatment Arm
34%
(60%)
(54%)
132/217
79/145
(45%)
(44%)
203/449
182/411
(36%)
(31%)
83/228
48/156
(48%)
(54%)
15/31
12/22
(28%)
(29%)
110/386
162/478
(36%)
(34%)
201/554
162/478
(Metroprolol)
BEST2
3,4
1354
1354
10%
(Bucindolol)
CIBIS-II3
3,4
1320
1327
34%
(Bisoprolol)
CARVEDILOL(U.S.)4
2-4
RALES5
3, 4
EPHESUS6
2-4
398
841
3313
696
882
3319
65%
30%
15%
References in slide notes.
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
SCD-HeFT: Primary Conclusions
1.
In class II or III CHF patients with EF < 35% on good
background drug therapy, the mortality rate for placebocontrolled patients is 7.2% per year over 5 years
2.
Simple, single lead, shock-only ICDs decrease mortality
by 23%
3.
Amiodarone, when used as a primary preventative agent,
does not improve survival
Bardy G et al.
NEJM 2005; 352:3
Mortality Benefit: Time Dependent
Current Recommendations
• ICD Implantation for
– Ischemic Cardiomyopathy > 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 > 35% and ≤ 45%
How Effective Are We In Getting
ICD Therapy to Eligible Patients?
Indication/
Estimated
Patient Groups
Net Prevalence
Estimated %
Penetration of Net
Prevalence
Class I
(AVID, MADIT, MUSTT,
MADIT-II, SCD-Heft)
1
Ruskin, N. J Cardiovascular Electrophysiologic, 2002;13:38-43.
2 Medtronic internal estimate.
670,000
~20% 1,2
Why Aren’t These Patients Getting ICD’s 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
Direct Medical Expenditures on Diseases
with High Mortality (2001 $US)
Dollars (Billions)
20
Despite the higher number of SCD
deaths, spending is lower than for
diseases with fewer annual deaths.
19.5
15
10
8.2
5
5
6
3.7
0
AIDS 1, 2
1
Breast Cancer 3 Lung Cancer 3
Stroke 4
Cardiac
Dysrhythmia 4
Bozzette et al., 1998
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
2
Comparison of Healthcare Costs
10.0
8.35
Annual Cost in Billions
9.0
8.97
9.04
8.0
7.0
6.0
5.0
4.0
3.0
2.30
2.0
1.0
0.0
ICD*
PTCA†
*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):130–9.
CABG+
Statins‡
Comparison of Healthcare Costs
350.0
294
Annual Cost in Billions
300.0
$11.6 B—estimated
amount due to
miscoding, insufficient
documentation, etc. in
Medicare
250.0
200.0
Healthcare
Administration1
(HCFA 2000 Financial Report)
150.0
100
100.0
50.0
2
0.0
ICD*
8
9
9
30
PTCA† CABG+ Statins‡
Economic impact
of overprescribing
antibiotics^
*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):130–9.
‡ 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.
Lost dollars from
health care fraud,
abuse and waste^^
Societal Spending on Other
Life-Saving Interventions 1
Cost/Life-Year
Intervention
Flashing lights at railroad crossings
$42,000
Flammability standard for upholstered furniture
$68,000
Airbags (vs. manual lap belts) in cars
$120,000
Annual mammography for women age 40-49
$190,000
Smoke detectors in homes
$210,000
Front disk (vs. drum) brakes in cars
$240,000
Strengthen buildings in earthquake-prone areas
$18,000,000
Ground fault circuit interrupters
$1,200,000
1. Tengs TO, et al. Five-Hundred Life-Saving Interventions and Their Cost-Effectivenss. Risk Analysis, Vol. 15, No. 3, 1995.
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 aren’t talking EF numbers to patients
»
Patients don’t know to ask about it
EF Program to Help educate and prepare
patients
Main Heart Patient Message:
“Get to know your EF number”
• Continue preventive • Follow-up echo and
care
clinic visit in 6
months
• Appointment to see an
electrophysiologist
Implantable Cardioverter Defibrillators in the
Early Days
Are All Defibrillators Created Equal?
• Single Chamber
• Dual Chamber
• Three Chamber (Bi-Ventricular, CRT)
BiVentricular Pacing
Corrects Dyssynchrony
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
●
CRT – Device Utilization
Riverside 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
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 mo’s (p<0.001)
• Mortality:
20% CRT vs. 30% Med Rx (p<0.002)
• Echo Parameters of LV Fxn, CHF Class, QOL:
– Better with CRT (p<0.01)
CRT – Who’s a candidate
Standard criteria: NYHA > III, EF < 35%, QRS >
120ms.
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.
Heart Disease
70
65
60
55
50
45
40
35
30
25
0
B
P<0.001
No concurrent
heart disease
P<0.001
Concurrent
heart disease
0
Month
12
Chronic AF
LV Ejection Fraction (%)
C
70
65
60
55
50
45
40
35
30
25
D
P<0.001
Inadequate
rate control
P<0.001
Adequate
rate control
0
Month
12
LV Functional Shortening (%)
LV Ejection Fraction (%)
A
LV Functional Shortening (%)
Effects of Concurrent Structural Heart Disease and Rate Control Before Ablation on LV
Function after Ablation Among Patients with CHF
DCM
40
35
30
No concurrent
heart disease
P<0.001
25
20
Concurrent
heart disease
15
P<0.001
10
0
0
Month
12
CHF
40
P<0.001
Inadequate
rate control
35
30
25
P<0.001
20
Adequate
rate control
15
10
0
0
Month
12
Improvement of CHF by Curative Ablation of
Atrial Fibrillation
•58 consecutive patients with CHF and LVEF≤45%
•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 (p=0.38)
•Increase in LVEF: 21% in CHF pts. (p<0.001 vs. non-CHF pts)
•Improvements in LVEF occurred regardless of whether there was
adequate rate control pre-procedure
Pulmonary Venous Anatomy
74 yo medically refractory AF, Echo – Normal
AA Rx - Verapamil, Rythmol, Betapace, Norpace
I
II
III
V1
RSPV
dist
RSPV
prox
LIPV
RA
*
Lasso Catheter
Circular Mapping & Ablation Catheter in
Right Superior Pulmonary Vein
Pulmonary
Veins
Left Atrium
Pulmonary
Veins
70 y/o Male with PAF – Progression of Fractionated
Egm to Organized Egm to Termination of
Arrhythmia – Anteroseptal Line
5
I
II
V1
ABL prox
ABL dist
CS prox
CS dist
6
3
4
The Bottom Line
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
Quality of Life