Transcript Dyspnea in a Heart Failure Patient - Dartmouth

Prevention of Sudden Cardiac
Death
Mark Greenberg, MD
Magnitude of Sudden Cardiac Arrest in
the U.S.
Stroke3
167,366
Lung Cancer2
157,400
1
2
3
4
Breast Cancer2
40,600
AIDS1
42,156
Sudden
cardiac arrest
claims more
lives each
year than
these other
diseases
combined
450,000
Sudden
Cardiac
Arrests4
#1 Killer in
the U.S.
U.S. Census Bureau, Statistical Abstract of the United States: 2001.
American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001.
2002 Heart and Stroke Statistical Update, American Heart Association.
Zheng Z. Circulation. 2001;104:2158-2163.
Treatments to Reduce Sudden Cardiac
Death
Correcting Ischemia
• Revascularization
• Beta-blocker
Preventing Plaque Rupture
• Statin
• ACE inhibitor
• Aspirin
Stabilizing Autonomic
Balance
• Beta-blocker
• ACE inhibitor
Zipes DP. Circulation. 1998;98:2334-2351.
Pitt B. N Engl J Med. 2003;348:1309-1321.
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
Secondary Prevention of SCD-Conclusions from Three RCT’s
• The ICD is first-line therapy for patients with
hemodynamically-compromising primary
ventricular tachyarrhythmias (relative mortality
reduction of 27% compared to medication).
• Benefit of ICD mainly with EF<35%, and is
independent of beta blocker use.
• Further study is required to assess the costefficacy of the ICD in other patient subsets
(EF>35%, well-tolerated VT, secondary VT/VF).
Evolution of ICD Therapy: 1980 to Present
1980
1985
1993
1996
2000
• First Human
Implant
• FDA Approval
of ICDs
• Smaller
Devices
• Steroid
Leads
• MADIT
• Cardiac
Resynchronization*
100,000
1999
1989
90,000
• MUSTT
• Transvenous
Leads
• Biphasic
Waveform
80,000
70,000
60,000
50,000
1988
1997/98
• Tiered
Therapy
• DC ICDs
• AT Therapies
• AVID
• CASH
• CIDS
40,000
30,000
20,000
10,000
0
1980
1985
Number of Worldwide ICD Implants Per Year
* Under clinical investigation in the US
1990
1995
2000 E
Implantable Cardioverter Defibrillator
First-line therapy for patients at risk for VT/VF
• Small devices, pectoral
implant site
• Transvenous, single incision
• Local anesthesia; conscious
sedation
• Short hospital stays
• Few acute complications
• Perioperative mortality < 1%
• Programmable therapy options
• Single- or dual-chamber therapy
• Battery longevity up to 9 years
• 80,000 implants/year (2000 E)1
1Morgan
Stanley Dean Witter. Investors Guide to ICDs. 2000.
Syncope with structural heart disease
is a risk factor for sudden cardiac
death.
“Reduced left ventricular ejection
fraction (LVEF) remains
the single most important risk factor
for overall mortality
and sudden cardiac death.”1
1Prior
SG, Aliot E, Blonstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of
Cardiology. Eur Heart J, Vol. 22; 16; August 2001.
MULTICENTER AUTOMATIC
DEFIBRILLATOR IMPLANTATION TRIAL-II
(MADIT-II)
1997-2001
A trial designed to evaluate the effect of prophylactic
ICD therapy on survival in patients with prior MI and
LV dysfunction.
Supported by a research grant from Guidant Corp.
MADIT-II: Eligibility
•
•
•
•
Chronic CAD with prior MI
EF<0.30
No requirement for NSVT or EPS
No upper age limitation
MADIT-II: MEDS at Last Follow-Up
CONV
•
•
•
•
•
percent
ACE inhibitors
Amiodarone
Antiarrhythmics
Beta-blockers
Digitalis
DEFIB
(n=490)
(n=742)
72
10
2
70
57
68
13
3
70
57
*No significant differences between CONV and DEFIB
groups.
MADIT-II: CONCLUSION
• In coronary patients with LVEF <0.30,
prophylactic ICD therapy is
associated with 31% reduction in
mortality.
• This improved survival is on top of
optimal medical Rx.
ICD Cost-Effectiveness Results for
High Risk Post-MI Patients
$100,000
Other Therapies
Expensive
$80,000
$57,300
$LYS
$60,000
Borderline
Cost-Effective
Conclusions
• ICD therapy is
cost-effective
for high risk
post MI
patients.
$44,300
$40,000
$28,400
Cost-Effective
$22,800
$20,000
$16,900
Highly
Cost-Effective
$0
8 yr
ICD
Transvenous
ICD
MADIT Patient1
Captopril
Post MI
EF < .402
1 Mushlin A. Circulation. 1998;97:2129-35.
2 Kupersmith J. Progress in Cardiovascular Diseases. 1995;37:307-46.
3 Kupperman M. Circulation. 1990;81:91-100.
Cardiac
Transplant
CHF
Transplant
Candidate2
• MUSTT patients
are similar to
MADIT patients.
Peritoneal
Dialysis3
ICD Trials Summary
60%
54%
70%
60%
50%
40%
31%
30%
31%
20% NS
20%
10%
0%
AVID1
3 years
1
CIDS2
3 years
MADIT3
2 years
The AVID Investigators. N Engl J Med. 1997;337:1576-1583.
2 Connolly SJ. Circulation. 2000; 101; 1297-1302.
3 Moss AJ. N Engl J Med. 1996;335;1933-1940.
MUSTT4
2 years
MADIT II5
2 years
4
Buxton AE. N Engl J Med. 1999; 341:1882-90.
5
Moss AJ. N Engl J Med. 2002;346:877-83.
MADIT II Milestones
2002-2003
NEJM publication
FDA approval
ACC/AHA/NASPE
Guidelines updated
BCBS, Aetna, Kaiser
recommend coverage
Modified CMS approval
CMS double bind
“You need an ICD, but it
may not be reimbursed.”
SCD-HeFT Hypothesis
In patients with moderately
symptomatic CHF and LVEF <=35%,
amiodarone and/or ICD added to
standard medical Rx will be
associated with reduced mortality
compared with standard medical Rx
alone.
SCD-HeFT Patient
Characteristics
•
•
•
•
•
•
•
Patients enrolled: 2521
NYHA Class: 70% NYHA II, 30% NYHA III
Median follow-up: 45.5 months
Median age: 60 years
% female: 23%
Median EF: 25%
Concomitant Rx: ACE 72%, beta
blocker 78%
Mechanism Linking MTWA to
Ventricular Arrhythmias
Long APD Region
Short APD Region
Long APD Short APD Long APD Short APD
Action Potential Alternans Leads
to T-Wave Alternans
Spatially Discordant Alternans Leads to
Dispersion of Recovery,
Wave Front Fractionation, and Reentry
Patient MS:
Modified Bruce Protocol
Equivalency Between TWA and EPS
+ 10 %
TWA +
EPS +
- 10 %
Event
Rate
TWA +
Time
1 year
“Ultimately,
risk stratification will
be important only if it can be
coupled with a therapeutic
intervention that reduces the
risk of dying.”
Zipes and Wellens. Sudden Cardiac Death. Circulation. 1998;98:2334-51.
High Risk Groups for SCD
Population Size
SCD Percent / Year
Total SCD / Year
High Coronary
Risk
Post MI
Heart Failure/
E F < 35%)
Syncope /
Heart Disease
Previous
VF / VT
0
1
2
5
(millions)
10
20
0
1
2
5 10 20 50
(percent)
0
50
100
200
300
(thousands)
Adapted from Myerburg
Sudden Cardiac Death:
Management Strategies
• Salvage and treat (too few are
salvaged).
• Predict and prevent
(pathophysiology complex, positive
predictive value of risk stratifiers
relatively low).