Download ICDs: What We Have Learned and Current Guidelines

ICDs: What We Have Learned
and Current Guidelines
Alberto Diaz, MD
Assistant Professor of Medicine, Case Western
Reserve University
MetroHealth Medical Center
Sudden Cardiac Death
• 450,000 deaths per year
• 50% of all cardiovascular
deaths
• Incidence: 1 to 2 per 1000
people per year.
Cardiac Death
65
Nonsudden
Sudden
60
50
45
40
35
30
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
Percent
55
Zheng, et al, Circ. 2001;104:2158-2163
Sudden Death
80
75
Percent
70
35-44
45-54
55-64
65-74
75-84
65
60
55
50
45
40
Age
Zheng, et al, Circ. 2001;104:2158-2163
Sudden Cardiac Death
• Is an epidemic
• Disproportionately affects younger,
less symptomatic heart failure patients
Protection: Device Therapy: The AVID Trial
• The Antiarrhythmics Versus
Implantable Defibrillators Trial
• 1016 patients from 56 world centers
with either resuscitated from SCD or
had symptomatic VT with LVEF
<0.40.
• Randomized to ICD or drug (97%
Amiodarone) therapy
• Primary end point was total mortality
• Mean follow-up was 18.2 months
AVID: Mortality
40
Percent Mortality
35
ICD Group
Drug Group
30
25
31
27
39
20
15
10
5
0
1 year
2 years
3 years
ICD Survival Benefit: Secondary Prevention
Studies
1
1
The AVID Investigators. N Engl J Med. 1997;337:1576-1583.
Kuck K. Circ.2000;102:748-754.
3 Connolly S. Circ. 2000;101:1297-1302.
2
2
3
The AVID Trial :Overall Conclusions
• ICDs are more effective than AADs in reducing arrhythmic
cardiac death1
• The results of AVID may be generalized for all patients
with VF and symptomatic VT. 1
• Patients in the Registry with a seemingly lower-risk
(asymptomatic VT, and VF/VT associated with a transient
or reversible cause) have a high mortality similar to higher
risk AVID patients.2
1 The
2
AVID Investigators, JACC 1999;34:1552-1559.
Anderson JL, et al. Circulation 1999; 99:1692-1699.
Ventricular Fibrillation
Applying Classification of Recommendations
and Level of Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies with
focused objectives
needed
Benefit ≥ Risk
Additional studies with
broad objectives needed;
Additional registry data
would be helpful
Risk ≥ Benefit
No additional studies
needed
Procedure/ Treatment
SHOULD be
performed/
administered
IT IS REASONABLE to
perform
procedure/administer
treatment
Procedure/Treatment
MAY BE CONSIDERED
Level of Evidence:
Level A:
Data derived from multiple randomized clinical trials or meta-analyses
Multiple populations evaluated;
Level B:
Data derived from a single randomized trial or nonrandomized studies
Limited populations evaluated
Level C:
Only consensus of experts opinion, case studies, or standard of care
Very limited populations evaluated
Procedure/Treatment
should NOT be
performed/administered
SINCE IT IS NOT
HELPFUL AND MAY
BE HARMFUL
Secondary Prevention
I IIa IIb
IIbIII
III
I IIa IIb III
I IIa IIb III
ICD therapy is indicated in patients who are survivors of
cardiac arrest due to ventricular fibrillation or
hemodynamically unstable sustained VT after evaluation to
define the cause of the event and to exclude any
completely reversible causes.
ICD therapy is indicated in patients with structural heart
disease and spontaneous sustained VT, whether
hemodynamically stable or unstable.
ICD therapy is indicated in patients with syncope of
undetermined origin with clinically relevant,
hemodynamically significant sustained VT or VF induced at
electrophysiological study.
Early Defibrillation With Early CPR Maximizes Survival
>3 Min from Collapse
to CPR
Survival (%)
<3 Min from Collapse
To CPR
70
70
60
44
50
40
7
30
20
39
31
10
22
0
<6
7-12
>12
Minutes Before Defibrillation
Closing the barn door after the
horse is in the meadow
Risk Factors For SCD
•Coronary artery disease
•Left ventricular
dysfunction
•Nonsustained Ventricular
Tachycardia
Potential treatments to prevent SCD
in high risk patients
• Optimal medical therapy for heart
failure and coronary artery disease
• Antiarrhythmic medicine treatment
• Prophylactic ICD therapy (Primary
Prevention)
Number of Deaths
Residual Risk of SCD in Treatment
Arms of CHF Beta Blocker Trials
1
% Sudden Death
of Total Death
31%
No. Pts in Treatment Arm: N = 1327
16 months
Average Follow-Up:
1 CIBIS-II
2
54%
N = 1990
12 months
Investigators. Lancet. 1999;353:9-13.
Study Group. Lancet. 1999;353:2001-2007.
3 Packer M. N Engl J Med. 1996:334:349-355.
2 MERIT-HF
3
54%
N = 696
6.5 months
Cardiac Arrhythmia Suppression Trial (CAST)
• Post myocardial infarction patients
• Open label titration to achieve PVC
suppression.
• After confirmation of suppression:
• Randomization to:
– Placebo
– Effective Drug (Flecainide/Encainide)
• Mean follow-up 10 months
Cardiac Arrhythmia Suppression Trial
(CAST)
Echt, et al., NEJM, 1991;324:781
Prevention: STAT CHF Trial
• Patients with cardiomyopathy and
LVEF <0.35.
• Randomized to Amiodarone, 300
mg/d vs placebo.
• 2 year survival did not differ
comparing the two limbs.
Primary Prevention ICD
Therapy
Closing the Barn Door Before The Horse Is In the meadow
MADIT Trial
• Multicenter Automatic Defibrillator
Implantation Trial
• Prophylactic ICD therapy
• 196 patients
– Prior MI
– LVEF <0.35
– Asymptomatic Nonsustained VT
MADIT Trial
MADIT-II: Eligibility
• Chronic CAD with prior MI
• EF<0.30
• No requirement for NSVT or
EPS
• No upper age limitation
MADIT-II: Design
• Randomization: ICD vs. No ICD
(3:2 ratio)
• Sequential design with preset
stopping boundaries for efficacy, no
difference, and inefficacy of ICD vs.
No ICD
Primary Outcome
Kaplan-Meier Survival by Treatment Group
0.78
0.69
P=0.007
(probability of survival)
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.
The Sudden Cardiac Death in Heart
Failure Trial: SCD-HeFT
• Design:
– Prospective, Multi-center, Randomized
– 2521 Patients enrolled
• Inclusion Criteria:
– NYHA class II/III due to ischemic or nonischemic dilated cardiomyopathy
– EF  35%
– CHF  3 months
– Age  18 years
– CHF treatment with vasodilators
– No cardiac arrest or episode of sustained VT
Bardy GH, et al. N Engl J Med. 2005;352:225-237
SCD-HeFT: Tested ICDs or Amiodarone on Top of
Conventional Medical Therapy (CMT)
Eligible Patients
Electrocardiography, Liver & Thyroid function tests,
Six Minute Walk, Holter Monitor and Chest Radiography
Randomization
1 Patient
CMT
Bardy GH, et al. N Engl J Med. 2005;352:225-237
1 Patient
CMT + Amiodarone
1 Patient
CMT + ICD
SCD HeFT Trial
Amiodarone vs. Placebo
ICD vs. Placebo
0.4
Hazard Ratio (97.5% Cl)
1.06 (0.86 - 1.30)
0.77 (0.62 - 0.96)
Mortality Rate
0.3
0.2
0.1
Amiodarone
Placebo
ICD
0.0
0
No. at Risk
Amiodarone
Placebo
ICD
12
24
36
48
60
280
304
304
97
89
103
Months of Follow-Up
845
847
829
772
797
778
Bardy GH. N Engl J Med. 2005;352:225-237.
715
724
733
484
505
501
P-Value
0.53
0.007
Conclusions
In NYHA class II or III CHF patients
with EF  35% on good background
drug therapy:
– ICD therapy significantly decreased the
relative risk of death by 23% (p-value
0.007)
– Resulting in an absolute reduction of 7.2% at
five years
– Amiodarone had no beneficial effect on
survival, despite the use of appropriate
dosage and reasonable compliance rates
Bardy GH, et al. N Engl J Med. 2005;352:225-237
Implantable Cardioverter-Defibrillators
I IIa IIb III
ICD therapy is indicated in patients with LVEF less than or
equal to 35% due to prior MI who are at least 40 days
post-MI and are in NYHA functional Class II or III.
I IIa IIb III
ICD therapy is indicated in patients with nonischemic DCM
who have an LVEF less than or equal to 35% and who are
in NYHA functional Class II or III.
I IIa IIb III
I IIa IIb III
ICD therapy is indicated in patients with LV dysfunction
due to prior MI who are at least 40 days post-MI, have an
LVEF less than or equal to 30%, and are in NYHA
functional Class I.
ICD therapy is indicated in patients with nonsustained VT
due to prior MI, LVEF less than or equal to 40%, and
inducible VF or sustained VT at electrophysiological study.
Implantable Cardioverter-Defibrillators
I IIa IIb III
ICD implantation is reasonable for patients with unexplained
syncope, significant LV dysfunction, and nonischemic DCM.
I IIa IIb III
I IIa IIb III
I IIa IIb III
I IIa IIb III
ICD implantation is reasonable for patients with sustained VT and
normal or near-normal ventricular function.
ICD implantation is reasonable for patients with HCM who have 1
or more major† risk factors for SCD.
ICD implantation is reasonable for the prevention of SCD in
patients with arrhythmogenic right ventricular
dysplasia/cardiomyopathy (ARVD/C) who have 1 or more risk
factors for SCD.
ICD implantation is reasonable to reduce SCD in patients with longQT syndrome who are experiencing syncope and/or VT while
receiving beta blockers.
Implantable Cardioverter
Defibrillators
All primary sudden cardiac death (SCD)
prevention implantable cardioverterdebrillator (ICD) recommendations apply
only to patients who are receiving optimal
medical therapy and have reasonable
expectation of survival with good functional
capacity for more than 1 year.
New England J of Med, August 1, 2002
To the Editor: If one assumes a conservative onetime cost of $30,000 per cardiac-defibrillator
implantation, heeding the call of Moss et al. to
provide an implantable cardiac defibrillator for
the estimated yearly flow of 400,000 new
patients would cost public and private payers
$12 billion annually. This cost alone is three
times the estimated 2003 budget for the Centers
for Disease Control and Prevention.
If physicians feel that ICD therapy is:
•Over-used
•Financially unviable
•Risks have been under represented
How do we apply the therapy to
those who are likely to need it?
Optimize specificity
Appropriate sensitivity
OR
How do we implant
devices in those
likely to use them
and not implant
devices in those
unlikely to?
Without a……
Nonsustained Ventricular Tachycardia
• Meta-analysis of 12 trials of
Electrophysiology Studies in patients
with NSVT.
• Sudden death or sustained
arrhythmia:
– Inducible Group: 18%
– Noninducible Group: 7%
– Positive Predictive Value: 18%
– Negative Predictive Value: 93%
T Wave Alternans
– Subtle alternation in the T wave during
higher atrial rates
– Current technology uses a bicycle to
increase atrial rate
– T Wave alternans is a noninvasive
marker of vulnerability to ventricular
arrhythmias
T Wave Alternans
T Wave Alternans Predicts Arrhythmia
Vulnerability
Rosenbaum, et al., NEOJM 1994;330:235
Developing an innovative approach for prevention and
treatment of sudden cardiac death using the noninvasive T
wave alternans test to guide ICD therapy
Synergistic Value of EPS and
MTWA Testing
EVENT RATE
0.20
0.15
EVENT RATE
0.20
0.15
0.10
P = 0.017
0.05
0.00
0.10
0.05
MTWA Abnormal / EPS +
MTWA Normal / EPS 0
3
6
9
MONTHS
12.6%
12
7.5%
5.0%
2.3%
0.00
MTWA Norm
EPS –
( n = 99 )
MTWA Abnorm
EPS ( n = 245 )
MTWA Norm
EPS +
( n = 66 )
MTWA Abnorm
EPS +
( n = 156 )
Conclusions:
• ICD therapy significantly reduces mortality for
patients who have sustained VT or a cardiac
arrest.
• Primary prevention of sudden death:
– Makes clinical sense because of the poor survival after
cardiac arrest
– Is proven to reduce mortality
– Has not been implemented consistently according to
ACC/AHA guidelines
• Better screening of patients at high risk of SCD
may increase guideline adherence
Thank You