Transcript No Slide Title

Efficacy Of ICDs For The Prevention
Of Sudden Death In Patients With
Hypertrophic Cardiomyopathy
*Maron BJ et al. N Engl J Med. 2000:342;365-373.
Hypertrophic Cardiomyopathy
Etiology:
Autosomal dominant trait caused by a
variety of genetic mutations of sarcomere
proteins
Prevalence:
Relatively common for a genetic disease,
although uncommon in cardiologic practice
(1:500 in general population)
Presentation:
Heterogeneous primary cardiac disease
with particularly diverse clinical,
morphologic and genetic features
Natural History:
Variable, often benign, but associated with
risk for sudden death in some patients
Causes of SCD in Young People
Congenital coronary
anomalies
(19%)
Mildly increased cardiac mass
(10%)
Ruptured aorta 5%
Tunnelled LAD 5%
Aortic stenosis 4%
Myocarditis 3%
HCM
(36%)
Dilated cardiomyopathy 3%
ARVC 3%
MVP 2%
CAD 2%
Other 6%
Maron BJ et al. Circulation. 1996;94:850-56.
Age at Death (years)
HCM: Modes of Death
90
80
70
60
50
40
30
20
10
0
73
56
45
Sudden
Heart Failure
Stroke
Profiles in Prognosis for HCM
Sudden
Death
Risk
Symptom
Progression
Spirito P et al. N Engl J Med. 1997;336:775-85.
EndStage
AF
Profile of Sudden Death in HCM
• Usually no or only mild prior symptoms
• Usually occurs while sedentary or with mild
physical exertion; not infrequently with
physical exertion
• May occur at any age; but most commonly in
the young
Mortality in HCM
16
Stroke
Heart Failure
Sudden
14
% Mortality
12
10
8
6
4
2
0
5-15
16-25
26-35
36-45
46-55
56-65
66-75
Age at Death or Most Recent Evaluation (years)
>75
Incidence of Sudden Death
(per 1000 person – yr)
Wall Thickness and Sudden Death In HCM
20
18
16
14
12
10
8
6
4
2
0
18.2
11.0
7.4
2.6
0
<15
16 - 19
20 - 24
25 - 29
> 30
Maximal Left-Ventricular-Wall Thickness (mm)
Spirito P. et al. N Engl J Med. 2000:342;1781.
Triggers of Sudden Death
Substrate
(Disorganized myocardial
architecture)
Ventricular Tachyarrhythmias
Maron BJ. Hypertrophic cardiomyopathy. Curr Prob Cardiol. 1993;18:639-704.
ICD
Strongest SCD Risk Factors:
Cardiac arrest/sustained VT
Family history of sudden death
Malignant genotype
Recurrent syncope
Multiple-repetitive NSVT
Exercise hypotension(?)
Massive LVH
Highest
Intermediate
Lowest
Maron BJ et al. Curr Prob Cardiol. 1993;18:637-704.
Amiodarone (?)
Previously Proposed Pharmacological
Therapy For Sudden Death
Prevention in HCM
Drugs
Limitation
ß-adrenergic blockers
verapamil
no data
procainamide
quinidine
proarrhythmia
amiodarone
unresolved efficacy;
chronic use unrealistic
ICD-HCM Trial:
Hypothesis
• Sudden cardiac death in HCM is triggered
by ventricular tachyarrhythmias that usually occur
unpredictably and without warning.
• The implantable defibrillator will reliably sense and
automatically terminate these arrhythmias when
they occur.
• This hypothesis can be confirmed by a carefully
designed retrospective study.
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Patient Selection Criteria
• Unequivocal diagnosis of HCM with two-dimensional
echocardiography
• Successful implantation of a defibrillator for the
purpose of sudden death prevention
• Minimum three month follow-up period after implant
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Definition of Implant Treatment Objectives
Primary:
Prevention
Prophylactic:
with > 1 risk factor
Secondary:
Prevention
Following cardiac
arrest or sustained VT
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Primary Prevention Risk Factors*
No. Patients
(n=128)
%
Syncope
41
32%
Family history of sudden death
due to HCM
39
30%
Nonsustained VT on Holter
32
25%
Massive LVH (> 30mm)
10
8%
*patients frequently had multiple risk factors
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD for HCM Clinical Trial:
Demographics
No. patients:
Male gender:
Age at implant:
128
70%
8-82 (mean 40)
52% < 40 years
25% < 30 years
Outcome:
Alive
Died
* end-stage disease; one with a prior appropriate discharge
126
2*
ICD-HCM Trial:
Demographics
Implant years:
Mean follow-up:
1984-98 (80% > 1994)
3.1 years
Mode of implant:
Transvenous
Thoracotomy
80%
20%
Device capability:
Bradycardia / ATP
Electrograms
80%
75%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Clinical and Echocardiographic Data
NYHA Class I
NYHA Class II
NYHA Class III / IV
Mean Max. LV wall thickness (mm)
Mean LV end-diastolic cavity (mm)
Mean left atrial dimension (mm)
LV outflow obstruction (basal grad. > 30mmHg)
Antiarrhythmic drugs
(amiodarone; sotalol; disopyramide)
Before ICD
After ICD
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
65%
21%
14%
23 + 7
44 + 8
44 + 6
18%
41%
32%
ICD-HCM Trial:
Clinical End-point
• Appropriate ICD termination of VT / VF, as surrogate
for sudden death (n=29)
• Based on analysis of stored ECG cycle length data /
electrograms (n=21)
• In absence of stored data, based on clinical
circumstances (n=8)
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial
Age at Implant
25
2° prevention
1° prevention
No. of Patients
20
15
10
5
0
<10
11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 61-65 66-70 71-75
Age At Implant (years)
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
>76
ICD-HCM Trial:
Appropriate Interventions
128 No. patients
29
Appropriate
discharges
Follow-up =
3.1 years
7.3% / yr
ICD discharge
rate
11.0%
4.5%
2º prevention
1º prevention
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial
1 prevention
Event-Free Survival
2 prevention
P=0.004
0
No. at risk
1 :
2 :
85
43
2
4
6
8
10
12
Years Post-Implant
39
17
17
16
3
6
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
1
3
0
1
0
1
14
16
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Age At 1st Intervention
70
60
Percent
50
40
30
20
10
0
<10
11-15
16-20
21-25 26-30
31-35
36-40
41-45
Age Groups (years)
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
46-50
51-55
56-60
61-65
66-70
>70
No. Patients
ICD-HCM Trial
Time to 1st Intervention
12
11
10
9
8
7
6
5
4
3
2
1
0
0-4
5-9
10-14 15-19 20-24
25-29
30-34 35-39 40-44 45-49 50-54
Months
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
55-59
60-64
65-69
>69
ICD-HCM Trial:
Number of Interventions
10
9
No. Patients
8
7
6
5
4
3
2
1
0
1
2
3
4
No. Appropriate Interventions
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
5

ICD-HCM Trial:
Arrhythmias Triggering ICD Interventions
VTVF
14%
VT 48%
only
VT and VF
9%
Bradyarrhythmias = 0
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
A
B
C
D
ICD-HCM Trial:
Interventions and Implant Justification
No. Patients
Appropriate
Interventions
VF or spontaneous VT
43
44%
Massive LVH
10
20%
Syncope
41
12%
Nonsustained VT on
Holter
32
6%
Family history of sudden
death
39
3%
Implant Justification
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Concomitant Drug Treatment
With
Appropriate
Discharge
Without
Appropriate
Discharge
No. patients
29
99
Pct. on anti-arrhythmic
drugs*
52%
21%
p < 0.04
* amiodarone, sotalol, disopyramide
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Complications
Complications
No. Patients
Inappropriate Discharges
Sinus tachycardia
13
AF with rapid ventricular rate
10
Lead dislodgement, disruption,
or oversensing
9
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Complications
Complications
No. Patients
Lead fracture / disruption
12
Infection / explant
2
Subclavian thrombus
1
Hemorrhage
1
Hematoma
1
Clinical depression
1
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial:
Conclusions
The implantable defibrillator in HCM:
• Is highly effective in terminating life threatening ventricular
tachyarrhythmias, often in young patients with few or no
symptoms
• Has demonstrated a life-saving role both for secondary
prevention (following aborted cardiac arrest or sustained VT)
and the prophylactic, primary prevention of sudden death in
patients judged to be at high-risk based on their clinical profile
• Has demonstrated primary VT / VF to be the principal
mechanism of sudden death
Maron BJ, et al. N Engl J Med. 2000;342:365-373.