Efficacy Of ICDs For The Prevention Of Sudden Death In Patients With Hypertrophic Cardiomyopathy
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Transcript of Efficacy Of ICDs For The Prevention Of Sudden Death In Patients With Hypertrophic Cardiomyopathy
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 diseasewith particularly diverse clinical, morphologic and genetic features
Natural History: Variable, often benign, but associated with risk for sudden death in some patients
Maron BJ et al. Circulation. 1996;94:850-56.
HCM(36%)
Congenital coronaryanomalies
(19%)
Mildly increased cardiac mass(10%)
Ruptured aorta 5%
Tunnelled LAD 5%
Aortic stenosis 4%
Myocarditis 3%
Dilated cardiomyopathy 3%
ARVC 3%MVP 2%
CAD 2%Other 6%
Causes of SCD in Young People
4556
73
0102030405060708090
Sudden Heart Failure Stroke
Age
at D
eath
(yea
rs)
HCM: Modes of Death
SuddenDeathRisk
SymptomProgression
End-Stage AF
Spirito P et al. N Engl J Med. 1997;336:775-85.
Profiles in Prognosis for HCM
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
02468
10121416
StrokeHeart FailureSudden
% M
orta
lity
Age at Death or Most Recent Evaluation (years)
5-15 16-25 26-35 36-45 46-55 56-65 66-75 >75
Mortality in HCM
Spirito P. et al. N Engl J Med. 2000:342;1781.
Wall Thickness and Sudden Death In HCM
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Maximal Left-Ventricular-Wall Thickness (mm)
02.6
7.4
11.0
18.2
<15 16 - 19 20 - 24 25 - 29 > 30
Inci
denc
e of
Sud
den
Dea
th(p
er 1
000
pers
on –
yr)
Myocardial
Ischemia Outflow
Obstruction
Substrate(Disorganized myocardial
architecture)
Intense physical
exertionAtria
lfib
rillat
ion
Ventricular Tachyarrhythmias
Triggers of Sudden Death
Maron BJ. Hypertrophic cardiomyopathy. Curr Prob Cardiol. 1993;18:639-704.
Highest
Intermediate
Lowest
ICD
Amiodarone (?)
Strongest SCD Risk Factors:Cardiac arrest/sustained VTFamily history of sudden deathMalignant genotypeRecurrent syncopeMultiple-repetitive NSVTExercise hypotension(?)Massive LVH
Maron BJ et al. Curr Prob Cardiol. 1993;18:637-704.
Previously Proposed Pharmacological Therapy For
Sudden Death Prevention in HCM
Drugs Limitationß-adrenergic blockers no dataverapamil
procainamide proarrhythmiaquinidine
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: Prophylactic:Prevention with > 1 risk factor
Secondary: Following cardiacPrevention arrest or sustained VT
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial: Primary Prevention Risk Factors*
*patients frequently had multiple 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%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
* end-stage disease; one with a prior appropriate discharge
ICD for HCM Clinical Trial: Demographics
No. patients: 128Male gender: 70%Age at implant: 8-82 (mean
40) 52% < 40 years 25% < 30 years
Outcome:Alive 126Died 2*
ICD-HCM Trial: Demographics
Implant years: 1984-98 (80% > 1994)Mean follow-up: 3.1 yearsMode of implant:
Transvenous 80%Thoracotomy 20%
Device capability:Bradycardia / ATP 80%Electrograms 75%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
ICD-HCM Trial: Clinical and Echocardiographic Data
NYHA Class I 65%NYHA Class II 21%NYHA Class III / IV 14%Mean Max. LV wall thickness (mm) 23 + 7Mean LV end-diastolic cavity (mm) 44 + 8Mean left atrial dimension (mm) 44 + 6LV outflow obstruction (basal grad. > 30mmHg) 18%Antiarrhythmic drugs (amiodarone; sotalol; disopyramide) Before ICD 41% After ICD 32%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
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.
0
5
10
15
20
25
2° prevention1° prevention
No.
of P
atie
nts
Age At Implant (years)<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 >76
ICD-HCM Trial Age at Implant
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
11.0% 4.5%
Follow-up = 3.1 years
ICD discharge rate
Appropriatedischarges
2º prevention 1º prevention
ICD-HCM Trial: Appropriate Interventions
7.3% / yr
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
128 No. patients
29
0 2 4 6 8 10 12 14 160.0
0.2
0.4
0.6
0.8
1.0
Years Post-Implant
Even
t-Fre
e Su
rviv
al 2 prevention1 prevention
P=0.004
ICD-HCM Trial
No. at risk1 : 85 39 17 3 1 0 02 : 43 17 16 6 3 1 1
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
0
10
20
30
40
50
60
70
Age Groups (years)<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 >70
Perc
ent
ICD-HCM Trial: Age At 1st Intervention
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
0123456789
101112
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 >69
Months
No.
Pat
ient
sICD-HCM Trial
Time to 1st Intervention
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
0123456789
10
1 2 3 4 5
No.
Pat
ient
s
No. Appropriate Interventions
ICD-HCM Trial: Number of Interventions
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
VF 29%only
VT 48%only
VT and VF9%
Bradyarrhythmias = 0
ICD-HCM Trial: Arrhythmias Triggering ICD Interventions
VTVF14%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
A
B
C
D
ICD-HCM Trial: Interventions and Implant Justification
Implant Justification No. PatientsAppropriate
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%
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
* amiodarone, sotalol, disopyramide
ICD-HCM Trial: Concomitant Drug Treatment
No. patients 29 99
Pct. on anti-arrhythmicdrugs* 52% 21%
p < 0.04
With Appropriate Discharge
Without Appropriate Discharge
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, 9or oversensing
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.