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

02468

101214161820

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


ICD-HCM Trial: Definition of Implant Treatment

Objectives Primary: Prophylactic:Prevention with > 1 risk factor

Secondary: Following cardiacPrevention arrest or sustained VT


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%


* 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%


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%


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)


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


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


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


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


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


0123456789

10

1 2 3 4 5

No.

Pat

ient

s

No. Appropriate Interventions

ICD-HCM Trial: Number of Interventions


VF 29%only

VT 48%only

VT and VF9%

Bradyarrhythmias = 0

ICD-HCM Trial: Arrhythmias Triggering ICD Interventions

VTVF14%


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%


* 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


ICD-HCM Trial:Complications

Complications No. Patients

Inappropriate Discharges

Sinus tachycardia 13

AF with rapid ventricular rate 10

Lead dislodgement, disruption, 9or oversensing


ICD-HCM Trial:Complications

Complications No. Patients

Lead fracture / disruption 12

Infection / explant 2

Subclavian thrombus 1

Hemorrhage 1

Hematoma 1

Clinical depression 1


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


efficacy of icds for the prevention of sudden death in patients with hypertrophic cardiomyopathy

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