RISK STRATIFICATION IN HYPETROPHIC RISK STRATIFICATION IN HYPETROPHIC CARDIOMYOPATHY . ICDs IN NORTHERN GREECECARDIOMYOPATHY . ICDs IN NORTHERN GREECE

PARASKEVAIDIS STELIOS, MD, PhDPARASKEVAIDIS STELIOS, MD, PhD

11stst Cardiology Department, AHEPA Hospital, Cardiology Department, AHEPA Hospital, Aristotle University Medical School, Aristotle University Medical School, Thessaloniki, GreeceThessaloniki, Greece

HCM AND SUDDEN CARDIAC DEATH (SCDHCM AND SUDDEN CARDIAC DEATH (SCD) )

•• HCM prevalence : 1:500 in general populationHCM prevalence : 1:500 in general population•• SCD is the most severe complication of HCMSCD is the most severe complication of HCM•• prevention prevention

ICD ICD

•• rate of SCD: rate of SCD: 1 % per year 1 % per year •• no relation between SCD risk and gender no relation between SCD risk and gender

SCD AND HCMSCD AND HCM

SCD: VT or VF, no bradyarrhythmiaSCD: VT or VF, no bradyarrhythmia

trigger: sinus tachycardia, trigger: sinus tachycardia,

sympathetic sympathetic

tonetone

SUDDEN CARDIAC DEATH IN YOUNG SUDDEN CARDIAC DEATH IN YOUNG ATHLETESATHLETES

HCMHCM--AETIOLOGY OF MORTALITY AND AGEAETIOLOGY OF MORTALITY AND AGE

Maron B, Circul 2010

ARRHYTHMOGENIC SUBSTRATEARRHYTHMOGENIC SUBSTRATE

myocardial disarray small vessel disease fibrosis

SCDSCD--HCM RISK STRATIFICATIONHCM RISK STRATIFICATION risk factors: applicable to 18risk factors: applicable to 18--50 yrs50 yrs

> 30 mm

Negative predictive value: 90% Positive predictive value :15-30%

SCDSCD--HCM RISK STRATIFICATIONHCM RISK STRATIFICATION

specific protein mutation (>1000 in 11 genes)specific protein mutation (>1000 in 11 genes)

electrophysiologic study (EPS)electrophysiologic study (EPS)

QT prolongationQT prolongation

signal averaged ECGsignal averaged ECG

heart rate variabilityheart rate variability

T wave alternans T wave alternans

do not contribute to risk stratificationdo not contribute to risk stratification

HCMHCM--LAMP2 cardiomyopathyLAMP2 cardiomyopathy (Lysosomal(Lysosomal--Associated Membrane Protein 2) Associated Membrane Protein 2) extreme hypertrophy, subaortic obstruction, microvascular extreme hypertrophy, subaortic obstruction, microvascular ischemia, diastolic dysfunction, refractory to ICD therapyischemia, diastolic dysfunction, refractory to ICD therapy

LV HYPERTROPHY AND SCD RISKLV HYPERTROPHY AND SCD RISK

MRIMRI--DELAYED ENHANCEMENT (DE) AND DELAYED ENHANCEMENT (DE) AND ARRHYTHMIASARRHYTHMIAS

MRIMRI--DELAYED ENHANCEMENT (DE)DELAYED ENHANCEMENT (DE)

TYPES OF HCMTYPES OF HCM

HCMHCM-- TIME FROM IMPLANT TO 1TIME FROM IMPLANT TO 1ST ST ICD INTERVENTIONICD INTERVENTION

• varies considerably• probability of 1st appropriate ICD intervention > 5yrs: 27%

ICD ICD -- HCMHCM

ICD ICD –– HCMHCM registry, registry, n= 506 (primary:383), mean age: 42 yrs, n= 506 (primary:383), mean age: 42 yrs,

Maron B et al, JAMA 2007

survival:92%

FIRST APPROPRIATE ICD INTERVENTIONFIRST APPROPRIATE ICD INTERVENTION PRIMARY vs SECONDARY PREVENTIONPRIMARY vs SECONDARY PREVENTION

Maron B et al, JAMA 2007

primary

secondary

SURVIVAL IN ICDSURVIVAL IN ICD-- HCMHCM

SurvivalSurvival (n=467): 92% at 4 yrs F/U(n=467): 92% at 4 yrs F/U

39 deaths39 deaths

Causes of death Causes of death

n=19: n=19: non HCM related non HCM related (cancer, renal (cancer, renal disease, CAD, accidents)disease, CAD, accidents)

n=20 n=20 HCM related HCM related (heart failure, stroke)(heart failure, stroke)

n=1 ICD malfunctionn=1 ICD malfunction

Maron B et al, JAMA 2007Maron B et al, JAMA 2007

INAPPROPRIATE ICD INTERVENTIONINAPPROPRIATE ICD INTERVENTION

overall : 27%overall : 27%

primary: 25%, secondary: 32%, primary: 25%, secondary: 32%, p=0.22p=0.22

Causes:Causes:

sinus tachycardiasinus tachycardia

atrial fibrillationatrial fibrillation

lead or programming malfunctionlead or programming malfunction

Leads: weakest link of the systemLeads: weakest link of the systemhigh activity level, body growth: high activity level, body growth: continuous continuous strain on leadsstrain on leads

Maron B et al, JAMA 2007

RATE OF APPROPRIATE ICD INTERVENTION/yrRATE OF APPROPRIATE ICD INTERVENTION/yr No. OF RISK FACTORSNo. OF RISK FACTORS--PRIMARY PREVENTIONPRIMARY PREVENTION

FIRST APPROPRIATE ICD INTERVENTIONFIRST APPROPRIATE ICD INTERVENTION NUMBER OF RISK FACTORSNUMBER OF RISK FACTORS

RATE OF APPROPRIATE ICD RATE OF APPROPRIATE ICD INTERVENTION/yr PER RISK FACTORINTERVENTION/yr PER RISK FACTOR

ALCOHOL SEPTAL ABLATION vs MYECTOMYALCOHOL SEPTAL ABLATION vs MYECTOMY

Appropriate ICD discharge rateAppropriate ICD discharge rate

Alcohol septal ablation: 10.3% /yr Alcohol septal ablation: 10.3% /yr

Myectomy: 2.6% /yr, Myectomy: 2.6% /yr, p=0.04p=0.04

transmural scar in alcohol septal ablation transmural scar in alcohol septal ablation

arrhythmiogenesis and arrhythmiogenesis and risk of SCDrisk of SCD

Maron B et al, JAMA 2007

MORTALITY AND RISK FACTORS IN HCMMORTALITY AND RISK FACTORS IN HCM n=1306, mean age: 47n=1306, mean age: 47

F/U: from the date of birthF/U: from the date of birth--not from first presentation of patientnot from first presentation of patient strongest risk factor : family history of SCD strongest risk factor : family history of SCD

Dimitrow PP et al, EHJ 2010

MORTALITY AND RISK FACTORS IN HCMMORTALITY AND RISK FACTORS IN HCM

Mortality without risk factors: 0.5 %/yr, Mortality without risk factors: 0.5 %/yr, F/U: 15 yrsF/U: 15 yrs

PATIENTS ICD DEMOGRAPHICS PATIENTS ICD DEMOGRAPHICS CAD vs HCMCAD vs HCM

TYPE OF ICD IN HCM TYPE OF ICD IN HCM

Boriani G et al, Circul 2004

VVIR DDDR

ICD implantation for HCMICD implantation for HCM AHEPA HospitalAHEPA Hospital

34/423 pts (8%)34/423 pts (8%)

Secondary prevention: 4 ptsSecondary prevention: 4 pts

Primary prevention: 30 ptsPrimary prevention: 30 pts

Mean F/U: 4 yrsMean F/U: 4 yrs

ICDICD--interventionintervention

SSececondary preventionondary prevention: 2/4 pts (50%): 2/4 pts (50%)1 shock, 1 ATP1 shock, 1 ATP

Primary preventionPrimary prevention: 8/30 pts (26%): 8/30 pts (26%)1 shock, 7 ATP1 shock, 7 ATP

Intervention rate: 7% per yearIntervention rate: 7% per year

ICDsICDs-- AHEPA HospitalAHEPA Hospital

Inappropriate therapyInappropriate therapy: 7 pts (21%): 7 pts (21%)AF (Atrial Fib): 4 ptsAF (Atrial Fib): 4 ptsSVT (Supravenricular Tachy): 2 ptsSVT (Supravenricular Tachy): 2 ptsST (Sinus Tachy): 1 pt ST (Sinus Tachy): 1 pt

InfectionInfection--lead fractionlead fraction4/34 pts (11,7%)4/34 pts (11,7%)

HCMHCM--CASECASEman, 63 yrs, HCM, syncope, nonsustained VT, ICD implantation (primary prevention)

11stst ICD THERAPY ICD THERAPY ATPATP (Antitachycardia pacing) 4 yrs after (Antitachycardia pacing) 4 yrs after

implantationimplantation

ATP

VT

V

V

A

A

NON SUSTAINED VTNON SUSTAINED VT--VFVF

A

V

VA

ICD implantation is reasonable for patients with HCM who have 1 or more major risk factor for SCD

Primary Prevention Primary Prevention class II a (C)class II a (C)

Secondary Prevention Secondary Prevention class I (A)class I (A)ICD therapy is indicated in pts surviving of cardiac arrest due to VF or unstable VT

HCMHCM-- ICD THERAPYICD THERAPY

Secondary Prevention Secondary Prevention patients surviving cardiac arrest or sustained VTpatients surviving cardiac arrest or sustained VT

Primary Prevention Primary Prevention •• single strong risk marker single strong risk marker ::

-- family history of SCDfamily history of SCD-- unexplained syncopeunexplained syncope-- massive LV hypertrophy massive LV hypertrophy

••

2 risk markers 2 risk markers : increased arrhythmia burden: strong : increased arrhythmia burden: strong consideration for an ICDconsideration for an ICD

•• strict adherence to the model requiring strict adherence to the model requiring

2 risk factors 2 risk factors for ICD consideration is not sustainablefor ICD consideration is not sustainable

PRIMARY PREVENTIONPRIMARY PREVENTION

patients in endpatients in end--stage phase with systolic dysfunction or stage phase with systolic dysfunction or LV apical aneurysm with regional scarring may be at LV apical aneurysm with regional scarring may be at increased risk and are potential ICD candidatesincreased risk and are potential ICD candidates

routine implantation of routine implantation of ICDsICDs after alcohol after alcohol septalseptal ablationablationwould appear unnecessary at present although would appear unnecessary at present although

consideration on a caseconsideration on a case--byby--case basis is advisable, case basis is advisable, particularly in patients with conventional risk factorsparticularly in patients with conventional risk factors

clinically stable patients > 65 years : higher threshold clinically stable patients > 65 years : higher threshold

for consideration of prophylactic for consideration of prophylactic ICDsICDs

PRIMARY PREVENTIONPRIMARY PREVENTION

ICD decision making, particularly in patients with 1 ICD decision making, particularly in patients with 1 risk factor, may take into account other risk factor, may take into account other considerations as: considerations as:

LV outflow obstruction LV outflow obstruction

contrast MRIcontrast MRI

clinical judgment of managing physician with clinical judgment of managing physician with

direct knowledge of the patientdirect knowledge of the patient’’s overall clinical s overall clinical profile and desireprofile and desire

THANK YOU FOR THE ATTENTIONTHANK YOU FOR THE ATTENTION