INTERNATIONAL HCM SUMMIT

Boston, MA October 2017

HYPERTROPHIC CARDIOMYOPATHY A Contemporary and Treatable Genetic Disease: Diagnosis, Heart Failure Management, and Prevention of Sudden Death

INTERNATIONAL HCM SUMMIT

HCM Summit VI

The ICD and Prevention of Sudden Death

Barry J. Maron MD HCM Institute Tufts Medical Center Boston MA.

Arrhythmogenic (Unstable) Myocardial Substrate in HCM

Sudden Death

Progressive Heart Failure

AF &

Stroke

End- Stage

Profiles in Prognosis for HCM

Benign/Stable (normal longevity)

HCM (36%)

Coronary Anomalies

(17%) M

yoca

rditi

s (6

%)

ARVC

(4%

) Aortic Rupture (3%) AS (3%)

Dilated CM (2%)

WPW (2%)

Sudden Death in Young Athletes

Maron, BJ et. al. Circulation 2009; 119:1085-1092

What Counts in HCM

Outcome

% LGE

SD Risk Factors

Apical Aneurysm

AF

Age

↓ EF

LV Obstruction

Magnitude LVH

Highest

Intermediate

Lowest

2° prevention Cardiac arrest/sustained VT

1° prevention Family history HCM-SD Unexplained syncope Multiple-repetitive NSVT (Holter) Abnormal exercise BP response LGE ≥ 15% of LV mass Massive LVH ≥ 30 mm LV apical aneurysm

Rare subgroups/potential arbitrators End-stage (EF < 50%) Marked LV outflow obstruction (rest) Modifiable Intense competitive sports CAD LGE ≥ 15% of LV mass Age ≥ 60y

Alcohol septal ablation (some pts)

ICD

2011 US/CANADA ACC/AHA Guidelines For HCM

0 2 4 6 8

10 12 14 16

<15 16-19 20-24 25-29 ≥30 Max. LV Wall Thickness (mm)

% P

atie

nts

With

SC

D

Hypertrophy Counts in HCM: Relation Between LV Thickness & SD

Spirito et al NEJM 2000;342:1778

Highest

Intermediate

Lowest

2° prevention Cardiac arrest/sustained VT

1° prevention Family history HCM-SD Unexplained syncope Multiple-repetitive NSVT (Holter) Abnormal exercise BP response LGE ≥ 15% of LV mass Massive LVH ≥ 30 mm LV apical aneurysm

Rare subgroups/potential arbitrators End-stage (EF < 50%) Marked LV outflow obstruction (rest) Modifiable Intense competitive sports CAD LGE ≥ 15% of LV mass Age ≥ 60y

Alcohol septal ablation (some pts)

ICD

2011 US/CANADA ACC/AHA Guidelines For HCM

0

10

20

30

40

50

60

70

Alive Non-CardiacDeath

Non-HCMCardiacDeath

EmbolicStroke

HeartFailure

SCD

% o

f HC

M C

ohor

t

65%

13% 12%

2% 1%

0.2%/y

Outcome of HCM Patients First Evaluated ≥ 60 Years

1%

HCM Death

Age Counts And Aging is Good in HCM

Maron ety al Circ

Maron et al Circulation 2013;127:585

TheESC-HCMpredic0onformulaforSDisasfollows:ProbabilitySCDat5years=1–0.998exp(Prognos0cindex);wherePrognos0cindex=[0.15939858xmaximalLVwallthickness(mm)]–[0.00294271xLVmaximalwallthick-ness2(mm2)]+[0.0259082xleWatrialdiameter(mm)]+[0.00446131xmaximal(rest/Valsalva)LVou[lowtractgradient(mmHg)]+[0.4583082xfamilyhistorySCD]+[0.82639195xNSVT]+[0.71650361xunexplainedsyncope]–[0.01799934xageatclinicalevalua0on(years)].

% P

atie

nts

With

/With

out

ICD

Inte

rven

tion/

Sudd

en D

eath

Appropriate ICD

Intervention

No Appropriate ICD

Intervention

ESC Risk Score

<4% <4% 4-6% 4-6% >6% >6% Risk/5y Risk/5y

<4% 4-6% >6% Risk/5y

Sudden Death

Limitations in ESC Sudden Death Risk Score (n=1649)

60%

26%

63%

9%

Maron et al AJC 2015;116:757

Prevention of Sudden Death in HCM

Dr. Michele Mirowski

N Engl J Med 1980;303:322.

ICD Performance in HCM 506

103

5.5%/y

Follow-up = 3.7 ± 3 years

ICD discharge rate

Appropriate Shocks (20%)

11%/y 4%/y

2º prevention 1º prevention

VT/VF

Maron et al JAMA 2007;298

0

1

2

3

4

5

6

7

1 2 ≥ 3

No. of Risk Factors for Primary Prevention

Rat

e of

App

ropr

iate

Inte

rven

tions

pe

r 100

per

son-

yr

3.8 3.0

4.1

Overall p=0.88

Appropriate Shocks (35%)

Maron et al JAMA 2007;298:405

ICD in HCM for Children / Adolescents

224

43

4.4% / yr

13%/yr 3%/y

No. Patients

Appropriate ICD Discharge (19%)

2° prevention 1° prevention

Follow-up= 4.3 ± 3.3 yr

Initial shock 9-23 y (mean= 17 y)

Maron et al. JACC 2013;61:1527

≤ 3 4 - 6

7 - 10 11-20

21-30 31-40 51-60

>90

Duration (months)

No.

Pat

ient

s

0 2 4 6 8

10 12 14 16

61-70 71-90

41-50

ICD in HCM: Time to First Shock

Maron et al JAMA 2007;298:405

HCM is Unpredictable

HCM—ICD Registry

29 (6%)

14

14

1

Deaths

ICD Malfunction

End-stage Embolic stroke

Cancer, sepsis, renal diseases, suicide, CAD,

accidents

No HCM

HCM

HCM- Arrhythmias

(nl EF)

Maron, BJ et. al. JAMA 2007;298:405

Expectations For HCM Patients After ICD Shocks

ICD shock

1%

0%

20%

30%

Sudden/HF Death

HF Hospitalization

HCM (@6 y)

CAD (MADIT II) @1 year:

Life-saving Prolongation of Life Maron BJ et al

In press

High risk

Some risk

Cardiologist

Patient

Autonomy

TRANSPARENCY / FULL DISCLOSURE / INFORMED CONSENT

?

Risk Factors Primary Prevention Decision Tree: ICD In HCM

Preservation of Life Recalls

Inappropriate Shocks Infection

Thrombosis

Lead Complications (5%/y)

Preservation of Life

Recalls Inappropriate Shocks

Infection Thrombosis

Lead Complications (5%/y)

Contemporary CV treatment options offer HCM patients a reasonable

aspiration for reduced mortality and extended longevity. The ICD has altered clinical course for many

patients creating the possibility of normal life expectancy even for

those @ high risk .

Decrease in Annual HCM Mortality Over 50 Years

4-6% (1975)

1.5-2.0%

0.5% (2017)

2000 (2000)