James Kadouch,VP MD SGLA

Carolina Underwriter Forum Charlotte NC March 16th 2017

Hypertrophic Cardiomyopathyan update

2

HCM : the tip of the iceberg

2

3

Case 1: medical history

A 36 year old non smoker male applies for life insurance.In 2007, SCD of his twin brother at 24 yo autopsy revealed HCM familial screening led to the diagnosis of HCM in his case too.He is asymptomatic except some palpitations now and then.On examination, the only abnormality is a systolic murmur 3/6 heard at the apex.

3

4

Case 1: recent cardiac evaluation

EKG shows a sinus rhythm 65 bpm ; thin q waves I,II,III,Avf,V4,V5,V6 ; inverted TW V4,V5,V6 ; LVH ( voltage criteria ).

Cardiac MRI : mid interventricular septum thickened 20 mm with late gadolinium enhancement.

24 hours Holter EKG monitoring : 25400 isolated and monomorphic PVCs without SVT or non SVT.

Stress Echo : normal BP response to exercise, no provoked LVOT obstruction.

4

5

Case 1 : question

What would you do ?

5

6

Agenda

1 Classification of cardiomyopathies

2 Definition

3 Etiology - Pathophysiolgy

4 Clinical manifestations and diagnosis

5 Differential diagnosis

6 Natural history

7 SCD risk stratification

8 Therapy

6

77

Classification

Unknown cause(primary)

Dilated

Hypertrophic

Restrictive

Arrhythmogenic right ventriculardysplasia

Non classified ( LV non compaction, stress cardiomyopathy)

Specific disease of myocardial muscle (secondary)

Infectious

Metabolic

Systemic disease

Hereditary

Toxic

Source : Br Heart J 1980; 44:672-673

WHOs cardiomyopathies classification

8

Ventricle dilatation and systolic dysfunctionDilated (congestive, DCM, IDC)

Inappropriate myocardial hypertrophy without HTN oraortic stenosis

Hypertrophic (IHSS, HCM, HOCM)

Abnormal filling and diastolic dysfunctionRestrictive (infiltrative)

Functionnal classification

9

A) Normal left ventricle

B) Dilated Cardiomyopathy

C) Hypertrophic Cardiomyopathy (HCM)

D) Restrictive cardiomyopathy

Different types of cardiomyopathies

10

1111

Definition

12

In an adult, HCM is defined by a wall thickness 15 mm in one or more LV myocardial segmentsas measured by any imaging technique (echocardiography, cardiac magnetic resonance imaging (CMR) or computed tomography (CT))that is not explained solely by loading conditions.

In children as in adults, the diagnosis of HCM requires an LV wall thickness more than two standard deviations greater than the predicted mean

Hypertrophic Cardiomyopathy : definition

12

Diverse hypertrophy locations in HCM

13

14

Etiology

15

Etiology

15

Basic unit of striated muscle : sarcomere

16

Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction

17

Dynamic gradient outflow 30 mm Hg at rest or provokedSystole

Abnormal diastolic LV filling and LV filling pressuresDiastole

myocardial mass, filling pressures, O demand Microvascular dysfunction Concomitant epicardial obstructive CAD Myocardial bridging of coronary arteries (LAD)

Myocardial ischemia

Pathophysiology

18

19

Clinical manifestations and diagnosis

Asymptomatic, Echocardiographic findings, abnormal ECG, family history

Dyspnea 90% cases Chest pain 75% cases Fatigue, syncope Palpitations, dizziness less frequent

Symptomatic

Clinical patterns

20

Systolic ejection murmur left lower sternal border

Sudden cardiac death Heart failure Stroke

Complications

21

Clinical recognition of HCM

Sports/Other screening(4%)

Adabag et al. AJC 2006;98:1507

22

ECG abnormalities precede development of LVH

ECG abnormalities

Abnormal EKG in 92 % cases.

LVH aspect and repolarization abnormalities in 70 % cases.

Marked left axis deviation favoring an intraventricular gradient.

Thin and deep Q waves in inferior/ lateral territory in 20 to 50 % cases.

In apical HCM, giant inverted T waves, > than 10 mm depth, and very big QRS complexes inthe lateral precordial chest leads.

Atrial fibrillation in 10 % cases.

23

ECG 1 HCM

Inverted T waves

24

Cornell index positive

ECG 2 HCM

25

QRS V2 and V3 > 45 mm

Inverted T waves

Cornell index positive

Concave ST elevationII-III-aVF

Perpendicular QRS axis

Thin Q waves

26

ECG abnormalities suggesting specific diagnoses

27

ECG abnormalities suggesting specific diagnoses

28

Echocardiography : Long axis parasternal view

LVLA

RV

AO

29

Transthoracic echocardiography (normal heart)

RV

29

LV

LA

AO

LV

RV

IVS

LVPW

30

Long axis parasternal view : HCM

31

Long axis parasternal view

31

Long axis parasternal view

33

4 Chambers apical view

34

5 Chambers apical view

34

35

Late-peaking dagger-shaped appearance

Cardiac MRI (HCM)

36

3737

Cardiac MRI (HCM)

38

Differential diagnosis

Amyloidosis, glycogen storage disease, Anderson-Fabrydisease, infant of a diabetic mother.Similar clinical aspect

Noonans syndrome, Friedreichs ataxia, familial restrictivecardiomyopathyGenetic

HTN , hypertrophy elderly people, athletesExcessive physiologic response

Other causes of hypertrophy

39

40

Natural history

Annual mortality 3% / year in HCM centers, but 1% / year in general population.

Higher risk of SCD in children up to 6% / year (decreased dramatically during last decade)

In most cases, hypertrophy increases.

Usually slow clinical deterioration.

Evolution to dilated cardiomyopathy in 10-15% cases.

Natural history of HCM

41

Mortsubite

Insuffisancecardiaque

ICterminale FA et AVC

Benign andStable ( normal

longevity )

PrognosticProfiles

Suddendeath

Heartfailure End Stage

AF and stroke

Clinical course and natural history

42

43

SCD risk stratification

44

SCDClinical

Morphology

Hemodynamicstatus Arrythmia

Ischemia

Genetic

SCD evaluation in HCM

1. Unexplained recent syncope

2. Family history of SD attributable to HCM in 1 1st or 2nd degree relatives

3. Massive LV hypertrophy (wall thickness 30 mm)

4. Hypotensive or blunted blood pressure response to exercise (max SBP rest SBP < 20or 25 mm Hg)

5. Multiple repetitive non sustained ventricular tachycardia on ambulatory (Holter) ECG monitoring

Major established risk markers of SD in HCM

45

A number of studies have reported a significant association with LVOTO and SCD.

Several unanswered questions remain, including the prognostic importance of provocable LVOTO and the impact of treatment (medical or invasive) on SCD.

Left ventricular outflow tractobstruction

LGE on CMR imaging is believed to represent myocardialfibrosis or scarring

Recent meta-analysis of 7 studies showed the presence ofLGE was associated with an increased risk for SCD (OR:3.41)

Late gadolinium enhancement

Some sarcomeric gene mutations may confer a higher risk ofSDGene mutations

Source : 2011 ACCF/AHA Guideline diagnosis and treatment of HCM.Circulation 2011;124:2761-96.

Other potential SCD risk modifiers

46

Young age ( 30 mm

Absence of BP elevation during exercise

Profile of high risk of SCD

47

No or moderate symptoms

No family history of SCD

No syncope

No NSVT ( Holter )

Intraventricular gradient < 30 mm Hg

Normal or mild enlargement of LA size

Normal exercise BP response

Moderate LVH ( < 20 mm )

Low risk patients of SCD

48

Source : Adapted from Maron B, Circulation 2010 et Guide ALD5 CMH, HAS 2011

Elev

HCM : SCD prevention

49

Source : http://www.doc2do.com/hcm/webHCM.html

ESC Risk Score

50

http://www.doc2do.com/hcm/webHCM.html

51

Therapy

Asymptomatic : surveillance

Moderate symptoms : medical therapy ( beta-blockers, calcium-blockers, disopyramide )

With LVOTO :myectomy or alcohol septal ablation No LVOTO : heart transplant

Severe symptoms and ineffective medical therapy

Therapy for patients with low risk of SCD

52

53

Therapy for patients with high risk of SCD : Implantable CardioverterDefibrillator ( ICD )

54

Ventricular septal myectomy ( Morrow procedure )

55

Alcohol Septal Ablation

56

Cases study

57

Case 1 : risk factors of SCD

Young age Brothers SCD

PVCsLate GDE

IVS thickness 20 mmNo SVT or non SVT

No LVOT obstructionNormal systolic BP to exercise

57

58

Case 2 : medical history

A 27 year old Japanese soccer player applies for life insurance.He had had an isolated syncopal episode while intensely training a year ago, but his medical history was otherwise unremarkable. On examination, he appeared fit. His vital signs were normal. The apical pulse was sustained on palpation and was not displaced. Auscultation revealed an S4 heart sound.

58

59

Case 2 : TTE

59

LV

LARA

RV

RV

LV

60

Kaplan-Meier 20 years survival curves in patients with apical HC

60

American Journal of Cardiology 2013; 112:1271

61

Case 3 : medical history

Non smoker male 40 yo , no HTN, no Rx, with a brother on dialysis.

61

62

Case 3 : TTE

62

MERCI

Slide Number 1HCM : the tip of the iceberg Case 1: medical historyCase 1: recent cardiac evaluationCase 1 : question AgendaSlide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14EtiologySlide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Long axis parasternal view : HCMLong axis parasternal viewSlide Number 324 Chambers apical view5 Chambers apical viewLate-peaking dagger-shaped appearance Slide Number 36Cardiac MRI (HCM) Slide Number 38Slide Number 39Slide Number 40Slide Number 41Slide Number 42Slide Number 43Slide Number 44Slide Number 45Slide Number 46Slide Number 47Slide Number 48Slide Number 49Slide Number 50Slide Number 51Slide Number 52Slide Number 53Slide Number 54Slide Number 55Slide Number 56 Case 1 : risk factors of SCD Case 2 : medical history Case 2 : TTEKaplan-Meier 20 years survival curves in patients with apical HCCase 3 : medical history Case 3 : TTESlide Number 63