Mucopolysaccharidoses and their

Cardiac Manifestations

Mucopolysaccharidoses and their

Cardiac ManifestationsSamuel Menahem

Head, Paediatric CardiologyMonash Medical Centre,

Consultant CardiologistDepartment of Cardiology, Royal Children’s Hospital,

Melbourne.

Samuel Menahem

Head, Paediatric CardiologyMonash Medical Centre,

Consultant CardiologistDepartment of Cardiology, Royal Children’s Hospital,

Melbourne.

HEART INVOLVEMENT IN MUCOPOLYSACCHARIDOSES

Accumulation of Abnormal Deposits +/- resultant reactions in :

Heart muscle - thickened, weak and/or stiff muscle (80% - autopsy series) Heart Valves - narrowed +/- leaky valves {60% - autopsy series} Blood Vessels of the heart - narrowing (30% - autopsy series)

ConsequencesConsequences

Nil-Unaffected individuals Limitation in function Need for medication Heart Failure Sudden Death Heart involvement increases with age (50%)

Additional ProblemsAdditional Problems

High blood pressure -lungs/body Abnormal ECG - problems with rhythm - prolonged QT interval

HEART INVOLVEMENT IN MUCOPOLYSACCHARIDOSES

Accumulation of Abnormal Deposits +/- resultant reactions in :

Heart muscle - thickened, weak and/or stiff muscle (80% - autopsy series) Heart Valves - narrowed +/- leaky valves {60% - autopsy series} Blood Vessels of the heart - narrowing (30% - autopsy series)

ConsequencesConsequences

Nil-Unaffected individuals Limitation in function Need for medication Heart Failure Sudden Death Heart involvement increases with age (50%)

Additional ProblemsAdditional Problems

High blood pressure -lungs/body Abnormal ECG - problems with rhythm - prolonged QT interval

Normal Heart and ArteriesNormal Heart and Arteries

RARA

LALA

RVRVLVLV

LigamentumLigamentum

AoAoPAPA

RA/LA =

Right & Left Atrium

RA/LA =

Right & Left Atrium

RV/LV =

Right & Left Ventricle

RV/LV =

Right & Left Ventricle

Ao =Aorta;

PA =Pulmonary Artery

Ao =Aorta;

PA =Pulmonary Artery

Heart ValvesHeart Valves

PP

AAMM

TT

Each side of the heart has two valvesThey control flow of blood into and out of the two ventricles (LV & RV).

The left sided valves are theMitral (M) - inflow

and Aortic (A) - outlet

The right heart valves are Tricuspid (T) - inflow

and Pulmonary (P) - outlet

Each side of the heart has two valvesThey control flow of blood into and out of the two ventricles (LV & RV).

The left sided valves are theMitral (M) - inflow

and Aortic (A) - outlet

The right heart valves are Tricuspid (T) - inflow

and Pulmonary (P) - outletRVRVLVLV

LALARARA

RVRVLVLV

AoAoPAPA

MainCirc.MainCirc.

LungCirc.LungCirc.

Lower systemiccirculation (abdo. & legs)

Lower systemiccirculation (abdo. & legs)

RightlungRightlung

LeftlungLeftlung

Upper systemiccirculation

(head & arms)

Upper systemiccirculation

(head & arms)

PAPAAoAo

AoAo

SVCSVC

IVCIVC

LPALPARPARPA

Normal Circulation

Normal Circulation

RARA

LALA

RVRVLVLV

IH (Hurler) Most severe - heart muscle thick/weakHeart vessels thickened - heart attack/anginaThickened/nodular leaky valves - mitral valve/aortic valve

IS (Scheie) Involve heart valves - aortic/mitral

II (Hunter) Heart Vessels - Heart attackThickened valves - mitral/aortic leak

IIIA (Sanfilippo) Aortic valve leak, mitral valve leak

IVA (Morquio) Heart wall, thickened/leaky valves - aortic/mitral

VI (Maroteaux-Lamy) Heart wall thickened/stiff, weakThickened/narrow/leaky valves - mitral/aortic valves

VII (Sly) Leaky valve aortic

IH (Hurler) Most severe - heart muscle thick/weakHeart vessels thickened - heart attack/anginaThickened/nodular leaky valves - mitral valve/aortic valve

IS (Scheie) Involve heart valves - aortic/mitral

II (Hunter) Heart Vessels - Heart attackThickened valves - mitral/aortic leak

IIIA (Sanfilippo) Aortic valve leak, mitral valve leak

IVA (Morquio) Heart wall, thickened/leaky valves - aortic/mitral

VI (Maroteaux-Lamy) Heart wall thickened/stiff, weakThickened/narrow/leaky valves - mitral/aortic valves

VII (Sly) Leaky valve aortic

TYPE OF HEART INVOLVEMENTTYPE OF HEART INVOLVEMENTTYPE OF HEART INVOLVEMENTTYPE OF HEART INVOLVEMENT

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T

Electrocardiogram (ECG)Electrocardiogram (ECG)

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T

Chest X-rayChest X-ray

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T

Cross sectional echocardiography (Echo)Cross sectional echocardiography (Echo)

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

Clinical Examination

ECG/Chest x-ray

Echocardiogram

Regular review

Medication

Catheter InterventionValve/heart vessels

Surgery

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T

HEART SYMPTOMS FROM OTHER ABNORMALITIESHEART SYMPTOMS FROM OTHER ABNORMALITIESHEART SYMPTOMS FROM OTHER ABNORMALITIESHEART SYMPTOMS FROM OTHER ABNORMALITIES

Upper Airway Obstruction

- Large tonsils/adenoids

Carbon dioxide retention - Right heart failure

- Low oxygen - left heart failure

Stiff Chest Wall

- Breathlessness

- May be aggravated by heart failure

Upper Airway Obstruction

- Large tonsils/adenoids

Carbon dioxide retention - Right heart failure

- Low oxygen - left heart failure

Stiff Chest Wall

- Breathlessness

- May be aggravated by heart failure

C O N C L U S I O N SC O N C L U S I O N SC O N C L U S I O N SC O N C L U S I O N S

Heart involvement common

Most minor and no treatment except follow up

May be helped with medication

Occasional catheter/surgery intervention

Look for “non-heart” causes for symptoms

Heart involvement common

Most minor and no treatment except follow up

May be helped with medication

Occasional catheter/surgery intervention

Look for “non-heart” causes for symptoms

A REVIEW OF MPS A REVIEW OF MPS

WITH WITH

CARDIAC INVOLVEMENTCARDIAC INVOLVEMENT

Alex LuMartin Delatycki

Samuel Menahem

Royal Children’s Hospital Melbourne

A REVIEW OF MPS A REVIEW OF MPS

WITH WITH

CARDIAC INVOLVEMENTCARDIAC INVOLVEMENT

Alex LuMartin Delatycki

Samuel Menahem

Royal Children’s Hospital Melbourne

MPS - RCHMPS - RCH

Born between 1957 - 1998

Confirmed Cases

Type I Hurler 38

Type II Hunter 18

Type III San Filippo 41

Type IV Morquio 5

Type VI Maroteaux-Lamy 7

MPS - RCHMPS - RCH

Born between 1957 - 1998

Confirmed Cases

Type I Hurler 38

Type II Hunter 18

Type III San Filippo 41

Type IV Morquio 5

Type VI Maroteaux-Lamy 7

Data available 14

Death 13 (1yr to 11 yrs)

Alive 1 (Bone marrow transplant at 17 months)

6 cases echo - Reduced LV contractility 2

- Mitral regurgitation 4 (mild) - thickened MV

- Aortic regurgitation 2 (mild/moderate) - thickened AV

- Dilated RV, thickened TV, PV 1

- Medical Treatment 1

Data available 14

Death 13 (1yr to 11 yrs)

Alive 1 (Bone marrow transplant at 17 months)

6 cases echo - Reduced LV contractility 2

- Mitral regurgitation 4 (mild) - thickened MV

- Aortic regurgitation 2 (mild/moderate) - thickened AV

- Dilated RV, thickened TV, PV 1

- Medical Treatment 1

Type I - Hurler n = 38Type I - Hurler n = 38Type I - Hurler n = 38Type I - Hurler n = 38

3 Autopsies

1. Intimal thickening of aorta and ventriclesDilated Hypertrophied LVThickened nodular mitral valveThickened aortic valveNarrowed coronary arteries

2. Intimal thickening aortaHypertrophied left ventricleNarrowed coronary arteries

3. Intimal thickening of aortaHypertropied LVNarrowed coronary arteries

3 Autopsies

1. Intimal thickening of aorta and ventriclesDilated Hypertrophied LVThickened nodular mitral valveThickened aortic valveNarrowed coronary arteries

2. Intimal thickening aortaHypertrophied left ventricleNarrowed coronary arteries

3. Intimal thickening of aortaHypertropied LVNarrowed coronary arteries

Type 1- HurlerType 1- HurlerType 1- HurlerType 1- Hurler

1 Bone marrow transplant - 17 months

Pre-transplant - mild MR, AR, TR

Post transplant - dilated LV, moderate MR, AR, mild TR improved clinical/biochemical parameters

1 Bone marrow transplant - 17 months

Pre-transplant - mild MR, AR, TR

Post transplant - dilated LV, moderate MR, AR, mild TR improved clinical/biochemical parameters

Type 1 - HurlerType 1 - HurlerType 1 - HurlerType 1 - Hurler

4 deaths (7 to 30 years)

Normal LV function 8

Thickened mitral valve, mild /moderate MR 8

Thickened aortic valve/mild AR 4

Mild AS 1

1 autopsy - thickened mitral valve and calcified mitral valve annulus, LV intimal thickening

4 deaths (7 to 30 years)

Normal LV function 8

Thickened mitral valve, mild /moderate MR 8

Thickened aortic valve/mild AR 4

Mild AS 1

1 autopsy - thickened mitral valve and calcified mitral valve annulus, LV intimal thickening

Type II Hunter n = 12Type II Hunter n = 12Type II Hunter n = 12Type II Hunter n = 12

Echo - 5 cases

Normal LV function 5

Moderate MS 1

Mild/Moderate AR 2

Thickened MV/AV 1

Prolapse of AMVL 1

Echo - 5 cases

Normal LV function 5

Moderate MS 1

Mild/Moderate AR 2

Thickened MV/AV 1

Prolapse of AMVL 1

Type III - San Filippo n = 25Type III - San Filippo n = 25Type III - San Filippo n = 25Type III - San Filippo n = 25

3 Autopsies

1 normal heart

1 thickening and nodules of AV/MV, narrowed coronary arteries

1 thickened MV/AV/PV

3 Autopsies

1 normal heart

1 thickening and nodules of AV/MV, narrowed coronary arteries

1 thickened MV/AV/PV

Type III - San FilippoType III - San FilippoType III - San FilippoType III - San Filippo

1 Normal heart

1 mildly thickened AV/MV mild AR

1 mildly thickened MV, mild AR

1 Normal heart

1 mildly thickened AV/MV mild AR

1 mildly thickened MV, mild AR

Type V - Morquio n=5Type V - Morquio n=5Type V - Morquio n=5Type V - Morquio n=5

Good LV function 5

Mild MR 4

Mild AR 2

Mild MS 3

LVH 1

Dilated LV 1

Good LV function 5

Mild MR 4

Mild AR 2

Mild MS 3

LVH 1

Dilated LV 1

Type VI - Maroteaux Lamy n=7Type VI - Maroteaux Lamy n=7Type VI - Maroteaux Lamy n=7Type VI - Maroteaux Lamy n=7

1 mitral valvotomy 13 years,

mitral valve replacement 14 years

aortic valvotomy

on medication

1 mitral valve replacement/aortic valvotomy for MS/AS

death

1 mitral valvotomy 13 years,

mitral valve replacement 14 years

aortic valvotomy

on medication

1 mitral valve replacement/aortic valvotomy for MS/AS

death

Type VI Maroteaux-LamyType VI Maroteaux-Lamy