Rimodellamento Ventricolare e Conversione del Rimodellamento: soni processi confrontabili nei due sessi?

Marisa Di DonatoIRCCS San Donato Hospital

University of Florence

Rimodellamento Ventricolare e Conversione del Rimodellamento: soni processi confrontabili nei due sessi?

Marisa Di DonatoIRCCS San Donato Hospital

University of Florence

Tenth International Symposium

HEART FAILURE & Co.CARDIOLOGY SCIENCE UPDATE FEMALE DOCTORS SPEAKING

ON FEMALE DISEASES

Milano9 - 10 aprile 2010

Sex impact on remodelingAging cardiomyopathy

Women Men

Preservation of cardiac weight Reduction in cardiac weight(1g/yr)

Preseravtion of myocytes number Reduction in myocytes number (64 millions /yr)

Preservation of myocytes volume Increase in myocytes volume

Constant mononucleate/binucleate myocytes ratio

Decreased mononucleate/binucleate myocytes ratio

Low apoptotic index Apoptotic index 3-fold higher than women

Decreased apoptotic rate Increased apoptotic ratePiro et al. JACC 2010;55:1057

Aging cardiomyopathy

• The basis for the differential impact of aging on the heart is unknown

• A potential explanation may be related to the higher cardiac work load of male hearts throughout life

• Another explanation could be the higher rate of apoptosis in men

Sex impact on remodelingResponse to Pressure Overload

Women

Earlier improvement in EF (after AVR)Greater degree of LVH Increased LV mass Increased RWT Smaller EDVI and ESVIPreserved LV functionLater onset of pump dysfunction Higher expression of beta myosin heavy chain

Higher expression of ANF mRNA

Men

Later improvement After AVR

Lower degree of LVH

Impaired LV functionEarlier onset of pump dydfunction

Lower expression of beta myosin heavy chain

Lower expression of ANF mRNA

Piro et al. JACC 2010;55:1057

Sex impact on remodelingResponse to Volume Overload

Women Men

Smaller EDV and ESV Larger EDV and ESV

Greater LV mass/volume ratio Lower LV mass/volume ratio

Concentric hypertrophy No concentric hypertrophy

No impairment in cardiac function Impairment in cardiac function

Minimal ventricular dilatation

No changes in myocardial compliance

Significant ventricular dilatation

Decreased ventricular compliance

Piro et al. JACC 2010;55:1057

Sex impact on remodeling Response to acute myocardial ischemia

Women Men

Lower apoptotic rate in peri-infarct zone 10-fold higher apoptotic rate in peri-infarct zone

Longer duration of the cardiomyopathyLater onset of cardiac decompensation

Shorter duration of the cardiomyopathyEarlier onset of cardiac decompensation

Longer interval between HF and TransplantationLower infarct expansion index

Shorter interval between HF and Transplantation

Higher infarct expansion index

Three times lower mortality Worse cardiac function

Better cardiac function Maladaptive remodeling

Better remodeling Significantly greater dilatationMyocytes hypertrophyPremature exracellular matrix degradationHigher number of neutrophylisIncreased activity of metalloproteinase

Piro et al. JACC 2010;55:1057

Sex impact on remodelingHeart Failure

Women Men

Preserved LV EF Impaired LV EF

Smaller LV End diastolic volume

Smaller Stroke Volume

Higher LV end diastolic pressure

More frequent congestive symptoms

Greater LV End diastolic volume

Greater Stroke Volume

Lower LV end diastolic pressure

Less frequent congestive symptoms

Greater impairment in diastolic filling Lower impairment in diastolic filling

Sex impact on remodeling and the role of estrogens

• The mechanism by which estrogens exert their cardio-protective effects are not completely understood

• Ovarian synthesis of estrogens is subject to dramatic changes during the course of life but intramyocardial synthesis is less influenced by such variations (Grohe 1998)

Sex impact on remodeling and the role of estrogens

• Metabolic and vascular effects • Endotelium-dependent flow-mediated dilatation and aortic

compliance are greater in women

• Estrogens reduce cytopatic damage associated with myocardial injury (less apoptosis)

• Androgens adversely affect myocardial healing (Higher rate of rupture in men) and promote cardiac remodeling and dysfunction

Diastolic Heart Failure

• The reduced ventricular dilatation during remodeling in women compared with men helps explain why approximately half of women presenting with HF symptoms have preserved EF, vs one/third of men(Cleland JC, Eur Heart J 2003)

• When affected by HF women are more likely than men to present with congestive symptoms

• Both men and women with diastolic dysfunction and preserved EF show an increase in End diastolic pressure-volume ratio

THE PROCESS OF POST_INFARCTION REMODELING

Gender & Heart Failure● Myocardial Changes

Myocyte lossNecrosisApoptosis

● Alterations in extracellular matrix● Matrix degradation● Replacement fibrosis

● Alteration in LV chamber geometry● LV dilation (SIZE)● Increased LV sphericity (SHAPE)● LV wall thinning (SHAPE)● Mitral valve incompetence (SIZE AND SHAPE)

IRCCS Policlinico San Donato

Sex Differeces after MI

0

10

20

30

40

50

60

Diabetes NYHA 3-4 Inferior Site

Men

Women

0.02

0.001

0.05

496 pts (89 women) San Donato Hospital (unpublished)

0

5

10

15

20

25

30

Concentric Eccentric Dialtation

Pattern of LV Remodeling after Myocardial InfarctionIn Women

%

Concentric Eccentric Dilatation

496 pts (89 women)San Donato Hospital (unpublished)

70

72

74

76

78

80

82

84

86

88

90

Concentric Eccentric Dialtation

Pattern of LV Remodeling after Myocardial InfarctionIn Men

Concentric Eccentric Dilatation

496 pts (89 women) San Donato Hospital (unpublished)

%

95

100

105

110

115

120

F M

EDVI(ml/m2)

68

70

72

74

76

78

80

82

F M

ESVI(ml/m2)

Sex impact on LV Remodeling after Myocardial Infarction

0.0010.001

496 pts (89 women) San Donato Hospital (unpublished)

0.335

0.34

0.345

0.35

0.355

0.36

0.365

0.37

0.375

0.38

0.385

F M

Sex impact on LV Remodeling after Myocardial Infarction

P 0.04

Relative wall Thickness

496 pts (89 women) San Donato Hospital (unpublished)

Sex impact on LV Remodeling after Myocardial Infarction

150

155

160

165

170

175

180

185

F M

LV Mass Index(g.m2)

41.5

42

42.5

43

43.5

44

44.5

45

45.5

46

46.5

F M

Left Atrium Size (mm)

0.0060.003

496 pts (89 women) San Donato Hospital (unpublished)

0

0.1

0.2

0.3

0.4

0.5

0.6

SI Diast SI Diast SI Syst SI Syst

Women Men

0.007

0.001

Sex impact on LV Shape after Myocardial Infarction

(Median Values)

SPHERICITY

INDEX

Sphericity Index= Short to Long axis ratio

San Donato Hospital (unpublished)

0

0.10.2

0.3

0.40.5

0.6

0.7

0.80.9

1

1 2MI N MI N

Sex impact on LV Apical Shape (Conicity Index) after MIDiastole

00.10.20.30.40.50.60.70.80.9

11.11.2

1 2

Systole

MI N MI N

0.001

0.0010.001

0.001

0.0001

0.01

Conicity Index (CI)=Apical to Short axis ratio

San Donato Hospital (unpublished)

Sex impact on Global and Regional LV shape after MI

L

S

A

Sphericity Index= S/L

Conicity Index= A/S

SI= 0.46CI=1.12

SI= 0.55CI=0.78

Is it possible to revert LV remodeling?

Is there a difference in women compared to men in reverting the remodeling process ?

Non pharmachologic approaches to revert/retard LV remodeling

● Cardiomyoplasty● Volume reduction surgery (Batista operation)● Mitral valve repair +/-CABG●VAD implantation● CRT ● LV reconstruction (Dor procedure)● Mannequin guided surgical ventricular restoration

(SVR- Menicanti)● Prosthetic restraint devices

● Cells replacement

Surgical technique

• Arrested heart• Use of intraventricular mannequin to re-size and re-shape• Complete coronary revascularization• Mitral repair through ventricular approach, if needed• Cryosurgery at the border of the lesion if VA present

San Donato Hospital, Milano Italy

Menicanti 2002

San Donato Hospital SeriesPts submitted to SVR (2001-2009)

O 496 Patients with previous MI:• 89 Women (age 68+/-10 yrs)**• 407 Men (age 64+/-9 yrs)

O NYHA III-IV:• Men 166/384 (43%)• Women 50/83 (56%)**

O CABG associated in 93% of women and 94% of men

O Mitral repair in 25% of men and 27% of women

O Operative mortality:

Men 27/408 (7.6%)

Women 9/89 (10%) NS

….SURGERY for LV remodelingPre

Post

Post

Pre

-30

-25

-20

-15

-10

-5

0

5

10

EDV ESV EF+

Women

-30

-25

-20

-15

-10

-5

0

5

10

EDV ESV EF

Men

Reverse remodeling at 12 months FUP induced by SVR

-35

-30

-25

-20

-15

-10

-5

0

1 2 3

Diastole

Systole

Long Axis Short Axis Apical Axis

Reverse remodeling at 12 months FUP induced by SVR

-35

-30

-25

-20

-15

-10

-5

01 2 3

Diastole

Systole

Long Axis Short Axis Apical Axis

Women Men

0

0.1

0.2

0.3

0.4

0.5

0.6

1 2 Pre-op Post-op Pre-op Post-op

Changes in Sphericity Index following SVR

Diastole

Systole

0.010.01

0.01

Kaplan Meier Survival Function

0 12 24 36 48 60 72 84 960

20

40

60

80

100Women (N=88)

Men (n=381)

months Follow-up

Cum

ulat

ive

Sur

viva

l

Sex impact following Surgical Ventricular Reconstruction for post-infarction LV remodeling

• LVR can revert the remodeling process both in men and women, by reducing Ventricular size and improving apical shape

• A more physiologic apex is the key to re-direct the blood flow towards the aorta and improving cardiac function

• Prognosis following LVR is not impacted by sex

Conclusions

Conclusions

• Regardless of age and menopause the remodeling process appears to be more favourable in women

• Women are more likely to present with “diastolic only” dysfunction and are at greater risk for low output syndrome acutely

• Lower awareness of heart disease in women is likely responsible for the worse outcome observed in some clinical series, and since this issue can be corrected,increased awareness of heart disease among women should still represent a number one priority

THANKS