Tenth International Symposium
HEART FAILURE & Co.
CARDIOLOGY SCIENCE UPDATE
FEMALE DOCTORS SPEAKING
ON FEMALE DISEASES
Milano
9 - 10 aprile 2010
Rimodellamento Ventricolare e Conversione del Rimodellamento:
soni processi confrontabili nei due sessi?
Marisa Di Donato
IRCCS San Donato Hospital
University of Florence
Sex impact on remodeling
Aging 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 rate
Piro 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 remodeling
Response to Pressure Overload
Women
Earlier improvement in EF (after AVR)
Greater degree of LVH
Increased LV mass
Increased RWT
Smaller EDVI and ESVI
Preserved LV function
Later 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 function
Earlier 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 remodeling
Response 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
Significant ventricular dilatation
No changes in myocardial compliance
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 cardiomyopathy
Later onset of cardiac decompensation
Shorter duration of the cardiomyopathy
Earlier onset of cardiac decompensation
Longer interval between HF and
Transplantation
Lower infarct expansion index
Shorter interval between HF and Transplantation
Three times lower mortality
Worse cardiac function
Better cardiac function
Maladaptive remodeling
Better remodeling
Significantly greater dilatation
Myocytes hypertrophy
Premature exracellular matrix degradation
Higher number of neutrophylis
Increased activity of metalloproteinase
Higher infarct expansion index
Piro et al. JACC 2010;55:1057
Sex impact on remodeling
Heart Failure
Women
Men
Preserved LV EF
Impaired LV EF
Smaller LV End diastolic volume
Greater LV End diastolic volume
Smaller Stroke Volume
Greater Stroke Volume
Higher LV end diastolic pressure
Lower LV end diastolic pressure
More frequent congestive symptoms
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
IRCCS Policlinico San Donato
THE PROCESS OF POST_INFARCTION
REMODELING
Gender & Heart Failure
● Myocardial Changes
Myocyte loss
Necrosis
Apoptosis
● 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)
Sex Differeces after MI
0.02
60
50
0.001
40
Men
30
0.05
20
Women
10
0
Diabetes
496 pts (89 women)
NYHA 3-4
Inferior Site
San Donato Hospital (unpublished)
Pattern of LV Remodeling after Myocardial Infarction
In Women
30
%
25
20
15
10
5
0
Concentric
Concentric
Eccentric
Eccentric
Dilatation
Dialtation
496 pts (89 women)
San Donato Hospital (unpublished)
Pattern of LV Remodeling after Myocardial Infarction
In Men
90
%
88
86
84
82
80
78
76
74
72
70
Concentric
Concentric
496 pts (89 women)
Eccentric
Eccentric
Dialtation
Dilatation
San Donato Hospital (unpublished)
Sex impact on LV Remodeling after Myocardial
Infarction
EDVI(ml/m2)
ESVI(ml/m2)
120
82
80
115
78
110
0.001
76
74
105
0.001
72
100
70
68
95
F
496 pts (89 women)
M
F
M
San Donato Hospital (unpublished)
Sex impact on LV Remodeling after Myocardial Infarction
Relative wall Thickness
0.385
0.38
0.375
0.37
0.365
P 0.04
0.36
0.355
0.35
0.345
0.34
0.335
F
496 pts (89 women)
M
San Donato Hospital (unpublished)
Sex impact on LV Remodeling after
Myocardial Infarction
LV Mass Index(g.m2)
Left Atrium Size (mm)
185
46.5
180
46
45.5
175
170
45
44.5
0.003
0.006
44
43.5
165
43
42.5
160
155
42
41.5
150
F
496 pts (89 women)
M
F
M
San Donato Hospital (unpublished)
Sex impact on LV Shape after Myocardial Infarction
Sphericity Index= Short to Long axis ratio
S
P
H
E
R
I
C
I
T
Y
0.007
0.6
0.001
0.5
0.4
0.3
0.2
I
N
D
E
X
0.1
0
SI Diast
Women
(Median Values)
SI Diast
Men
SI Syst
SI Syst
San Donato Hospital (unpublished)
Sex impact on LV Apical Shape (Conicity Index) after MI
Diastole
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Systole
0.001
MI
1
1.2
1.1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
N
0.01
0.001
MI
2
N
Conicity Index (CI)=
Apical to Short axis ratio
0.0001
0.001
0.001
MI
1
N
MI
2
N
San Donato Hospital
(unpublished)
Sex impact on Global and Regional LV shape after MI
SI= 0.46
CI=1.12
SI= 0.55
CI=0.78
L
S
A
Sphericity Index= S/L
Conicity Index= A/S
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
San Donato Hospital, Milano Italy
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
Menicanti 2002
San Donato Hospital Series
Pts 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 remodeling
Pre
Pre
Post
Post
Reverse remodeling at 12 months FUP
induced by SVR
EDV
ESV
+10
EF
EDV
ESV
10
5
0
-5
5
0
-5
-10
-10
-15
-20
-25
-30
-15
-20
-25
-30
Women
Men
EF
Reverse remodeling at 12 months FUP
induced by SVR
Long Axis
Long Axis
Short Axis Apical Axis
0
Short Axis Apical Axis
0
1
2
3
-5
-5
-10
-10
1
2
3
-15
Diastole
-15
Diastole
-20
Systole
-20
Systole
-25
-25
-30
-30
-35
-35
Women
Men
Changes in Sphericity Index following SVR
0.01
0.01
Diastole
0.6
0.01
0.5
0.4
0.3
Systole
0.2
0.1
0
Pre-op
1
Post-op
Pre-op
2
Post-op
Sex impact following Surgical Ventricular Reconstruction
for post-infarction LV remodeling
Cumulative Survival
Kaplan Meier Survival Function
Women (N=88)
100
Men (n=381)
80
60
40
20
0
0
12
24
36
48
60
72
months Follow-up
84
96
Conclusions
• 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 redirect the blood flow towards the aorta and
improving cardiac function
• Prognosis following LVR is not impacted by
sex
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