IGHC
Dementia
Diagnostic criteria for subclinical
systolic and diastolic LV function
JRP A3
Tatiana Kuznetsova, Jan A. Staessen
University of Leuven, Belgium
Heart failure Stages of heart failure
Stage A: asymptomatic subjects with normal LV structure and function at
high risk for HF, because of hypertension, obesity and/or diabetes;
Stage B: asymptomatic patients with structural and/or functional LV
abnormalities;
Stage C: symptomatic patients with structural and/or functional LV
abnormalities;
Stage D: patients with refractory symptoms of heart failure.
ACC/AHA Guidelines, Circulation 2005; 112: 1825-52
Heart failure Background and objectives
Above age 65, the incidence of overt HF is currently ~10/1000 person-years.
Because of the ageing of populations, the prevalence of HF will rise by 50%
over the next 10-15 years, increasing health care costs. 50% of HF patients
die within 4 years. The diagnosis of asymptomatic LV dysfunction
(imaging + biomarkers) is key in the prevention and treatment of HF.
Objectives:
 To explore (using TDI) the prevalence of asymptomatic systolic and
diastolic LV dysfunction in a general population;
 To identify (cross-sectionally and prospectively) risk factors and
biomarkers for LV dysfunction.
IGHC
Outline of presentation
Methods:
 Epidemiological approach;
 Echocardiography for cardiac phenotyping;
Results:
 Systolic LV dysfunction;
 Diastolic LV dysfunction;
Conclusions.
IGHC
JRP A3
Dementia
Methods
Epidemiological approach – echocardiography
EPOGH
Epidemiological methods
Randomly recruited nuclear and complex (Belgium) families;
Standardised and validated questionnaires in 8 languages;
BP at baseline: 2 x 5 conventional BP readings at home,
5 BP readings at examination centre, and 24-h ABPM;
Large number of intermediate phenotypes: blood and 24-h urine samples
(biobank);
Technical examinations: ECG, vascular and cardiac phenotypes;
Longitudinal FU (median 15 y in Belgium and 5 years in other centres).
EPOGH
Standardised echocardiographic protocol
Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO);
A single observer is performing all echocardiographic examinations by
means of Vivid 7 ultrasound scanner (GE Vingmed, Horten, Norway)
according to a standardised protocol;
All echocardiographic examinations are stored in digital format on a local
network for off-line reading (EchoPac, GE and SPEQLE, University of
Leuven);
Leuven is the core centre for cardiac and arterial phenotyping, management
of samples, database construction, and statistical analysis.
IGHC
Dementia
Subclinical LV dysfunction
Systolic
SysLVF
Background
Conventional echocardiography enables the assessment of
global LV systolic function: FS or EF;
Colour tissue Doppler imaging makes it possible to specifically
evaluate the longitudinal and radial components of regional LV
systolic function.
Strain
Echocardiographic characteristics
Women (n=243)
Men (n=237)
83 (17)
98 (20)†
0.37 (0.071)
0.37 (0.072)
69.6 (7.3)
67.8 (7.2)**
Strain longitudinal (%)
23.0 (3.7)
22.7 (3.6)
SR longitudinal (1/s)
1.31 (0.26)
1.31 (0.23)
Strain radial (%)
60.7 (12.5)
57.6 (12.9)*
SR radial (1/s)
3.44 (0.86)
3.34 (0.82)
Conventional
LV mass index (g/m2)
RWT
EF (%)
TDI
* p0.05; ** p0.01; † p0.001
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Strain
Longitudinal and radial S and SR by age
70
4.0
65
113
n=48
104
55
60
50
25
32
24
N=52
23
22
21
20
48
Strain rate (1/s)
Strain (%)
60
3.5
43
3.0
2.5
1.5
1.4
123
1.3
123
86
48
1.2
1.1
Age group (years)
p-values for trends  0.001
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Strain
Longitudinal strain vs WT, WHR and BW
Longitudinal
Radial
40
100
35
80
30
25
60
20
40
Strain (%)
15
10
20
0.2
0.3
0.4
0.5
RWT
0.6
0.7
40
0.2
0.3
45
60
0.4
0.5
RWT
0.6
0.7
75
105
120
100
35
80
30
25
60
20
40
15
10
20
0.6
p-values 0.001
0.7
0.8
0.9 1.0
WHR
1.1
1.2
90
Weight (kg)
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Strain
Summary of stepwise selection*
Variable
Par Est (SE)
R2 (%)
p-value
Strain longitudinal (%)
Age (+10 years)
- 0.35 (0.14)
8.4
.007
RWT (+0.1)
- 0.74 (0.26)
8.4
.001
WHR (+0.1)
- 0.59 (0.28)
1.5
.010
Strain radial (%)
Age (+10 years)
- 1.08 (0.48)
8.4
.027
RWT (+0.1)
- 2.57 (1.02)
2.0
.010
BW (+1 kg)
- 0.15 (0.05)
5.7
.0004
Ejection fraction (%)
Age (+10 years)
+ 1.59 (0.26)
16.1
< .0001
RWT (+0.1)
+ 1.67 (0.49)
2.2
.001
* p<0.10 – significance level for entry into the model
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Strain
Proposal for reference values* for S and SR
Healthy reference group
(n=239)
Strain (%)
Longitudinal
> 18.5
Radial
> 44.5
SR (1/s)
Longitudinal
> 1.00
Radial
> 2.45
*Upwards rounded the 5th percentiles
Strain
Annexin A5
Annexins are Ca2+ and phospholipid binding proteins;
Annexin A5 participates in the regulation of ion (Ca2+) currents across
the cardiomyocyte membrane;
Ravassa et al. showed that the upregulation of myocardial Annexin A5 is
associated with impairment of LV systolic function (EF) in patients with
HF (Eur Heart J 2007; 28: 2785-91).
Strain
Radial strain vs annexin A5
n = 265
r = –0.13
adjusted p = 0.006
100
Radial Strain, %
90
80
70
60
50
40
30
20
0.56
3.16
1
1.78
Annexin A5, ng/mL
5.62
Strain
Conclusions of this section
LV strain and strain rate, as measured by 1-dimensional colour Doppler
imaging in a general population, decreased with age, body weight, central
obesity, and RWT.
LV strain and strain rate are sensitive tools for the detection of subclinical
systolic dysfunction associated with abdominal obesity and LV remodelling.
The clinical applicability of strain and strain rate in the stratification and/or
in the administration of treatment remains to be established.
This cross-sectional study shows that LV radial strain decreased with plasma
Annexin A5.
IGHC
Dementia
Subclinical LV dysfunction
Diastolic
Transmitral and pulmonary vein blood
flows, and pulsed TDI
DiaHF
A
DiaHF
Age-specific percentiles of E/A and E/Ea
in 392 “healthy” subjects
2.75
10
2.50
9
E/Ea ratio
E/A ratio
2.25
2.00
1.75
1.50
8
75%
7
0.75
0.50
50%
25%
97.5%
6
75%
5
50%
25%
2.5%
4
1.25
1.00
97.5%
2.5%
3
Age group (years)
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
DiaHF
Classification of LV diastolic dysfunction
1 group - impaired relaxation (n=53; 9.8%; NT-proBNP 269 pmol/l*):
E/A:
abnormally low age-specific values
E/Ea:
normal range (< 8.5)
2 group – elevated E/Ea (end-diastolic LV filling pressure?) (n=76; 14.1%;
NT-proBNP 302 pmol/l*):
E/A:
normal age-specific range;
E/Ea:
> 8.5
(Adur < ARdur) + 10
 3 group – elevated E/Ea ratio and an abnormally low age-specific E/A (n=18;
3.4%; NT-proBNP 245 pmol/l*)
* p ≤0.05 vs normal: 214 pmol/l
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
DiaHF
Diastolic dysfunction stages*
DIASTOLIC HEART FAILURE
Pseudonormal
Impaired Relaxation
Normal
Restrictive
LV Press
LA Press
E
E
Pulmonary
Vein
Velocity
E
A
Mitral
Doppler
Velocity
PVs
E
A
A
PVs
PVs
PVd
PVd
PVd
PVd
PVa
PVs
PVa
Sm
Sm
Sm
Em
Em
PVa
PVa
Sm
Doppler
Tissue
Imaging
Am
A
Em
Am
Em
Am
Am
Zile MR et al, Circulation 2002; 105:1387-93
DiaHF
Correlates of LV diastolic dysfunction
OR
95% CI
Age (+10 years)
2.71
2.02-3.61
<0.0001
Women
1.63
0.86-3.09
0.13
BMI (+5 kg/m2)
2.07
1.42-3.04
0.0002
Heart rate (+10 bpm)
1.55
1.16-2.10
0.0035
SBP (+10 mm Hg)
1.27
1.07-1.69
0.0052
Use of β-blockers
1.94
0.98-3.84
0.056
Insulin (2 µU/ml)
1.43
1.03-1.93
0.032
Serum creatinine (+10 µmol/l)
1.33
1.05-1.69
0.018
NT-pro BNP (2 pmol/ml)
2.20
1.47-3.31
0.0001
0.5
1.0
1.5
2.0
2.5
3.0
3.5
p-value
4.0
Odds ratio
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
DiaHF
Conclusions
LV diastolic dysfunction in a random population sample, as estimated from
echocardiographic measurements, is common (27.3%).
Our findings are clinically relevant, because patients with subclinical
diastolic dysfunction often progress to overt HF.
TDI is a sensitive method for the detection of early diastolic (and systolic)
LV dysfunction in a general population, particularly in subjects with LV
remodelling and normal EF.
EPOGH
Team work
Katholieke Universiteit Leuven, B
JA Staessen, T Kuznetsova, Y Jin,
L Thijs, T Richart
Jagiellonian University Cracow, PL
K Kawecka-Jaszcz, K Stolarz
Universitá degli Studi di Padova, I
E Casiglia, V Tikhonof
Institute of Internal Medicine, RU
Y Nikitin, S Malyutina, G Simonova
University of Gdánsk, PL
K Narkiewicz, W Sakiewicz, A Rojch
EPOGH
Team work (2)
Charles University Pilzen, CZ
J Filipovsky, J Kucerová
Universidad de Navarra, E
J Diez, S Ravassa, A González
B López
Universitá di Milano, I
G Bianchi, P Manunta,
C Lanzani, L Tizzoni
Universität Münster, D
E Brand, SM Herrmann, Hasenkamp S
Universiteit Maastricht, NL
H Struijker-Boudier, S Heymans
University of Lausanne, CH
M Burnier, M Bochud, M Maillard
University of Leicester, UK
N Samani, V Codd