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DementiaIGHC
Tatiana Kuznetsova, Jan A. Staessen University of Leuven, Belgium
Diagnostic criteria for subclinical
systolic and diastolic LV functionJRP A3
Stages of heart failureStages 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 objectivesBackground 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.
Heart failure
Methods: Epidemiological approach; Echocardiography for cardiac phenotyping;
Results: Systolic LV dysfunction; Diastolic LV dysfunction;
Conclusions.
Outline of presentationOutline of presentationIGHC
MethodsEpidemiological approach – echocardiography
DementiaIGHC JRP A3
Epidemiological methodsEpidemiological 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 protocolStandardised 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.
EPOGH
Subclinical LV dysfunctionSystolic
DementiaIGHC
BackgroundBackground
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.
SysLVF
Echocardiographic characteristicsEchocardiographic characteristics
Women (n=243) Men (n=237)
Conventional
LV mass index (g/m2) 83 (17) 98 (20)†
RWT 0.37 (0.071) 0.37 (0.072)
EF (%) 69.6 (7.3) 67.8 (7.2)**
TDI
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)
* p0.05; ** p0.01; † p0.001
Strain
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Longitudinal and radial S and SR by age Longitudinal and radial S and SR by age Strain
p-values for trends 0.001 Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
70
65
60
55
5025
24
23
22
21
20
<30
30-39
40-49
50-59
60-69
≥70
4.0
3.5
3.0
2.51.5
1.4
1.3
1.2
1.1
<3030-
39 40-
49 50-
59 60-
69 ≥70
n=48
43113
104 60
32
N=52 48
123
123
8648
Str
ain
(%
)
Str
ain
rat
e (1
/s)
Age group (years)
Longitudinal strain vs WT, WHR and BW Longitudinal strain vs WT, WHR and BW Strain
p-values 0.001
0.2 0.3 0.4 0.5 0.6 0.7
10
15
20
25
30
35
40Longitudinal
RWT0.2 0.3 0.4 0.5 0.6 0.7
20
40
60
80
100Radial
RWT
0.6 0.7 0.8 0.9 1.0 1.1 1.2
10
15
20
25
30
35
40
WHR45 60 75 90 105 120
20
40
60
80
100
Weight (kg)
Str
ain
(%
)
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Summary of stepwise selection*Summary of stepwise selection*
* p<0.10 – significance level for entry into the model
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
Strain
Kuznetsova T et al, Eur Heart J 2008; 29: 2014-23
Proposal for reference values* for S and SR 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
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).
Annexin A5Annexin A5Strain
Radial strain vs annexin A5 Radial strain vs annexin A5 Strain
20
30
40
50
60
70
80
90
100
0.56 1 1.78 3.16 5.62
n = 265 r = –0.13 adjusted p = 0.006
Annexin A5, ng/mL
Rad
ial S
trai
n, %
Conclusions of this sectionConclusions 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.
Strain
Subclinical LV dysfunctionDiastolic
DementiaIGHC
Transmitral and pulmonary vein blood flows, and pulsed TDI Transmitral and pulmonary vein blood flows, and pulsed TDI
A
DiaHF
Age-specific percentiles of E/A and E/Ea in 392 “healthy” subjectsAge-specific percentiles of E/A and E/Ea in 392 “healthy” subjects
2.75
2.50
2.25
2.00
1.75
1.50
1.25
1.00
0.75
0.50
<3030-
39 40-
49 50-
59 ≥60
97.5%
75%
50%25%2.5%
<3030-
39 40-
49 50-
59 ≥60
10
9
8
7
6
5
4
3
97.5%
75%
50%
25%
2.5%
Age group (years)
E/A
rat
io
E/E
a ra
tio
DiaHF
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
Classification of LV diastolic dysfunctionClassification of LV diastolic dysfunction
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
DiaHF
* p ≤0.05 vs normal: 214 pmol/l
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*)
Diastolic dysfunction stages*Diastolic dysfunction stages*
Zile MR et al, Circulation 2002; 105:1387-93
DiaHF
Normal
DIASTOLIC HEART FAILURE
Pseudonormal RestrictiveImpaired Relaxation
LV Press
LA Press
Mitral DopplerVelocity
PulmonaryVein
Velocity
DopplerTissue
Imaging
EE
EE
A AA
PVs PVsPVs
PVs
PVdPVd
PVd PVd
PVa PVa PVaPVa
A
Sm Sm Sm Sm
Em
Em
Em
EmAm
Am
Am
Am
Correlates of LV diastolic dysfunctionCorrelates of LV diastolic dysfunction
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
2.71 2.02-3.61 <0.0001
Women 1.63 0.86-3.09 0.13
2.07 1.42-3.04 0.0002
1.55 1.16-2.10 0.0035
SBP (+10 mm Hg) 1.27 1.07-1.69 0.0052
1.94 0.98-3.84 0.056
Insulin (2 µU/ml) 1.43 1.03-1.93 0.032
1.33 1.05-1.69 0.018
2.20 1.47-3.31 0.0001
OR 95% CI p-value
Age (+10 years)
BMI (+5 kg/m2)
Heart rate (+10 bpm)
Use of β-blockers
Serum creatinine (+10 µmol/l)
NT-pro BNP (2 pmol/ml)
Odds ratio
DiaHF
Kuznetsova T et al, Circulation Heart Failure 2009; 2:105-112
Conclusions 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.
DiaHF
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
Team work Team work EPOGH
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
Team work (2)Team work (2)EPOGH
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