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