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Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European The InGenious HyperCare European Network Excellence in phenotyping: Network Excellence in phenotyping: Assessment of left Assessment of left ventricular function ventricular function

Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

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Page 1: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Tatiana Kuznetsova

University of Leuven, Belgium

The InGenious HyperCare European Network The InGenious HyperCare European Network

Excellence in phenotyping:Excellence in phenotyping:

Assessment of left ventricular Assessment of left ventricular functionfunction

Page 2: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

OutlineOutlineOutlineOutline

Systolic function

Diastolic function

Echocardiographic protocol (JRP A3)

LVFLVF

Page 3: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Systolic functionSystolic functionSystolic functionSystolic function

Conventional echocardiography enables the assessment

of LV dimensions, volumes, sphericity index, and severity

of mitral regurgitation;

HF due to systolic dysfunction is relatively easy to

diagnose by echocardiography.

(dilated left ventricle with a reduced ejection fraction)

LVFLVF

Page 4: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

• Radial function

• Longitudinal

• Circumferential

Components of regional functionLVFLVF

Without the longitudinal component, sarcomere shortening would lead to an EF < 30%.

Page 5: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Tissue Doppler imagingTissue Doppler imagingTissue Doppler imagingTissue Doppler imaging

Tissue Doppler Imaging (TDI) makes it possible to

specifically evaluate the longitudinal and radial

components of regional LV systolic function.

Measurements of myocardial deformation with the

Doppler technique have been validated using

microcrystals and MRI (Urheim S, Circulation 2000;

Edvardsen T, Circulation 2002).

LVFLVF

Page 6: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Basal segments of inferior and infero-

lateral walls

AVC MVO

Timeintegration

Peak systolic SR End-systolic S

StrainStrain rate

AVC MVO

LVFLVF Off-line analysisOff-line analysisOff-line analysisOff-line analysis

SPEQLE: Software Package for Echocardiographic Quantification, Leuven; version 4.06

Page 7: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Inter-observer differences in percent Inter-observer differences in percent versus average of two readingsversus average of two readingsInter-observer differences in percent Inter-observer differences in percent versus average of two readingsversus average of two readingsLVFLVF

Bland and Altman, 1986

Mean of 2 readings

Longitudinal Strain

0.16 0.20 0.24 0.28 0.32

-20

-10

0

10

20

14.1%

-1.38%

-16.8%

%

2 o

bse

rver

s

Radial Strain

0.4 0.5 0.6 0.7 0.8 0.9 1.0

-20

-10

0

10

20

18.9%

0.97%

-17.0%

Page 8: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Longitudinal S and SR by RWT Longitudinal S and SR by RWT Longitudinal S and SR by RWT Longitudinal S and SR by RWT LVFLVF

Mean values are adjusted; * P 0.05 ***P0.001

Longitudinal Strain

RWT < 0.43 RWT 0.43

20

21

22

23

24

***

%

Strain Rate

RWT < 0.43 RWT 0.43

1.20

1.25

1.30

1.35

1.40

RWT < 0.43N=335

RWT 0.43N=75*1/

s

Page 9: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Regional LV geometry Regional LV geometry Regional LV geometry Regional LV geometry LVFLVF

Wall stress related to:

•Pressure ↑ → σ ↑

•Shape, cavity size ↑ → σ ↑

•Wall thickness ↑ → σ ↓

σ = P x R / 2WT

Since R curvature is larger in longitudinal direction, the stress on longitudinal fibres is

higher, they show decreased deformation first.

Page 10: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Systolic functionSystolic functionSystolic functionSystolic function

TDI, compared with conventional echocardiography, is a more

sensitive method for the detection of LV systolic dysfunction,

particularly in subjects with LV remodelling and normal EF.

Our observations underscore the importance of normal long axis

function in maintaining a coordinated ventricular contraction.

The clinical utility of strain and strain rate in risk stratification or as

therapeutic target remains to be established.

LVFLVF

Page 11: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Diastolic functionDiastolic functionDiastolic functionDiastolic function

About 50% of patients with new onset of HF do have a normal EF

(HF with preserved EF).

HF with preserved EF is associated with a high mortality rate,

comparable to that of patients with reduced EF.

(Bhatia R.S., N Engl J Med 2006; Bursi F., JAMA 2006)

Assessment of diastolic function requires conventional and

Tissue Doppler Imaging

LVFLVF

Page 12: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Transmitral blood flow vs pulsed Transmitral blood flow vs pulsed Tissue Doppler ImagingTissue Doppler Imaging Transmitral blood flow vs pulsed Transmitral blood flow vs pulsed Tissue Doppler ImagingTissue Doppler Imaging

EA

Ea Aa

LVFLVF

Page 13: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

LVFLVF

Ea

5 10 15 20 25

-7

-5

-3

-1

1

3

5

7

5.26%

0.72%

-3.83%

%

2 o

bse

rver

s

Aa

2.5 5.0 7.5 10.0 12.5 15.0 17.5

-7

-5

-3

-1

1

3

5

7

0.26%

4.48%

-3.96%%

Mean of 2 readings

Inter-observer differences in percent Inter-observer differences in percent versus average of two readingsversus average of two readingsInter-observer differences in percent Inter-observer differences in percent versus average of two readingsversus average of two readings

Bland and Altman, 1986

Page 14: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Determinants of TDI velocitiesDeterminants of TDI velocitiesDeterminants of TDI velocitiesDeterminants of TDI velocities

Stepwise analysis:

Ea: age, BMI, DBP, LVMI; LV length, EF;

Aa: age, HR, DBP, LV length, EF;

Ea/Aa: age, BMI, HR, DBP.

Intrafamilial correlation coefficients (P<0.0001 for all) were:

Ea: 0.43;

Aa: 0.41;

Ea/Aa: 0.46.

LVFLVF

Page 15: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Echocardiographic performance protocolEchocardiographic performance protocolEchocardiographic performance protocolEchocardiographic performance protocolEchoEcho

A single observer performs all echocardiographic examinations by means of

Vivid 7 ultrasound scanner (GE Vingmed, Horten, Norway)

Standardized echocardiography scanning sequence (about 40 min,

page 76-77 MOP JRP A3)

Correct orientation of the ultrasound beam and imaging planes to LV

structure and blood flow is essential

All echocardiographic examinations in a digital format are stored on a local

network for off-line reading by two independent observers (EchoPack, GE

and SPEQLE, University of Leuven)

Page 16: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Methods to limit echocardiographic Methods to limit echocardiographic measurement variabilitymeasurement variabilityMethods to limit echocardiographic Methods to limit echocardiographic measurement variabilitymeasurement variability

Use echocardiography central reading laboratory:

a. Minimize number of readers,

b. Monitor reader variability,

c. Rapid communication with study sites on study quality.

Standardized “hands-on” training of sonographers onsite.

Monitoring of sonographers for technical quality; encode study

quality in database.

American Society of Echocardiography Recommendations for Use of Echocardiography in Clinical Trials. J Am Soc Echocardiogr 2004;17:1086-1119

EchoEcho

Page 17: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Methods to limit echocardiographic Methods to limit echocardiographic measurement variabilitymeasurement variabilityMethods to limit echocardiographic Methods to limit echocardiographic measurement variabilitymeasurement variability

Reading off-line strategies:

1. Batch read when possible to minimize systematic temporal drifts;2. Average multiple beats (minimum of 3);3. Single reader preferable.

Establish acquisition and reader variability:

1. Test-retest of small sample of participants, ie, same participant repeated over small interval, same machine, same sonographer, same reader;

2. Blind duplicates for inter-reader and intra-reader variability assessment.

EchoEcho

Page 18: Tatiana Kuznetsova University of Leuven, Belgium The InGenious HyperCare European Network Excellence in phenotyping: Assessment of left ventricular function

Katholieke Universiteit Leuven, B JA Staessen, T Kuznetsova, T Richart

Jagiellonian University Cracow, PL K Kawecka-Jaszcz, K Stolarz, M Loster

Medical University of Gdansk, PL K Narkiewicz, W Sakiewicz, A Rojek

Universitá degli Studi di Padova, I E Casiglia, V Tikhonoff

Hospital Universitari Valencia, SP E Lurbe, J Alvarez

Institute of Internal Medicine, RU Y Nikitin, S Malyutina, A Ryabikov

Echo-centersEcho-centersEcho-centersEcho-centersJRP A3JRP A3