Tatiana Kuznetsova University of Leuven, Belgium

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

2. LVF Outline • Systolic function • Diastolic function • Echocardiographic protocol (JRP A3)

3. LVF Systolic 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)

4. LVF Components of regional function • Radial function • Longitudinal • Circumferential Without the longitudinal component, sarcomere shortening would lead to an EF < 30%.

5. LVF Tissue Doppler imaging • Tissue DopplerImaging (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).

6. LVF Off-line analysis Strain Strain rate AVC MVO Time integration AVC MVO Basal segments of inferior and infero-lateral walls Peak systolic SR End-systolic S SPEQLE: Software Package for Echocardiographic Quantification, Leuven; version 4.06

7. LVF Inter-observer differences in percent versus average of two readings Mean of 2 readings Bland and Altman, 1986

8. LVF Longitudinal S and SR by RWT Mean values are adjusted; * P0.05 ***P0.001

9. LVF Regional LV geometry • 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.

10. LVF Systolic 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.

11. LVF Diastolic 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

12. LVF Transmitral blood flow vs pulsed Tissue Doppler Imaging A E Aa Ea

13. LVF Inter-observer differences in percent versus average of two readings Mean of 2 readings Bland and Altman, 1986

14. LVF Determinants 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.

15. Echo Echocardiographic performance protocol • 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)

16. Echo Methods to limit echocardiographic measurement 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

17. Echo Methods to limit echocardiographic measurement variability Reading off-line strategies: Batch read when possible to minimize systematic temporal drifts; Average multiple beats(minimum of 3); Single reader preferable. Establish acquisition and reader variability: Test-retest of small sample of participants, ie, same participant repeated over small interval, same machine, same sonographer, same reader; Blind duplicates for inter-reader and intra-reader variability assessment.

18. JRP A3 Echo-centers 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, IE Casiglia, V Tikhonoff Hospital Universitari Valencia, SPE Lurbe, J Alvarez Institute of Internal Medicine, RU Y Nikitin, S Malyutina, A Ryabikov