Quantifying LV function how good are we?

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Quantifying LV function how good are we? Professor Alan G Fraser Wales Heart Research Institute Cardiff University, U.K. Support for research from Hitachi Aloka, & GE Ultrasound

Visual assessment of synchronicity Computer-simulated regional delay Kvitting et al, J Am Soc Echo 1999; 12: 698

EQUALIS Diagnosis of regional wall motion 100 80 60 40 20 Fall 1, Segment 13 * Echocardiography Quality Control Project: Case #1 80 60 40 20 Fall 1, Segment 15 * 0 Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi 0 Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi Antal 1 18 82 6 Antal 7 30 65 5 60 50 40 30 20 10 0 Fall 1, Segment 12 * Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi Antal 1 5 44 54 2 60 50 40 30 20 10 0 * Fall 1, Segment 9 Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi Antal 1 57 45 2 70 Fall 1, Segment 6 60 50 40 30 * 20 10 0 Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi Antal 15 65 24 3 Independent reporting by 106 Swedish centres in 2008 Courtesy of Dr Odd Bech-Hansson 100 80 60 40 20 0 * Fall 1, Segment 3 Ej bedömbar Normalt Hypokinesi Akinesi Dyskinesi Antal 91 16

Inter-observer reproducibility of visual grading of regional wall motion 11 experienced observers Intra-class correlation coefficients (each observer vs others) 0.79 0.71 0.37 Normal, hypokinetic, or akinetic Normal, or abnormal Hypokinetic, or not Akinetic, or not 180 segments from 105 studies Blondheim DS et al, JASE 2010; 23: 258-64

Limitations of wall motion scoring Subjective interpretation of motion & thickening Learning curve, operator-dependent Sub-optimal reproducibility even in expert centres Insensitive for detecting single vessel disease Categorical outcomes, not a graded response Improved by LV opacification with echo contrast Remains a subjective diagnosis So why is it still used in stress echocardiography?

EQUALIS Echocardiography Project Case #1 Courtesy of Dr Odd Bech-Hansson

EQUALIS Echocardiography Quality Control Project Independent analysis in 106 Swedish centres 60 Ejektionsfraktion, intervall Case #1: Left ventricular ejection fraction 40 20 0 <20 20-29 30-39 40-49 50-59 >60 Antal N 14 53 29 6 2 2 Simpson EF by 5 investigators: mean 34 % (range 32-36 %)

Observer bias in visual estimation of LVEF Distribution Cumulative frequency Expected normal value N = 6,026 LVEDD LVEF Berger AK et al, JACC 1999; 34: 1831 Observed value

Visual assessment of LV ejection fraction 105 echo studies interpreted by 12 observers Coefficient of variation 11% Bias -8 to +4% Blondheim DS et al, JASE 2010; 23: 258-64

A4C A2C End-diastole End-systole Modified Simpson s method of discs Biplane planimetry LVEDV LVESV SV EF

Systematic review of LV quantification by echo McGowan JH et al, Am Heart J 2003; 146: 388-97

Contrast echo enhancement of LV borders Recommended if <80% of endocardium not seen

Accuracy of contrast echo to quantify LV function, compared to magnetic resonance imaging (n 110) Limits of agreement -18% to +8% -8% to +4% Malm S et al et al, JACC 2004; 44: 1030-5

Non-invasive measurement of global LV function Comparison of imaging modalities Enddiastolic volume (ml) Endsystolic volume (ml) Ejection fraction (%) Cineventriculography, biplane 187 ± 105 90 ± 84 56.2 ± 18.3 100 Magnetic resonance imaging, SAX 174 ± 50 84 ± 45 54.1 ± 12.9 55 Unenhanced echocardiography 115 ± 53 62 ± 48 50.9 ± 15.3 115 Contrast-enhanced echocardiography 147 ± 60 73 ± 56 54.6 ± 16.8 115 n Hoffmann R et al, Eur Heart J 2005; 26: 607-16

Three dimensional echocardiography Real-time 3D echocardiography avoids foreshortening of the LV Real-time 3D echocardiography allows automated quantification Courtesy of Luigi Badano

Contrast echo to improve LV cavity opacification Real-time 3D stress echocardiography LA Brodin

Utility of contrast for LV opacification Real-time 3D stress echocardiography RT3D + LVO Segments analysable 76% 90% Image quality index 2.2 3.1 Diagnosis of ischaemia by territory (n=108) 79% 88% kappa 0.26 0.59 by patient (n=36) 72% 89% kappa 0.43 0.77 Nemes A et al, Am J Cardiol 2007; 99: 275-8

Quantification of LV function: inter-machine comparison Volumetric 3D (Philips ie33) vs speckle 3D (Toshiba Artida 4D) n 120 comparable & reproducible interchangeable.. in daily clinical practice Kleijn SA et al, Am J Cardiol 2011; 108: 1038-44

Diagnostic imaging the choice QUALITATIVE Subjective Insensitive Imprecise Variable Categorical Quick

Cognitive psychology models of diagnostic reasoning Type 1 Intuitive Type 2 Analytical Heuristic Reflexive Fast Vulnerable to bias Prone to error Deductive Deliberate Slow Consistent Scientific Croskerry P et al, J Roy Coll Physicians Edin 2011; 41: 155-62

Diagnostic imaging the choice QUALITATIVE Subjective Insensitive Imprecise Variable Categorical Quick QUANTITATIVE Objective More sensitive Precise Reproducible Continuous Time-consuming

How could we improve diagnostic accuracy?.. by exploiting computing and information technology Normative databases Compare each patient to normal values that reflect age, gender, BMI, and risk factors Automated quantification / analysis Integrated clinical decision aids, algorithms Parametric visual displays of quantitative data measurements, significance levels, z scores

A new concept for diagnosis: a statistical atlas An average heart with population variability Atlas Radial velocity (mm/s) Long. velocity (mm/s) Healthy subjects Derived from fully automated 3D/4D analysis of velocity using tracking technique Temporal display of mean velocities with variance, at a particular location Duchateau N et al, Med Image Analysis 2011; 15: 316-28

Local maps at fixed time t p-value (log scale) Red = large abnormality Parametric displays of statistically abnormal myocardial motion Spatiotemporal maps of abnormality Apex Time p-value (log scale) Base IVC Systole Diastole Blue = Inward (vp<0) Red = Outward (vp>0) Duchateau N et al, Med Image Analysis 2011; 15: 316-28

Percentage difference required The implications of reproducibility 60 50 The reference change value 40 30 20 10 CV 20% CV 10% CV 5% CV 2% 0 0 20 40 60 80 100 Sample size Courtesy of Professor Frank Dunstan

Statistical power by sample size & reproducibility Significant differences that can be demonstrated Number of subjects per sample Coefficient of variation 2% 5% 10% 20% 30% 1 6 14 28 55 83 10 2 4 9 18 26 20 1 3 6 12 19 50 1 2 4 8 12 100 1 1 3 6 8

How good are we at quantifying LV function? Each echo lab needs its own quality control