The Basics of Systolic Function

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1 The Basics of Systolic Function James D. Thomas, MD, FACC, FASE Director, Center for Heart Valve Disease Bluhm Cardiovascular Institute Professor of Medicine, Feinberg School of Medicine, Northwestern University Chicago, Illinois Relations with Industry: GE, Abbott, Edwards (honoraria)

2 If you can t measure it, it doesn t exist. AN DeMaria

3 Which is More Remarkable?? That a hollow muscular shell can eject 100 ml at 140 mmhg That this same hollow muscular shell can fill with 100 ml at 10 mmhg That it can fill with 100 ml at 10 mmhg in <200 msec during exercise

4 LV Pressure Systolic and Diastolic Function Myocardium to Ventricle Tissue Elastance Activation Stress/strain Relationship Geometry 20g 20g Systole Pressure-Volume Curve h Diastole LV Volume

5 Pressure (mmhg) 200 Transition from Systole to Diastole P-V Curves as a Function of Time Systole Diastole Volume (ml)

6 Myocardial Architecture is Complex Fitted transmural fiber field Peter Hunter Nielsen PMF, LeGrice IJ, Smaill BH & Hunter PJ. Am. J. Physiol. 260 (4), H1365-H1378, 1991

7 Nielsen, LeGrice, Smaill & Hunter. Am J Physiol 1991; 260: H1365 Fiber Orientations Epicardium Mid-wall Endocardium Left-handed helix Circumferential Right-handed helix

8 Collagen Orientation & Density Courtesy of Peter Hunter

9 Courtesy of Peter Hunter Myocyte Organization

10 Mechanics of the Heart Our Imaging Planes Are Not Fiber-Oriented base-apex shortening circumferential shortening axial twist (shear) wall thickening MRI Nash MP and Hunter PJ. J. Elasticity. 61(1-3): , 2001

11 Subendocardial Strains base apex radial circumferential Complex combinations of linear and shear strains

12 So you can see it s pretty complicated And that s BEFORE we get serious with the physics and math! Reaction-diffusion Fluid flow Finite elasticity Electro-magnetic Galerkin finite element method

13 The Heart is an Elegantly Complex Machine Fiber Sheet Oriented LV Strain Model J. Hassan P. Hunter Any echo measure of systolic function is mere approximation

14 Quantitation in Echocardiography Systolic function Dimensions, volumes and ejection fraction Stroke volume and cardiac output 3D methods Advanced methods Strain imaging

15 Lang et al. JASE 2005; 18: M-Mode Estimation of Volumes and EF 2D-guided M-mode V = [7.0/(2.4+D)]D 3 EF = [EDD 2 - ESD 2 ]/EDD 2 + Apex (0, 5, 10%)

$volume = 27 ml; ejection fraction$

16 Quantification of Stroke Volume 2-D Echo Volumetric Assessment LVEDV 105 ml LVESV 78 ml Stroke volume = 27 ml; ejection fraction = 26%

17 Lang et al. JASE 2005; 18: Biplane Methods Better in Asymmetric Ventricles

18 Popovic et al. Circulation 1994; 90: Simple Methods Still Give Insight Impact of Thrombolysis (T+/-) and Vessel Patency (P+/-) on Ejection Fraction Post MI EF [%] T: p=0.029 P: p=0.081 T+P- T-P Time from Infarct [Days] T+P+ T-P+

19 Contrast Helps with Quantitation Polar bear in a snowstorm Ah, better!

20 Contrast Improvs Estimation of LV Volume Yields Results Closer to CT/MR No contrast Contrast Thomson et al: JACC 2001; 38:

21 Quantitation in Echocardiography Systolic function Volumes and ejection fraction Stroke volume and cardiac output 3D methods Advanced methods Strain imaging

23 Measurement of Flow in LVOT

24 Measurement of Flow in RVOT

25 Velocity Automated Calculation of Cardiac Output Apical Long-Axis View SV = r v(r,t) dr dt Profile Distance Region of Interest Sun et al, Circulation 1997; 95:

26 Accuracy of ACM LVOT SV vs Pulsed Doppler Stroke Volume by ACOM (ml) r=0.95 y=0.98x-0.03 p< ² V=-1.3±5 ml n= Stroke Volume by PWAO (ml) Sun et al, Circulation 1997; 95: Difference in Stroke Volume (ACOM-PWAO,ml) Average Stroke Volume by ACOM and PWAO (ml) Mean + 2SD Mean Mean - 2SD

28 Automated 3D Flow More Accurate Than 2D Thavendiranathan et al. JASE 2012; 25: 56-65

29 Quantitation in Echocardiography Systolic function Volumes and ejection fraction Stroke volume and cardiac output 3D methods Advanced methods Strain imaging

30 We Really Have Come a Long Way

31 Nine-Plane Visualization of 3D Echo Quantitation similar to MRI

32 Lang et al. JASE 2015; 28: 1-39 Normal 3D LV Volumes

33 Conditions Where LV Volume/Function are Critical Cardiomyopathy Indications for ICD and BiV pacing Oncology Monitoring effects of chemotherapy Valvular heart disease Monitoring progression in aortic and mitral regurgitation

34 Practical Barriers to 3D Echocardiography How to manage the workflow Extensive experience/comfort in 2D acquisition and review 3D acquisition and analysis are separate tasks: 1 or 2 sonographers? Is 3D software integrated into review software or separate? DICOM format only recently approved (but little penetration into the market now and the files are huge)

35 Practical Barriers to 3D Echocardiography How to pay for this Currently no separate CPT code for 3D echo Most billing done under CPT s and 76377

36 Medicare Reimbursement Modality Tech Prof Total 2D echo D addon Bundled Actual 3D reimbursement averages ~$38

37 Would Separate 3D Echo code be Beneficial? Not necessarily Imaging (and particularly echo) under intense scrutiny for rapidly rising utilization The pie is not getting bigger, so an increase in one piece will mean a decrease in another piece Comprehensive 3D echo code might lead to a devaluation in 2D reimbursement

38 3D Echocardiography Strategies for Clinical Use Transthoracic echo (LV volumes) Identified key indications for 3D volumes (cardiooncology, device implantation, valve regurgitation) Core group of sonographers trained for mechanics pod Database modified to code 3D volumes Transesophageal echo (visualizing 3D structures) Repeated training on acquisition and vendor software Sonographer to assist less trained staff and fellows Expectation that 3D will be done on all valve cases

39 Growth in 3D Volumes with Time Number of TTE studies with 3D volumes '09 '10 '11 '12 '13 Year

40 So Contrast: good 3D volumes: good Contrast + 3D: great? Not so fast.

41 Patients seen in cardio-oncology clinic Exams with 2D and 3D echo without and with contrast Up to 5 exams over one year 56 patients selected with constant GLS What was variability of each EF estimation method? JACC 2013; 64: 77-84

42 Temporal Variability in EF 3D volumes were most reproducible Universal contrast worsened this Use contrast when you need it! JACC 2013; 64: 77-84

43 Quantitation in Echocardiography Systolic function Volumes and ejection fraction Stroke volume and cardiac output 3D methods Advanced methods Strain imaging

44 Myocardial Strain: What is It?? Strain: dimensionless index of change in length Strain ( ) = L-L 0 / L 0 LV strain may offer a pure index of regional LV function but is difficult to measure L 0 L

45 From Sarcomere to Stroke Volume A Little Goes a Long Way! Diastole 2.07 Systole ml SL = 13% epi = 7% mid = 15% endo = 26% 20 ml rad = +37% 1.4 cm 1.0 cm EF = 60% Diastole Systole

46 Longitudinal Strain by Speckle Tracking Normal Subject

47 Longitudinal Strain Dilated Cardiomyopathy

48 Apical 2 Chamber Normal Apical Long-Axis Apical 4 Chamber

242 normal patients from Cleveland, Brisbane and Aachen, age 18-80

49 242 normal patients from Cleveland, Brisbane and Aachen, age Imaged with GE Vivid 7 and analyzed with EchoPAC JACC Imaging 2009; 2: 80-84

50 Global Longitudinal Strain is 18.6±1.5% Absolute Strain Rate Falls With Age Age groups Marwick et al. JACC Imaging 2009; 2:

51 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid

52 MRI vs Echo Strain for Infarct Size Large infarct Medium infarct 115 g 36 g r r c l c l Gjesdal et al. Circ Img 2008; 1:

53 Detection of 30 g MI Size Strain WMSI Echo EF MRI EF Area under Curve Echo EF 0.81 MRI EF 0.90 WMSI 0.90 Strain 0.95 Gjesdal et al. Clinical Science 2007; 113:

54 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

55 Strain Imaging Diastolic Index SI-DI = % of systolic wall thickening lost in the first 1/3 of diastole: (A-B)/A Ishii et al. JACC 2009; 53:

56 60-year-old Male: Exertional Angina Radial Strain Before and After Exercise mid-sep mid-post Baseline immediately after 5 min after Ishii et al. JACC 2009; 53:

57 60-year-old Male: Effort Angina Left coronary artery (#7: 99% #9:90% stenosis) Ishii et al. JACC 2009; 53: Right coronary artery

58 Predictive Accuracy of SI-DI for Detecting Coronary Stenoses Ishii et al. JACC 2009; 53:

59 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

60 Assessment of Myocardial Viability Improvement in Ejection Fraction vs Resting Radial Strain and MRI Markers Echo Radial Strain Gd-MRI Becker et al. JACC 2008; 51:

61 Prediction of Regional and Global Recovery vs Resting Radial Strain and MRI Markers Becker et al. JACC 2008; 51:

62 Post-Systolic Strain vs Recovery of Function Post NSTEMI Initial pattern LCx occlusion PSS Post-PCI r = p < Eek et al. EJE 2011; 12: 483-9

63 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

64 Myocardial Mechanical Dispersion 85 patients after myocardial infarction with ICD 2.3 ( ) years follow up Haugaa et al. JACC Img 2010; 3:

65 Myocardial Mechanical Dispersion 85 patients after myocardial infarction with ICD N=23 N=47 N=38 Haugaa et al. JACC Img 2010; 3: ( ) years follow up

66 85 post MI patients meeting ICD criteria Followed until arrhythmia requiring appropriate ICD intervention No difference in EF: 34±11% vs 35±9% Mechanical dispersion: 85±29 msec vs 56±13 msec, p<0.001 Haugaa et al. JACC Img 2010; 3:

67 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

68 Can Echo and Biomarkers Predict Chemo-Induced LV Dysfunction? Sawaya et al. AJC 2011; 107:

69 ROC Curves for 3 Month Findings to Predict 6 Month Cardiotoxicity GLS Troponins Sawaya et al. AJC 2011; 107:

71 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

72 Increased Strain After Percutaneous AVR Pre Post

73 Impact of Strain on Post MVr LV function 233 Pts, Prediction of 12+ month LVEF<50% GLS = % 90% sensitivity, 79% specificity Predictors of LV dysfunction OR p GLS <19.9% 23.2 <0.001 LVESD>40mm GLS accounted for 3.3x more variance than EF EF<60% Symptoms AF = 69.1, p<0.001 Witkowski et al. EHJ-CVI 2013; 14 :69-76

74 Clinical Applications of Strain Imaging Coronary artery disease Detection and sizing of myocardial infarction Detection of myocardial ischemia Assessment of myocardial viability Prediction of post-mi arrhythmias Detection of subclinical LV dysfunction Chemotherapy Valvular heart disease Cardiomyopathy Amyloid Assessment of RV function

75 HCM Phelan, Collier et al. Heart 2012; 98: AS

76 Amyloid: Apex > 2x Base & Mid Phelan, Collier et al. Heart 2012; 98:

77 Differentiation of Amyloid, HHD, and HCM Value of Strain Maps 20 level 3 echo readers reviewed 24 cases of LVH 8 amyloid, 8 HTN, 8 HCM Full echo Doppler data presented but NOT strain or clinical info Readers chose 1 of 3 dx, and listed their confidence Exercise repeated some weeks later with reorded cases, now including GLS and strain maps Reader concordance improved with strain data ( = 0.28 to 0.57) Reader confidence improved with strain data (p<0.001) Reader accuracy improved with strain data (65% to 82%, p<0.001) Especially for amyloid! Sensitivity Specificity (%) (%) Accuracy (%) PPV (%) NPV (%) Base Read Strain Read P < <0.001 <0.001 <0.001 Phelan, et al. JASE 2014; 27:

78 25 cases each of amyloid, Fabry, Friedreich ataxia, HTN and controls Liu et al. Circ CVI 2013; 6:

79 Emerging Applications Transmural strain 3D strain

Switzerland, UK, Austria) All Caucasian, 156M, 147F 3D strain using Toshiba Results Minor gender difference

80 EHJ-CVI 2015;16: healthy subjects, years 10 centers in 8 countries (US, Spain, Germany, Netherlands, Hungary, Switzerland, UK, Austria) All Caucasian, 156M, 147F 3D strain using Toshiba Results Minor gender difference (GLS) Significant age effect (GLS falls, others rise) Area strain most reproducible (5% relative standard error), vs GLS 8%, GCS 6%, and GRS 15%» Segmental strain worse (11-28%) p = 0.04 p < p = 0.04 p = 0.005

81 Achilles Heel: Intervendor Reproducibility

82 Imagine This Situation 61 yr. old real estate agent Avid bowler, no symptoms AVA = 0.85 cm 2 Peak/mean grad. = 72/46 mm Hg No surgery now, follow-up in one year

83 One Year Later Our Bowler Returns for Follow-Up Staff: Wait we can t image him on the GE machine Sonographer: Why not. It s a good machine. Staff: That s irrelevant. We studied him on an ATL machine last year, and we know ATL and GE give different gradients. He always needs to be studied with an ATL. Sonographer: But we got rid of the ATL last week. Staff: Uh, oh

84 Intervendor Reproducibility in Normals V1: GE V2: Philips V3: Toshiba Radial Circumferential Longitudinal Vendor 1 vs 2 Vendor 1 vs 3 Vendor 2 vs 3

85 Great Collaboration Between EACVI and ASE Luigi Badano Jim Thomas

86 Standardization in Several Settings Reliability of the reference method Synthetic data First focus of the task force In vitro models Experimental Animals In vivo (patients) All levels have benefits and require attention Courtesy Jan D Hooge Level of realism of the data set

87 ourtesy Jan D Hooge Tracking examples Philips

JASE 2015; 28: 183-93 Agreement on Nomenclature Display Timing of

88 JASE 2015; 28: Agreement on Nomenclature Display Timing of end-diastole Timing of end-systole Mathematical definition of strain Regions of interest

89 D hooge et al. EHJ-CVI 2015 (on line)

90 One week: 22nd - 26th April 2013, Leuven 7 machines: Esaote MyLab Alpha GE Vivid E9 Hitachi-Aloka Prosound Alpha7 CV Philips ie 33 Samsung EKO 7 Siemens SC 2000 Toshiba Artida 2 independent Epsilon EchoInsight softwares: Tomtec Image Arena JASE 2015; 28:

91 Inter-Vendor Comparison Study Energetics: 7 machines (1000 W) 21 persons (250 W) 12 kw power + heat! Courtesy of Jens-Uwe Voigt

92 GLS AV (%) Mean GLS Values All Vendors Hitachi-A. Esaote GE Philips Samsung Siemens Toshiba Epsilon Tomtec Mean of all JASE 2015; 28:

93 Regression Analysis All Vendors vs Average Values Hitachi-A. Esaote GE -30 y = 0.94x R² = y = 1.01x 0.52 R² = y = 1.10x R² = Philips Samsung Siemens -30 y = 1.01x R² = y = 1.03x R² = y = 1.03x 0.06 R² = Toshiba Epsilon Tomtec -30 y = 0.90x - 1,00 R² = y = 0.85x 1.99 R² = y = 1.13x R² = JASE 2015; 28:

94 Mean error (%) Intraobserver mean error (%) Interobserver Variability, GLS vs EF EF is worst! Hitachi-A. Esaote GE Philips Samsung Siemens Toshiba Epsilon Tomtec EFbi Intervendor Variability, GLS vs Other Parameters 10 5 GLS is best! GLS JASE 2015; 28: E E/A IVS LVEDD PW GLSAV

95 Yang et al. JASE 2015; 28: 642-8

96 Strain Standardization Task Force Next Steps Regional longitudinal strain Circumferential and radial strain RV strain Atrial strain Strain from 3D echoes

97 One week: Inter-Vendor Clinical Study Round 2 20th - 24th April 2015, Leuven 7 machines: Esaote MyLab Alpha GE Vivid E9 Hitachi-Aloka Prosound Alpha7 CV Philips ie 33 Samsung EKO 7 Siemens SC 2000 Toshiba Artida 2 independent Epsilon EchoInsight softwares: Tomtec Image Arena Subjects: 63 pts, many with regional dysfunction All with MRIs with Gd Focus on regional strain Courtesy of Jens-Uwe Voigt

98 The Heart is an Elegantly Complex Machine Fiber Sheet Oriented LV Strain Model J. Hassan P. Hunter

99 Thanks!

New Approaches to Systolic Function: Strain Imaging

New Approaches to Systolic Function: Strain Imaging James D. Thomas, MD, FACC, FASE Director, Center for Heart Valve Disease Bluhm Cardiovascular Institute Professor of Medicine, Feinberg School of Medicine,