Strain Imaging: Myocardial Mechanics Simplified and Applied

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9/28/217 Strain Imaging: Myocardial Mechanics Simplified and Applied John Gorcsan III, MD Professor of Medicine Director of Clinical Research Division of Cardiology VECTORS OF CONTRACTION Shortening Thickening Twisting Disclosures: Research grant from Hitachi-Aloka, Medtronic, GE and Biotronik Gorcsan J. 217 Calculation of Strain From Speckle Tracking Not Dependent on Doppler Angle Strain = Change in Length Original Length LONGITUDINAL STRAIN IMAGING % Lengthening or Thinning Frame 1 Frame 1 + n % Shortening or Thickening Modified from Kawagishi, K Strain = Change in Length / Original Length Longitudinal Strain LV Shortening End- Diastole End- Systole % Longitudinal Strain End-Diastole Strain = % Change in Length End-Systole - 23% End Diastole End Systole Gorcsan J. 217 Gorcsan J. 217 1

9/28/217 Global Longitudinal Strain (GLS) Average Strain Global Longitudinal Strain (GLS) Average Strain Apical 4-Chamber Polar (Bull s Eye) Plot Apical 4-Chamber Apical 2-Chamber Apical Long-Axis Apical 2-Chamber Gorcsan J. 217 Apical Long-Axis Gorcsan J. 217 What is Normal? Global Longitudinal Strain N = 2,597 GLS Values Vary by Vendor, Gender and Age GE GLS: -15.7 to -21.1%, mean -19.7% Philips Toshiba Yingchoncharoen Marwick et al. JASE 213;26:185 Plana et al. J Am Soc Echocardiogr 214;27:911-39 Normal Strain Values Threshold for Abnormal Global Longitudinal Strain Global Strain Must Relate to Ejection Fraction Normal GLS:> -17% Borderline GLS: between -17% and -15% Clearly Abnormal GLS: < -15% Think of GLS in absolute values (I Prefer to Forget the sign) Gorcsan J. 217 LV Deformation = LV Blood Ejection Gorcsan 217 2

9/28/217 Mathematical Linear Relationship of GLS to EF Linear Fit EF = 3 (GLS) Echo vs. Cardiac Magnetic Resonance Echocardiogram Cardiac Magnetic Resonance -1-2 -3 ECG GLS 1ms Normal Systolic Function Time (ms) (CMR-EF=62%) ECG Normal Normal Heart Failure Patient -1-2 -3Systolic Dysfunction (CMR-EF=26%) ECG ECG GLS 1ms Time (ms) Echocardiogram - 1-2 1ms - 3 p <.1 3 R =.88 FT CMR-GLS (%) 2 1 ECG Normal GLS Time (ms) n=73 GLS vs. EF ST Echo-GLS (%) 3-2 1 p <.1 R =.85 n=68-1 -2 GLS 1ms Time (ms) Time (ms) -3-3 Basal-Septal Mid-Septal Apical-Septal Apical Lateral Mid-Lateral Basal-Lateral Global Longitudinal Strain (GLS) Onishi T, Gorcsan et al. JASE 215-1 GLS -2 1ms 2 4 6 8 2 4 6 8 CMR-EF (%) CMR-EF (%) EF = 3* GLS + 8 Onishi T, Gorcsan et al. JASE 215 Differences in EF and Strain LV Hypertrophy What Additional Information? GLS as a Marker for Scar Myocardial Scar by Late Gadolinium Enhancment CMR ENDOCARDIAL SCARRING N = 59 LS MIDMYOCARDIAL SCARRING Lumens et al. 216 INFARCT SIZE (G) N = 38 GLOBAL STRAIN (%) Gjesdal et al.clinical Science (27) 113, 287 296 LS TRANSMURAL SCARRING LS Kansal et al. Eur Heart J Cardiovasc Imaging 212 3

9/28/217 Strain is Additive to EF Ejection Fraction Blood Displacement Strain is Additive to EF Far Ends of Spectrum Strain Wall Properties of Disease Hypertrophy Fibrosis More Reproducible than EF Very Low EF High EF Gorcsan J. 217 Low EF Patients N = 1,65 Heart Failure Clinic Patients N = 1,65 Heart Failure Clinic Patients Cardiac Resynchronization Therapy Treatment for Low EF Wide QRS Heart Failure Echo Parameters Two-site LV Pacing 4

9/28/217 Baseline Global Strain is Associated with Outcome After CRT Survival probability (%) 1 8 6 4 2 Global Longitudinal Strain N=25 Routine CRT Indications QRS > 12m2 HF Hospitalization or Death p=.2 ; HR 2.1, 95% CI 1.45-3.5 1 2 3 4 Follow-Up Time (years) GLS -9% GLS>-9% GLS -9% 93 77 65 56 45 N = 89 LVEF < 35% QRS < 13 ms Echo Dyssynchrony Randomized to: CRT Off CRT On EchoCRT: CRT in Narrow QRS Increase in All-Cause Mortality HR = 1.81 (1.11, 2.93) p=.2 GLS>-9% 112 69 52 42 33 Delgado-Montero, Gorcsan et al, Circ CV Imaging 216 Ruschitzka et al. NEJM 213 September 3 n = 755 GLS and Cardiovascular Mortality CRT On vs. CRT Off * p =.8 GLS and Cardiovascular Mortality CRT On vs. CRT Off GLS < 6.2%, CRT-Off Cardiovascular Deaths (%) n = 755 GLS > 6.2%, CRT-Off GLS > 6.2%, CRT-On GLS < 6.2%, CRT-Off GLS < 6.2%, CRT-On *p=.7 vs. other groups, HR=5.7 (95% CI 1.61-2.13), * GLS < 6.2%, CRT-On < 6.2% 6.2-7.9% 7.9-1.1% >1.1% Global Longitudinal Strain (absolute values) Bax Gorcsan et al. EHJ 216 (Figure Unpublished) Years from Randomization Bax Gorcsan et al. EHJ 216 Features of Additive Risk LOW EF LOW GLS Dyssynchrony J. Gorcsan Euro-Echo Imaging 216 5

9/28/217 GLS and Asymptomatic Severe MR with Preserved EF 737 patients Severe MR LVEF > 6% Non dilated LV ESD < 4.cm ESDi < 3.3cm/m 2 GLS and Asymptomatic Severe MR with Preserved EF: Risk of Death n = 737 Worse Strain Risk of Death Better Strain -2% Worse Strain Neurocardiac Injury in Subarachnoid Hemorrhage Cerebral T Waves GLS to Assess Neurocardiac Injury in Subarachnoid Hemorrhage 255 patients 52±1 yrs 72% female GLS in ICU (mean 2 days from bleed) Strain feasible on 221 Kagiyama Gorcsan et al. ASE 217 LVEF (%) 8 7 6 5 4 Relationship of GLS to EF in Subarachnoid Hemorrhage N = 221 GLS and In-Hospital Mortality with Subarachnoid Hemorrhage Mortality % 25 Linear relationship, P =.13 2 15 1 N = 221 3 5 2 5 1 15 2 25 3 Kagiyama Gorcsan et al. ASE 217 GLS (%) (absolute values) 5 1% 1 15% 15 2% 2 25% 25 3% Kagiyama Gorcsan et al. ASE 217 GLS (absolute values) 6

9/28/217 Potential Factors in Neurocardiac Injury Subarachnoid Hemorrhage Catecholamine Surge % 25 2 15 1 Global Longitudinal absolute values Controls (n=5) Hypertensive Heart Disease (n=44) * HFpEF (n=219) * Individual Susceptibility 5 Myocyte Injury Impaired Myocardial Perfusion Kagiyama Gorcsan et al. * p<.1 vs. Controls and Hypertensive Heart Disease Kraigher-Krainer, Solomon et al. JACC 214;63:447 56 Association of GLS with Biomarkers for Heart Failure (NT-proBNP) GLS Predictive of Survival in Patients with ESRD and Preserved EF N = 48 African Americans with ESRD on Hemodialysis LV EF > 5% Baseline GLS Prospectively enrolled and followed 1.9 years GLS was predictive of All Cause Mortality GLS Cut-Off < 16% (absolute values) Hazard ratio 1.15, 95% confidence interval 1.2 to 1.3, p =.2, Kraigher-Krainer, Solomon et al. JACC 214;63:447 56 Pressman G Gorcsan J et al. Am J Cardiol 215 Nov 15;116(1):161-4. CASE STUDY 62 year old man with weight loss, gastroparesis, dyspnea and edema. Base Mid Apex Gorcsan J. MSE 217 7

9/28/217 Segmental Longitudinal Strain Normal Subject Our Patient Apical Sparing Apical Longitudinal Strain Sparing in Amyloidosis Examples of Increase Wall Thickness No Amyloidosis Examples of Cardiac Amyloidosis Basal Strain = - 21.1% Mid Strain = - 22.3% Apical Strain = -25.3% Basal Strain = - 5.% Mid Strain = - 5.8% Apical Strain = -17.2% Amyloid Heart Disease Phelan Thomas JD, Heart 212 Prevalence of Abnormal Echo Indices in Cardiac Amyloidosis n = 172 patients with Cardiac Amyloidosis n=8 with Light Chain Immunoglogulins n=36 transthyretin-related mutant form n=56 Nonmutant transthyretin-related amyloidosis GLS Predicts Survival in Cardiac Amyloidosis Quarta, Solomon et al. Circulation. 214;129:18 184-1849 Quarta, Solomon et al. Circulation. 214;129:18 184-1849 An 85 year woman with progressive shortness of breath and syncope n = 125 patients with Severe AS Preop GLS GLS Quartile 1 and 2 GLS Quartile 3 GLS Quartile 4 Severe Aortic Stenosis Peak Velocity 5 m/sec Peak Gradient 1 mmhg, Mean Gradient 69 mmhg AVA =.6 cm 2 8

9/28/217 Cardio-oncology Progress in Cancer Survival Rates GLS was Additive to Clinical Features and EF n = 125 Substantial improvements in cancer patient survival. 14.5 million cancer survivors in the US Leads to a higher prevalence of patients with cancer and cardiovascular disease DeSantis C.E., Lin C.C., Mariotto A.B., et al; Cancer treatment and survivorship statistics, 214. CA Cancer J Clin. 214;64:252-271. GLS was Additive to EF to Predict Chemo Cardiotoxicity Strain New Directions: Fusion imaging Ultrasound system Fluoroscopy Angiographic System N = 24 patients with cardiotoxicity GLS < 11% Nigishi Marwick et al. JASE 213 Strain Activation: Early Late Fusion imaging RV 3D SPECKLE TRACKING C3 C4 C5 RAO View LAO View 9

9/28/217 RV 3D Strain and Volume in Pulmonary Hypertension PH Patients Normal Control RV Adapted RV Adapted Remodeled RV Adverse Remodeled estimate spap 2mmHg spap 44mmHg spap 86mmHg spap 83mmHg End Systole (ml) End Systole (ml) End Systole (ml) End Systole 12 18 22 volume curve volume curve volume curve volume curve global area strain global area strain global area strain global area strain (ml) 28 Pulmonary Hypertension Patients Hospitalization, Death or Lung Transplantation Number at risk RV Adapted Probability of Freedom From Hospitalization, Death or Lung Transplantation (%) 1 RV Adapted 9 8 7 RV Adapted Remodeled 6 5 4 3 n=92 RV Adverse Remodeled 2 Log rank P<.1 1 P=.1 vs. RV Adapted P=.4 vs. RV Adapted Remodeled 1 2 3 4 5 6 Months 51 47 44 43 43 39 37 RV Adapted Remodeled 28 2 18 16 14 13 13 RV Adverse Remodeled 13 7 7 5 2 2 2 RVEF 5% G-AS -39% RVEF 41% G-AS -28% RVEF 27% G-AS -24% RVEF 18% G-AS -14% Ryo Gorcsan et al. Circ CV Imaging May 215 3D RA Strain Analysis: Pulmonary Hypertension vs. Control Normal Control Pulmonary Hypertension Patient 3D RA Volume 3D RA Global Area Strain 3D RA Volume 3D RA Global Area Strain Freedom from Clinical Events (%) 1 8 6 4 2 3D RA Strain and Clinical Outcomes Pulmonary Hypertension Patients Hospitalization, Death or Lung Transplantation N = 54 patients RA 3D Global Area Strain > 17% RA 3D Global Area Strain 17%* 1 2 3 4 5 6 Follow up, Months *P<.1 HR 13.4 (95%CI 3.7-45.8) Freedom from Clinical Events (%) 1 8 6 4 RA max Volume Index < 56ml/m 2 2 RA max Volume Index 56ml/m 2 * 1 2 3 4 5 6 Follow up, Months *P<.1 HR 8.66 (95%CI 2.8 26.6) Freedom from Clinical Events (%) 1 8 6 4 2 RA Emptying Fraction > 19% RA Emptying Fraction 19%* 1 2 3 4 5 6 Follow up, Months *P<.1 HR 8.66 (95%CI 2.8 26.6) Sugahara Gorcsan et al. Sugahara Gorcsan et al. Strain Imaging into the Future J Am Soc Echocardiogr 215;28:183-93 ASE Announcement: Myocardial Strain Imaging Acceptance of New CPT Category III code, 39X9T Introduced January, 216. Category III codes are not yet reimbursed: Often lead to the adoption of payable codes by CMS and other payers. Take Home Messages Speckle Tracking Strain has emerged as the most useful new echocardiographic tool to assess myocardial function. Global Longitudinal Strain is best represented in the literature as being a sensitive measure additive to EF. Most Promising New Clinical Applications: Adding to EF in Heart Failure to Enhance Prognosis Cardiac Amydoidosis Valvular Heart Disease Neurocardiac Injury Cardio-oncology 3D Strain has promise for the future! Gorcsan J. 217 1