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Stress Echocardiography Susan A. Raaymakers, MPAS, PA-C, RDCS (AE)(PE) Radiologic and Imaging Sciences - Echocardiography Grand Valley State University, Grand Rapids, Michigan 1 Brief History 1980s Improvement in image quality Development of digital acquisition technology (“frame grabbers”) 2 Physiologic Basis 1930s: Tennant and Wiggers Relationship between systolic contraction and myocardial blood supply to the left ventricle Demonstrated rapid and predictable development of dyskinesis 3 Physiologic Basis Physiologic stress results in An increase in heart rate and Contractility HR and contractility maintained by an increase in myocardial blood flow 4 Physiologic Basis Increase in Systolic wall thickening Endocardial excursion Global contractility Leads to decrease in end-systolic volume Increase in ejection fraction May be blunted in advanced age, hypertension or in presence of beta blocker 5 therapy Physiologic Basis Presence of coronary artery stenosis Increased oxygen demand not adequately accommodated (supply-demand mismatch) Development of ischemic cascade 6 Physiologic Basis Stressor elimination Myocardial oxygen demand is reduced and ischemia resolves Normalization may occur rapidly Typically recovery takes 1 to 2 minutes depending on severity of ischemia Stunned myocardium: functional abnormalities persist after transient ischemia for a longer period May last days or weeks 7 Utility Of Echocardiography In Conjunction With Stress Testing Wall motion abnormalities at rest Infarction Cardiomyopathy Myocarditis Left bundle branch block Hypertension/afterload mismatch Hibernating myocardium Stunned myocardium Toxins (e.g., alcohol) Postoperative state Paced rhythm Right ventricular volume/pressure overload Wall Motion abnormalities during stress Ischemia Translational cardiac motion Cardiomyopathy Rate-dependent left bundle branch block 8 Methodologies Advantage: versatility Exercise Treadmill Supine bicycle Upright bicycle Handgrip Stair step Non-exercise Dobutamine Dipyridamole Adenosine Pacing 9 Treadmill Most commonly form of stress testing in U.S. Provides useful clinical information Exercise capacity Blood pressure response Arrhythmias Protocols: Bruce, Balke, Naughton, etc. 10 Treadmill Addition of echocardiography Not intended to alter exercise protocol Echocardiography images obtained pre- and post- exercise Challenge of obtaining images immediately post exercise Ischemia may resolve quickly after exercise Must obtain images with 1 to 1.5 minutes 11 Treadmill Exercise Stress Echocardiography Traditional approach Parasternal long-axis Parasternal short-axis Apical four chamber Apical two chamber 12 Treadmill Exercise Stress Echocardiography Protocol Patient is prepared for treadmill stress testing Instructions provided on transition from the treadmill to the examination table after exercise Resting echocardiographic images obtained, reviewed, and stored (both digitally and on videotape) Standard treadmill exercise examination performed Patient moves as quickly as possible after exercise to the examination table Post exercise imaging acquiring and recorded on videotape and digitally Digital images reviewed and representative loops selected Digital images stored on permanent medium 13 Treadmill Exercise Stress Echocardiography Rapid Recovery – Images acquired in 75 seconds Anterior ischemia Long and short axis Four chamber Resolved in two chamber over the course of post-stress image acquisition 14 Supine Bicycle Exercise Stress Echocardiography Rapid Recovery - Images acquired in 75 seconds Apical Wall Motion Abnormality 15 Bicycle Ergometry Stationary bicycle ergometry: first form of exercise in conjunction with echocardiography Currently: Availability of supine bicycle systems permit a variety of patient positions Advantage: ability to image throughout exercise, particularly at peak stress Avoids potential problem of rapid recovery Allows onset of wall motion abnormality to be documented Wall motion abnormalities are more easily seen in peak exercise versus post exercise Image acquisition is less rushed lending itself to better quality 16 images Bicycle Ergometry Disadvantage Workload Bicycling in supine position may be uncomfortable for some patients Supine position appears to facilitate the induction of ischemia Perhaps by increasing venous return and preload Associated with greater blood pressure response Ischemia occurs at a lower heart rate during supine versus upright exercise 17 Bicycle Ergometry Protocol Patient prepared for standard stress testing Patient instructed how to perform bicycle exercise Patient positioned on supine ergometer and secured in place Rest images obtained (table inclined to optimize images) Exercise protocol begins at a workload of 25 W and a cadence of 60 rpm Images monitored throughout exercise At peak exercise, a full series of images is obtained After cessation of exercise, wall motion is monitored to document resolution of induced ischemia Representative images are selected and rearranged for digital storage 18 Dobutamine Stress Echocardiography Dobutamine: synthetic catecholamine causes Inotropic and chronotropic effects Affinity for ß1, ß2 and α receptors in the myocardium and vasculature Cardiovascular effects are dose dependent Augmented contractility occurring at lower doses followed by a progressive chronotropic response at increasing doses Peripheral effects may result in either predominant: Vasoconstriction or vasodilation Changes in vascular resistance (i.e. blood pressure) are unpredictable 19 Dobutamine Stress Echocardiography Distinction between exercise and Dobutamine Change in venous return is increased in exercise Autonomic nervous system-mediated changes in systemic and pulmonary vascular resistance are quite different Heart rate is less important with Dobutamine compared with exercise Ischemia may be induced even if target heart rate is not achieved due to greater augmentation of contraction Primary indication for Dobutamine as a substitute for exercise stress echocardiography Patients unwilling or unable to exercise adequately Detection of viable myocardium 20 Dobutamine Stress Echocardiography Atropine May be used in conjunction with Dobutamine to augment heart rate increases Patients on beta blockers 21 Protocol for Dobutamine Stress Echocardiography Patient preparation for stress testing IV access obtained Digital images obtained for baseline study Continuous EKG and BP monitoring Dobutamine infusion of 5 (or 10) µg/kg/min Infusion rate is increased every 3 minutes to doses of 10, 20, 30, and 40 µg/kg/min EKG, Echocardiograms and BP are monitored continuously Low-dose images are acquired at 5 or 10 µg/kg/min (at first sign of increased contractility) Atropine in aliquots of 0.5 to 1.0 mg can be given during the mid and high doses to augment the heart rate response Mid-dose images are acquired at either 20 or 30 µg/kg/min Peak images are acquired before termination of the infusion Post-stress images are recorded after return to baseline The patient is monitored until he or she returns to baseline status 22 End Points and Reasons to Terminate Dobutamine Infusion During Stress Testing Exceeding target heart rate of 85% age-predicted maximum Development of significant angina Recognition of a new wall motion abnormality Arrhythmias such as atrial fibrillation or non-sustained ventricular tachycardia Limiting side effects or symptoms 23 Safety of Dobutamine Short-half life May be utilized in patients with bronchospastic disease Common side effects Minor arrhythmias Palpitations or anxiety 24 Dipyridamole and Adenosine Potent vasodilators Adenosine: short-acting direct coronary vasodilator Dipyridamole: slower acting. Inhibits adenosine uptake Adenosine and dipyridamole generally cause changes less significant and shorter lived than Dobutamine Used in nuclear imaging studies more often than echocardiography 25 Choosing Among the Different Stress Modalities 26 Interpretation of Stress Echocardiography Most analyzed based on subjective assessment of regional wall motion Wall thickness and endocardial excursion at baseline and during stress Normal response is development of global hyperdynamic wall motion Some heterogeneity of response may be expected 27 Abnormal response to exercise Increase in LV systolic dimension Increase in RV 28 Strain Rate Imaging Relies on tissue Doppler imaging to quantify myocardial deformation in response to applied stress Strain Simply the change in length of tissue that occurs when force is applied Strain rate First derivative of strain or how strains changes over time 29 Strain Rate Imaging Measured as difference in velocity between two points normalized for the distance between them Theoretic advantages: Relative independence of translational movement and tethering This will be covered in more depth in future lecture 30 Wall Motion Score Index 16 segment 1989 ASE recommendation 6 segments both basal and mid ventricular levels (12 total) 4 segments at apex Commonly used in echocardiography Nuclear perfusion imaging, cardiovascular magnetic resonance and cardiac computed tomography commonly use more segments Did not include apical cap 31 Wall Motion Score Index 17 segment model 2002 American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging attempt to establish common segmentation for all types of imaging Includes apical cap 32 Wall Motion Score Index 1: normal 2: hypokinesis 3: akinesis 4: dyskinesis 5: aneurysmal 6: akinetic/scar 7: dyskinetic/scar 33 Characterization of Wall Motion Hypokinesis Mildest form of abnormal function Preservation of some degree of thickening and inward motion of endocardium during systole but less than normal (<5 mm of endocardial excursion) Truly abnormal if: Limited to a region or territory that corresponds to the distribution of one coronary artery and Associated with normal (or hyperdynamic) wall motion elsewhere Tardokinesis Delayed, sometimes post systolic, inward motion or thickening 34 Characterization of Wall Motion Akinesis Dyskinesis Absence of systolic myocardial thickening and endocardial excursion Most extreme form of a wall motion abnormality Systolic thinning and outward motion or bulging of the myocardium during systole Scar Thin and/or highly echogenic 35 Example of Wall Motion Scoring Index 36 Wall Motion Response to Stress Wall motion that increases or augments with stress is normal Development of wall motion abnormalities with stress is considered resultant of ischemia Abnormal segments at rest remaining unchanged with stress: infarcted sans additional ischemia Hypokinetic baseline that worsens with exercise: ischemic 37 Localization of Coronary Artery Lesions Practical Application Predict presence of disease in specific coronary arteries or branches In general Stress echocardiography is more sensitive in patients with multi-vessel disease in comparison to single-vessel disease More accurate specifically identifying disease in the left anterior descending artery or right coronary artery in comparison to left circumflex Variability in coronary artery distribution Left circumflex versus right coronary artery distribution not always possible 38 Localized Apical Ischemia Induced with Dobutamine Normal at 20 µg/kg/min stage Abnormal at higher stage and heart rate 39 Previous Anterior MI, Development of Inferior Ischemia Baseline: basal inferior wall akinesis Entire inferior wall dyskinesis 40 Multi-Vessel Disease 41 Correlation with Symptoms and Electrocardiographic Changes Most instances ECG, symptoms and echocardiography concordance Discordance Limitation of interpretation of ECG changes and symptoms Virtually every study indicates Wall motion more sensitive and specific than symptoms and/or ST-segment changes for CAD Echo relied upon heavily for final report Most common indications for echocardiography with stress testing due to anticipation of abnormal or non-diagnostic ECG 42 Detection of Coronary Artery Disease – False Negatives Single Vessel Sensitivity is higher with multivessel disease Left ventricular hypertrophy Studies shown: patients with LVH in setting of normal mass (small chamber size) have a disproportionately high frequency of false-negative results Concentric remodeling (thick walls with small internal chamber size): common finding in elderly patients with hypertension (Smart et al., 2000) Authors postulated blunted increase in endsystolic wall stress at peak Dobutamine infusion may account for reduced sensitivity in this subgroup 43 Detection of Coronary Artery Disease – Significant LVH W/CAD 44 Detection of Coronary Artery Disease – False Negative: Left Bundle Branch Block Abnormal septal motion both at rest and stress Preservation of septal thickening Evidence against ischemia as cause of abnormal endocardial excursion 45 Comparison with Nuclear Techniques Gold standard: angiographic testing Nuclear: more sensitive Echocardiographic: more specific Overall accuracy: nuclear and echocardiography are similar Both operator dependent Advantages of echocardiography: versatility of technique, lower cost of test, and avoidance of radiation exposure 46 Stress Echocardiography After Revascularization Used to Evaluate initial success of the procedure Look for recurrence of disease Assess symptoms in patients with known CAD 47 Pre-Operative Risk Assessment Non-cardiac surgery Dobutamine stress echocardiography most commonly used Absence of inducible wall motion abnormality Very favorable prognosis with negative predictive value of 93% to 100% Predictive ability: identification of patients who subsequently experience perioperative events 48 Stress Echocardiography in Women Higher rates of false positive ECG response 49 Assessment of Myocardial Viability Viable Myocardium that has potential for functional recovery Stunned or hibernating More severe wall motion abnormality, less likely to be viable (i.e. dyskinetic regions are less viable than hypokinetic regions) Thinned, scarred segments likely to be nonviable Resting echocardiogram non-sensitive, need stress echocardiography (Dobutamine) 50 Assessment of Viability Anterior And Lateral Viability Is Demonstrated 51 Use of Myocardial Contrast Techniques in Stress Echocardiography Two Distinct Categories Left ventricular opacification for border enhancement Covered in previous lecture Myocardial perfusion imaging Perfusion defect precedes regional wall motion abnormality Differing protocols Bolus vs. continuous infusion Continuous vs. intermittent triggered imaging Most studies rely on vasodilator stress (dipyridamole or adenosine) to induce regional changes in blood flow 52 Use of Myocardial Contrast Techniques in Stress Echocardiography Vasodilator and intermittent triggered imaging during continuous infusion of an experimental agent Displayed image recorded from the fourth cycle after bubble destruction (long enough for contrast to adequately replenish within the tissue) Peak exercise: bubbles should refill more quickly (one to two cycles) due to vasodilation Approval for contrast agents for specific purpose of perfusion imaging is not yet approved by U.S. Food and Drug Administration Experimental and clinical studies have demonstrated feasibility of myocardial perfusion studies in comparing with nuclear and angiography 53 Use of Myocardial Contrast Techniques in Stress Echocardiography Following image Delay in rate of replenishment of the microbubbles: inferior wall perfusion defect 54 Use of Myocardial Contrast Techniques in Stress Echocardiography 55 Stress Echocardiography in Valvular Heart Disease Echocardiogram and stress echocardiogram Study (Gauer et al., 2003) 1,272 consecutive patients 5% significant mitral regurgitation 13% aortic regurgitation Approximately 1% each aortic or mitral stenosis 56 Stress Echocardiography in Valvular Heart Disease Utilization Specifically For Valvular Heart Disease Correlation Of Symptoms With Severity Some patients with relatively mild disease may have significant increase in mean gradient during exercise MS: may have inappropriate increase in pulmonary artery pressure MR: unexpected worsening with exercise Worsening of mitral regurgitation has been reported in the absence of ischemia or LV dilation 57 Stress Echocardiography in Valvular Heart Disease Utilization specifically for valvular heart disease LV dysfunction and moderate aortic valve gradient Resting study often fails to differentiate between moderate and severe aortic stenosis based on gradient alone Dobutamine Increasing transvalvular flow can be used to distinguish moderate 58 Stress Echocardiography in Valvular Heart Disease Review of Utilization of Dobutamine Stress Echocardiography for Aortic Stenosis Dobutamine infusion 5 µg/kg/min If leaflets are relatively flexible (mild to moderate stenosis) Valve area will increase in response to increasing stroke volume Increase in velocity outflow tract will be much greater than that of the jet Ratio of LVOT/Ao velocity will increase Example: Baseline: LVOT velocity of 1.0 and Ao velocity of 2.0 (ratio ½) Exercise: LVOT velocity 2.0 and Ao velocity of 2.0 (ratio 1/1) 59 Stress Echocardiography in Valvular Heart Disease Review of Utilization of Dobutamine Stress Echocardiography for Aortic Stenosis True severe aortic stenosis is associated with a fixed valve area Maximal velocity of both outflow tract and jet will proportionately increase Ratio of LVOT/Ao peak velocity remains the same Example: Baseline: LVOT velocity of 1.0 and Ao velocity of 2.0 (ratio ½) Exercise: LVOT velocity 2.0 and Ao velocity of 4.0 (ratio 2/4 or 1/2) Limitation: study non-diagnostic if ventricular does not respond to Dobutamine with an increase in contractility, which may occur with significant coronary artery disease 60 Stress Echocardiography in Valvular Heart Disease Review of Utilization of Dobutamine Stress Echocardiography for Aortic Stenosis Rest: 0.6/2.8 = 0.21 20 mcg/kg: 0.8/3.6 = 0.22 30 mcg/kg: 0.9/3.8 = 0.23 61 Stress Echocardiography in Valvular Heart Disease Prosthetic valves Detection of exercise Increase substantially with exercise Helpful in understanding differences in hemodynamics of different prosthetic valves Patient-prosthetic valve mismatch Induced changes in pulmonary artery pressure in patients with chronic lung disease LVOT obstruction 62 Practice 63 Review What type of test is this? Is this a normal response? 64 Review What type of test was performed? Would you consider this as a normal response? 65 Review What type of test is being performed? Is this normal? 66 Review What type of test is being performed? Is this a normal response? 67 Review What type of test is being performed? Is this a normal response? 68 Review What type of test is being performed? Is this a normal response? 69 Review What type of test is being performed? Is this a normal response? 70 Review History: patient with diabetes, smoking and peripheral vascular disease What type of test is being performed? Is this a normal response? 71 Sources Feigenbaum H, Armstrong W. (2004). Echocardiography. (6th Edition). Indianapolis. Lippincott Williams & Wilkins. Goldstein S., Harry M., Carney D., Dempsey A., Ehler D., Geiser E., Gillam L., Kraft C., Rigling R., McCallister B., Sisk E., Waggoner A., Witt S., Gresser C.. (2005). Outline of Sonographer Core Curriculum in Echocardiography. Otto C. (2004). Textbook of Clinical Echocardiography. (3rd Edition). Elsevier & Saunders. Reynolds T. (2000). The Echocardiographer's Pocket Reference. (2nd Edition). Arizona. Arizona Heart Institute. 72