Dobutamine stress echocardiography

Uses of dobutamine stress echocardiography, low flow low gradient AS, Pulmonary hypertension, dobutamine stress echocardiography in Myocardial viability testing

1. Dobutamine stress ECHOcardiography Presenter: Dr. Himanshu Rana

2. Stress ECHOcardiography D ynamic evaluation of cardiac structure & function during physical exercise or pharmacologic simulation of exercise by increased HR, CO & myocardial oxygen demand Stress echocardiographic imaging techniques may be used to evaluate for myocardial ischemia, viability & valvular dysfunction

3. Why Echo in comparison to SPECT, PET etc.

4. Principles of pharmacologically induced stress Exercise-induced physiologic stress - preferred as Assessment of patient’s functional capacity & symptoms reproducibility All major guidelines recommend exercise over pharmacological stress ECHO Patients unable to exercise, pharmacologic stress should be pursued. Commonly used pharmacologic stressors include vasodilators such as adenosine & dipyridamole , or inotropes, such as dobutamine .

5. Treadmill stress echo Difficult to image while walking Able to get image only post exercise Peak exercise image is not obtainable Should acquire image with in 1 to 1.5 min of exercise Exercise capacity Blood pressure response Arrythmia assesment

6. Do a bicycle ergometry Done in supine position & able to image throughout exercise Image is obtainable at peak exercise Ischemia can induce at lower HR because of increased venous return & preload in supine position can cause a greater BP response Difficult to attain the adequate stress

7. Information obtained from Exercise Stress but not available with Pharmacological Test

8. Situations where Pharmacological Stress is preferred to Exercise Stress

9. ISCHEMIC CASCADE

10. In the absence of a flow-limiting coronary stenosis, physiologic stress results in Increase in Heart rate Contractility Systolic wall thickening Endocardial excursion Global contractility Ejection fraction Decrease in end-systolic volume

11. severity of the wall motion abnormality (hypokinesis versus dyskinesis) will depend on Magnitude of the blood flow change Spatial extent of the defect The presence of collateral blood flow Duration of ischemia.

12. Dobutamine A cts on β1- receptors to increase cardiac contractility & HR β2- receptors to cause peripheral vasodilatation. O nset of action is 1–2 min & t1/2 is approx. 2 min

13. At low doses - recruits potentially contractile myocardium, & increases myocardial contractility At high dose - increases myocardial oxygen demand So if flow limiting stenosis present - myocardial ischaemia & deterioration of regional function d/t demand/supply mismatch.

14. Goal of DSE T o detect myocardial ischemia in early stages of CAD by identifying RWMAs under conditions of pharmacologic stress. Coronary flow limitation initially causes diastolic dysfunction followed by manifestations of ischemia, including the visualization of systolic dysfunction.

15. Why dobutamine is the stress agent during echo?

16. Adenosine – direct coronary vasodilator Dipyridamol – inhibit adenosine uptake As pharmacological stressor both are less poplular Redistibution can occur without RWMA Better suited for nucler imaging that relay on redistirbution

17. HOW TO PERFORM DSE & PROTOCOL

18. Testing Pre-requisites The protocol was defined by ASE(2007) & ESE(2008) Machine should have the ability to trigger image acquisition based on ECG Also machine should have split screen & quadruple screen so that simultaneous comparison of image is possible Contrast enhancement should be considered to augment endocardial definition when ≥ 2 contiguous endocardial segments not visualized at rest .

19. Testing protocol Typically fasting for 4 hrs The sn of DSE for detection of ischemia may be reduced by β - B’s , CCB’s, and nitrates Stop all negative chronotropic agents and nitrates 8 to 12 hr before procedure – unless, goal is to assess efficacy of anti-ischemic regimen Graded dobutamine infusion given typically @ starting dose of 5 μg /kg/min

20. Dobutamine dose increased every 3–5 minutes to doses of 10, 20, 30 & finally to 40 μg /kg/min The goal is to achieve heart rate 85% of MPHR for patient’s age L ow-dose dobutamine stage is optimal for detection of ischemia & assessment of viability by searching for “ biphasic response” Therefore , if viability assessment is the principal aim, the initial dose is often lowered to 2.5 μg /kg/min.

21. If THR is not achieved with dobutamine alone, atropine ( max. dose 2 mg, divided into four 0.5 mg doses) can be added Some also consider trial of increased dose of dobutamine (50 μg /kg/min) if patient is close to achieving 85 % MPHR I mages at each echocardiographic window are obtained during rest, low-dose, intermediate dose, peak-dose & post-stress

22. End points of the DSE protocol Achievement of the THR Detection of moderate wall motion abnormalities in ≥ 2 territories Symptomatic or sustained arrhythmias, H ypotension or severe hypertension (typically SBP 220–240 mmHg or DBP 120 mmHg), or Patient’s inability to tolerate the test Significant ST-T changes In some cases, reversal of RWMA is assessed with addition of post-stress beta-blockers (typically 1–5 mg of iv metoprolol ).

23. Testing interpretation Stress report must mention the adequacy of stress achievement of THR or estimated workload, symptoms , blood pressure response , any electrocardiographic (ischemic or arrhythmic) & echocardiographic changes. The typical stress echocardiography report should comment both on global LV function and regional LV function , along with summative comment on the significance of the findings

24. Hyperdynamic ventricular response Increase in endocardial excursion ≥ 5 mm Uniform thickening during systole Increase in LVEF with decrease in end- sysolic volume NORMAL RESPONSE?

25. CATEGORIZATION OF WALL MOTION HYPOKINESIA AKINESIA DYSKINESIA TARDOKINESIA LESS THAN 30% WALL THICKENING OR <5 MM ENDOCARDIAL EXCURSION LESS THAN 10 % WALL THICKENING SYSTOLIC THINNING AND OUTWARD BULGING DELAYED INWARD MOTION AND THICKENING Ischemic response is generally defined as decreased wall thickening in ≥1 segment

26. Pseudodyskinesia ( R aisinghani sign) Diastolic flattening of dyskinetic motion of inferoseptal & inferobasilar segments d/t diaphragmatic compression f/b systolic bulging Causes: Liver failure with severe ascites Hepatomegaly Pregnancy 3 rd trimester Where a myocardial territory augments its contraction at low dose but becomes hypokinetic/ akinetic at higher doses Biphasic response

27. Absolute Contraindication Uncontrolled hypertension: >180/100(resting) or symptomatic hypertension HCM(significant rest LVOT gardient ≥ 30mm Hg)* Malignant ventricular arrhythmia Recent MI( within 3 days) Unstable angina Aortic dissection

28. Relative contraindications Aortic aneurysms Carotid disease Heart failure Cardiomyopathies Intracranial aneurysms History of CVA or TIA

29. SIDEFECTS AND COMPLICATIONS

30. Side effects Dobutamine Anxiety Nausea Headache Palpitation flushing, paresthesia , urinary urgency, Atropine Urinary retention, Increased intraocular pressure, Delirium, Flushing, Constipation and delayed gastric emptying, Nausea, Dry mouth, and Weakness

31. Safety of dobutamine stress echocardiography Decreased blood pressure/Hypotension(1.7%), Hypertension (1.3%), Supraventricular tachycardia (1.3%), Atrial fibrillation (0.9%), Atrioventricular block (0.23%), Ventricular tachycardia (0.15%), Ventricular fibrillation (0.04%), Coronary artery spasm (0.14%), Myocardial infarction (0.02%), Cardiac rupture (0.002 %) , and Cerebrovascular disorder (0.005%).

32. Indications - dobutamine stress echocardiography Indication Assessment Risk stratification of IHD Presence & extent of ischemic myocardium as well as viable and/or hibernating myocardium Mitral stenosis(MS) Indicated in asymptomatic patients with severe MS, Patients having symptoms discordant with rest echocardiographic measures of stenosis, Assessment of transvalvular gradients at stress Aortic stenosis(AS) Differentiation of low gradient AS versus pseudostenosis , and Prognosis in low gradient AS ( eg , assessment of contractile reserve) Pulmonary hypertension Assessment of pulmonary artery systolic pressure at stress when patient is unable to exercise

33. Ischemic Heart disease Stress echocardiography has highest sp (88%) among ischemic tests including exercise ECG testing, thallium perfusion imaging, SPECT & PET, hence high NPV More recent data suggest that in patients with LVH, stress echocardiography may be the test of choice in an ischemic evaluation Also, heterogenous uptake of radionuclide due to LVH may generate a high false positive rate of perfusion imaging, which is not applicable to stress echocardiography

34. MEAN SENSITIVITY OF DSE DISEASE SENSITIVITY SVD 74% 2VD 86% 3VD 92% ARTERY INVOLVED SENSITIVITY LCX 55% LAD 72% RCA 76

35. X – not visualised

36. Normal WMSI-1 at baseline and stress Any score>1-abnormal Good prognostic value Help to approach in a standardized and systematic way

37. False negative Submaximal stress Late image acquisition Single vessel disease especially LCx territory Marked LVH and small LV cavity Beta blocker and antianginal Elderly women

38. F alse positive Hypertensive response to stress Coronary spasm due to dobutamine Paradoxical septal motion in LBBB Myocardial infarction(old) Cardiomyopathy Myocarditis Hibernating myocardium Stunned myocardium Postoperative state Right ventricular volume/pressure overload

39. Myocardial viability

40. DEFINITION IMPROVEMENT IN WALL MOTION ABNORMALITY BY ATLEAST ONE GRADE IN 2 OR MORE SEGMENTS DURING STRESS.

41. Types of response Biphasic response- most specific sign of viability Sustained improvement-viable stunned, remodeled or myopathic Deterioration-critical low flow No response- akinetic remain akinetic (non viable scarred)

42. Four or more segments out of a total of 16 displaying a biphasic response exhibited a specificity of 81% for predicting a ≥5% increase in post-revascularization EF at a median 14-month follow-up of ICMP, with sn of 83% if the EF was >35% & of 92% if the EF was ≤35 %. DSE one week after MI with either an ischemic or biphasic response has a sensitivity of 82% and a specificity of 80% for detecting a residual stenosis subtending an area of hibernating myocardium . Myocardial viability identified with stress echocardiography is associated with improved survival after revascularization

43. Its been shown that the combined nitroglycerin and dobutamine stress echocardiogram had the highest specificity (83%) but rest-redistribution thallium single proton emission tomography had the highest sensitivity (95%) for detecting viable myocardium.

44. VALVULAR DISEASE

45. Stress echocardiography has the ability to comprehensively assess valvular function, both at rest & during stress & indirectly evaluate hemodynamics in real time. Stenosis & regurgitation of all valves can be evaluated with stress echocardiography MC stress echocardiogram applications are in left-sided stenotic lesions. Exercise echocardiography is the general technique for assessment of valvular disease except in aortic stenosis with left ventricular dysfunction. There are limited data for assessment of AR & MR by DSE, as there is concern that the afterload-reducing properties of dobutamine will reduce the degree of valvular regurgitation.

46. Mitral stenosis The 2007 ASE guidelines recommend stress echocardiography for evaluation of asymptomatic patients with echocardiographically severe mitral stenosis and patients with symptoms disproportionate to their echocardiographic disease The ability to evaluate both valvular function and dynamic transvalvular gradients is particularly helpful in patients whose symptoms are more severe than their resting echocardiographic evaluation would suggest.

47. A multivariate analysis of rheumatic MS defined a transmitral mean gradient ≥18 mmHg as “high risk” & best predictor of future events ( eg , heart failure related to mitral stenosis, surgical or balloon intervention, hemodynamically significant arrhythmia, or death) with sn - 90 % & sp - 87 %. These high-risk patients likely warrant more aggressive clinical care and consideration for earlier more aggressive interventions

48. Whenever there is an Increse in flow rate across aortic valve Associated increase in valve area If flow rate is low valve opening get inhibited lead to underestimation of valve area This phenomina is a practical challenge for the doctor because when LV dysfunction is present quantitative assessment of AS is difficult Aortic stenosis

49. Patients with a low LVEF (< 35%–40%) and a low mean transvalvular gradient (<30–40 mmHg), called “low-gradient low output aortic stenosis”, pose a diagnostic dilemma. This is one of the clinical situations where DSE is uniquely helpful. It is very difficult to determine if they have true stenosis & should be considered for valve replacement, or instead have “ pseudostenosis ”, namely LV dysfunction that makes aortic valve appear stenotic , but carries a high risk of dying with valve replacement.

50. DSE can be uniquely useful in differentiating these patients and determining who might benefit from surgical intervention Specifically , patients with aortic valve pseudostenosis are able to increase their aortic valve area & decrease the transaortic gradient in response to dobutamine on In contrast, patients with true aortic stenosis are unable to increase their valve area in response to an increased cardiac output, and instead the transvalvular gradient increases

51. Another use of DSE in AS is to assess contractile reserve. Contractile reserve is defined as a 20% increase in stroke volume (as assessed by the left ventricular outflow tract velocity time integral) or a 20% relative increase in ejection fraction For patients with low gradient aortic stenosis, surgery is most beneficial for those with documented left ventricular contractile reserve The postoperative outcomes for patients with low gradient aortic stenosis and without contractile reserve is poor

52. Cut Offs for Diagnosis Contractile Reserve – 20% of stroke volume Valve area improvement to differentiate true from Pseudostenosis – 0.2% Asymptomatic Sev AS, mean gradient rise on exercise - > 20 mmHg

53. Pulmonary hypertension Doppler evaluation of the TR velocity is used to estimate RVSP with a derivation of the Bernoulli equation (RVSP & PASP will be equal except in RVOTO & PS). Doppler evaluation is feasible both at rest and under stress, It may be helpful in quantifying the severity of pulmonary hypertension as well as detecting occult or exercise-induced pulmonary hypertension.

54. A TR velocity ≤2.5 m/sec at rest corresponds to PASP of ≤35 mmHg (assuming RAP of 10 mmHg) & defines ULN at rest. DSE may be used for detecting pulmonary hypertension secondary to left-sided valvular disease such as MR & AS, although exercise is preferable to DSE if patient can exercise, & also for regurgitant lesions. Detection of elevated PASP during stress predicts poorer outcomes in these patients & should prompt consideration of more aggressive valvular intervention

55. PRETRANSPLANT EVALUATION Patients with ESRD are at increased risk of CAD, and CVD is the mc cause of death after renal transplant. So, accurate assessment of extent & severity of CAD prior to renal transplant is essential. The accuracy of DSE for detecting CAD in ESRD patients is variable ( sn 37%–95% & sp 71%–95 %) Recent Cochrane analysis of pretransplant cardiac imaging modalities found DSE to be superior to myocardial perfusion imagng for CAD detection in pre-renal transplant patients.

56. DSE is also often performed as part of the preoperative evaluation for liver transplantation its overall sensitivity for CAD is poor, but the test has a reasonable NPV in this population, making it useful to exclude CAD and perioperative events. DSE as an echocardiographic modality also gives the option of estimating RVSP may be important given the possibility of portopulmonary hypertension

57. DSE IN WOMEN Women often present with symptoms considered atypical of CAD & are more underdiagnosed and undertreated. Stress echocardiography provides prognostic information, even after controlling for clinical and laboratory data, in women with known or suspected CAD. When exercise ECG was directly compared with exercise echocardiography in women, exercise or stress echocardiography had a higher sensitivity (81% versus 77%) and specificity (80% versus 56%) for the detection of CAD.

58. Exercise echocardiography also provided the “best balance” between accuracy and cost for the diagnosis of CAD in women . When echocardiography was compared directly with stress thallium-201 SPECT, there was no difference in diagnostic accuracy. These benefits of exercise echocardiography are believed to be shared by DSE, but exercise would remain the preferred stress modality if the patient is able to exercise . For young and middle-aged women, stress echocardiography avoids the long-term risk of radiation-induced carcinogenesis in other analogous radionuclide-based cardiac imaging modalities.

59. THANK YOU