PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY

1. DR PRADEEP SREEKUMAR SENIOR RESIDENT DEPT. OF CARDIOLOGY GOVT. MEDICAL COLLEGE CALICUT PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY

2. Stressechocardiography was introduced in the early 1980s • Reliable and cost effective method for both the diagnosis and risk stratification of patients with suspected or known CAD. • Use has increased exponentially worldwide and is continuing to expand.

3. Stressechocardiography may be performed in conjunction with dynamic exercise (treadmill or bicycle). • In patients who are unable to exercise, pharmacological agents may be used, such as dobutamine or dipyridamole.

4. Indications : • Diagnosis of ischemia • Risk stratification before major non-cardiac surgery, especially vascular • After AMI: – Early wall motion abnormality predicts new event. – Remote wall motion abnormality predicts multivessel disease. – Viability of akinetic area: • Sustained improvement: Good prognosis • Biphasic response: Good prognosis with revascularisation, poor without

5. Indications : • Before PCI / CABG: Significance of stenosis. (NB: only most severe stenosis usually responsive). Viability • Assess aortic stenosis with poor LV function. Generally low gradient and low area. With low dose Dobutamine: – Increase in gradient: significant AS, – increase in aortic valve area: poor hemodynamics and non-significant AS.

6. Stress modalities •Exercise Sitting bicycle Supine bicycle Threadmill • Pharmacological Dipyridamole – vasodilating Adenosine – vasodilating Dobutamine-Contractility and HR increase

7. Contraindications: • Dobutamine Uncontrolled hypertension: >220/120 (resting) hypertrophic obstructive cardiomyopathy. Malignant ventricular arrhythmia. • Dipyridamole: AV-block COPD

8. With any form of stress testing echocardiographic images are first acquired digitally during rest in parasternal and apical views. • Subsequently, stress images are acquired during low, intermediate, and peak stress.

9. Rest and stress images are interpreted for global and regional left ventricular (LV) size, shape, and function. • A normal response is when, during stress, the LV size becomes smaller compared to rest, while the shape is maintained and there is increased endocardial excursion and systolic wall thickening

10. Dobutamine, which is a sympathomimetic agent, is particularly useful in patients with an existing resting wall thickening abnormality. • Low doses of dobutamine increases myocardial perfusion, recruits potentially contractile myocardium, and hence increases myocardial contractility in dysfunctional myocardium if there is sufficient contractile reserve (viability).

11. At high dose, however, dobutamine increases myocardial oxygen demand and in the presence of flow limiting stenosis will result in demand/supply mismatch leading to myocardial ischaemia, resulting in deterioration of regional function (biphasic response). • Thus, dobutamine at low doses depicts the presence of myocardial viability, while at high doses uncovers myocardial ischaemia .

12. Dipyridamole may be used as an alternative to dobutamine but it produces infrequent wall thickening abnormalities even in the presence of significant flow limiting coronary stenosis

13. Stress echocardiography is based on the fundamental causal relationship between induced myocardial ischemia and left ventricular regional wall motion abnormalities. • Mason and colleagues used M-mode echocardiography to study 13 patients with coronary artery disease and 11 age-matched control subjects during supine bicycle exercise

14. PHYSIOLOGIC BASIS Tennant and Wiggers observed the relationship between systolic contraction and myocardial blood supply to the left ventricle. With the induction of ischemia, these investigators demonstrated the rapid and predictable development of systolic bulging (or dyskinesis). This observation established the link between induced ischemia and transient regional myocardial dyssynergy, recorded echocardiographically as the development of wall motion abnormality after the application of a stressor

15. 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

16. Blunted in the setting of advanced age hypertension beta-blocker therapy Absence of the hypercontractile state in response to stress should be considered an abnormal response.

17. In the presence of a coronary stenosis, the increase in myocardial oxygen demand that occurs in response to stress is not matched by an appropriate increase in supply. • If the supply-demand mismatch persists, a complex sequence of events known as the ischemic cascade develops.

18. The ischemic cascade

19. After the development of a regional perfusion defect, a wall motion abnormality will occur, characterized echocardiographically as a reduction in systolic thickening and endocardial excursion.

20. The severity of the wall motion abnormality (hypokinesis versus dyskinesis) will depend on several factors like • Magnitude of the blood flow change • Spatial extent of the defect • The presence of collateral blood flow • Duration of ischemia. • Deterioration in regional wall motion,is a specific and predictable marker of regional ischemia

21. Once the stressor is eliminated, myocardial oxygen demand decreases and ischemia resolves. • Normalization of wall motion may occur rapidly, although typically the complete recovery of normal function takes 1 to 2 minutes-depends on the severity and duration of ischemia.

22. Stunned myocardium is the term applied when functional abnormalities persist after transient ischemia for a longer period. Although a reversible process, stunning may last days or even weeks if the ischemia is severe and prolonged.

23. Causes of Wall Motion Abnormalities Wall Motion Abnormalities at Rest • Myocardial Infarction • Cardiomyopathy • Myocarditis • Hibernating myocardium • Stunned myocardium • Postoperative state • Left bundle branch block • Hypertension • Right ventricular volume/pressure overload

24. Wall Motion Abnormalities during Stress • Ischemia • Rate-dependent bundle branch block

25. Dobutamine Stress Echocardiography • Dobutamine is a synthetic catecholamine that causes both inotropic and chronotropic effects through its affinity for β1, β2, and α receptors in the myocardium and vasculature. • Because of differences in affinity, the cardiovascular effects of dobutamine are dose dependent, with 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, so changes in vascular resistance (i.e., blood pressure) are unpredictable.

26. The net effect of these interactions is a combined increase in contractility and heart rate with an associated increase in myocardial oxygen demand. • If coronary flow reserve is limited, myocardial oxygen demands will eventually exceed supply and ischemia will develop.

27. DOBUTAMINE VS EXERCISE • The change in venous return that typically accompanies leg exercise is less pronounced with dobutamine. • In addition, the autonomic nervous system mediated changes in systemic and pulmonary vascular resistance are different with exercise compared with dobutamine

28. Heart rate response is less important with dobutamine compared with exercise, and ischemia can often be induced even if target heart rate is not attained. • The lower heart rate achieved during dobutamine but produces greater augmentation in contractility. • Thus, the two modalities produce ischemia by different mechanisms. • As a result, the parameters that define an adequate level of stress are also different.

29. Protocol for Dobutamine Stress Echocardiography • Digital images are acquired at baseline (these loops are displayed and used as reference throughout the infusion). Continuous electrocardiogram and blood pressure monitoring are established. • Dobutamine infusion is begun at a dose of 5 (or 10) µg/kg/min. The infusion rate is increased every 3 minutes to doses of 10, 20, 30, and 40 µg/kg/min. • The echocardiogram, electrocardiogram, and blood pressure are monitored continuously. Low-dose images are acquired at either 5 or 10 µg/kg/min (at the first sign of increased contractility).

30. Atropine 0.5 to 1.0 mg can be given during the mid- and high-dose stages 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 till return to baseline status

32. Reasons to Terminate the 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 • A decrease in systolic blood pressure >20 mm Hg from baseline • Arrhythmias such as atrial fibrillation or nonsustained ventricular tachycardia • Limiting side effects or symptoms

33. Because of the short half-life of dobutamine, inducible ischemia can be readily reversed through termination of the infusion. In severe cases or when the ischemic manifestations persist, a short-acting intravenous beta-blocker (such as metoprolol or esmolol) is effective. Symptoms palpitations anxiety. Arrhythmias seen include: premature ventricular contractions atrial arrhythmias Nonsustained ventricular tachycardia (3% )of patients

34. In one series of 1,118 patients referred for dobutamine stress echocardiography, there were no incidents of death, myocardial infarction, or sustained ventricular tachycardia or fibrillation (Mertes et al., 1993).

35. No absolute contraindications to dobutamine stress testing. • Dobutamine echocardiography has been safely performed in patients with recent myocardial infarction, extensive left ventricular dysfunction, abdominal aortic aneurysm, syncope, aortic stenosis, hypertrophic cardiomyopathy, history of ventricular tachycardia, and aborted sudden death. • Safe in patients with bronchospastic lung disease.

36. Dipyridamole and Adenosine • Unlike dobutamine, Adenosine works by creating a maldistribution phenomenon by preventing the normal increase in flow in areas supplied by stenotic coronary arteries. • In more extreme cases, flow may actually be diverted away from abnormal regions (so-called coronary steal), resulting in true ischemia. • Adenosine is a potent and short-acting direct coronary vasodilator. Dipyridamole is slower acting and its effects result from inhibition of adenosine uptake.

37. The development of a wall motion abnormality is predicated on the ability to create sufficient maldistribution of regional blood flow to result in an ischemia-induced wall motion abnormality. • Compared with dobutamine, these changes are more subtle and short-lived

38. Redistribution of regional blood flow can occur without an associated wall motion abnormality. • Vasodilator stress agents may be better suited to imaging techniques that rely on relative changes in perfusion rather than the development of a wall motion abnormality. • Dipyridamole and adenosine have been commonly used with nuclear imaging techniques

39. Analyzed based on a subjective assessment of regional wall motion, comparing wall thickening and endocardial excursion at baseline and during stress. • The rest or baseline echocardiogram is first examined for the presence of global systolic dysfunction or regional wall motion abnormalities . • Subtle abnormalities at baseline, such as hypokinesis of the inferior wall, may occur in the absence of coronary artery disease and represent a cause of false-positive results.

40. Limitation of interpretation is the subjective and nonquantitative nature of wall motion analysis. • Calculation of the ejection fraction at rest and during stress, is technical challenging and rarely performed in routine practice. • A more practical approach involves the estimation of left ventricular volume changes during stress. • The normal response to stress includes a decrease in both end-systolic and end-diastolic volume that can be visually appreciated using side-by-side inspection of images. • Failure of the end-systolic size to decrease is an abnormal response. An increase in volume with stress often indicates severe and extensive (i.e., multivessel) disease.

41. Strain rate imaging • Relies on tissue Doppler imaging to quantify myocardial deformation in response to applied stress. • Strain is the change in length of a segment of tissue that occurs when force is applied. • Strain rate is how strain changes over time. • When assessed using the Doppler technique, strain rate can be measured as the difference in velocity between two points normalized for the distance between them. • Strain and strain rate have been examined as objective, quantifiable markers of ischemia during stress testing.

42. One approach involves determining the myocardial velocity gradient, which is the difference between the systolic velocities of the endocardium versus the epicardium (normalized for wall thickness). • Normally, the endocardium has a higher velocity than the epicardium, and this difference is frequently diminished with ischemia

43. One approach (endorsed by the American Society of Echocardiography) divides the left ventricle into 16 segments and then grades each segment on a scale from 1 to 4 in which • 1 normal, • 2 hypokinesis, • 3 akinesis, • 4 dyskinesis. Wall motion is analyzed at baseline, and a wall motion score index is generated according to the formula

45. Hypokinesis • Hypokinesis is the mildest form of abnormal wall motion. • It is defined as the preservation of thickening and inward motion of the endocardium during systole but less than normal. • It has been defined arbitrarily as less than 5 mm of endocardial excursion

46. Hypokinesis is most likely to be truly abnormal if it is limited to a region or territory that corresponds to the distribution of one coronary artery and is associated with normal (or hyperdynamic) wall motion elsewhere. • Tardokinesis– a form of hypokinesis. delayed, sometimes postsystolic, inward motion or thickening.

47. Akinesis is defined as the absence of systolic myocardial thickening and endocardial excursion. • Dyskinesis is the most extreme form of a wall motion abnormality and is defined as systolic thinning and outward motion or bulging of the myocardium during systole. • A left ventricular segment that is thin and/or highly echogenic indicates the presence of scar.

48. Segments that are abnormal at rest and remain unchanged with stress are generally best interpreted as showing evidence of infarction without additional ischemia. • Hypokinetic areas that worsen during stress are usually labeled ischemic. These may represent a combination of previous nontransmural infarction and induced ischemia. • Segments that are akinetic or dyskinetic at baseline, even if wall motion worsens during stress, are best interpreted as indicating infarction, and the ability to detect additional ischemia in such segments is limited.

49. Comparison with Nuclear Techniques

50. Prognostic Value of Stress Echocardiography • An abnormal exercise echocardiogram generally identifies patients at increased risk of cardiac events. • The echocardiographic findings that have been correlated with risk include a new wall motion abnormality, rest and exercise wall motion score index, and end-systolic volume response. • In most series, echocardiographic evidence of ischemia was the most potent marker of high-risk status and has consistently been a better discriminator than other variables, such as exercise-induced ST-segment depression