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The Use of Treadmill Stress Echocardiography
after Myocardial Infarction

Charles G. Vasey, MD

Asheville Cardiology Associates, PA, Asheville, NC, USA

INTRODUCTION
   As the treatment of myocardial infarction has evolved over the past several decades, so has the evaluation of the post-infarction patient. To best utilize echocardiography in evaluating patients who have suffered myocardial infarction (MI), it has become increasingly important to consider their initial therapy. The administration of thrombolytic agents and more recently percutaneous catheter intervention (PCI) early in the course of myocardial infarction have diminished mortality. Early investigations evaluating the utility of standard treadmill testing after MI in patients without reperfusion therapy have become less relevant to a patient population at substantially less risk of a subsequent event. Nonetheless, the majority of infarct patients will not receive early intervention. The goals of the noninvasive evaluation of the post infarct patient therefore remain largely unchanged and include an assessment of (1) resting LV systolic function, (2) the presence of multivessel coronary artery disease, (3) the presence or absence of provocable ischemia and myocardial viability and (4) the risk of reinfarction and death. By providing an accurate answer to these and other questions, echocardiography performed at rest and in conjunction with various forms of stress testing can substantially enhance the accuracy of risk stratification in the post infarct patient and appropriately define the need for invasive evaluation and intervention. This discussion will consider pharmacologic and exercise stress testing, but will focus predominantly on the utility of treadmill stress echocardiography both early and late after MI.

Clinical Parameters
   The value of echocardiography in the evaluation of the post infarct patient cannot be considered without regard to clinical context. The TIMI-2 trial identified five clinical factors that were useful for risk stratification: age greater than 70, rales in more than one third of the lung fields, atrial fibrillation, hypotension and sinus tachycardia [5]. Mortality at six weeks ranged from 1.5% in patients with none of these risk factors to 17.2% in patients with four or more. Patients whose clinical profile alone identifies an increased mortal risk need not undergo any additional testing prior to angiography.

Resting Left Ventricular Function
   Reduced left ventricular function after MI has been repeatedly demonstrated to predict an adverse outcome [11,27] Resting left ventricular function can be assessed by either radionuclide ventriculography or echocardiography. Echocardiography provides an assessment of valvular function, diastolic filling, pericardial abnormalities and the presence or absence of ventricular thrombus and mechanical complications, including myocardial or septal rupture and papillary muscle dysfunction, generally at lesser cost. While radionuclide ventriculography is inherently more quantitative, the subjective nature of estimated ejection fraction by echo has not compromised its clinical utility. Use of the American Society of Echocardiography 16-segment model to provide a wall motion score index (WMSI) provides additional standardization. The value of resting echocardiography in identifying patients at increased risk of developing congestive failure, ventricular dysrhythmia or dying after MI has been demonstrated in patients receiving thrombolytic therapy [14] and in those who did not [8,12].

   Unless seeking to answer a specific clinical question pertaining to one of issues noted above, resting echocardiography is not indicated in patients who have early angiography and percutaneous catheter intervention in that an estimate of ventricular function will in general be provided by contrast ventriculography at the time of the procedure.

STRESS ECHOCARDIOGRAPHY EARLY AFTER MI
Exercise Stress Echocardiography
   The number of studies attesting to the accuracy of treadmill stress echo in identifying patients at risk for an adverse outcome early after myocardial infarction is small [1,8,20]. Data was collected prior to the advent of fibrinolytic therapy, few patients have been studied, the timing of the stress test has been variable and follow-up has been relatively brief (Table 1). The ability of a negative test to identify low risk patients was reasonably consistent but the positive predictive value varied widely. While it's reasonable to apply those results to patients in the current era who fail to receive thrombolytic agents or PCI, applicability to those patients who do is uncertain. Penco et al, however compared exercise echo in 153 patients who had not undergone reperfusion therapy with 62 who had received a thrombolytic agent and found the results to be similar, suggesting the feasibility of extrapolating early data at least to patients who undergo thrombolysis [15].

Table 1

   Quintana et al, more recently utilized bicycle stress earlier in the post-infarct course to predict mortality over three years with similar result [19].

    The sensitivity of treadmill stress echo after MI in detecting multivessel CAD ranges from 55% to 82% [20,22], with specificities of 88 to 95 [8,20] again defined in a very small patient population. (Video 1)

Video 1

   Quad screen display of apical images with the resting 4- and 2-chamber views compared to immediate post exercise views. At rest there is inferior scar. After exercise, multivessel coronary artery disease is signaled by the presence of inferior peri-infarct hypokinesis and remote anterior hypokinesis. Intracavitary echoes are the result of high-gain setting to maximize endocardial visualization.

   Exercise echocardiography has only recently been demonstrated to be of benefit in defining myocardial viability after MI [7] Dobutamine stress echo has been used extensively for that purpose as noted in the following discussion. The rationale for both techniques lies in the ability of catecholamines to stimulate hypocontractile or stunned myocardium, inducing restoration or enhanced vigor of contraction. In the case of dobutamine the stimulus is exogenous, while exercise results in the release of endogenous catecholamines that in theory have a similar effect. Hoffer et al studied 52 patients with an initial MI. Each had both a low level dobutamine stress test (5, 10 and 15 mcg/kg/min.) and supine bicycle stress echocardiography with continuous imaging during exercise. At repeat echocardiography after one month, the ability of each test to predict functional recovery was comparable (Table 2).

Table 2

Pharmacologic Stress Echocardiography
   While an extensive review of the uses of dobutamine stress echo (DSE) is beyond the scope of this discussion, suffice it to say that pharmacologic stress testing has a number of advantages in the post-infarct patient in comparison to treadmill exercise testing. Patients can be studied safely very early after MI [25] and at rest, enhancing the ease of imaging, at the expense of losing information pertaining to exercise duration and ST depression.

   The reported ability of (DSE) to detect multivessel CAD in patients after MI has varied widely, ranging in sensitivity from 57% to 90% and in specificity from 67% to 97% [10,22,11,25].

   The predictive value of DSE after MI has been studied extensively. Table 3 displays the positive and negative predictive values of DSE as reported by a number of authors. In general, the ability of DSE to consistently identify patients at increased risk for an adverse event after MI has been disappointing. The relatively high negative predictive values suggest that a non-ischemic test result portends a good prognosis and may be clinically more useful. Although DSE has been shown to accurately predict the presence or absence of viable myocardium after MI [26], confirmation of viability has not added significantly to the prognostic assessment of post MI patients [18]. Patients enrolled in these studies had received thrombolytic therapy with a frequency approximating that seen in clinical practice, hence these results may be extrapolated to current practice more readily than those of treadmill testing post MI, with the probable exception of patients having urgent PCI.

Table 3

    Dipyridamole stress echocardiography (DPE) has been extensively studied outside the United States, where it has been less popular. Dipyridamole acts to create a relative steal phenomenon and hence has been suggested to be more applicable to nuclear perfusion imaging than echocardiography. Nonetheless, the available data pertaining to DPE after MI rivals all other forms of stress echocardiography (Table 4). The positive predictive value of DPE has been disappointing in comparison to DPE, however.

Table 4

Exercise Treadmill Stress Echo Late after MI
   There is very little data relating to maximal stress echocardiography late after myocardial infarction. That is somewhat surprising in that a common management algorithm after uncomplicated myocardial infarction has included a low level exercise test and, in patients without exercise-induced ischemia, a maximal stress test four to six weeks later. In theory, any noninvasive testing modality providing an index of left ventricular function and detecting stress-induced ischemia should be an ideal means of evaluating the postinfarct patient. To determine the value of maximal stress echocardiography late after myocardial infarction, we studied 203 patients who had a Bruce protocol exercise treadmill test four to six weeks after uncomplicated myocardial infarction, none of whom had undergone percutaneous or surgical revascularization [27]. A minority had received thrombolytic therapy. The results of echocardiography defined four patient groups: Group 1, normal exercise echo; Group 2, normal resting wall motion with exercise-induced ischemia; Group 3, abnormal resting left ventricular function with no exercise-induced ischemia; and Group 4, abnormal left ventricular function with exercise-induced ischemia. Patients were followed for up to 77 months (range 1-77, mean 43). The results, including that of the treadmill test, are shown in Table 5.

Table 5

    ST-segment response on the treadmill had no predictive value. The presence of an exercise-induced wall motion abnormality increased the likelihood of cardiac death to a marginally significant level (p equals 0.9). By multivariate analysis, a resting ejection fraction of less than 40% (rr 4.93 95% CI 1.96-12.42, p less than 0.001); diabetes (rr 3.12, 95% CI 1.16-8.35, p equals 0.024); age greater than 70 years (rr 2.67, 95% CI 1.07-6.64, p equals 0.035), were the most potent predictors of mortality. The presence of exercise-induced ischemia approximately doubled the risk of subsequent cardiac death (7% in patients without myocardial ischemia versus 15% with myocardial ischemia). These results are applicable to a minority of patients who have suffered myocardial infarction. Patients who undergo urgent coronary angiography and percutaneous intervention have defined left ventricular function and coronary anatomy and were excluded from consideration in this study. These results do suggest that patients who (1) do not undergo early angiography because of physician preference or lack of available facilities, or (2) are treated pharmacologically or with thrombolytic therapy and who do not demonstrate either spontaneous or inducible ischemia in the early postinfarct period will continue to be candidates for late risk stratification in the outpatient setting. Treadmill stress echocardiography is an ideal means of evaluating these patients.

CONCLUSION
    Echocardiography, at rest and in combination with various forms of stress, provides significant prognostic information in postinfarct patients. The choice of a resting study alone versus pharmacologic or treadmill stress echocardiography in the early postinfarct period can best be made with attention to clinical factors, cost, the patient's ability and desire to exercise, and local expertise. Treadmill stress echocardiography early after myocardial infarction is of benefit in patients who have not had reperfusion therapy, and possibly to detect myocardial viability in patients who have had thrombolysis. Treadmill stress echocardiography late after myocardial infarction in patients not undergoing early intervention also adds useful prognostic information.

REFERENCES

1. Applegate RJ, Dell'Italia L J, Crawford MH. Usefulness of two-dimensional echocardiography during low-level exercise testing early after uncomplicated myocardial infarction. Am J Cardiol 1987;60:10-14.

2. Carlos M, Smart S, Wynsenn J. Dobutamine stress echocardiography for risk stratification after MI. Circulation 1997;95:1402-1410.

3. Franklin K, Marwick T. Use of stress echocardiography after myocardial infarction. Cardiol Clin of North America 17:521, 1999.

4. Gorscan J, Lazar JM, Schulman DS, et al: Comparison of left ventricular function by echocardiographic automated border detection and by radionuclide ejection fraction. Am J Cardiol 72:810, 1993

5. Greco CA, Salustri A, Seccareccia F, et al: Prognostic value of dobutamine echocardiography early after uncomplicated acute myocardial infarction: A comparison with exercise electrocardiography. J Am Coll Cardiol 29:261, 1997

6. Hillis LD, Forman S, Braunwald E. Risk stratification before thrombolytic therapy in patients with acute myocardial infarction. The Thrombolysis in Myocardial Infarction (TIMI) Phase II Co-Investigators. J Am Coll Cardiol 1990:16:313-5.

7. Hoffer E, Dewé W, Celentano C, et al: Low level exercise echocardiography detects contractile reserve and predicts reversible dysfunction after myocardial function,. Comparison with low-dose dobutamine echocardiography. J Am Coll Cardiol 1999;34:989-97

8. Jaarsma W, Visser C, Kupper A, et al. Usefulness of two-dimensional exercise echocardiography shortly after myocardial infarction. Am J Cardiol 1986; 57:86-90.

9. Kan G, Visser CA, Koolen JJ, et al: Short- and long-term predictive value of admission wall motion score in acute myocardial infarction. A cross-sectional echocardiographic study of 345 patients. Br Heart J 56:422, 1986

10. Lanzarini L, Cavalotti CV, Poli A, et al: [Results and prognostic significance of echocardiography- dobutamine + atropine test in recent non-Q wave myocardial infarction]. [Italian] Giornale Italiano di Cardiologia 26:261, 1996

11. Minardi G,Di Segni M., Pulignano G, et al: Diagnostic and prognostic value of dipyridamole and dobutamine stress echocardiography in patients with Q-wave acute myocardial infarction. Am J Cardiol 80:847, 1997

12. Multicenter Postinfarction Research Group: Risk stratification and survival after myocardial infarction. N Engl J Med 1993;309:331-6.

13. Nishimura RA, Reeder GS, Miller FA, et al: Prognostic value of predischarge 2-dimensional echocardiogram after acute myocardial infarction. Am J Cardiol 53:429, 1984

14. Peels KH, Visser CA, Dambrink JH, et al: Left ventricular wall motion score as an early predictor of left ventricular dilation and mortality after first anterior infarction treated with thrombolysis. The CATS Investigators Group. Am J Cardiol 77:1149, 1996

15. Penco M. Romano S, Vizza CD, et al: At risk myocardium after acute infarct treated with fibrinolysis: Assessment using exertion echocardiography and clinico-prognostic significance. Cardiologia 41:861, 1996

16. Picano E, Sicari R, Landi P, et al: Prognostic value of myocardial viability in medically treated patients with global left ventricular dysfunction early after acute uncomplicated myocardial infarction: A dobutamine stress echocardiographic study. Circulation 98:1078, 1998

17. Picano E, Landi P, Bolognese L, et al. Prognostic value of dipyridamole echocardiography early after uncomplicated myocardial infarction: a large-scale multicenter trial: EPIC Study. Am J Med 1993;95:608-610.

18. Previtali M, Fetiveau R, Lanzarini L, et al: Prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography early after acute myocardial infarction treated with thrombolysis. J Am Coll Cardiol 32:380, 1998

19. Quintana M, Lindvall K, Ryden L, Brolund F. Prognostic value of predischarge exercise stress echocardiography after acute myocardial infarction. Am J Cardiol 1995; 76:1115-1121.

20. Ryan T, Armstrong WF, O'Donnel JA, Feigenbaum H. Risk stratification following acute myocardial infarction during exercise two-dimensional echocardiography. Am Heart J 1987;114:1305-1316.

21. Salustri A, Ciavetti M, Seccareccia F. Prediction of cardiac events after uncomplicated acute myocardial infarction by clinical variables and dobutamine stress test. J Am Coll Cardiol 1999;34:435-40

22. Schroeder K, Voller H, Dingerkus H, et al: Comparison of the diagnostic potential of four echocardiographic stress tests shortly after acute myocardial infarction: submaximal exercise, transesophageal atrial pacing, dipyridamole, and dobutamine-atropine. Am J Cardiol 77:909, 1996

23. Sclavo MG, Noussan P, Pallisco O, et al: Usefulness of dipyridamole-echocardiographic test to identify jeopardized myocardium after thrombolysis. Limited clinical predictivity of dipyridamole-echocardiographic test in convalescing acute myocardial infarction: Correlation with coronary angiography. Eur Heart J 13:1348, 1992

24. Sicari R, Picano E, Landi P, et al: Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction. Echo Dobutamine International Cooperative (EDCI) Study. J Am Coll Cardiol 29;254, 1997

25. Smart S, Knickelbine T, Steiber T. Safety and accuracy of dobutamine-atropine stress echocardiography for the detection of residual stenosis of the infarct related artery and multivessel disease during the first week after MI. Circulation 1997;95:1394-1401.

26. Smart SC, Sawada S, Ryan T, et al. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation 1993;88:405-415.

27. Vasey C, Usedom J, Woodard S, et al: Prediction of cardiac events after uncomplicated acute myocardial infarction: The role of maximal treadmill stress echocardiography. J Am Soc Echocardiography 2001;41:38-43.

28. Volpi A, De Vita C, Franzosi MG, et al: Determinants of 6-month mortality in survivors of myocardial infarction after thrombolysis: Results of the GISSI-2 database. Circulation 88:415-429,1995

 

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2nd Virtual Congress of Cardiology

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