Use of exercise echocardiography to evaluate patients after coronary angioplasty

dogenous platelets, allowing transfused platelets to and sustained increment in circulating platelet count and clinical hemostasis. remain in the circulation. Profound thrombocytopenia in these cases occurred following first time abciximab exposure. As 1. EPIC Investigators. Use of a monoclonal antibody directed against the platelet abciximab therapy was associated with a 6.6% in- glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med cidence of developing an immune response (IgG),’ 1994;330:956-961. re-exposure of these patients to abciximab may be 2. Lincoff AM, Tcheng JE, Bass TA, Popma JJ, T&stein PS, Kleiman HF, Musco MH, Cabot CE, Berdan LG, Califf RM, Top01 EJ. A associated with profound thrombocytopenia in ad- NS,Weisman multicenter, randomized, double-blind pilot trial of standard versus low dose dition to anaphylactoid reactions or lack of phar- weight-adjusted heparin in patients treated with the platelet GP IIb/IIIa receptor c7E3 during percutaneous coronary revascultization (abstr) J Am macologic efficacy. It is unknown whether or not antibody Cdl Cardiol 1995;25:80A. patients with profound thrombocytopenia following 3. Berkowitz SD, Sane DC, Shavender JH, Sigmon KN, Top01 EJ, Califf RM. ‘ ‘first time” abciximab exposure have cross reactive Analysis of the occurrence and clinical significance of thrombocytopenia with (abciximab) in the EPIC trial (abstr), J Am Coil Cardiol 1996;27:82A. antibodies to abciximab. A rapid strip test assay for 4.c7E3 Imbacb P. New clinical aspects of immune thrombocytopenic purpura (ITP). human antichimeric antibody is currently under de- In: Immunotherapy with Intravenous Immunoglobulins. London: Academic velopment and should facilitate safe retreatment with Press, 1991~239-243. 5. Berchtold P, McMillan R. Intravenous immunoglobin: new aspects of mechabciximab as well as give insight into the “back- anism of action in chronic ITP. In: Imbach P. ed. Immunotherapy with Intraground” prevalence of cross reactive antibodies in venous Immunoglobulins. London: Academic Press, 1991:245-252. 6. Dwyer JM. Manipulating the immune system with immune globulin. N Engl patients without prior abciximab exposure. Jk’ed 1992; 326:107-116. In summary, first time abciximab administration was associated with acute profound thrombocytopenia in 4 of 575 consecutive patients. Therapy with platelet transfusion is associated with a rapid

Use of Exercise Linda J. Crouse,

Echocardiography to Evaiuate After Coronary Angioplasty

MD, James L. Vacek,

MD, Gary

ercutaneous transluminal coronary angioplasty P (PTCA) has become a safe and effective treatment for coronary artery disease. Increased operator experience and skill and technologic advances have resulted in higher primary success rates and less frequent complications. Nevertheless, restenosis still occurs in 25% to 40% of patients within 6 months after successful treatment, 1 and it is often clinically silent until myocardial perfusion becomes critically reduced, producing unstable angina, myocardial infarction, or sudden death.’ Timely identification of restenosis after PTCA is paramount if these complications are to be avoided. Symptoms do not reliably indicate coronary patency, 3 and the limitations of exercise electrocardiography are magnified in patients with PTCA.4 Stress thallium scintigraphy has also proved disappointing as a screening test for restenosis. 5,6 Exercise echocardiography is a sensitive, specific, and highly accurate test for detecting and localizing compromised myocardial vascular supply in patients being screened for coronary artery disease7-” and those who have undergone coronary artery bypass surgery.‘2,13 The results of exercise echocardiography also correlate closely with angiographic findings before and in the early phase after From the Mid-America Heart Institute and St. Luke’s Hospital, Kansas City, Missouri. Dr Crouse’s address is: Mid-America Cardiology Associates, P.C., 4321 Washington, Suite 4000, Kansas City, Missouri 64 1 1 1. Manuscri t received September 18, 1995; revised manuscript received an cf accepted June 3, 1996.

0 1996 by Excerpto All rights reserved.

Medica,

Inc.

7. Mak KH, Kottke-Marchant K, Brooks LM, Apheart KL, Top01 EJ. Potential value of platelet GPIIblIIla antagonist for treating hepmin-induced thrombocytopenia (HIT) (abstr) J Am Coil Cardiol 1996;27:3 16A. 8. Bauman MA, Mentore JE, Aster RH, Anderson T. Urgent treatment of idiopathic thrombocytopenic purpum with single dose gamma-globulin infusion followed by platelet transfusion. Ann Int Med 1986;104:808-817.

D. Beauchamp,

Patients

MD, and Paul H. Kramer,

MD

PTCA.‘43’5 In this study, we evaluated the use of exercise echocardiography to identify restenosis after PTCA. ... The study population consisted of all PTCA patients who underwent exercise echocardiography during a l-year period and subsequently underwent angiography. At our center, patients undergo serial evaluation of symptomatic status and exercise echocardiography as part of a restenosis surveillance program. In general, evaluations are performed within 10 days of PTCA, at 2 months, at 4 to 6 months, and annually or semiannually thereafter. Angiography is performed at the discretion of the referring physician, usually because of recurrent or persistent symptoms, an abnormal stress electrocardiogram, or an TABLE I Detection

of Angiogrophically Confirmed Restenosis After Angioplasty in 157 Patients: Comparison of Exercise Echocardiography, Exercise Electrocardiography, and Symptomatic Status Predictive Accuracy

Test

Exercise

Sensitivity

Specificity

Positive

Negative

95%

82%

95%

82%

51%

73%

88%

28%

46%

24%

70%

10%

echocardiography Exercise electrocardiography Symptoms

0002.9

149/96/S

PII SOOOZ-9149(96)00583-E

15.00

1163

images can then be displayed in a continuously recycling “tine-loop” format. Next, patients performed maximal, symptom-limited, treadmill exercise using the Bruce or modified Bruce protocol. Immediately after completing exercise, and without a “cooldown” period, patients returned to the examination table and resumed the left lateral decubitus position. As rapidly as possible, echocardiographic images in all 4 views were acquired and recorded as described above. In general, postexercise imaging was completed within 60 seconds after the end of exercise. Imaging was then continued through the remainder of the recovery phase or for 3 minutes if wall motion had returned to normal. All exercise echocardiograms were interpreted by an experienced observer who was not aware of the patient’s symptomatic status or the results of exercise electrocardiography. The digitized images acquired at rest were displayed side by side with those obtained after exercise. The display software allows for the simultaneous display of rest and exercise images in 2 views in a “quad-screen” format. Regional wall motion in each view was described for each segment: anterior, anteroseptal, apical, anterolateral, lateral, posterior, inferoposterior, inferior, and right ventricular. In general, to predict the extent and distribution of coronary stenoses from exercise-induced wall motion abnormalities, the observer was aware of the original coronary anatomy and the site(s) of PTCA. The reason for this is that regional wall motion is interpreted differently depending on whether the corresponding vessel was treated or untreated. In regions perfused by undilated vessels, FIGURE 1. Rest /A, C, E, G/ and postexercise (B, 0, f, /i/ echocardiograms wall motion is defined as normal only if it (end-systolic frames) from a patient with high-grade disease in the left anterior descending and diagonal coronary arteries. Although the patient had a is hypercontractile after exercise. In normal ST-segment response and no s mptoms during treadmill exercise, the regions perfused by vessels subjected to echocardiographic images show that x e anteroseptal and apical walls are PTCA, wall motion is defined as normal if akinetic after exercise. contractile function merely improves with exercise, even if it is not hypercontractile. abnormal exercise echocardiogram. Thus, patients in No patient was excluded from analysis because of this study are a high-risk subgroup of patients who technical difficulty (e.g., poor imaging quality) or because of medications that might interfere with underwent PTCA. Exercise echocardiography was performed as fol- exercise tolerance, such as fl blockers. lows. First, patients were placed in the left lateral Coronary arteriograms were evaluated by expedecubitus position, and resting echocardiographic rienced angiographers who were not involved in inimages were acquired in 4 views (parasternal long- terpreting the exercise echocardiograms. Coronary and short-axis and apical 2- and 4-chamber) with a stenoses were assessedqualitatively and graded ac2.5-MHz transducer and a Hewlett-Packard 500K cording to the estimated percent reduction in vessel echocardiograph and recorded on l/2-inch video- diameter. A stenosis was defined as hemodynamitape. Images were also obtained with a digital system tally significant if it produced ~-50% reduction in (Nova Microsonics PreVue processor) that is trig- vessel diameter. This level was selected because it gered by the electrocardiogram to acquire 8 echo- corresponds to a 75% reduction in cross-sectional cardiographic images at 50-ms intervals during sys- area and because using a higher percentage would tole of a single cardiac cycle. This sequence of result in more false-negative results. 1164

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trocardiography, and symptomatic status, as determined by correlation with the angiographic findings, are summarized in Table I. Exercise echocardiograms obtained before and after PTCA are shown in Figures 1 and 2. Exercise echocardiography correlated well with the angiographic findings. Exercise echocardiograms showed abnormal wall motion in the distribution of the restenosed vessel in 140 of 147 cases (95% sensitivity); the remaining 7 had normal wall motion. In 38 patients without angiographically confirmed restenosis, 31 had normal exercise echocardiograms (82% specificity) ; the remaining 7 had abnormal wall motion in the distribution of the dilated vessel. However, within 1 month after echocardiography, 3 of these 7 patients were hospitalized with unstable angina and underwent angiography, which demonstrated restenosis, and 1 was hospitalized with myocardial infarction due to occlusion of the previously dilated artery. In this high-risk population in which the prevalence of angiographically defined coronary restenosis was 79%, the positive and negative predictive accuracies of exercise echocardiography were 95% and 82%, respectively. Exercise electrocardiography and symptomatic status correlated poorly with the angiographic findings. The exercise electrocardiogram was abnormal in only 73 of 147 patients with restenosis (5 1% sensitivity) ; it was normal in 70 (4 patients with left bundle branch block were excluded from this analysis). Of 38 patients without restenosis, 1 was excluded because of left bundle branch block. The stress electrocardiogram was normal in 27 of the remaining patients (73% specificity). The predictive accuracy of an FIGURE 2. Rest (A, C, E, G) and postexercise (B, D, F, /fj images obtained abnormal exercise electrocardiogram was after percuiuneous transluminal coronary angioplasty in the same patient 88%, but the predictive accuracy of a normal whose images are shown in Figure 1. The patient underwent cathekrizatest was only 28%. The presence or absence tion for recurrent “anginal” symptoms. Catheterization showed only a 10% lesion in the previously dilated vessels (left anterior descending and diagoof angina had a sensitivity of 46% and a nal coronary arteries). specificity of 24%, respectively, for the presence or absence of restenosis. The presence . . . of recurrent angina had a predictive accuracy of The study population consisted of 157 patients, 70%, but the absence of angina had a predictive ac123 men and 34 women, aged 38 to 82 years (mean curacy of only 10% (80 of 89 patients). 59). The interval between PTCA and the last exerIn addition to its ability to identify or rule out cise echocardiogram before follow-up angiography restenosis after PTCA, exercise echocardiography ranged from 1 day to 26 1 weeks (mean 35 weeks). was useful for evaluating nondilated vessels. ExerThe interval between this exercise test and the fol- cise echocardiograms were normal in 17 of 23 palow-up angiogram ranged from 1 day to 9 weeks tients (74%) with <50% angiographic stenosis in (mean 2 weeks). Of the 157 patients, 124 (79%) nondilated vessels and were abnormal in 126 of 134 underwent angioplasty, follow-up exercise echocar- vessels in which angiography showed ~50% stediography, and angiography within a 9-month pe- nosis (sensitivity 94%). ... riod. Angiography showed restenosis in 147 of 185 vessels (79%) in 147 patients; 38 vessels were patAlthough its biology and natural history are varient. The sensitivity, specificity, and predictive ac- able, coronary atherosclerosis generally develops curacy of exercise echocardiography, exercise elec- gradually over an extended period. In contrast, reBRIEF REPORTS 1165

stenosis after PTCA usually occurs rapidly as a result of intimal hyperplasia, in most cases within 6 months.’ If it has not occurred within 1 year, restenosis it is very unlikely to develop. Rapid progression of intimal hyperplasia may explain the brief interval between the first signs of coronary insufficiency (recurrent symptoms, abnormal stress test) after PTCA and critical reductions in myocardial perfusion resulting in unstable angina, myocardial infarction, and sudden death. Close surveillance during the first 6 months after PTCA has been advocated to identify restenosis and allow intervention to forestall its dire consequences. The results of the present study show that exercise echocardiography is an excellent means of achieving this goal. All patients in our study underwent angiography because of abnormal stress test results or recurrent symptoms. Hence, there was a high pretest likelihood of finding restenosis at angiography and, in fact, the restenosis rate was 79%. Such a bias would be expected to augment the positive predictive accuracy of the screening indicators evaluated in the present study. Therefore, it is not surprising that exercise echocardiography, stress electrocardiography, and symptomatic status had positive predictive accuracies of 95%, 88%, and 70%, respectively. However, this same bias would also be expected to reduce the negative predictive accuracy of these indicators, and, indeed, stress electrocardiography and symptomatic status had negative predictive accuracies of only 28% and lo%, respectively. In contrast, exercise echocardiography had a negative predictive accuracy of 82%. These findings suggest that although recurrent angina tends to indicate recurrent disease, the absence of symptoms does not reliably indicate freedom from coronary stenosis. Similarly, stress electrocardiography had limited sensitivity ( 5 1% ) , and normal results correlated poorly with the absence of significant stenosis, which indicates that this test is also poorly suited for surveillance of PTCA patients. This test’s value is further limited by its unreliability in patients with bundle branch block or resting repolarization abnormalities and those taking medications such as ,l?blockers. Routine follow-up of PTCA patients with exercise echocardiography will likely identify hemodynamically significant stenoses even in asymptomatic patients. Because familiarity and proficiency with this technique grow, it will assume a prominent role in the surveillance of patients who have undergone PTCA. Finally, routine use of exercise echocardi-

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ography in this setting is a potentially cost-saving strategy, because it identifies patients without restenosis who might otherwise undergo expensive and invasive angiography to evaluate recurrent symptoms or an abnormal exercise electrocardiogram. Exercise echocardiography is a sensitive, specific, and highly accurate method for detecting restenosis and progressive compromise of untreated arterial segments after PTCA. It is far more reliable in predicting the status of coronary anatomy in such patients than exercise electrocardiography or symptomatic status. 1. Holmes DR, Vlietstra RE, Smith HC, et al. Restenosis after percutaneous transluminal coronary angioplasty: a report from the PTCA registry of the National Heart, Lung, and Blood Institute. Am J Cardiol 1988;53:77C-81C. 2. Simonton CA, Mark DB, Hinohara T, Rendall DS, Phillips HR, Peter RH, Behar VS, Kong Y, O’Callaghan WG, O’Connor C. Late restenosis following emergent coronary angioplasty for acute myocardial infarction: comparison with elective coronary angioplasty. JAm Co11 Cardiol 1988;11:698-705. 3. Gmentzig AR, King SB III, Schlumpt M, Siegenthaler W. Long-term followup after percutaneous transluminal coronary angioplasty: the early Zurich experience. NEngl JMed 1987;316:1127-1132. 4. Bengtson JR, Mark DB, Honan JE, Rendall DS, Hinohara T, Stack RS, Hlatky MA, Califf RM, Lee KL, Pryor DB. Detection of restenosis after elective percutaneous transluminal coronary angioplasty using the exercise treadmill test. Am .I Cardiol 1990;65:28-34. 5. Breiblatt WM, W&land FL, Spaccavento LJ. Stress thallium-201 imaging after coronary angioplasty predicts restenosis and recurrent symptoms. J Am Coil Cardiol 1988;12:1199-1204. 6. Manyti DE, Knudtson M, Kloiber R, Roth D. Sequential thallium-201 myocardial perfusion studies after successful percutaneous transluminal coronary angioplasty: delayed resolution of exercise-induced scintigraphic abnormalities. Circulation 1988;77:86-95. 7. Armstrong WF, O’Donnell J, Dillon JC, McHetuy PL, Morris SN, Feigenhaum H. Complementary value of two-dimensional exercise echocardiography to routine treadmill exercise testing. Ann Intern Med 1986;105:829-835. 8. Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O’Donnell J, McHenry PW. Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease. JAm Co11 Cardiol 1983;2: 1085- 1091. 9. Armstrong WF, O’Donnell J, Ryan T, Feigenbaum H. Effect of prior myocardial infarction and extent and location of coronary disease on accuracy of exercise echocardiography. JAm Co0 Cardiol 1987;10:531-538. 10. Ryan T, Vasey CG, Presti CF, O’Donnell JA, Feigenbaum H, Armstrong WF. Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest. J Am Coil Cardiol 1988;11:993-999. 11. Grouse L, Harbrecht JJ, Vacek JL, Rosamond TL, Kramer PH. Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography. Am J Cardiol 1991;67:1213-1218. 12. Grouse LJ, Vacek IL, Beauchamp GD, Porter CB, Rosamond TL, Kramer PH. Exercise echocardiography after coronary artery bypass grafting. Am J Cardiol 1992;70:572-576. 13. Presti CF, Armstrong WF, Feigenbaum. Comparison of echocardiography at peak exercise and after bicycle exercise in evaluation of patients with known or suspected coronary artery disease. JAm Sac Echo 1988;1:119-126. 14. Broderick T, Sawada SG, Armstrong WF, Ryan T, Dillon JC, Bourdillon PDV, Feigenbaum H. Improvement in rest and exercise-induced wall motion abnormalities after coronary angioplasty: an exercise echocardiographic study. J Am Cdl Curdiol 1990;15:591-599. 15. Labovitz AJ, Lewen M, Kern MJ, Vandormael M, Mmsek DC, Byers SL, Pearson AC, Chaitman BR. The effects of successful mCA on left ventricular function: assessment by exercise echocardiography. Am Heart J 1989;117:1003-1008.

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