lectrocardiographic dictive of Successf Peter Clemmensen, MB, E. agnus Ohman, MB, Dorina C. Sevilia, MD, Steve peck, MS, Nancy B. Wagner, BA, Peter S. Quigley, MB, Peer Grande, MD, PhD, Kerry L. Lee, PhD, and Galen S. Wagner, MD
The ability of the electrocardiographic ST segment to predict successful reperfusion after thrombolytic therapy remains controversial. To evaluate whether angiographically determined reperfusion could be predicted from changes in ST-segment elevation, the sum of ST-segment elevation in affected leads of the electrocardiogram was compared before and after thrombolytic therapy in 53 patients with acute myocardial infarction (AMI). Reperfusion status of the infarct-related artery was determined angiographically -2 mm resolution in ST elevation or depression and 13 mm reduction in T-wave height without considering the patients’ baseline ST-T changes.Also, this study might have included patients Representative
Infarct Location
Leads
with silent coronary reocclusion since patency was determined up to 10 days after thrombolysis. Krucoff et allo found that achievement of a stable ST segment within 100 minutes after completed streptokinaseinfusion was 89% sensitive and 82% specific for the detection of reperfusion. However, their method was based on 3-lead Holter monitoring which is not routinely available and detection of steady state requires continued ST-segment measurementduring a 24- to 48-hour period. Hogg and co-workers,sobservingthe maximally deviated lead on the standard 1Zlead electrocardiogram, found that a 50% reduction in ST elevation was 67% specific and 93% sensitivefor infarct artery patency. However, the test population was small (n = 17) with only 3 patients having occluded coronary arteries. Part of the controversy on the ST segment as an indicator of reperfusion might result from methodologic differences between the studies, and the fact that the number of electrocardiographic leads considered in these studies rarely exceeded3. It has been shown that quantification of the ST elevation in all affectedelectrocardiographic leads during acute coronary occlusion correlates with both development of new wall motion abnormalities and the final AM1 size in nonreperfused patients.15-17Thus, considering all affected electrocardiographic leads should theoretically prove superior to single lead analysis. For this purpose, continuous ST-segment monitoring has recently becomeclinically available through microprocessor-drivenreal-time 12lead electrocardiographs.19 By describing the entire spectra of sensitivities and specificities, the present study demonstrateshow the electrocardiogram as a noninvasive marker of reperfusion is vulnerable to the arbitrary or qualitative “cutoff’ values of ST-segment shift used in previous studSum of ST Elevation
Smm Inferior 2.5 mm (50% decrease)
Before
7mm
After
4 mm
anterior
(43% decrease)
1410
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
FIGURE 3. Example of study patients with inferior (fop) and anterior (below) infarct k&ion. The leads with the maximal STsegment change (II, Ill and aVF for inferior and VI, V2 and Vs for anterior) are presented from before thrombolytic therapy (before) and at the time of initial coronary angiography (after). The measurements at right refer to the sum of ST elevation in those leads.
ies9J1J2J8Clinical use of the results of the present study might be expected to produce the following outcome.Of 100 patients treated with a thrombolytic agent associatedwith an 80% reperfusion rate, 26 patients would be recommendedfor emergent cardiac catheterization, basedon the predictive values found in the present study. Of the 26 patients, 16 nonreperfused patients would be correctly identified, but the angiography would reveal that reperfusion had already occurred in the other 10. Only 4 patients without reperfusion would be falsely considered as reperfused, and thus miss the opportunity of a rescue procedure, whereas 70 patients would have a correct noninvasive diagnosis of reperfusion. Other investigators have evaluated enzymatic methods as markers of reperfusion, particularly creatine kinase,its isoenzymesand isoforms, but a clinically useful algorithm based on these serum markers has not yet been developed.20-22 The current limitations of these methods include lack of rapid analytic techniques and standardized techniques between laboratories. Unlike the standard electrocardiogram, the analytic kits for determining cardiac enzymes varies between institutions, and therefore “methods” for detection of reperfusion established in one laboratory may not agree with others. However, it is possible that combinations of electrocardiographic and serum markers of reperfusion may prove superior to either method used alone. Acknowledgment: We are indebted to housestaff, technicians, cardiology fellows and attending physicians in the interventional catheterization laboratory at Duke University, and to Belinda Barrett and Sylvester Cherry for preparation of the manuscript.
EFERENCES
1. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded?Circulation 1989;19:414-444. 2. Van EssenR, Mcrx W, Effert S. Spontaneouscourseof ST-segmentelevation in acute anterior myocardial infarction. Circulation 1979$9:105-l 12. 3. Muller JE, Maroko PR, Braunwald E. Evaluation of precordial electrocardiographic mapping as a meansof assessingchangesin myocardial ischemic injury. Circulation 1975;52:16-27. 4. Maroko PR, Libby P, Covell JW, Sobel BE, RossJ, Braunwald E. Prccordial ST segmentelevation mapping:an atraumatic methodfor assessingalterations in the extent of myocardial ischemic injury. Am d Cardiol 1972;29:223-230. 5. BlankeH, Scherff F, Karsch KR, Levine RA, Smith H, Rentrop P. Electrocardiographic changesafter streptokinasc induced recanalization in patients with acute left anterior descendingartery obstruction. Circulation 1983;68:406-412. 6. Von EssenR, Schmidt W, Uebis R, Edelmann B, Effert S, Silny J, Rau G. Myocardial infarction and thrombolysis. Electrocardiographic short term and long term results using prccordial mapping. Br Heart J 1985;54&10. 7. Hackworthy RA, SorensenSG, Fitzpatrick PG, Barry WH, Menlove RL, Rothbard RL, Anderson JL. Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of randomized multiccnter study of intravenous anisoylatedplasminogenstreptokinaseactivator complex (APSAC) versus intracoronary streptokinase in acute myccardial infarction. Am Heart J 1988;116: 903-913. . AndersonJL, Marshall HW, Askins JC, Lutz JR, SorensenSG, Menlove RL, Yanowitz FG, Hagan AD. A randomizedtrial of intravenousand intracoronary streptokinasein patients with acute myocardial infarction. Circulation 1984;
70:606-618.
9. Hogg KJ, Hornung RS, Howic CA, Hocking N, Dunn FG, Hillis WS. Electrocardiographic prediction of coronary artery patency after thrombolytic treatment in acute myocardial infarction: use of the ST-segmentas non-invasive marker. Br Heart J 1988;60:27S-280. 10. Krucoff MW, Green CE, Satler LF, Miller FC, Pallas RS, Kent KM, Del Negro M, Pearle DL, Fletcher RD, Rackley CE. Noninvasive detection of coronary artery patency using continuous ST-segmentmonitoring. Am J Cardiol 1986;57:916-922. 11. Richardson Xi, Morton P, Murtagh JG, Scott ME, O’Keeffe B. Relation of coronary arterial patency and left ventricular function to electrocardiographic changesafter streptokinasetreatment during acute myocardial infarction. Am J Cardiol 1988;61:961-965. 12. Califf RM, O’Neil W, Stack RS, Aronson L, Mark DB, Mantel1 S, George BS, Candela RJ, Kereiakes DJ, Abbottsmith C, Top01EJ and the TAM1 Study Group. Failure of simple clinical measurementsto predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988;108:658-662. 13. The TIMI Study Group: The Thrombolysis in Myocardial Infarction (TIMI) Trial. N Engl J Med 1985;312:932-936. 14. Yusuf S, Lopez R, Maddison A, Maw P, Ray N, McMillian S, Sleight P. Value of electrocardiogram in predicting and estimating infarct size in man. Br Heart J 1979;42:286-293.
II. Aldrich HR, Wagner NB, Boswick J, Corsa A, JonesMG, Grande P, Lee KL, Wagner GS. Use of initial ST-segment deviation for prediction of final electrocardiographic size of acute myocardial infarcts. Am J Cardiol 1988; 61:749-753.
16. ClemmensenP, Grande P, Wagner NB, Aldrich HR, Wagner GS. The evaluation of formulas for estimating the final size of acute myocardial infarcts from quantitative ST segmentelevation on the initial standard 12 lead ECG. J Electrocardiol 1991;24:inpress. 17. Cohen M, Scharpf SJ, Rentrop KP. Prospective analysis of electrocardiographic variables as markers for extent and location of acute wall motion abnormalities observed during coronary angioplasty in human subjects. J Am Coil Cardiol 1987;10:17-24. 18. Kircher BJ, Top01EJ, O’Neil WW, Pitt B. Prediction of infarct coronary artery recanalization after intravenous thrombolytic therapy. Am J Cardiol 1987;59:513-515. 19. KrucoCf MW, Wagner NB, Pope JE, Mortara DM, Jackson YR, Bottner RK, Wagner GS, Kent KM. The portable programmable microprocessor-driven real-time ll-lead electrocardiographic monitor: a preliminary report of a new device for the non-invasivedetection of successfulrcperfusion or silent coronary reocclusion. Am .I Cardiol 1990;65:143-148. 20. Jaffe AS, Serota H, Grace A, Sobel BE. Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction. Circulatim 1986;74:105-109. 21. ChristensonRH, Ohman EM, ClemmensenP, Grande P, Toffaletti J, Silverman LM, Vollmer RT, Wagner GS. Characteristics of creatine kinase-MB and MB isoforms in serum after reperfusion in acute myocardial infarction. Clin Chem 1989;35:2179-2218. 22. Garabedian HD, Gold HK, Yasuda T, JohnsJA, Finkelstein DM, Gaivin RJ, Cobbaert C, Leinbach RC, Collen D. Detection of coronary artery reperfusion with creatine kinase-MB determination during thrombolytic therapy: correlation with acute angiography. J Am CON Cardiol 1988;11:729-734.
PPENDIX Method for calculating sensitivity, specificity and predictive values of the ST segment for identification of patients with reperfusion of the infarct-related artery. SENSITIVITY = number of patients with reperfusion and percent ST change criteria present/number of patients with reperfusion. SPECIFICITY = number of patients without reperfusion and without percent ST change criteria present/number of patients without reperfusion. POSITIVEPREDICTIVEVALUE r= number of patients with reperfusion and percent ST change criteria present/number of patients with percent ST change criteria present. NEGATIVE PREDICTIVEVALUE = number Of patients without reperfusion and without percent ST change criteria present/ number of patients without percent ST change criteria present.
THE AMERICAI\J JOURNAL OF CARDIOLOGY
DECEMBER 95, 1990
The ability of the electrocardiographic ST segment to predict successful reperfusion after thrombolytic therapy remains controversial. To evaluate whether angiographically determined reperfusion could be predicted from changes in ST-segment elevation, the sum of ST-segment elevation in affected leads of the electrocardiogram was compared before and after thrombolytic therapy in 53 patients with acute myocardial infarction (AMI). Reperfusion status of the infarct-related artery was determined angiographically -2 mm resolution in ST elevation or depression and 13 mm reduction in T-wave height without considering the patients’ baseline ST-T changes.Also, this study might have included patients Representative
Infarct Location
Leads
with silent coronary reocclusion since patency was determined up to 10 days after thrombolysis. Krucoff et allo found that achievement of a stable ST segment within 100 minutes after completed streptokinaseinfusion was 89% sensitive and 82% specific for the detection of reperfusion. However, their method was based on 3-lead Holter monitoring which is not routinely available and detection of steady state requires continued ST-segment measurementduring a 24- to 48-hour period. Hogg and co-workers,sobservingthe maximally deviated lead on the standard 1Zlead electrocardiogram, found that a 50% reduction in ST elevation was 67% specific and 93% sensitivefor infarct artery patency. However, the test population was small (n = 17) with only 3 patients having occluded coronary arteries. Part of the controversy on the ST segment as an indicator of reperfusion might result from methodologic differences between the studies, and the fact that the number of electrocardiographic leads considered in these studies rarely exceeded3. It has been shown that quantification of the ST elevation in all affectedelectrocardiographic leads during acute coronary occlusion correlates with both development of new wall motion abnormalities and the final AM1 size in nonreperfused patients.15-17Thus, considering all affected electrocardiographic leads should theoretically prove superior to single lead analysis. For this purpose, continuous ST-segment monitoring has recently becomeclinically available through microprocessor-drivenreal-time 12lead electrocardiographs.19 By describing the entire spectra of sensitivities and specificities, the present study demonstrateshow the electrocardiogram as a noninvasive marker of reperfusion is vulnerable to the arbitrary or qualitative “cutoff’ values of ST-segment shift used in previous studSum of ST Elevation
Smm Inferior 2.5 mm (50% decrease)
Before
7mm
After
4 mm
anterior
(43% decrease)
1410
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
FIGURE 3. Example of study patients with inferior (fop) and anterior (below) infarct k&ion. The leads with the maximal STsegment change (II, Ill and aVF for inferior and VI, V2 and Vs for anterior) are presented from before thrombolytic therapy (before) and at the time of initial coronary angiography (after). The measurements at right refer to the sum of ST elevation in those leads.
ies9J1J2J8Clinical use of the results of the present study might be expected to produce the following outcome.Of 100 patients treated with a thrombolytic agent associatedwith an 80% reperfusion rate, 26 patients would be recommendedfor emergent cardiac catheterization, basedon the predictive values found in the present study. Of the 26 patients, 16 nonreperfused patients would be correctly identified, but the angiography would reveal that reperfusion had already occurred in the other 10. Only 4 patients without reperfusion would be falsely considered as reperfused, and thus miss the opportunity of a rescue procedure, whereas 70 patients would have a correct noninvasive diagnosis of reperfusion. Other investigators have evaluated enzymatic methods as markers of reperfusion, particularly creatine kinase,its isoenzymesand isoforms, but a clinically useful algorithm based on these serum markers has not yet been developed.20-22 The current limitations of these methods include lack of rapid analytic techniques and standardized techniques between laboratories. Unlike the standard electrocardiogram, the analytic kits for determining cardiac enzymes varies between institutions, and therefore “methods” for detection of reperfusion established in one laboratory may not agree with others. However, it is possible that combinations of electrocardiographic and serum markers of reperfusion may prove superior to either method used alone. Acknowledgment: We are indebted to housestaff, technicians, cardiology fellows and attending physicians in the interventional catheterization laboratory at Duke University, and to Belinda Barrett and Sylvester Cherry for preparation of the manuscript.
EFERENCES
1. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded?Circulation 1989;19:414-444. 2. Van EssenR, Mcrx W, Effert S. Spontaneouscourseof ST-segmentelevation in acute anterior myocardial infarction. Circulation 1979$9:105-l 12. 3. Muller JE, Maroko PR, Braunwald E. Evaluation of precordial electrocardiographic mapping as a meansof assessingchangesin myocardial ischemic injury. Circulation 1975;52:16-27. 4. Maroko PR, Libby P, Covell JW, Sobel BE, RossJ, Braunwald E. Prccordial ST segmentelevation mapping:an atraumatic methodfor assessingalterations in the extent of myocardial ischemic injury. Am d Cardiol 1972;29:223-230. 5. BlankeH, Scherff F, Karsch KR, Levine RA, Smith H, Rentrop P. Electrocardiographic changesafter streptokinasc induced recanalization in patients with acute left anterior descendingartery obstruction. Circulation 1983;68:406-412. 6. Von EssenR, Schmidt W, Uebis R, Edelmann B, Effert S, Silny J, Rau G. Myocardial infarction and thrombolysis. Electrocardiographic short term and long term results using prccordial mapping. Br Heart J 1985;54&10. 7. Hackworthy RA, SorensenSG, Fitzpatrick PG, Barry WH, Menlove RL, Rothbard RL, Anderson JL. Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of randomized multiccnter study of intravenous anisoylatedplasminogenstreptokinaseactivator complex (APSAC) versus intracoronary streptokinase in acute myccardial infarction. Am Heart J 1988;116: 903-913. . AndersonJL, Marshall HW, Askins JC, Lutz JR, SorensenSG, Menlove RL, Yanowitz FG, Hagan AD. A randomizedtrial of intravenousand intracoronary streptokinasein patients with acute myocardial infarction. Circulation 1984;
70:606-618.
9. Hogg KJ, Hornung RS, Howic CA, Hocking N, Dunn FG, Hillis WS. Electrocardiographic prediction of coronary artery patency after thrombolytic treatment in acute myocardial infarction: use of the ST-segmentas non-invasive marker. Br Heart J 1988;60:27S-280. 10. Krucoff MW, Green CE, Satler LF, Miller FC, Pallas RS, Kent KM, Del Negro M, Pearle DL, Fletcher RD, Rackley CE. Noninvasive detection of coronary artery patency using continuous ST-segmentmonitoring. Am J Cardiol 1986;57:916-922. 11. Richardson Xi, Morton P, Murtagh JG, Scott ME, O’Keeffe B. Relation of coronary arterial patency and left ventricular function to electrocardiographic changesafter streptokinasetreatment during acute myocardial infarction. Am J Cardiol 1988;61:961-965. 12. Califf RM, O’Neil W, Stack RS, Aronson L, Mark DB, Mantel1 S, George BS, Candela RJ, Kereiakes DJ, Abbottsmith C, Top01EJ and the TAM1 Study Group. Failure of simple clinical measurementsto predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988;108:658-662. 13. The TIMI Study Group: The Thrombolysis in Myocardial Infarction (TIMI) Trial. N Engl J Med 1985;312:932-936. 14. Yusuf S, Lopez R, Maddison A, Maw P, Ray N, McMillian S, Sleight P. Value of electrocardiogram in predicting and estimating infarct size in man. Br Heart J 1979;42:286-293.
II. Aldrich HR, Wagner NB, Boswick J, Corsa A, JonesMG, Grande P, Lee KL, Wagner GS. Use of initial ST-segment deviation for prediction of final electrocardiographic size of acute myocardial infarcts. Am J Cardiol 1988; 61:749-753.
16. ClemmensenP, Grande P, Wagner NB, Aldrich HR, Wagner GS. The evaluation of formulas for estimating the final size of acute myocardial infarcts from quantitative ST segmentelevation on the initial standard 12 lead ECG. J Electrocardiol 1991;24:inpress. 17. Cohen M, Scharpf SJ, Rentrop KP. Prospective analysis of electrocardiographic variables as markers for extent and location of acute wall motion abnormalities observed during coronary angioplasty in human subjects. J Am Coil Cardiol 1987;10:17-24. 18. Kircher BJ, Top01EJ, O’Neil WW, Pitt B. Prediction of infarct coronary artery recanalization after intravenous thrombolytic therapy. Am J Cardiol 1987;59:513-515. 19. KrucoCf MW, Wagner NB, Pope JE, Mortara DM, Jackson YR, Bottner RK, Wagner GS, Kent KM. The portable programmable microprocessor-driven real-time ll-lead electrocardiographic monitor: a preliminary report of a new device for the non-invasivedetection of successfulrcperfusion or silent coronary reocclusion. Am .I Cardiol 1990;65:143-148. 20. Jaffe AS, Serota H, Grace A, Sobel BE. Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction. Circulatim 1986;74:105-109. 21. ChristensonRH, Ohman EM, ClemmensenP, Grande P, Toffaletti J, Silverman LM, Vollmer RT, Wagner GS. Characteristics of creatine kinase-MB and MB isoforms in serum after reperfusion in acute myocardial infarction. Clin Chem 1989;35:2179-2218. 22. Garabedian HD, Gold HK, Yasuda T, JohnsJA, Finkelstein DM, Gaivin RJ, Cobbaert C, Leinbach RC, Collen D. Detection of coronary artery reperfusion with creatine kinase-MB determination during thrombolytic therapy: correlation with acute angiography. J Am CON Cardiol 1988;11:729-734.
PPENDIX Method for calculating sensitivity, specificity and predictive values of the ST segment for identification of patients with reperfusion of the infarct-related artery. SENSITIVITY = number of patients with reperfusion and percent ST change criteria present/number of patients with reperfusion. SPECIFICITY = number of patients without reperfusion and without percent ST change criteria present/number of patients without reperfusion. POSITIVEPREDICTIVEVALUE r= number of patients with reperfusion and percent ST change criteria present/number of patients with percent ST change criteria present. NEGATIVE PREDICTIVEVALUE = number Of patients without reperfusion and without percent ST change criteria present/ number of patients without percent ST change criteria present.
THE AMERICAI\J JOURNAL OF CARDIOLOGY
DECEMBER 95, 1990
