- Email: [email protected]
Diagnosis and management of acute myocardial infarction
Diagnosis and management myocardial infarction
of acute
Mario S. Verani, MD, FACC,FACP Nuclear cardiology offers techniques for assessing cardiac perfusion and function that provide useful information for diagnosing and managing acute myocardial infarction (MI). In particular, myocardial perfusion imaging provides important data on infarct size and myocardial viability that can help determine the best treatment strategies for patients with acute MI. First-pass or blood pool radionuclide angiographic assessment of ventricular ejection fraction remains an important prognostic indicator in acute MI, regardless of whether thrombolytic therapy is used. Comparative studies of radiotracer techniques and coronary angiography show that myocardial perfusion and ejection fraction can predict the risk of future cardiac events reliably in patients with acute MI, whereas the anatomic data provided by coronary angiography (e.g., degree of stenosis and presence of multivessel disease) have little prognostic value. Managed-care organizations could reduce costs and improve patient outcomes by relying more on nuclear cardiology and less on angiography in the management of patients with acute MI. (J Nucl Cardiol 1997;4:S158-63.) risk stratification * perfusion scintigraphy - ejection Key Words: acute myocardial infarction fraction * adenosine l
It is generally agreed that patients with acute myocardial infarction (MI) need to be evaluated with respect to their risk of developing cardiac events after they are discharged home. What is not agreed on is how best to use our resources to achieve this evaluation. The goal is straightforward: first, we want to identify patients who are in good condition and who have a very small risk for future events-these patients should be managed conservatively; second, we want to identify patients who may also be in apparent good condition but who are at increased risk for further cardiovascular events and who should be evaluated invasively and undergo myocardial revascularization. Role of Nuclear Cardiology
in Acute MI
In patients who have an acute MI, nuclear cardiology can help to evaluate at least five parameters: 1. Acute myocardial necrosis 2. Infarct size 3. Myocardium that may be salvaged by thrombolytic therapy or angioplasty 4. Myocardial ischemia 5. Left ventricular and right ventricular ejection fraction From the Section of Cardiology, Baylor College of Medicine and the Methodist Hospital, Houston, Texas. Presented at the Forty-fourth Annual Meeting of the American College of Cardiology, Orlando, Fla., March 23, 1996. Reprint requests: Mario S. Verani, MD, Section of Cardiology, the Methodist Hospital, Baylor College of Medicine, 6550 Fannin, SM-677, Houston, TX 77030. Copyright 0 1997 by American Society of Nuclear Cardiology. 1071-3581/97/$5.00 + 0 43/O/79776 S158
The first four parameters are obtained by myocardial perfusion imaging with single-photon emission computed tomography (SPECT). Ejection fraction measurements, which are obtained by first-pass or blood pool radionuclide angiography, are of major importance, and are probably underused, in the management of acute MI. All five items, even infarct size, comprise useful assessments for the management of acute MI, primarily because they help cardiologists determine appropriate treatment and serve as prognostic indicators for a patient’s risk of future cardiac events. Nuclear cardiology, therefore, plays a major role in the risk stratification of patients with acute MI. Risk Stratification
in the Prethrombolytic
Era
A review by Brown’ summarizes most of the data known about myocardial perfusion imaging for risk stratifying patients with acute MI. Indicators of high risk for future cardiac events, after an MI, include: Presence of transient (reversible) perfusion defects, which reflect myocardial viability Number of perfusion defects Extent of fixed perfusion defects, which reflects infarct size Increased lung uptake of “‘Tl In addition, the LVEF emerged as a powerful determinant of prognosis, with a reduced value imparting a high risk for cardiac death and a normal or slightly depressed level indicating a good survival rate2 (Figure 1).
Verani Diagnosis and management of acute MI
Journal of Nuclear Cardiology Volume 4, Number 2;S158-63
Although many patients undergo cardiac catheterization after MI, studies show that coronary angiography in general provides no additional prognostic advantage over myocardial perfusion imaging.‘%3,4 As health-care delivery moves toward a managed-care structure, significant cost savings could be realized if one could reduce the number of unnecessary cardiac catheterizations in patients with acute MI. Diagnosis
of Car&c
Necrosis
Traditionally, g9mTc-labeled pyrophosphate was used to determine cardiac necrosis.s Today, physicians use g9”Tc-labeled pyrophosphate only in rare cases, such as when patients are seen late (when enzymes have returned to normal levels) or in patients with left bundle branch block that may preclude the diagnosis of acute MI. l1 ‘In-labeled antimyosin, a radiolabeled antibody, has been tested in several medical centers to image infarct size.5z7It has recently been cleared for commercial availability by the US Food and Drug Administration. Neither one of these agents, however, provides early diagnosis of infarction. A newer radiotracer, 99mT~labeled glucarate, may allow for earlier imaging of infarct size, but more studies need to be conducted to confirm this point. Infarct Sizing We studied 99”Tc-labeled sestamibi (Cardiolite; DuPont, Wilmington, Del.) for evaluation of infarct size in a canine modeL8 After creating infarctions with coronary ligation, the size of radiotracer defects on 99”Tc-labeled sestamibi SPECT images was compared with pathologic infarct size determined by triphenyltetrazolium chloride staining. As Figure 2 indicates, the measurements were comparable, with a good correlation between SPECT and pathologic infarct size. Clearly, it is possible to measure infarct size with SPECT. Surgicaiiy Removed Human Hearts Verify Radiotracer Assessments Patients undergoing heart transplantation provide a unique opportunity to compare actual infarct size with that determined by radiotracer techniques. Our laboratory recently performed a study in which patients about to undergo heart transplantation were injected with 99”Tc-labeled sestamibi before surgery.9 When the hearts were removed, they were imaged by SPECT, as well as by planar imaging of the individual heart slices, after the heart had been sectioned by the pathologist. The linear correlation (Figure 3) between results of radiotracer imaging and pathology findings (measure-
s159
50 z? .L 5
2
40
z
N=799 Mean EF=46%
.g 30 E 5 t;j 20 P c 0 b
10
0
0 15 0 Radionuclide N-0 21
30 45 60 75 Ejection Fraction (%) 244 382 152
Figure 1. One-year cardiac mortality rates after MI in Multicenter Postinfarction Research Group Study. Strong relationship between ejection fraction (EF) and mortality rate can be appreciated. Prognosis is especially poor for ejection fractions of less than 30%. Approximately two thirds of all patients have ejection fractions of 45% or greater and thus have very low l-year mortality rates (<5%). (Reprinted by permission of The New England Journal of Medicine from The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331-6. Copyright 1983, Massachusetts Medical Society.)
ment of infarcted or fibrotic tissues) provided tangible evidence of nuclear cardiology’s capability to measure the extent of myocardial scarring, or infarct size. With respect to viable myocardium, the surgically removed hearts also showed good agreement between results of 99”Tc-labeled sestamibi and pathologic findings, in that a high degree of correlation was found between the level of 99mT~ in the myocardium and the amount of viable myocardium in the samples examined. Management: Risk Stratification Postthromboiytic Era
in the
It has been suggested that the nuclear cardiology parameters that were so powerful for risk stratification in the prethrombolytic era may no longer apply to patients managed in the postthrombolytic era. I disagree with this idea, on the basis of the evidence discussed below. LVEFZStill an Important Prognostic Indicator in the Thromboiytic Era. In the “prethrombolytic era,” LVEF was clearly a major factor in determining prognosis. Today, when many patients receive emergency
S160
Verani Diagnosis and management of acute MI
3-
Journal of Nuclear Cardiology March/April 1997, Part 2
4
p=NS I
I
T p=NS I
1 Sclnti-
o-
Sclntigraphic (Planar)
Scintigraphic (Torn01
Oceluded Bed
Pathologic (TTC)
-
0
20 40 Pathologic Size (TTC) % LV
Figure 2. Comparison of planar scintigraphic perfusion defect size and occluded vascular bed size (left panel) and tomographic (Tomo) and pathologic infarct sizes (middle and right panels) in 13 dogs with permanent coronary occlusion. (LV, left ventricle; TTC = triphenyltetrazolium chloride; NS, not significant; SEE, standard error of estimate.) (Reprinted with permission from American College of Cardiology. Verani MS et al. J Am Co11 Cardiol 1988;12:1573-81.) 70
. /
60
.
.
l * .
.
.
t
/ .
. . . Y=6.45 + 0.96X FO.88, p~o.001
/ 0 0
10
20
30
40
50
60
70
% SCAR BY PATHOLOGY Figure 3. Linear regression analysis between tomographic defect size and pathologic scar size. (Reproduced with permission from Medrano R et al. Circulation 1996;94:1010-7. Copyright 1996, American Heart Association.)
thrombolytic how
therapy and undergo acute angioplasty,
does LVEF
fare as a risk factor?
Compared
with
patients we evaluated 10 to 15 years ago, patients with acute MI today tend to be younger, to have had fewer
prior infarctions, and to have a “more preserved” LVEF, especially if they participated in one of the landmark multicenter clinical trials that evaluated thrombolytic therapy such as the Thrombolysis in Acute Myocardial InfarctionlO and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trials. l l For patients in the second Thrombolysis in Acute Myocardial Infarction Trial, the average LVEF was greater than 50%. lo Similarly, in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial, the average LVEF for all patients was greater than 50%. On that basis alone, one would expect that these study populations comprised low-risk patients, with a higher rate of single-vessel disease, a higher frequency of early invasive evaluation (catheterization) and revascularization, a lower mortality rate, a lower rate of future cardiac events, and better health in general. With today’s typical lower-risk patient type, one might expect to find it more difficult than in the past to identify which patients are at risk for future cardiac events. Several studies have investigated this issue, particularly as it relates to LVEF. From a multicenter study done in The Netherlands, Simoons et a1.12 collected data on three parametersLVEF, residual stenosis in the infarct-related artery, and number of stenosed arteries (i.e., one-vessel vs multives-
Veraui Diagnosis and management of acute MI
Journal of Nuclear Cardiology Volume 4, Number 2;S158-63
S161
60 50 40 30 20 10 0 +
+
+
+
-
-
-
-
lvef < 40%
+
+
-
-
+
+
-
-
irv
> 90%
+
-
+
-
+
-
+
+
vd
2-3
Figure 4. Five-year mortality Institute of The Netherlands, in 40%, stenosis greater than 90% (Reprinted with permission from Cardiol 1989;14:1609-15.)
rates after thrombolytic therapy in Interuniversity Cardiology relation to presence (+) or absence (-) of LVEF (Iv& less than in infarct-related vessel (irv), or two- or three-vessel disease (vd). the American College of Cardiology. Simoons ML et al. J Am Co11
se1 disease)-in 422 patients who had received thrombolytic therapy (intracoronary or intravenous) for acute MI (Figure 4). Of those three parameters, LVEF clearly emerged as the most important. Patients with an LVEF of less than 40% were at high risk (>20%) for future cardiac events. When the LVEF was greater than 40%, even patients with greater than 90% residual stenosis and two- or three-vessel disease were at fairly low risk ( 12% of the left ventricle) had significantly higher (7%) mortality rates (p < 0.001). We have recently found that the total perfusion defect size (i.e., the total extent of infarct and stressinduced ischemia), obtained from an exercise *‘IT1 SPECT study 7 to 10 days after MI, can serve as a reliable prognostic indicator.15 In this study, all patients underwent thrombolytic therapy, exercise “lT1 SPECT,
and coronary angiography. The data indicated that when perfusion defects were less than 20% of the left ventricle, the event-free survival rate was very high. On the other hand, patients with perfusion defects of greater than 20% of the left ventricle had a much higher rate of cardiac events. In this study, other factors were also predictive. The presence or absence of ischemia made a statistically significant difference @ < O.Ol)in future event rates. In addition, patients with an LVEF of greater than 40% were at lower risk than patients with an LVEF of less than 40%. Mahmarian et a1.4 used adenosine ‘OIT1 SPECT in 146 patients 2 to 5 days after MI. About half of these patients were treated with thrombolytic agents. The study eliminated patients who underwent early revascularization (in response to multiple or large perfusion defects or a high degree of ischemia). The remaining 92 patients were followed up for 2 years.r6 Approximately one third of these patients had additional events, such as unstable angina, nonfatal recurrent MI, congestive heart failure, and cardiac death. One of the main determinants of post-MI prognosis was the total perfusion defect size. Patients with defect sizes of less than 20% of the left ventricle were at lower risk for events than were those with larger infarcts. Whether patients underwent thrombolytic therapy made no difference in the prognostic capacity of this simple parameter. By combining two parameters, LVEF and size of the ischemia (i.e., reversible perfusion defect size in the left
Verani Diagnosis and management of acute MI
“0 ~
10
20
30
Journal of Nuclear Cardiology March/April 1997, Part 2
40
TOTAL ISCHEMIA
50
(%LV)
ventricle), we were able to assign fairly accurate risk predictions. For example, a patient with a very poor LVEF (about 20%) and a significant amount of ischemia (20% to 30% of the left ventricle) had a 75% probability of having a future cardiac event (Figure 5). Conversely, a patient with a normal LVEF and minimal or no ischemia had a very low probability of a future cardiac event (
0
40
20
60
60
-INFARCT ZONE ISCHEMIA
100
(%)
and Conclusion
Nuclear cardiology studies are useful for both the diagnosis and management of acute MI. With respect to risk stratification, radiotracer techniques provide several prognostic indicators of a patient’s risk for future cardiac events. No justification exists, from studies in the literature, for routine coronary angiography in patients with uncomplicated acute MI. Cardiologists seem to underuse nuclear studies in the management of patients with acute MI, whereas an excess of these patients routinely undergo coronary angiography in the absence of solid indications. Many patients with acute MI are categorized as low risk by nuclear cardiology techniques. They could be treated medically with good outcomes, and the healthcare system could save a sizable sum of money by avoiding unnecessary catheterizations and revascularizations in patients at such low risk.
References
“0
C
10
20
30
TOTAL ISCHEMIA
40
50
(%LV)
Figure 5. Cox regression models display l-year risk for cardiac event according to LVEF (LV ejection fraction) and total left ventricular ischemia (A) or scintigraphic variables (B). Regression model for predicting infarct-free survival is displayed (C). Diagonal lines = representative isobars of percent risk. Patient risk for any cardiac event (A), or specifically death and nonfatal reinfarction (C), increases as total left ventricular ischemia increases and LVEF decreases or as total perfusion defect size and percent infarct zone ischemia increase (B). For any given LVEF (A and C) or perfusion defect size (B), risk varies widely depending on amount of ischemia. LVEF and scintigraphic results for each of 92 patients who did (solid circles) or did not (open circles) have subsequent cardiac event over entire follow-up period are plotted against calculated risk at 1 year (A and B). Patients are plotted (C) according to death (triangles), nonfatal reinfarction (solid circles), or neither of these events (open circles). (Reprinted with permission from the American College of Cardiology. Mahmarian JJ et al. J Am Co11 Cardiol 1995;25:1333-40.)
1. Brown KA. Prognostic value of thallium-201 myocardial perfusion imaging: a diagnostic tool comes of age. Circulation 1991;83:36381. 2. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309: 331-6. 3. Sanz G, Castaner A, Betriu A, Magrina .I, Roig E, Co11S, et al. Determinants of prognosis in survivors of myocardial infarction: a prospective clinical angiographic study. N Engl .I Med 1982306: 1065-70. 4. Mabmarian JJ, Pratt CM, Borges-Neto S, Cashion WR, Roberts R, Verani MS. Quantification of the infarct size by thallium-201 single-photon emission computed tomography during acute myocardial infarction in man: comparison with enzymatic estimates. Circulation 1988;78:831-9. 5. Iskandrian AS, Verani MS. Scintigraphic techniques in acute ischemia syndromes. In: Nuclear cardiac imaging: principles and applications. Philadelphia: FA Davis, 1996:327-56. 6. Johnson LL, Lenick KS, Coromilas J, Seldin DW, Esser PD, Zimmerman JM, et al. Measurement of infarct size and percent myocardium infarcted in a dog preparation with single photonemission computed tomography, thallium-201, and indium 11 lmonoclonal antimyosin Fab. Circulation 1987;76:181-90. 7. Johnson LL, Seldin DW, Becker LC, LaFrance ND, Liberman HA,
Journal Volume
8.
9.
10.
11.
of Nuclear 4, Number
Cardiology 2;S158-63
James C, et al. Antimyosin imaging in acute transmural myocardial infarction: results of a multicenter clinical trial. J Am Co11 Cardiol 1989;13:27-35. Verani MS, Jeroudi MO, Mahmarian JJ, Boyce TM, Borges-Neto S, Pate1 B, et al. Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile. J Am Co11 Cardiol 1988;12:1573-81. Medrano R, Lowry RW, Young JB, Weilbaecher DG, Michael LH, Afridi I, et al. Assessment of myocardial viability with technetium99m sestamibi in patients undergoing cardiac transplantation: a scintigraphic-pathologic study. Circulation 1996;94:1010-7. TIM1 Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasmingen activator in acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial. N Engl J Med 1989;320:618-27. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673-82.
Diagnosis
and management
Verani of acute MI
S163
12. Simoons ML, Vos J, Tijssen JG, Vermeer F, Verheugt FW, Krauss XH, et al. Long term benefit of early thrombolytic therapy in patients with acute myocardial infarction. J Am Co11 Cardiol 1989;14:1609-15. 13. Cerqueira MD, Maynard C, Ritchie JL, Davis KB, Kennedy JW. Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction Trials. J Am Co11 Cardiol 1992;20:1452-9. 14. Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ, Gibbons RJ. Infarct size after acute myocradial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality. Circulation 1995;92:334-41. 15. Dakik HA, Mahmarian JJ, Kimball KT, Koutelou MG, Medrano R, Verani MS. Prognostic value of exercise thallium-201 tomography in patients treated with thrombolytic therapy during acute myocardial infarction. Circulation 1996;94:2735-42. 16. Mahmarian JJ, Mahmarian AC, Marks GF, Pratt CM, Verani MS. Role of adenosine thallium-201 tomography for defining long-term risk in patients after acute myocardial infarction. J Am Co11 Cardiol 1995;25:1333-40.
of acute
Mario S. Verani, MD, FACC,FACP Nuclear cardiology offers techniques for assessing cardiac perfusion and function that provide useful information for diagnosing and managing acute myocardial infarction (MI). In particular, myocardial perfusion imaging provides important data on infarct size and myocardial viability that can help determine the best treatment strategies for patients with acute MI. First-pass or blood pool radionuclide angiographic assessment of ventricular ejection fraction remains an important prognostic indicator in acute MI, regardless of whether thrombolytic therapy is used. Comparative studies of radiotracer techniques and coronary angiography show that myocardial perfusion and ejection fraction can predict the risk of future cardiac events reliably in patients with acute MI, whereas the anatomic data provided by coronary angiography (e.g., degree of stenosis and presence of multivessel disease) have little prognostic value. Managed-care organizations could reduce costs and improve patient outcomes by relying more on nuclear cardiology and less on angiography in the management of patients with acute MI. (J Nucl Cardiol 1997;4:S158-63.) risk stratification * perfusion scintigraphy - ejection Key Words: acute myocardial infarction fraction * adenosine l
It is generally agreed that patients with acute myocardial infarction (MI) need to be evaluated with respect to their risk of developing cardiac events after they are discharged home. What is not agreed on is how best to use our resources to achieve this evaluation. The goal is straightforward: first, we want to identify patients who are in good condition and who have a very small risk for future events-these patients should be managed conservatively; second, we want to identify patients who may also be in apparent good condition but who are at increased risk for further cardiovascular events and who should be evaluated invasively and undergo myocardial revascularization. Role of Nuclear Cardiology
in Acute MI
In patients who have an acute MI, nuclear cardiology can help to evaluate at least five parameters: 1. Acute myocardial necrosis 2. Infarct size 3. Myocardium that may be salvaged by thrombolytic therapy or angioplasty 4. Myocardial ischemia 5. Left ventricular and right ventricular ejection fraction From the Section of Cardiology, Baylor College of Medicine and the Methodist Hospital, Houston, Texas. Presented at the Forty-fourth Annual Meeting of the American College of Cardiology, Orlando, Fla., March 23, 1996. Reprint requests: Mario S. Verani, MD, Section of Cardiology, the Methodist Hospital, Baylor College of Medicine, 6550 Fannin, SM-677, Houston, TX 77030. Copyright 0 1997 by American Society of Nuclear Cardiology. 1071-3581/97/$5.00 + 0 43/O/79776 S158
The first four parameters are obtained by myocardial perfusion imaging with single-photon emission computed tomography (SPECT). Ejection fraction measurements, which are obtained by first-pass or blood pool radionuclide angiography, are of major importance, and are probably underused, in the management of acute MI. All five items, even infarct size, comprise useful assessments for the management of acute MI, primarily because they help cardiologists determine appropriate treatment and serve as prognostic indicators for a patient’s risk of future cardiac events. Nuclear cardiology, therefore, plays a major role in the risk stratification of patients with acute MI. Risk Stratification
in the Prethrombolytic
Era
A review by Brown’ summarizes most of the data known about myocardial perfusion imaging for risk stratifying patients with acute MI. Indicators of high risk for future cardiac events, after an MI, include: Presence of transient (reversible) perfusion defects, which reflect myocardial viability Number of perfusion defects Extent of fixed perfusion defects, which reflects infarct size Increased lung uptake of “‘Tl In addition, the LVEF emerged as a powerful determinant of prognosis, with a reduced value imparting a high risk for cardiac death and a normal or slightly depressed level indicating a good survival rate2 (Figure 1).
Verani Diagnosis and management of acute MI
Journal of Nuclear Cardiology Volume 4, Number 2;S158-63
Although many patients undergo cardiac catheterization after MI, studies show that coronary angiography in general provides no additional prognostic advantage over myocardial perfusion imaging.‘%3,4 As health-care delivery moves toward a managed-care structure, significant cost savings could be realized if one could reduce the number of unnecessary cardiac catheterizations in patients with acute MI. Diagnosis
of Car&c
Necrosis
Traditionally, g9mTc-labeled pyrophosphate was used to determine cardiac necrosis.s Today, physicians use g9”Tc-labeled pyrophosphate only in rare cases, such as when patients are seen late (when enzymes have returned to normal levels) or in patients with left bundle branch block that may preclude the diagnosis of acute MI. l1 ‘In-labeled antimyosin, a radiolabeled antibody, has been tested in several medical centers to image infarct size.5z7It has recently been cleared for commercial availability by the US Food and Drug Administration. Neither one of these agents, however, provides early diagnosis of infarction. A newer radiotracer, 99mT~labeled glucarate, may allow for earlier imaging of infarct size, but more studies need to be conducted to confirm this point. Infarct Sizing We studied 99”Tc-labeled sestamibi (Cardiolite; DuPont, Wilmington, Del.) for evaluation of infarct size in a canine modeL8 After creating infarctions with coronary ligation, the size of radiotracer defects on 99”Tc-labeled sestamibi SPECT images was compared with pathologic infarct size determined by triphenyltetrazolium chloride staining. As Figure 2 indicates, the measurements were comparable, with a good correlation between SPECT and pathologic infarct size. Clearly, it is possible to measure infarct size with SPECT. Surgicaiiy Removed Human Hearts Verify Radiotracer Assessments Patients undergoing heart transplantation provide a unique opportunity to compare actual infarct size with that determined by radiotracer techniques. Our laboratory recently performed a study in which patients about to undergo heart transplantation were injected with 99”Tc-labeled sestamibi before surgery.9 When the hearts were removed, they were imaged by SPECT, as well as by planar imaging of the individual heart slices, after the heart had been sectioned by the pathologist. The linear correlation (Figure 3) between results of radiotracer imaging and pathology findings (measure-
s159
50 z? .L 5
2
40
z
N=799 Mean EF=46%
.g 30 E 5 t;j 20 P c 0 b
10
0
0 15 0 Radionuclide N-0 21
30 45 60 75 Ejection Fraction (%) 244 382 152
Figure 1. One-year cardiac mortality rates after MI in Multicenter Postinfarction Research Group Study. Strong relationship between ejection fraction (EF) and mortality rate can be appreciated. Prognosis is especially poor for ejection fractions of less than 30%. Approximately two thirds of all patients have ejection fractions of 45% or greater and thus have very low l-year mortality rates (<5%). (Reprinted by permission of The New England Journal of Medicine from The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331-6. Copyright 1983, Massachusetts Medical Society.)
ment of infarcted or fibrotic tissues) provided tangible evidence of nuclear cardiology’s capability to measure the extent of myocardial scarring, or infarct size. With respect to viable myocardium, the surgically removed hearts also showed good agreement between results of 99”Tc-labeled sestamibi and pathologic findings, in that a high degree of correlation was found between the level of 99mT~ in the myocardium and the amount of viable myocardium in the samples examined. Management: Risk Stratification Postthromboiytic Era
in the
It has been suggested that the nuclear cardiology parameters that were so powerful for risk stratification in the prethrombolytic era may no longer apply to patients managed in the postthrombolytic era. I disagree with this idea, on the basis of the evidence discussed below. LVEFZStill an Important Prognostic Indicator in the Thromboiytic Era. In the “prethrombolytic era,” LVEF was clearly a major factor in determining prognosis. Today, when many patients receive emergency
S160
Verani Diagnosis and management of acute MI
3-
Journal of Nuclear Cardiology March/April 1997, Part 2
4
p=NS I
I
T p=NS I
1 Sclnti-
o-
Sclntigraphic (Planar)
Scintigraphic (Torn01
Oceluded Bed
Pathologic (TTC)
-
0
20 40 Pathologic Size (TTC) % LV
Figure 2. Comparison of planar scintigraphic perfusion defect size and occluded vascular bed size (left panel) and tomographic (Tomo) and pathologic infarct sizes (middle and right panels) in 13 dogs with permanent coronary occlusion. (LV, left ventricle; TTC = triphenyltetrazolium chloride; NS, not significant; SEE, standard error of estimate.) (Reprinted with permission from American College of Cardiology. Verani MS et al. J Am Co11 Cardiol 1988;12:1573-81.) 70
. /
60
.
.
l * .
.
.
t
/ .
. . . Y=6.45 + 0.96X FO.88, p~o.001
/ 0 0
10
20
30
40
50
60
70
% SCAR BY PATHOLOGY Figure 3. Linear regression analysis between tomographic defect size and pathologic scar size. (Reproduced with permission from Medrano R et al. Circulation 1996;94:1010-7. Copyright 1996, American Heart Association.)
thrombolytic how
therapy and undergo acute angioplasty,
does LVEF
fare as a risk factor?
Compared
with
patients we evaluated 10 to 15 years ago, patients with acute MI today tend to be younger, to have had fewer
prior infarctions, and to have a “more preserved” LVEF, especially if they participated in one of the landmark multicenter clinical trials that evaluated thrombolytic therapy such as the Thrombolysis in Acute Myocardial InfarctionlO and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trials. l l For patients in the second Thrombolysis in Acute Myocardial Infarction Trial, the average LVEF was greater than 50%. lo Similarly, in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial, the average LVEF for all patients was greater than 50%. On that basis alone, one would expect that these study populations comprised low-risk patients, with a higher rate of single-vessel disease, a higher frequency of early invasive evaluation (catheterization) and revascularization, a lower mortality rate, a lower rate of future cardiac events, and better health in general. With today’s typical lower-risk patient type, one might expect to find it more difficult than in the past to identify which patients are at risk for future cardiac events. Several studies have investigated this issue, particularly as it relates to LVEF. From a multicenter study done in The Netherlands, Simoons et a1.12 collected data on three parametersLVEF, residual stenosis in the infarct-related artery, and number of stenosed arteries (i.e., one-vessel vs multives-
Veraui Diagnosis and management of acute MI
Journal of Nuclear Cardiology Volume 4, Number 2;S158-63
S161
60 50 40 30 20 10 0 +
+
+
+
-
-
-
-
lvef < 40%
+
+
-
-
+
+
-
-
irv
> 90%
+
-
+
-
+
-
+
+
vd
2-3
Figure 4. Five-year mortality Institute of The Netherlands, in 40%, stenosis greater than 90% (Reprinted with permission from Cardiol 1989;14:1609-15.)
rates after thrombolytic therapy in Interuniversity Cardiology relation to presence (+) or absence (-) of LVEF (Iv& less than in infarct-related vessel (irv), or two- or three-vessel disease (vd). the American College of Cardiology. Simoons ML et al. J Am Co11
se1 disease)-in 422 patients who had received thrombolytic therapy (intracoronary or intravenous) for acute MI (Figure 4). Of those three parameters, LVEF clearly emerged as the most important. Patients with an LVEF of less than 40% were at high risk (>20%) for future cardiac events. When the LVEF was greater than 40%, even patients with greater than 90% residual stenosis and two- or three-vessel disease were at fairly low risk (
and coronary angiography. The data indicated that when perfusion defects were less than 20% of the left ventricle, the event-free survival rate was very high. On the other hand, patients with perfusion defects of greater than 20% of the left ventricle had a much higher rate of cardiac events. In this study, other factors were also predictive. The presence or absence of ischemia made a statistically significant difference @ < O.Ol)in future event rates. In addition, patients with an LVEF of greater than 40% were at lower risk than patients with an LVEF of less than 40%. Mahmarian et a1.4 used adenosine ‘OIT1 SPECT in 146 patients 2 to 5 days after MI. About half of these patients were treated with thrombolytic agents. The study eliminated patients who underwent early revascularization (in response to multiple or large perfusion defects or a high degree of ischemia). The remaining 92 patients were followed up for 2 years.r6 Approximately one third of these patients had additional events, such as unstable angina, nonfatal recurrent MI, congestive heart failure, and cardiac death. One of the main determinants of post-MI prognosis was the total perfusion defect size. Patients with defect sizes of less than 20% of the left ventricle were at lower risk for events than were those with larger infarcts. Whether patients underwent thrombolytic therapy made no difference in the prognostic capacity of this simple parameter. By combining two parameters, LVEF and size of the ischemia (i.e., reversible perfusion defect size in the left
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ventricle), we were able to assign fairly accurate risk predictions. For example, a patient with a very poor LVEF (about 20%) and a significant amount of ischemia (20% to 30% of the left ventricle) had a 75% probability of having a future cardiac event (Figure 5). Conversely, a patient with a normal LVEF and minimal or no ischemia had a very low probability of a future cardiac event (
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and Conclusion
Nuclear cardiology studies are useful for both the diagnosis and management of acute MI. With respect to risk stratification, radiotracer techniques provide several prognostic indicators of a patient’s risk for future cardiac events. No justification exists, from studies in the literature, for routine coronary angiography in patients with uncomplicated acute MI. Cardiologists seem to underuse nuclear studies in the management of patients with acute MI, whereas an excess of these patients routinely undergo coronary angiography in the absence of solid indications. Many patients with acute MI are categorized as low risk by nuclear cardiology techniques. They could be treated medically with good outcomes, and the healthcare system could save a sizable sum of money by avoiding unnecessary catheterizations and revascularizations in patients at such low risk.
References
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Figure 5. Cox regression models display l-year risk for cardiac event according to LVEF (LV ejection fraction) and total left ventricular ischemia (A) or scintigraphic variables (B). Regression model for predicting infarct-free survival is displayed (C). Diagonal lines = representative isobars of percent risk. Patient risk for any cardiac event (A), or specifically death and nonfatal reinfarction (C), increases as total left ventricular ischemia increases and LVEF decreases or as total perfusion defect size and percent infarct zone ischemia increase (B). For any given LVEF (A and C) or perfusion defect size (B), risk varies widely depending on amount of ischemia. LVEF and scintigraphic results for each of 92 patients who did (solid circles) or did not (open circles) have subsequent cardiac event over entire follow-up period are plotted against calculated risk at 1 year (A and B). Patients are plotted (C) according to death (triangles), nonfatal reinfarction (solid circles), or neither of these events (open circles). (Reprinted with permission from the American College of Cardiology. Mahmarian JJ et al. J Am Co11 Cardiol 1995;25:1333-40.)
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