Stress radionuclide studies after acute myocardial infarction: Changes with revascularization

Stress radionuclide studies after acute myocardial infarction: Changes with revascularization Isabel Coma-Canella,

M D , FESC, F A C C , M a r i a d e l Val G 6 m e z ,

MD,

L u i s a S a l a z a r , M D , a n d F~lix G a l l a r d o , M D

Background. Successful revascularization of ischemic asynergic myocardium should be followed by improvement in contractile function. However, a clear improvement is not always observed. Assessment of contractile reserve may allow a better evaluation of procedural results. Methods and Results. To assess the changes in global and regional left ventricular ejection fraction (EF), as well as the contractile reserve after revascularization, equilibrium radionuclide angiography was performed in 16 patients with acute myocardial infarction who had periinfarct redistribution (observed in stress-rest-reinjection thallium single-photon emission computed tomography). Regional EF was defined in the asynergic region at rest, which corresponded to the infarct plus periinfarct areas. Both thallium single-photon emission computed tomography and equilibrium radionuclide angiography were performed at rest and during stress with dobutamine, up to a maximal dose of 40 Bg/kg/min. The same studies were repeated 8 + 6 months after successful revascularization (nine coronary angioplasties and seven bypass procedures). After intervention, the thallium defect score decreased significantly at rest and during stress. Global EF changed from 45% +10% to 47% +11% (difference not significant) at rest and from 49% + 12% to 63% + 13% (p = 0.0001) at peak stress. Regional EF changed from 27% + 8% to 35% + 18% (p = 0.03) at rest and from 29% + 10% to 56% + 21% (p = 0.0001) at peak stress. Conclusions. In patients with asynergy caused by periinfarct ischemia, there can be an increase in regional but not global EF at rest after revascularization. However, both parameters improve at peak dobutamine dose. This indicates an improvement in contractile reserve. (J Nucl Cardiol 1996;3:403-9.) Key Words: hibernation • stunning • dobutamine • radionuclide studies Segmental left ventricular asynergy is usually present after acute myocardial infarction (AMI). In some cases part of the asynergy can be reversible, either spontaneously 1~3or by means of revascularization. 4-6 Echocardiographic studies show improvement in contractility with low dobutamine doses when the asynergic segment is viable. 7 With high doses, the contractility of stunned myocardium improves, whereas that of hibernating myocardium worsens) '9 However, it is not easy to evaluate subtle changes in contractility with echocardiography during inotropic stimulation. In common practice the evaluation is subjective and frequently unreliable. Quantitative radionuclide angiography, in spite of its limita-

tions, is more objective in the assessment of changes in contractility. Stress radionuclide studies of perfusion and function performed in the same patient can provide interesting information about the presence and extent of hibernation after AMI. The same studies repeated after revascularization could permit good assessment of not only the degree of reperfusion but also changes in regional and global ejection fraction (EF) and contractile reserve. To test this hypothesis, a selected group of patients postinfarction submitted to revascularization underwent radionuclide studies with dobutamine before and after the procedure.

From the CardiologyDivision, La Paz Hospital, and the Department of Nuclear Medicine, Carlos III Hospital, Madrid, Spain. Received for publication Sept. 20, 1995; revision accepted March 4, 1996. Reprint requests: Isabel Coma-Canella, MD, Departamento de Cardiologfa, Clfnica Universitaria, Facultad de Medicina, Universidad de Navarra, Aptdo 4209, 31080 Pamplona, Spain. Copyright © 1996 by American Society of Nuclear Cardiology. 1071-3581/96/$5.00+0 43/1/73247

METHODS Patient Population. A total of 16 patients (15 men) submitted to revascularization were included in this study. The mean age was 57 + 9 years. All patients had severe periinfarct ischemia according to scintigraphic findings. The electrocardiographic infarct location was anterior in nine patients and inferior or posteroinferior in seven. Radionuclide studies at rest and during stress with dobutamine were performed before 403

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Coma-Canella et al. Radionuclide studies after AMI: Revascularization

and after revascularization. All the patients were in sinus rhythm at the time of these studies. Dobutamine Stress Test. Dobutamine was infused 16 + 4 (+SD) days after AMI. The infusion was given in incremental doses of 10 gg/kg/min every 5 minutes to a maximum of 40 gg/kg/min. Cuff blood pressure and 12-lead electrocardiogram were taken at baseline and 5-minute intervals. Criteria for stopping the infusion have been described previously.i°

Single-Photon Emission Computed Tomography. When the maximal dose of dobutamine was achieved, 2.5 mCi (90 MBq) 2°~TI was injected. Except in patients who had angina, the last dobutamine dose was maintained during the time of imaging acquisition (15 to 20 minutes). Thallium images were obtained with a wide-field-of-view rotating gamma camera (Orbiter-Siemens, Chicago, Ill.), equipped with an all-purpose, parallel-hole collimator. The camera was rotated over a 180-degree arc in an elliptic orbit about the thorax at 6-degree increments for 30 seconds each. Delayed images were acquired 3 to 4 hours later. In every case 1 mCi 2°1TI was reinjected after acquisition of delayed images and a third imaging acquisition was performed. Tomograms were analyzed in three planes: short axis, horizontal long axis, and vertical long axis. Approximately 12 slices were taken in each plane. The stress, delayed, and reinjection images were analyzed in blinded fashion by two observers by a qualitative method," and a score was given to each patient. No significant differences were noted between the two observers. The left ventricular myocardium was divided into nine segments by dividing the anterior, inferior, and lateral walls and septum into a basal and apical segment, including an extra segment for the apex. The score given to each segment was as follows: 0, normal perfusion; 1, hypoperfusion in half a segment; 2, hypoperfusion in one segment or lack of perfusion in half a segment; and 3, lack of perfusion in one segment. Every patient had a score for stress, a score for the delayed image, and another for reinjection. The lowest score was chosen for the rest imaging. Redistribution was calculated comparing stress and rest images. A redistribution score greater than 1 was considered to indicate ischemia. A redistribution score greater than 3 was considered to indicate severe ischemia.

EquilibrlumRadionuciideAnglocardiography(ERNA). ERNA was performed t or 2 days after thallium tomography. The patient's erythrocytes were labeled by an in vivo method with an intravenous injection of 10 gg/kg stannous pyrophosphate followed 10 minutes later by 15 to 25 mCi (550 to 900 MBq) 99mTc-labeled pertechnetate. The scan image was acquired with a gamma camera with an all-purpose parallel-hole collimator. The patient was supine and the collimator was aligned in a 30- to 50-degree left anterior oblique position (the best septal image), with a 5-degree caudal tilt. Radionuclide counts were collected with a matrix size of 64 x 64 pixels, and the cardiac cycle was gated into 26 frames/cycle with a nuclear medicine computer system (Digital Equipment MicroDelta, Chicago, Ill.). The heart was magnified to improve wall motion assessment. The acquisition was stopped when 10 million counts were accumulated in one window. The acquisition lasted 15 to 20 minutes. After baseline imaging acquisition was

JOURNALOF NUCLEARCARDIOLOGY September/October 1996

completed, dobutamine was infused as described previously, with electrocardiographic and blood pressure control. ERNA imaging was performed again at the end of the test, and the maximal dose of dobutamine was maintained throughout the time of stress imaging acquisition. The second imaging acquisition also lasted 15 to 20 minutes. Data processing had the following steps: (1) spatial and temporal filtering was performed with a Wiener filter; (2) after an area of interest was generated in the left ventricle by a semiautomatic method, the time-activity curve was constructed; and (3) EF was calculated as (net end-diastolic counts - net end-systolic counts)/net enddiastolic counts. Regional EF was obtained by dividing the end-diastolic region of interest into nine segments (Figure 1). It was calculated from maximal and minimal counts in all regions, with the end-diastolic centroid used as a common center. According to our data, the regional EF of the anteroseptal segments 4-6 was considered abnormal when it was less than 35%. A regional EF of the inferoapical (segments 7 and 8) and posterolateral segments (segments 9 and 1) less than 45% was abnormal. Segments 2 and 3 involving the valve planes were excluded for the measurement of regional contractility. For each patient the average regional EF of the hypokinetic segments was determined at baseline and compared with the regional EF of the same segments during stress. Both global and regional EF were measured at rest and peak stress. The stress-induced increase was the difference between peak stress and rest values. This change was also termed contractile reserve. A dobutamine-induced increase in regional EF of less than 10% was considered no change. To assess the changes in EF with revascularization (values after intervention minus values before intervention), a 5% change was accepted as an increase in EF, because a change of less than 5% could be due to intraobserver variation.

Comparison Between Perfusion and Radionuclide Imaging. Because there are many more myocardial perfusion segments than regional EF segments, to compare both images it was assumed that the hypokinetic segments of the ERNA at rest corresponded to the infarct plus perinfarct areas. For this reason, the regional EF of the hypokinetic segments was compared with the score of the fixed plus periinfarct reversible defects on perfusion imaging. 1° Because this study is focused on infarct and periinfarct regions, the EF of these regions will be termed regional EF. Coronary Anglography. Coronary angiography was performed in every patient within 10 days of radionuclide studies. Lesions greater than 50% in a principal coronary artery or a major branch were considered significant. Multivessel disease was present when two or three coronary arteries were stenotic. The presence or absence of collateral circulation was also analyzed. Revascularization Procedures. Nine patients were submitted to percutaneous transluminal coronary angioplasty: eight had one-vessel disease. One patient, with two-vessel disease, underwent angioplasty of the two stenotic vessels. Seven patients (six with multivessel and one with one-vessel disease) were submitted to coronary artery bypass. All major stenotic vessels were bypassed.

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Coma-Canella et al. Radionuclide studies after AMI: Revascularization

iN/ill ~ GEF 53%

"~

BASELINE

5

~

i

GEF 48%

D O B U T A M IN E

405

Region 2:1:59% 61% Region 3: 52% Region 4: 29% Region 5: 27% Region 6: 35% Region 7: 47% Region 8: 61% Region 9: 60% Region 1: 44% Region 3: 43% Region 4: 17% Region 5: 11% Region 6: 41% Region 7: 65% Region 8: 64%

Region9: 45%

RI

Figure 1. Preintervention study of patient with anteroseptal myocardial infarction. Top, Radionuclide angiography in diastole (left) and systole (right). Both global EF (GEF) and regional EF of hypokinetic area (regions 4 and 5) decrease during dobutamine infusion. Bottom, Horizontal long-axis view of thallium tomography during dobutamine (DB) and reinjection (RI). There is fixed apical defect with perinfarct apical and septal ischemia at peak stress. Time to Intervention. The time elapsed from AMI to intervention was 4.2 _+4 months. Reasons for delay in intervention were either a waiting list for surgery or clinical change. Two patients who refused intervention soon after AMI underwent revascularization several months later because of refractory angina. Cardiac catheterization was repeated in five patients in whom the delay was greater than 4 months. Radionuclide studies were repeated before a delayed intervention in one patient. Follow-up. Scintigraphic studies were repeated 8 + 6 months after intervention. The patients submitted to coronary angioplasty underwent repeat coronary angiography between 3 and 6 months after the procedure. They were excluded if significant restenosis was present. In one patient who refused anglographic control, scintigraphic studies were performed 1 month after angioplasty, when he was symptom free. In another patient, postangioplasty studies were performed on two occasions: 1 and 6 months after the procedure. Patients submitted to coronary bypass were included in the study if they remained symptom free and without electrocardiographic signs of perioperative infarct. One patient underwent two radionuclide studies after surgery: 2 and 8 months later. Data of the last study were chosen for analysis in the two patients who underwent repeat studies.

Statistics. Descriptive statistics are expressed as mean + SD. Data before revascularization were compared with data of the same patient after the procedure. The Student t test for paired or unpaired data was used to compare two means. Correlations between numeric data were calculated by Pearson's correlation coefficient. Significance was assumed if p < 0.05. Ethics, The study protocol was approved by the Ethical Committee of the hospital. Informed consent was obtained from the patients.

RESULTS Coronary Angiography. Single-vessel disease was present in n i n e patients and multivessel disease in seven. The infarct-related artery was severely stenotic but patent in all but two cases. Collateral circulation to the occluded artery was visible in both. Z°'TI Single-Photon Emission Computed Tomography. In every patient there was at least one area of hypoperfusion during stress with partial redistribution at rest, which corresponded to the electrocardiographic

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Coma-Canellaet al. Radionuclide studies after AMI: Revascularization

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Table 1. Scintigraphic data: comparison b e t w e e n before and after intervention Rest

Stress

Before

After

p Value

Before

After

7_+4 GEF(%) 4 5 + 1 0 REF(%) 2 7 ± 8

3_+3 47±11 35±18

0.002 NS 0.03

12±3 49+12 29±10

4+3 63+t3 56±21

T score

Redistribution p Value Before After p Value

0.001 0.0001 0.0001

6±3

1±2

Stress-induced changes Before

After

p Value

4±8 2±9

17±6 21±10

0.00002 0.00001

0.00001

GEl:, Global ejection fraction; NS, not significant; REF,regional ejection fraction.

infarct location. Redistribution was detected in the pertinfarct areas in all cases. Distant redistribution was also observed in three of them. Changes with intervention are shown in Table 1. ERNA. Values before and after intervention can be seen in Table 1. Before intervention. Before intervention global EF at rest was less than 40% in six patients. No significant change was induced with dobutamine, in either the entire group of patients or those with the lowest EF. In every patient some hypokinetic area was detected at rest. The anteroseptal segments were hypokinetic in 11 patients, the inferoapical segments in 14, and the posterolateral segments in five. More than 1 region was involved in 12 cases. The anterior infarcts had segmental anteroseptal or inferoapical hypokinesia or both. The inferior infarcts had inferoapical or posterolateral hypokinesia or both. The resting regional EF of the hypokinetic segments was less than 30% in nine patients and between 30% and 40% in seven. The lowest resting regional EF was 10%. Negative values (representing dyskinesia) were not found in any patient. No significant change was induced with dobutamine. Changes with intervention. The resting global EF decreased in three patients, increased in four, and did not change in nine. The peak stress global EF increased in 14 patients, decreased in one, and failed to change in one. The resting regional EF decreased in four patients, increased in nine, and failed to change in three. In five of the seven patients without an increase of resting regional EF, there was an increase in peak stress values. The peak stress regional EF increased in 14 patients and decreased in two. These two patients with anterior infarction and septal asynergy had paradoxic septal motion after heart surgery. Figures 1 and 2 correspond to the same patient before (Figure 1) and after (Figure 2) revascularization. R e l a t i o n s h i p s B e t w e e n Time o f Revascularization and C h a n g e s in Ventricular Function. In the five

patients submitted to two angiographic studies before intervention, no changes in coronary lesions or left ventricular function were observed between studies. In

the patient submitted to a second radionuclide study before the delayed intervention, results were identical to those of the first study. No significant correlation was found between the time elapsed from AMI to revascularization and the increase in ventricular function after the procedure. However, a weak (r = 0.60) but significant ( p = 0 . 0 1 ) correlation was found between the months elapsed from intervention to the second radionuclide study and the improvement in resting global EF. The two patients with repeat studies after revascularization had a greater improvement in resting EF in the second study, although thallium defects were unchanged. Therefore the correlation was stronger (r=0.62; p = 0.006) when the two studies of these patients were included: the longer the time elapsed after revascularization, the greater the improvement. A similar but nonsignificant correlation was seen with regional EE DISCUSSION Postinfarct Asynergy. Left ventricular EF is an important prognostic variable after AMI. 1z13 For this reason, patients with depressed values must be investigated thoroughly for the presence of potentially reversible asynergy. Although different methods have been described for the diagnosis of this condition, none of them is completely reliable. In fact, the gold standard for reversibility is improvement in asynergy after revascularization. 14 At present, positron emission tomography is considered the best prospective method for the diagnosis of viability, 15 but it is expensive and cannot be performed routinely. Although echocardiography with low and high dobutamine doses can theoretically identify hibernation, 8'9'16 the assessment of contractility changes in the infarct area is difficult and subjective. We have used the combination of thallium scintigraphy and ERNA with high dobutamine doses for the detection of severe ischemia. According to previous experience with dobutamine, 1° periinfarct redistribution is associated with depressed contractile reserve in patients with severe ischemia. In the case of necrosis no redistribution is detected, and in the case of stunning,

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@

BASELINE

Region 1: 44% Region 2: 52% Region 3: 45% Region 4: 43% Region 5: 52% Region 6: 50% Region 7: 62% Region 8: 57% Region 9: 52%

DOBUTAMINE

Region 1: 76% Region 2: 72% Region 3: 67% Region 4: 69% Region 5: 72% Region 6: 79% Region 7: 87% Region 8: 69% Region 9: 73%

GEF 54%

GEF 79%

407

DB ,,,,,,

,

,

RI Figure 2. Postintervention study of same patients as shown in Figure 1. Regional ejection fraction of regions 4 and 5 has become normal. Resting global EF (GEF) has not changed. However, there is important increase in both global EF and regional EF during dobutamine. Apical defect in reinjection (RI) images is smaller than before intervention. (DB, Dobutamine.) radiotracer uptake may be normal 17 or temporarily reduced, 1. but contractile reserve is excellent. 19'2° In patients with severe ischemia, a fixed defect mimicing necrosis can be seen in delayed images. In these cases reinjection can help to identify viable tissue. 2''= However, a large area of necrosis surrounded by a small area of ischemic tissue is not expected to improve with revascularization. The technique of maintaining the highest dobutamine dose during the time of image acquisition has been used previously. 1°'24 Rapid redistribution occurring in the period between the cessation of stress and the completion of imaging is not missed if the stress is maintained. This study shows that combined studies of perfusion and function are useful in the evaluation of patients after infarction. Although simultaneous studies of perfusion and function can be performed with 99mTc-labeled sestamibi by use of first-pass radionuclide angiography, thallium may be more reliable than sestambi for viability, 25 and ERNA techniques are the preferred method when serial acquisitions are necessary during a brief period. 26 Although the normal dobutamine-induced increase in EF has not been well established, previous 23

studies = have shown dobutamine to induce a greater increase than exercise. Therefore an increase of less than 10% has been considered a subnormal response. Our patients had moderately depressed global EF with severe periinfarct redistribution and regional asynergy. The subnormal dobutamine-induced changes in ventricular function were presumed to be due to severe ischemia. All these data were suggestive of periinfarct hibernating myocardium, potentially reversible with revascularization. Changes with Intervention. Thallium defect size decreased after revascularization. Both the stress-induced defect and the resting defect were significantly smaller after the procedure. Therefore thallim studies in these patients overestimated infarct size. Viability was detected but underestimated, in spite of the use of reinjection after delayed i m a g e s . 21'22 No significant improvement in resting global EF was seen after revascularization, in either the entire group or the six patients with an EF less than 40%. Only the resting regional EF of the hypokinetic area increased significantly. However, seven patients failed to show that increase. Juxtaposition of viable dysfunctional seg-

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Coma-Canella et al. Radionuclide studies after AMI: Revascularizafion

ments and nonviable dysfunctional zones can limit functional recovery o f the former because o f tethering by the latter. Another explanation might be prolonged stunning after revascularization. The apparent lack of improvement was unmasked by inotropic stimulation. Previous studies have shown an improvement in regional 7'z8 and global 29'3° left ventricular function after revascularization o f hibernating myocardium. Others 31'32 have, found that coronary angioplasty improves the response of the E F to exercise but does not influence the EF at rest in patients after infarction. Zaret et al. 32 found only a mild transitory improvement of peak exercise EF. Dobutamine probably has a greater value to assess changes in contractile reserve, because it increases EF more than exercise. In our patients the lack o f improvement in global EF could be due to (1) a small contribution of regional E F to global contractility; (2) compensatory hypercontractility in nonischemic regions at the time of preintervention studies, no longer present in the second study; or (3) postrevascularization stunning. The most noteworthy change was the improvement in peak stress global and regional EF after revascularization. The stress-induced changes also increased significantly. Therefore there was a significant improvement in left ventricular contractile reserve. Both the decrease in thallium defect size and the increase in contractile reserve after intervention suggest that the procedure was successful and the dysfunction reversible. Postrevascularization Stunning. The small increase in resting regional EF and the important increase in the same parameter at peak stress are suggestive of postischemic stunning. 33 Although stunning after A M I is believed to last no more than days to weeks, 34 its duration may be longer. 35 Our data suggest that invasive revascularization of hibernating myocardium some weeks or months after A M I can unmask longer periods of stunning. Combined stress studies of perfusion and function are useful not only to identify hibernating myocardium but also to assess changes with revascularization. Study Limitations. Automatic quantification of hypoperfusion was not performed in every case. For this reason, only a semiquantitative subjective score was given. In spite o f that, changes in defect score were significant. The correspondence between tomographic thallium segments and planar E R N A regions is not exact. However, its validity for practical purposes is confirmed by the significant changes in regional E F with revascularization, even in a small number of patients. Both the time from A M I to intervention and the time from intervention to radionuclide studies varied widely. In spite of that, no differences in ventricular function or coronary lesions were detected in these patients when angiography was repeated immediately before interven-

JOURNALOFNUCLEARCARDIOLOGY September/October 1996

tion. Variability in time from intervention to repeat radionuclide studies was probably responsible for changes in resting EF. Although the number of patients is small, changes in regional EF and peak stress contractility were significant. Conclusions. In patients with asynergy caused by periinfarct ischemia, an increase in resting regional EF can be found after revascularization. However, resting global EF may fail to show a significant change. In these patients both regional and global EF improve at peak dobutamine dose, and the contractile reserve shows a significant increase. Measurements of contractile reserve are useful to assess postrevascularization improvement.

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