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Enhanced detection of viable myocardium by technetium 99m - tetrofosmin imaging after nisoldipine administration

Peix Amalia; Ponce Felizardo; López Adlin; Llerena Lorenzo; Pérez Horacio; Paredes Angel; Castillo Maritza; Maltas Ana Ma.; García-Barreto David

Institute of Cardiology, Havana, Cuba

Abstract
Introduction
Material and Methods
Results
Discussion
Conclusions

Abstract
Introduction: We have reported that nisoldipine improved detection of viability by increasing affected wall motion secondary to coronary vasodilation.
Objectives: To verify if regional tetrofosmin defects uptake would be significantly reduced at a second scan if the tracer injection was preceded by oral administration of nisoldipine, as welll as to assess the value of this response in predicting the postrevascularization outcome of asynergic myocardium.
Material and Methods: Seventeen prerevascularization patients with prior myocardial infarction and significant coronary stenosis, underwent two technetium 99m - tetrofosmin studies: one at rest and the other after 10 mg oral nisoldipine administration. All patients were also studied by radionuclide angiography before and 2 months after coronary revascularization (either surgical or by angioplasty).
Results: At rest 99mTc-tetrofosmin, 102 segments had normal uptake, 28 showed moderately reduced uptake and 20 had severely reduced uptake. Of these 20 segments, 65% had increased uptake after nisoldipine (from 43± 3% to 79± 13% of peak activity, p<0.001). seventy-six percent of segments with reversible 99mTc-tetrofosmin defects and abnormal function showed functional recovery after revascularization, while 92% of segments with irreversible 99mTc-tetrofosmin defects did not.
Discussion: In order to distinguish between a peripheral or local vasodilator effect of nisoldipine's action on the ischemic zone, we compared the results of rest - nisoldipine perfusion with those of the functional recovery postrevascularization, and we found a good concordance (76% of patients). Considering the segment analysis, there was also a good concordance (89% for the moderate defects and 70% for the severe ones). It was mainly in severe defects, which corresponded to severe ischemia, where there was a greater increase in myocardial uptake after nisoldipine, probably due to its pharmacologic action on collateral circulation.
Conclusion. Nisoldipine - induced changes in 99mTc-tetrofosmin perfusion imaging improve the detection of hypoperfused but still viable myocardium in patients with myocardial infarction.

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Introduction: As with other Tc-labeled compounds such as sestamibi and teboroxime, the tetrofosmin lack of redistribution may decrease its accuracy in the diagnosis of myocardial viability.

We have reported that nisoldipine (a second generation dihydropyridine) improved detection of viability by increasing perfusion and affected wall motion secondary to coronary vasodilation.

This study was performed to verify whether regional tetrofosmin uptake defects would be significantly reduced at a second scan if the tracer injection was preceded by oral administration of nisoldipine, as well as to assess the value of this response in predicting the postrevascularization outcome of asynergic myocardium.

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Material and Methods: We studied seventeen consecutive patients who had a previous documented Q-wave myocardial infarction (MI). Most of the patients (n = 12) had symptoms with episodes of stable angina, class II. The other 7 patients had no symptoms. Eight patients had left ventricular (LV) dysfunction with LV ejection fraction (LVEF) < 50%. Characteristics of the patients are summarized in Table 1.

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All patients were studied after withdrawal of calcium channel blocker therapy for at least 72 hours; all other medication was continued.

Every patient underwent 99mTc-tetrofosmin scintigraphy under baseline conditions and after nisoldipine administration. A radionuclide angiography (RNA) at rest was performed 48 hours apart. The RNA was repeated 58 ± 20 days after coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), to determine both global and regional LV function.

Coronary Angiography: Cardiac catheterization, including selective coronary angiography in multiple projections was performed within 15 days before the scintigraphy. The main epicardial coronary arteries were evaluated by two observers, and each vessel was graded as having significant stenosis if the lesion restricted the lumen by ³ 50%.

Technetium-99m-Tetrofosmin Scintigraphy Two 99mTc-tetrofosmin scintigraphies were performed by planar technique the same day: one at rest and the other one hour after oral administration of 10 mg nisoldipine.

Anterior, 45-degree left anterior oblique (LAO), and 70-degree lateral projections were obtained.

Each projection was divided as follows: anterior: anterolateral, inferior, and apical segments; 45-degree LAO: septal, inferoapical, and posterolateral segments; 70-degree lateral: anterior, posterior, and apical segments.

Regional 99mTc-tetrofosmin uptake underwent quantitative analysis. In each projection the myocardial segment with the maximum counts was considered the normal reference region. 99mTc-tetrofosmin uptake in all other segments was then expressed as the percentage of the activity measured in the reference region.

A myocardial segment was considered abnormal if stress 99mTc-tetrofosmin uptake was > 2 SD below the mean observed in the same region for normal subjects. Segments with abnormal uptake were subgrouped as moderate (³ 50% of peak activity) and severe (< 50% of peak activity) defects. A segment with reduced activity on rest 99mTc-tetrofosmin was considered reversible if the activity increased ³ 10% after nisoldipine; while it was considered irreversible if the activity did not increase ³ 10% or increase ³ 10% but remained < 50% after nisoldipine.

Radionuclide Angiography: After in vivo labeling of red blood cells with 17 MBq of 99mTc per kg of body weight, imaging was performed in the 35-degree LAO, anterior and 70-degree lateral projections. Sixteen 64 x 64 frames corresponding to an average cardiac cycle were acquired until 3 x 106 counts were accumulated. The LVEF was determined by the standard method. A significant change in postrevascularization RNA was defined by modification of the global LVEF of ³ 4 units compared with the baseline value and an improvement of segmental contractility.

For regional wall motion analysis we considered the same segments per projection as in the scintigraphy, and the motion of each segment was evaluated with the following score: 0 = normokinesis, 1 = mild hypokinesis, 2 = severe hypokinesis, 3 = akinesis, and 4 = dyskinesis. According to the comparison between the pre and the postrevascularization scores, each asynergic segment was classified as either improved (wall motion score decrease ³ 1 grade) or unchanged.

Statistical Analysis: Values were expressed as mean ± SD. The continuous variables were analyzed with a paired Student's t test. McNemar's test was used for comparison between 99mTc-tetrofosmin scintigraphy and ventricular function (pre vs postrevascularization) . A probability value of p < 0.05 was considered significant.

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Results: Technetium - 99m - Tetrofosmin Imaging Table 2 shows the hemodynamic response to nisoldipine. No significant differences were seen in heart rate and blood pressure.

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A total of 150 segments (98%) were analyzed. On rest 99mTc-tetrofosmin images, 102 had normal tracer uptake (93 ± 7% of peak activity), while 28 showed moderate (67 ± 5% of peak activity) and 20 severe reduction (44 ± 2% of peak activity) of tracer uptake.

Normal segments at rest did not show significant differences in myocardial uptake after nisoldipine administration, while segments with moderate and severe defects significantly increased uptake (Table 3).

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Of the 20 segments with severe defects at rest, 13 (65%) improved after nisoldipine (from 43 ± 3% to 79 ± 13% of peak activity, p < 0.001).

Follow-up after Coronary Revascularization: Complete revascularization of all stenosed major coronary epicardial vessels was achieved using multiple bypass grafting in 9 patients and PTCA in 8. Mean LVEF rose from 50 ± 10% at baseline to 55 ± 11% postrevascularization. An increase ³ 4 ejection fraction units was observed in 11 patients.

Twenty-seven baseline asynergic segments had postrevascularization wall motion improvement, whereas 21 were unchanged.

Analyzing the LVEF plus segmental contractility postrevasularization improvement and the 99mTc-tetrofosmin uptake (rest vs nisoldipine), a 76% agreement (13 of 17 patients) was seen (Figure 1).

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Of the 21 segments with moderate defects on rest 99mTc-tetrofosmin which were reversible after nisoldipine, 18 showed functional recovery postrevascularization; while of the 7 irreversible segments, none reovered (89% agreement) (Figure 2).

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Of the 13 segments with severe defects on rest 99mTc-tetrofosmin which were reversible after nisoldipine, 8 showed functional recovery after coronary revascularization; while of the 7 irreversible segments, only 1 recovered (70% agreement) (Figure 3).

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The majority of segments (76%) with reversible 99mTc-tetrofosmin defects after nisoldipine and abnormal LV function showed improved wall motion after coronary revascularization (Figure 4). Conversely, the majority of segments (92%) with irreversible99mTc-tetrofosmin defects after nisoldipine and impaired LV function did not improve wall motion after coronary revascularization (Figure 4).

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Discussion:  Myocardial perfusion imaging with 99mTc-labeled agents such as sestamibi or tetrofosmin has been used recently for the assessment of myocardial viability.

In previous studie we used nisoldipine as vasodilator, because dihydropyridines produce arterial vasodilation with the consequent afterload and end-diastolic LV pressure reduction. This originates a transient flow increase to the ischemic zone, with a demonstrable effect on LV wall motion and also on perfusion on viable zones.

In order to distinguish between a peripheral or local vasodilator effect of nisoldipine's action on the ischemic zone, we compare the results of rest - nisoldipine perfusion with those of the functional recovery postrevascularization, and we found a good concordance (76% of patients). Considering the segment analysis, there was also a good concordance (89% for the moderate defects and 70% for the severe ones).

The absence of a significant difference in heart rate and blood pressure between baseline and postnisoldipine scintigraphies could be explained by a diminished peripheral vasodilator response, supporting a selective action on coronary arteries.

One limitation in our study was that postnisoldipine 99mTc-tetrofosmin imaging was performed five hours after rest 99mTc-tetrofosmin imaging, and part of the 99mTc-tetrofosmin injected for the rest study would still be present at the time when postnisoldipine imaging was performed; thus, recognition of small changes in 99mTc-tetrofosmin uptake may be difficult when there is such an underlying background.

Conclusions:  Nisoldipine - induced changes in 99mTc-tetrofosmin perfusion imaging improves the detection of hypoperfused but still viable myocardium in infarcted patients.

 

Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to image-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.

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