Sestamibi Single-photon Emission Computed Tomography Research Articles

Improved detection of left main coronary artery disease with attenuation-corrected SPECT

Background. Myocardial perfusion imaging has demonstrated a limited sensitivity as a means of accurately identifying left main (LM) coronary disease. Because regional quantitative perfusion biases are eliminated with attenuation corrected (AC) single photon emission computed tomography (SPECT), as compared with uncorrected (NC) SPECT, we hypothesized that AC SPECT would demonstrate increased diagnostic accuracy for the detection of significant LM coronary stenosis. Methods and Results. We studied 28 patients (23 men, 5 women; mean age, 66 ± 9 years) with significant LM stenoses (≥50%) and 34 control patients (27 men, 7 women; mean age, 65 ± 11 years) with 2-vessel coronary disease. Rest thallium-201 and stress technetium 99m sestamibi SPECT imaging with and without AC were performed, as described earlier. Both AC and NC images were analyzed visually and quantitatively in comparison with corresponding normal databases. A greater sensitivity for detection of an LM defect pattern (64% vs 7%,P = .0009) with equivalent specificity (94% vs 100%, P = not significant) was demonstrated by means of visual analysis of AC SPECT images. More disease was demonstrated in a greater number of territories with AC SPECT images than with NC images (2.14 ± 0.97 for AC images vs 1.43 ± 0.84 for NC images, P = .0001). Similar improvement in the detection of LM disease was shown by means of automated quantitative analysis (57% for AC SPECT vs 14% for NC SPECT,P = .0005), again with no loss in specificity. Conclusions. AC SPECT with the University of Michigan method in consecutive patients with LM stenoses and a select control population with severity matched multivessel coronary disease significantly improved the diagnostic accuracy of myocardial perfusion imaging for the identification of LM coronary disease, compared with uncorrected SPECT. (J Nucl Cardiol 2000;7:639-48.)

Noninvasive characterization of stunned, hibernating, remodeled and nonviable myocardium in ischemic cardiomyopathy

OBJECTIVESWe evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction.BACKGROUNDMyocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging.METHODSWe studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred.RESULTSSevere regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p < 0.05).CONCLUSIONSIt is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.

Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary artery disease: limitations and concordance

OBJECTIVESWe sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD).BACKGROUNDBoth DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared.METHODSTo investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin’s technique.RESULTSThe 183 patients (mean age: 60 ± 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed).CONCLUSIONSDobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Approach to superior mediastinal parathyroid adenomata via resection of the medial third of the clavicle

Resection of the medial third of the clavicle is a safe and effective surgical approach for exposure of the uppermost portion of the superior anterior and posterior mediastinum for resection of parathyroid adenomata. Two patients underwent this transclavicular approach to resect parathyroid adenomata of the anterior and posterior superior mediastinum following initial negative cervical exploration. One patient had 3 previous operations performed elsewhere resulting in a permanent vocal-cord paralysis. Preoperative localization in both patients included, but was not limited to, Tc-99m sestamibi single-photon emission computed tomography (SPECT), and 1 patient had a positive emission tomography (PET) scan. One adenomata was deep to the left sternoclavicular junction and left sternothyroid muscle, and the other 7 cm caudad in the posterior mediastinum affixed to the thoracic esophagus and thoracic vertebra. There were no major intraoperative or postoperative complications following resection of the medial third of the clavicle; however, 1 patient had a temporary vocal-cord paralysis. Resection of the medial third of the clavicle provides excellent surgical access to parathyroid adenomata located in the uppermost superior anterior mediastinum and the posterior superior mediastinum. Tc-99m sestamibi SPECT and PET images are valuable in the location of such adenomata. In 1 of the patients, PET imaging confirmed the location.

Nitrate-enhanced gated technetium 99m sestamibi SPECT for evaluating regional wall motion at baseline and during low-dose dobutamine infusion in patients with chronic coronary artery disease and left ventricular dysfunction: Comparison with two-dimensional echocardiography

Background. The value of gated single photon emission computed tomography (SPECT) in the assessment of wall motion (WM) in patients with severe perfusion defects and in the evaluation of low-dose dobutamine (LDD)-induced changes is not yet established. In patients with chronic coronary artery disease who have left ventricular (LV) dysfunction, the results of nitrate-enhanced technetium 99m sestamibi (sestamibi) gated SPECT for the evaluation of resting and LDD WM were compared with those of baseline and LDD echocardiography (LDDE). Methods and Results. Thirty-seven patients underwent echocardiography and nitrate-enhanced sestamibi gated SPECT within 1 week at rest and during LDD infusion. WM was scored from 1 (normal) to 4 (dyskinetic) by using a 16-segment model. Segments with sestamibi uptake less than 30% were considered unsuitable for WM analysis (36 of 592 segments). Echocardiography was technically unreliable in 10 of 592 segments. The precise agreement between echocardiography and gated SPECT for baseline regional WM was 68.4% (kappa = 0.54), without significant differences for the involved coronary artery territory. The agreement for ± 1 WM scoring was 96.5% (kappa = 0.94). Contractile reserve during LDD was detected by means of echocardiography in 36% and by means of sestamibi gated SPECT in 33% of baseline asynergic segments. Agreement for detection of WM improvement in response to LDD was 74% (kappa = 0.41). The overall and ± 1 WM score agreement for LDD WM was 67.5% (kappa = 0.50) and 94.7% (kappa = 0.91), respectively. A significant correlation between echocardiography and gated SPECT was observed for both baseline (ρ = 0.78) and LDD (ρ = 0.74) WM score index. Conclusions. In patients with coronary artery disease who have LV dysfunction, nitrate-enhanced sestamibi gated SPECT allows a reliable WM evaluation, both at rest and during LDD infusion, in almost all segments and provides results in agreement with LDDE. (J Nucl Cardiol 2000;7:426-31.)

Accuracy of exercise stress technetium 99m sestamibi SPECT imaging in the evaluation of the extent and location of coronary artery disease in patients with an earlier myocardial infarction

Background. This study assessed the accuracy of exercise methoxy isobutyl isonitrile (MIBI) single photon emission computed tomography (SPECT) in the evaluation of the extent of coronary artery disease (CAD) in patients with an earlier myocardial infarction. Methods and Results. We studied 135 patients (mean age, 57 ± 10 years; 115 men) at a mean of 4.1 years (median, 1 year) after myocardial infarction with symptom-limited bicycle exercise stress and rest MIBI SPECT imaging. Coronary angiography was performed within 3 months. Significant CAD was defined as a stenosis of 50% or larger in luminal diameter in 1 or more major coronary arteries. Myocardial perfusion defects (fixed, reversible, or both) were detected in 107 of the 113 patients with significant CAD and in 10 of the 22 patients without significant CAD (sensitivity, 95%; CI, 91 to 99; specificity, 55%; CI, 46 to 63, and accuracy, 88%; CI, 82 to 94). The specificity rate increased to 73% (CI, 65 to 80) by using only reversible perfusion defects as a means of predicting CAD. Reversible perfusion abnormalities were more frequent in patients with multivessel CAD than in patients with single-vessel CAD (51 of 64 [80%] vs 27 of 49 [55%], P < .01). Myocardial perfusion abnormalities in 2 vascular regions, which is suggestive of multivessel CAD, were detected in 35 of the 64 patients with and in 9 of the 71 patients without multivessel CAD (sensitivity for detecting CAD in more than one vascular region, 55%; CI, 46 to 63, specificity, 87%; CI, 81 to 93, and accuracy, 72%; CI, 64 to 80). The sensitivity rates for the diagnosis of left anterior descending coronary artery, left circumflex, and right coronary artery based on any defect were 80%, 70%, and 63%, respectively. The corresponding specificity rates were 70%, 76%, and 73%, respectively. Conclusions. Exercise MIBI SPECT imaging is an accurate method for the diagnosis and localization of CAD in patients with an earlier myocardial infarction. The technique provides a high specificity and moderate sensitivity for the diagnosis of multivessel CAD on the basis of myocardial perfusion abnormalities in more than 1 vascular region. (J Nucl Cardiol 2000;7:432-8.)

Comparison of baseline and low-dose dobutamine technetium-99m sestamibi scintigraphy with low-dose dobutamine echocardiography for predicting functional recovery after revascularization

Injection of sestamibi during low-dose dobutamine (LDD) infusion might improve tracer ability to detect viable myocardium. This study investigated the potential value of LDD technetium-99m sestamibi (sestamibi) single-photon emission computed tomography (SPECT) in predicting functional recovery after revascularization by comparing its results with those of sestamibi SPECT at rest and of LDD echocardiography. Before revascularization, 23 patients with chronic coronary artery disease and regional left ventricular dysfunction underwent sestamibi SPECT at rest and, on a separate day, LDD echocardiography and sestamibi SPECT with tracer injection during LDD infusion. Echocardiography at rest was repeated after revascularization. Semiquantitative sestamibi uptake results (grading from 0 = normal to 4 = absent) and wall motion (grading from 1 = normal to 4 = dyskinesia) were evaluated with a 16-segment model. The ventricular wall was divided into 3 vascular territories. At follow-up, 20 of 32 asynergic vascular territories showed functional recovery, whereas 12 showed no changes. For prediction of functional recovery, LDD SPECT achieved better accuracy than SPECT at rest (87% vs 65%, p <0.05); positive and negative predictive values of LDD SPECT were 90% and 83%, respectively, which was not significantly different from the related LDD echocardiographic values (84% and 69%). Thus, LDD sestamibi SPECT appears to be a promising method for detecting myocardial viability, which provides better accuracy than sestamibi SPECT at rest, and achieves predictive values comparable to those of LDD echocardiography.

Infarct size determination by technetium 99m sestamibi single-photon emission computed tomography predicts survival in patients with chronic coronary artery disease

Background The prognostic value of infarct size quantification by technetium 99m sestamibi single-photon emission computed tomography (SPECT) in patients with chronic coronary artery disease (CAD) has not been established. Methods and Results Between September 1994 and May 1995, 1323 patients with known or suspected CAD were referred for perfusion imaging for clinical reasons and had infarct size determined by quantitative SPECT imaging. Patients underwent exercise stress (61%), pharmacologic stress (37%), and rest imaging (3%). Patients were excluded if they had cardiomyopathy, valvular heart disease, or myocardial infarction within 3 weeks of the SPECT study. There were 1224 patients who formed the study group. Follow-up was 94% complete at a median of 1.9 ± 0.4 years. Sixty-five percent of patients had no measurable infarct. Among the patients with measurable infarcts, the mean infarct size by sestamibi imaging was 15.0% ± 14.5% of the left ventricle (25% of infarcts ≤5% of the left ventricle and 25% of infarcts ≥19% of the left ventricle). By using stepwise regression analysis, age, diabetes, and hypercholesterolemia were all clinical predictors of overall death (P <.05). For cardiac death, only age and diabetes were significant. After adjusting for these clinical variables, infarct size remained an independent predictor of overall death (P =.001) and survival free of cardiac death (P =.0002). However, when first-pass left ventricular ejection fraction was added to the models, infarct size was no longer significant. Conclusions Infarct size determination by SPECT 99mTc sestamibi can predict subsequent death in patients with chronic CAD, although ejection fraction appears to have greater prognostic value. (Am Heart J 2000;140:61-6.)

A minimally invasive method for creating coronary stenosis in a swine model for MRI and SPECT imaging.

To develop a less-invasive method for creating coronary stenosis in an animal model for the study of myocardial perfusion defects by using magnetic resonance imaging (MRI) and single-photon-emission computed tomography (SPECT). Eleven farm pigs were instrumented with an MR-compatible coronary flow-reduction fitting in the left anterior descending coronary artery (LAD). These fittings were turned from a nylon rod, tapered from a maximum outer diameter of 3 mm, and drilled to a specified inner diameter (depending on the degree of coronary stenosis desired). The flow-reducing fittings were delivered over a coronary guidewire and advanced to a wedge position in the proximal LAD with an angioplasty catheter via a carotid artery approach. Perfusion determined by contrast-enhanced MRI at peak dipyridamole stress was compared with that obtained by 99mTc sestamibi SPECT. Radiolabeled microspheres were injected at rest, after stenosis implantation, and at peak pharmacological stress to establish the severity of the coronary lesion. Coronary stenosis was successfully created in seven animals. Mild coronary stenoses (<60%) were created in four animals. Significant coronary stenoses (80%-90%) were created in three animals. Thrombosis of the coronary flow-reducing fittings was observed in four animals, leading to sudden death in three animals and myocardial infarction in one animal. This method of angioplasty-guided, LAD coronary stenosis creation in a swine model presents a less-invasive alternative to open-chest techniques such as hydraulic occluders and ameroid constrictors.

Comparison of electrocardiographic-gated technetium-99m sestamibi single-photon emission computed tomographic imaging and rest-redistribution thallium-201 in the prediction of myocardial viability

Although the combined assessment of perfusion and function using rest electrocardiographic (ECG)-gated technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) imaging has been shown to improve sensitivity and accuracy over perfusion alone in the prediction of myocardial viability, no data are available comparing this technique with rest-redistribution thallium-201. Thirty patients with coronary artery disese and left ventricular dysfunction (ejection fraction ≤40%) underwent rest-redistribution thallium-201 and rest ECG-gated Tc-99m sestamibi SPECT imaging before revascularization and rest ECG-gated Tc-99m sestamibi SPECT imaging at 1 or 6 weeks after revascularization. All thallium-201 and Tc-99m sestamibi images were interpreted by a consensus agreement of 3 experienced readers without knowledge of patient identity or time of imaging with Tc-99m sestamibi (before or after revascularization) using a 17-segment model. Concordance between techniques for the prediction of viability was 89% (κ 0.556 ± 0.109). With rest-redistribution thallium-201, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 95%, 59%, 88%, 78%, and 86%, respectively. With rest ECG-gated Tc-99m sestamibi SPECT imaging, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 96%, 55%, 87%, 80%, and 86%, respectively (p = NS vs rest-redistribution thallium-201). Although both techniques are comparable for detecting viable myocardium, rest ECG-gated Tc-99m sestamibi SPECT imaging allows direct assessment of both myocardial perfusion and ventricular function, which may be clinically useful in patients who require assessment of myocardial viability.

Power Doppler harmonic imaging: A feasibility study of a new technique for the assessment of myocardial perfusion

Background The aim of the study was to assess the feasibility of a new technique, power Doppler harmonic imaging (PDHI), for assessing myocardial perfusion through a venous injection of microbubbles, with the use of a new ultrasound contrast agent. Methods and Results Fifteen patients with known coronary artery disease and a resting perfusion abnormality on Tc-99m sestamibi single-photon emission computed tomography (SPECT) underwent PDHI at rest during intravenous injections of 2 to 3 mL of Sonovue (Bracco SpA, Milan, Italy), a new second-generation ultrasound contrast agent. Myocardial perfusion was determined to be present or absent by use of a 5-segment model by 2 blinded observers for both PDHI and SPECT. Of a total of 75 possible myocardial segments, 7 (9%) were not analyzed because of obvious artifacts on PDHI. SPECT showed perfusion defects in 40 of the remaining 68 segments, whereas PDHI showed 39 defects. There was high concordance between the 2 imaging modalities for the presence (93%) as well as the location (96% for the anteroseptal region, 93% for the inferoposterior region, and 87% for the apical region) of the defects. Conclusions These preliminary results suggest that PDHI is a feasible technique for the detection of resting myocardial perfusion defects in patients with coronary artery disease after a venous injection of a new second-generation ultrasound contrast agent.

Accuracy of dobutamine technetium 99m sestamibi SPECT imaging for the diagnosis of single-vessel coronary artery disease: Comparison with echocardiography

Background Recent experimental studies have shown that technetium 99m methoxyisobutyl isonitrile (MIBI) underestimates flow heterogeneity induced by dobutamine and that this might have an impact on the sensitivity of dobutamine M1131 in patients with single-vessel coronary artery disease (CAD). This study compares the accuracy of dobutamine MIBI single-photon emission computed tomography (SPECT) and simultaneous echocardiography in the diagnosis of single-vessel CAD. Methods and Results Ninety-one patients age 57 ± 12 years) with single-vessel CAD or without significant CAD were studied with dobutamine up to 40 μg/kg per minute)-atropine up to 1 mg) stress echocardiography DSE) and simultaneous MIBI SPECT imaging. CAD was predicted on the basis of myocardial ischemia transient wall motion abnormalities by DSE and reversible perfusion defects by MIBI). Ischemia was detected by MIBI in 30 of the 54 patients with and in 10 of the 37 patients without significant single-vessel CAD sensitivity 56%, confidence interval [cl]45 to 66; specificity 73%, Cl 64 to 82; accuracy 63%, Cl 53 to 73). Ischemia was detected by DSE in 30 patients with and in 6 patients without significant CAD (sensitivity of DSE 56%, Cl 45 to 66; specificity 84%, Cl 76 to 91; accuracy 67%, CI 57 to 77, P = not significant vs MIBI). For both imaging methods, sensitivity was significantly higher in patients with left anterior descending than in patients with left circumflex or right coronary artery stenosis (75% vs 40%, P < .05). The addition of echocardiography to MIBI did not improve the diagnostic accuracy (68% Cl 59 to 78, P = not significant vs DSE or MIBI alone). Conclusions DSE and MIBI SPECT imaging have similar moderate sensitivity for the diagnosis of single-vessel CAD. Sensitivity of each of these techniques is higher in patients with left anterior descending than in patients with left circumflex or right coronary artery stenosis. There is no improvement of diagnostic accuracy by use of the combination of both techniques.

Incremental prognostic value of rest-redistribution (201)Tl single-photon emission computed tomography.

The incremental prognostic value of rest-redistribution (201)Tl compared with stress and rest perfusion abnormalities has not been defined. We identified 458 patients who underwent rest (201)Tl /stress (exercise or adenosine) (99m)Tc sestamibi single-photon emission computed tomography (SPECT) and had late (18 to 24 hours) (201)Tl imaging, were not revascularized within 60 days of SPECT, and were followed up at >1 year. SPECT images were visually analyzed with the use of a 20-segment model on a scale of 0 to 4. Thirty-seven cardiac deaths (CDs) and 17 nonfatal myocardial infarctions occurred. Univariate Cox proportional hazards analysis showed that the presence of a large amount of rest (201)Tl reversibility (rest-late summed difference score [SDS] of >8) was a significant predictor of CD (chi(2) = 5.77, P = 0.02) and CD or myocardial infarction (chi(2) = 5.3, P = 0.02). The CD rate was 9.3% y(-1) in patients with rest-late SDS of >8 compared with 3.6% y(-1) in patients with a mild/moderate amount of rest reversibility (rest-late SDS 3 to 8) and 3.4% y(-1) in patients with no rest reversibility (rest-late SDS <3) (P = 0.029). Kaplan-Meier survival analysis demonstrated significantly lower cumulative survival rates in patients with rest-late SDS of >8 (P = 0.01). Multivariate Cox proportional hazards analysis demonstrated that the presence of a large amount of resting reversibility was an independent and incremental predictor of CD after adjustment for stress and rest perfusion information. Multivariate logistic regression analysis demonstrated that resting reversibility was not an independent predictor of referral to coronary angiography and revascularization. The identification of a large amount of resting (201)Tl reversibility is an independent predictor of CD over stress and rest perfusion abnormalities.

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: Results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) Trial

OBJECTIVESThe Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size.BACKGROUNDReperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects.METHODSThe AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6 ± 1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke).RESULTSIn all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89).CONCLUSIONSMany agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Comparison of dobutamine echocardiography, dobutamine sestamibi, and rest-redistribution thallium-201 single-photon emission computed tomography for determining contractile reserve and myocardial ischemia in ischemic cardiomyopathy

Both dobutamine stress echocardiography (DSE) and myocardial perfusion scintigraphy are used to assess myocardial viability. Few studies have compared the data on myocardial viability and ischemia by low and peak dose DSE and myocardial perfusion imaging in the same patients. Fifty-four patients (45 men and 9 women aged 65 ± 9 years) with ischemic cardiomyopathy (mean ejection fraction 24 ± 9%) underwent rest 4-hour redistribution thallium-201 single-photon emission computed tomography (SPECT), low and peak dose DSE, and dobutamine sestamibi SPECT. A total of 864 segments were analyzed (16 segments/patient). Wall motion abnormality was present in 796 segments (92%), and contractile reserve during dobutamine infusion was seen in 400 of these segments (50%). Contractile reserve was seen in 331 of 509 hypokinetic segments (65%) and 69 of 287 akinetic/dyskinetic segments (24%) (p <0.001). Contractile reserve was more frequent in segments with normal thallium uptake (64%), reversible thallium defects (42%), or mild to moderate fixed thallium defects (48%) than severely fixed defects (22%) (p <0.05 each). Concordant information about viability by thallium imaging and DSE was obtained in 62% of segments. Dobutamine sestamibi ischemia was seen in 518 of 796 segments (65%) compared with 265 segments (33%) by DSE (p <0.001). Scintigraphic ischemia was noted in 126 of 195 segments (65%) demonstrating biphasic response, 129 of 205 segments (63%) showing sustained improvement, 42 of 70 segments (60%) deteriorating during dobutamine infusion, and 221 of 326 (68%) demonstrating no change (p = NS). Thus, in patients with ischemic cardiomyopathy, contractile reserve is more frequent in hypokinetic segments than akinetic/dyskinetic segments. The number of segments with normal or near-normal thallium uptake or with scintigraphic ischemia is significantly greater than the number of those capable of increasing contractile function or demonstrating an ischemic response during dobutamine echocardiography.

Gene therapy for myocardial angiogenesis

In patients in whom antianginal medications fail to provide sufficient symptomatic relief, additional interventions such as angioplasty or bypass surgery may be required. Although both types of intervention have been shown to be effective for various types of patients, a certain group of patients may not be candidates for either intervention because of the diffuse nature of their coronary artery disease. Moreover, there are many patients in whom recurrent narrowing and/or occlusion of bypass conduits after initially successful surgery has left the patient again symptomatic with no further angioplasty or surgical option. Ischemic muscle represents a promising target for gene therapy with naked plasmid DNA. Intramuscular transfection of genes encoding angiogenic cytokines, particularly those naturally secreted by intact cells, may constitute an alternative treatment strategy for patients with extensive tissue ischemia in whom contemporary therapies (antianginal medications, angioplasty, bypass surgery) have previously failed or are not feasible. This strategy is designed to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries, a strategy termed “therapeutic angiogenesis.” Preclinical animal studies from our laboratory have established that intramuscular gene transfer may be used to successfully accomplish therapeutic angiogenesis. More recently, phase 1 clinical studies from our institution have established that intramuscular gene transfer may be used to safely and successfully accomplish therapeutic angiogenesis in patients with critical limb ischemia. The notion that this concept could be extrapolated to the treatment of chronic myocardial ischemia was demonstrated in our laboratory by administering recombinant human vascular endothelial growth factor (VEGF) to a porcine model of chronic myocardial ischemia. Recent experiments performed in this same porcine model of myocardial ischemia have shown that direct intramyocardial gene transfer of naked plasmid DNA encoding VEGF (phVEGF 165, the identical plasmid used in our previous animal and human clinical trials) can be safely and successfully achieved through a minimally invasive chest wall incision. Finally, initial results have supported the concept that intramyocardial injection of naked plasmid DNA encoding VEGF can achieve therapeutic angiogenesis, as demonstrated by clinical improvement in patient symptoms and improved myocardial perfusion shown by single-photon emission computed tomography–sestamibi imaging. (Am Heart J 1999;138:S132-S141.)

Transient left ventricular dilation at quantitative stress-rest sestamibi tomography: Clinical, electrocardiographic, and angiographic correlates

Background. Few data are available regarding the incidence and significance of transient left ventricular (LV) dilation on stress sestamibi single photon emission computed tomography (SPECT), which is different from thallium-201 studies because images are acquired late after tracer injection. Methods. We studied 234 patients with ischemic heart disease and interpretable electrocardiograms undergoing stress-rest sestamibi SPECT on separate days. Sestamibi uptake defect extent was quantified on SPECT polar maps. Epicardial and endocardial transient dilation indexes (TDI) were also calculated. Results. According to our normal TDI values, 148 patients (63%) had no dilation and 86 patients (37%) had abnormal endocardial TDI; a global LV dilation (abnormal endocardial and epicardial TDI) was observed in 19 patients (8%). ST-segment depression was more frequent in patients with transient LV dilation (55%) than in those without (36%; P <.01), as were the extent of stress hypoperfusion (13% ± 12% vs 6% ± 7% in patients with no dilation; P <.001) and the angiographic severity score (11.4 ± 5.9 vs 9.2 ± 3.7; P < .05). At multivariate analysis, stress hypoperfusion was the sole predictor of transient LV dilation. Conclusions. Transient LV cavity dilation is frequent on stress sestamibi SPECT. Ventricular cavity dilation is more common than global dilation and suggests subendocardial ischemia. It is related to a greater amount of jeopardized myocardium and is strongly associated with electrocardiographic signs of ischemia.

Comparative performance of gated perfusion SPECT wall thickening, delayed thallium uptake, and F-18 fluorodeoxyglucose SPECT in detecting myocardial viability

To evaluate the comparative abilities of gated single photon emission computed tomography (SPECT) wall thickening, delayed thallium-201 (Tl-201) SPECT, and F-18 fluorodeoxyglucose (FDG) SPECT in detecting myocardial viability, 23 patients with previous myocardial infarction and clinically suspected viability were studied. Each patient had at least 1 extensive fixed perfusion defect on rest/stress technetium-99m sestamibi SPECT. A total of 41 major vascular territories had fixed defects. The mean (± SD) left ventricular ejection fraction determined from gated perfusion SPECT was 26% ± 11%. Wall thickening was assessed in a semiquantitative fashion by the regional increase in myocardial intensity during systole and was considered normal when a ≥20% increase was observed. Tl-201 SPECT was acquired 4 hours after resting tracer injection was administered. Viability was considered present when regional defect Tl-201 count density, determined by quantitative analysis, was >20% greater than that on the resting sestamibi scan. FDG SPECT was performed independently with a 10 mCi F-18 FDG dose after oral glucose loading was performed. A camera equipped with ultrahigh energy collimation was used. Quantitative criteria for viability were the same as for Tl-201. In the 23 patients viability within the fixed sestamibi defects was manifest by preserved wall thickening in 8 patients, delayed Tl-201 uptake in 10 patients, and FDG uptake in 18 patients. Nine major vascular territories with fixed defects were judged viable by wall thickening, 11 by Tl-201 SPECT, and 24 by FDG SPECT ( P = .0009). We conclude that FDG SPECT demonstrates more evidence of myocardial viability than either gated sestamibi wall thickening or delayed Tl-201 SPECT.

The prognostic value of a normal Tc-99m sestamibi SPECT study in suspected coronary artery disease

Background. Myocardial perfusion is widely used for risk stratification of patients with suspected or known coronary artery disease (CAD). Recent years have seen an increasing demand for screening of such patients. The value of a normal stress thallium-201 scanning is well established. The advent of technetium 99m-sestamibi single photon emission computed tomography (SPECT) has enhanced the profile of nuclear cardiology even further as a reliable test for screening. However, in spite of previous reports, there is paucity of large-scale data regarding the prognostic value of a normal Tc 99m-sestamibi scanning result. Methods. The aim of our study was to assess the incidence of cardiac death and non-fatal myocardial infarction in patients with an intermediate probability of coronary artery disease (CAD). A total of 473 patients with normal stress Tc-99m-sestamibi SPECT were monitored for 30 ± 16 (6 to 56) months to assess serious cardiac events. There were 272 men and 201 women, with a mean age of 56 ± 2 years, of whom 89% had symptoms suggestive of CAD, 65% had an abnormal exercise electrocardiography, 6% had known CAD, and 5% had a high risk of CAD. The average workload was 9.14 metabolic equivalents, peak exercise heart rate was 93% ± 13% of the age predicted target. Results. The annualized mortality rate was 0.2% (95% CI 0.02% to 0.7%) and no infarctions occurred in this group. Conclusions. A normal stress Tc-99m-sestamibi is highly predictive of a benign outcome, even in patients with intermediate probability of CAD.

Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging

Background. Previous studies have shown that gated single photon emission computed tomography (SPECT) technetium 99-labeled sestamibi imaging provides accurate and reproducible measurement of left ventricular (LV) ejection fraction (EF), wall motion, and thickening. This study examined the reliability of gated SPECT sestamibi imaging in measuring LV end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV). Methods and Results. Gated SPECT measurements were compared with an independent nongeometrie method based on thermodilution SV and first-pass radionuclide angiographic EF (using a multicrystal gamma camera). Twenty-four patients aged 58 ± 11 years underwent cardiac catheterization and coronary angiography for evaluation of chest pain syndromes. None had primary valvular disease, intracardiac shunts, or atrial fibrillation. Results. The correlation between the two methods were as follows: EDV: r = 0.89, P < .001; ESV: r = .938, P < .001; SV: r = 0.577, P < .001. Bland-Altman plots showed mean differences (± standard deviation [SD]) for EDV of −14.3 ± 33.3 mL, for ESV of −0.4 ± 23.7 mL, and for SV of −13.9 ± 15.2 mL. The reproducibility of measuring EDV and ESV by gated SPECT was very high (r = 0.99 each). Conclusion. Gated 99mTc-labeled sestamibi SPECT provides reproducible LV volume measurements. With validation of volume measurement, gated SPECT provides comprehensive assessment of regional and global LV function. This information is important in many patient groups such as those with ischemic cardiomyopathy, concomitant coronary and valve disease, and those who have had myocardial infarction. It will also be useful to assess the incremental value of LV volumes in risk assessment.