High-frequency QRS analysis to supplement ST evaluation in exercise stress electrocardiography: Incremental diagnostic accuracy and net reclassification.

BACKGROUND: Exercise stress electrocardiography (ECG) alone is underutilized in part due to poor diagnostic accuracy. High-frequency QRS analysis (HF-QRS) is a novel tool to supplement ST evaluation during stress ECG. We compared the diagnostic accuracy and net reclassification of HF-QRS analysis compared with ST evaluation for substantial myocardial ischemia by exercise SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: Exercise SPECT MPI was performed in 257 consecutive eligible patients (mean age 59 ± 12, 67% male). An ischemic HF-QRS pattern was defined as a ≥ 1 µV absolute reduction and a ≥ 50% relative reduction of the root-mean-square of the 150-250 Hz band signal in ≥ 3 leads. Left ventricular ischemia of ≥ 10% on SPECT MPI was the diagnostic standard for substantial myocardial ischemia. HF-QRS analysis demonstrated incremental diagnostic value to ST evaluation plus clinical risk factors (AUC 0.804 vs 0.749, P < .0001). A HF-QRS + ST -analysis strategy identified 92.3% of subjects with substantial ischemia and no abnormality in 59.9% of the cohort. No cardiac events occurred in patients without substantial ischemia identified by HF-QRS analysis. CONCLUSIONS: In this prospective analysis, exercise stress ECG with HF-QRS analysis identified any and substantial ischemia with high diagnostic accuracy and may allow more than half of referred patients to safely avoid imaging.

The prevalence and predictive accuracy of quantitatively defined transient ischemic dilation of the left ventricle on otherwise normal SPECT myocardial perfusion imaging studies.

AIM: TID in the setting of otherwise normal MPI has been suggested as a marker of high risk CAD. In this study we estimate the variance of TID in a normal population and the statistical frequency of false positive TID. This will provide an indirect measurement of predictive accuracy (PA) in a mixed referral population. OBJECTIVE: To study the PA of TID in otherwise normal MPI. METHODS: 688 consecutive patients were studied. We defined TID according to the standard method at 2 cut-off values; 1SD and 2SD, and also by a BSA normalized volume difference with gender-specific 2SD limits (NrVD). RESULTS: 457 patients with otherwise normal MPI were analyzed. PA of TID at 1SD was 4% and 26% at 2SD. PA was slightly higher (42%) using the NrVD, however, still too low to be clinically useful as a high-risk marker. PA of TID in patients with perfusion abnormalities was 58% at 1SD, 80% at 2SD and slightly higher (93%) by NrVD. CONCLUSIONS: In the setting of otherwise normal MPI, elevated TIDr has a low prevalence and poor predictive accuracy and should not be considered summarily as a marker of high risk CAD.

Prognosis in patients achieving ≥10 METS on exercise stress testing: was SPECT imaging useful?

BACKGROUND: The benefit of myocardial perfusion imaging (MPI) over exercise ECG stress testing alone is unclear in individuals attaining a workload of ≥10 METS. The purpose of this prospective study is to determine mortality and nonfatal cardiac events in patients at either intermediate pretest risk for CAD or patients with known CAD, achieving ≥10 METS regardless of peak exercise heart rate. The authors previously reported a low prevalence of significant ischemia in this patient cohort. METHODS: Baseline characteristics, ECG stress test findings, and perfusion and function results from quantitative gated (99m)Tc-SPECT MPI were compared by achievement of a maximum age-predicted heart rate ≥85% in 509 consecutive patients who reached ≥10 METS. Events including all-cause and cardiac mortality, non-fatal myocardial infarction (MI), and late revascularization (>4 weeks after MPI) were prospectively collected. RESULTS: Of the 509 patients achieving ≥10 METS, follow-up for mortality was obtained in 463 (91%). Those lost to follow-up were older and had higher rates of tobacco use. The prevalences of CAD risk factors, prior known CAD, and MPI abnormalities were higher for the 68 patients failing to reach 85% of their target heart rate. The rate of ≥10% left-ventricular (LV) ischemia by MPI remained very low irrespective of attained heart rate (0.6% (3/463)). Six (1.2%) had an LVEF < 40%. Death occurred in 12 (2.6%) patients, one of which was classified as cardiac (0.1%/year). The other 11 deaths were related to cancer. Additionally, there were three nonfatal MIs (0.7 %) and one late revascularization (0.2%). Only one of these patients had any ischemia on MPI. No cardiac event patient had exercise ST depression or ≥5% LV ischemia. CONCLUSIONS: Thus, patients at intermediate risk for CAD or known CAD achieving ≥10 METS have a very low prevalence of ≥10% LV ischemia and very low rates of cardiac mortality, nonfatal MI, and late revascularization, irrespective of heart rate achieved. Cardiac events did not correlate with abnormalities on the index MPI study. These results suggest that patients who attain ≥10 METS during exercise stress have an excellent prognosis over an intermediate term of follow-up, regardless of peak exercise heart rate achieved. The added value of MPI to standard exercise ECG testing in this population is questionable.

Comparison between angiography and fractional flow reserve versus single-photon emission computed tomographic myocardial perfusion imaging for determining lesion significance in patients with multivessel coronary disease.

We hypothesized that myocardial perfusion imaging (MPI) would fail to identify all vascular zones with the potential for myocardial ischemia in patients with multivessel coronary disease (MVD). MPI is based on the concept of relative flow reserve. The ability of these techniques to determine the significance of a particular stenosis in the setting of MVD is questionable. Fractional flow reserve (FFR) can determine the significance of individual stenoses. Thirty-six patients with disease involving 88 arteries underwent angiography, FFR, and MPI. FFR was performed using a pressure wire with hyperemia from intracoronary adenosine. Myocardial perfusion images were analyzed quantitatively and segments assigned to a specific coronary artery. The relation between FFR and perfusion was determined for each vascular zone. Of the 88 vessels, the artery was occluded (n=20) or had an abnormal FFR

The role of quantitation in clinical nuclear cardiology: the University of Virginia approach.

Measurement of regional myocardial tracer concentration after stress and at rest allows the establishment of normal standards for myocardial perfusion and reversibility and provides a reference from which to determine disease severity and change in response to treatment. Using the partial-volume effect, we can also conveniently estimate regional myocardial thickening fractions corresponding to the same segments used for perfusion quantitation. This adds close comparison of perfusion and function as an aid to viability assessment and for recognition of possible ischemic dysfunction in cases of balanced ischemia or globally exhausted coronary flow reserve. Volume measurements are added to routinely determine body surface area-normalized end-systolic and end-diastolic volume indices. Left ventricular ejection fraction is estimated from both volume measurements and from regional thickening fractions. Reduced regional thickening fractions and elevated end-systolic volume index are early indicators of myopathy, and these measurements may add significant information to the traditional perfusion study, particularly in cases of hypertrophy and diastolic dysfunction.

Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses.

BACKGROUND: Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses. METHODS AND RESULTS: At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92+/-0.11 versus 0.51 +/- 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N-DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin. CONCLUSIONS: Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.

Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease.

OBJECTIVES: We hypothesized that combining functional assessment to perfusion enhances the ability of electrocardiographic gating Tc-99m sestamibi single photon emission computed tomography (gated SPECT) myocardial perfusion imaging (MPI) to detect defects in multiple vascular territories in patients with severe three-vessel coronary artery disease (3VD). BACKGROUND: In patients with 3VD, perfusion defects in multiple vascular territories may not always be evident due to globally reduced perfusion. METHODS: Gated SPECT MPIs were interpreted sequentially with perfusion first, followed by combined perfusion/function, in 143 patients with angiographic 3VD and a control group of 112 non-3VD patients. All patients underwent coronary arteriography within one month of MPI. RESULTS: In 3VD patients, combined perfusion/function analysis yielded significantly greater numbers of abnormal segments/patient (6.2 +/- 4.7 vs. 4.1 +/- 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. In the control group, there were no differences between the combined perfusion/function and perfusion alone interpretations. Multivariate analysis of 15 different clinical, stress, and scintigraphic variables in all patients revealed age (p < 0.0001) and number of abnormal vascular territories by combined perfusion/function (p < 0.0001) to be the most powerful predictors of 3VD. Addition of functional data to clinical, stress, and perfusion yielded a significant increase in the predictive value of 3VD (global chi-square: 131.7 vs. 89.8, p < 0.00001). Specificity of combined perfusion/function analysis was not lower than perfusion alone (72% vs. 69%, p = NS). CONCLUSIONS; Adjunctive assessment of function with perfusion by gated SPECT MPI enhances the detection of defects in multiple vascular territories in patients with severe 3VD, without adversely affecting its specificity.

Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A(2A)-receptor-mediated coronary vasodilation.

OBJECTIVES: The study was done to determine the effects of propranolol, enalaprilat, verapamil, and caffeine on the vasodilatory properties of the adenosine A(2A)-receptor agonist ATL-146e (ATL). BACKGROUND: ATL is a new adenosine A(2A)-receptor agonist proposed as a vasodilator for myocardial stress perfusion imaging. Beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium blockers are commonly used for the treatment of coronary artery disease (CAD), and their effect on ATL-mediated vasodilation is unknown. Dietary intake of caffeine is also common. METHODS: In 19 anesthetized, open-chest dogs, hemodynamic responses to bolus injections of ATL (1.0 microg/kg) and adenosine (60 microg/kg) were recorded before and after administration of propranolol (1.0 mg/kg, ATL only), enalaprilat (0.3 mg/kg, ATL only), caffeine (5.0 mg/kg, ATL only), and verapamil (0.2 mg/kg bolus, ATL and adenosine). RESULTS: Neither propranolol nor enalaprilat attenuated the ATL-mediated vasodilation (225 +/- 86% and 237 +/- 67% increase, respectively, p = NS vs. control). Caffeine had an inhibitory effect (97 +/- 28% increase, p < 0.05 vs. control). Verapamil blunted both ATL- and adenosine-induced vasodilation (63 +/- 20% and 35 +/- 7%, respectively, p < 0.05 vs. baseline), and also inhibited the vasodilation induced by the adenosine triphosphate-sensitive potassium (K(ATP)) channel activator pinacidil. CONCLUSIONS: Beta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A(2A)-agonists, whereas verapamil attenuated this vasodilation through inhibition of K(ATP) channels. The inhibitory effect of verapamil and K(ATP) channel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A(2A)-receptor agonists should be evaluated in the clinical setting to determine their potential for reducing the sensitivity of CAD detection with perfusion imaging.

The effects of enhanced external counterpulsation on myocardial perfusion in patients with stable angina: a multicenter radionuclide study.

BACKGROUND: Enhanced external counterpulsation (EECP) reduces angina and extends time to exercise-induced ischemia in patients with symptomatic coronary disease. One- and two-center studies and a retrospective case series reported that EECP improves myocardial perfusion in stable angina pectoris. We sought to critically evaluate and quantify the effect of EECP on myocardial perfusion. METHODS: In 6 US university hospitals, EECP was performed for 35 hours in patients with class II to IV angina who had exercise-induced myocardial ischemia. Symptom-limited quantitative gated technetium Tc 99m sestamibi single photon emission computed tomography exercise perfusion imaging was performed at baseline and 1 month post-EECP. Sestamibi was injected at the same heart rate in both stress tests. Single photon emission computed tomography images were read at a blinded core laboratory. RESULTS: Thirty-seven patients were enrolled, 34 of whom completed pre- and post-EECP stress testing. The mean age was 61 +/- 10 years, 81% were male, 78% had prior revascularization, and 68% had 3-vessel disease. The mean angina class decreased from 2.7 +/- 0.7 at baseline to 1.7 +/- 0.7 after EECP (P < .001). Exercise duration increased from 9.1 +/- 3.7 minutes at baseline to 10.2 +/- 3.6 minutes post-EECP (P = .03). The average percentage of tracer uptake, magnitude of reversibility, average thickening fraction, and the left ventricular ejection fraction remained unchanged after EECP. CONCLUSIONS: We confirm previous report that EECP reduces angina and improves exercise capacity. There were no significant changes in mean defect magnitude, amount of reversibility, thickening fraction, and ejection fraction measured using myocardial quantitative single photon emission computed tomography imaging when compared at identical pre- and post-EECP heart rates.

Incremental value of cardiac imaging in patients presenting to the emergency department with chest pain and without ST-segment elevation: a multicenter study.

BACKGROUND: We hypothesized that imaging of regional myocardial function (RF) and perfusion (PER) will add incremental value for both diagnosis and short-term prognosis to routine demographic, clinical, and electrocardiographic findings in patients presenting to the emergency department (ED) with chest pain and without ST-segment elevation on the electrocardiogram. METHODS: We compared contrast echocardiography (CE) with gated single-photon emission computed tomography (SPECT) for this purpose. Both CE and SPECT readings included separate and composite assessments of both RF and PER. Adverse events in the first 48 hours after ED presentation included acute myocardial infarction, emergent revascularization, and cardiac-related death. RESULTS: Concordance between CE and SPECT was 77% (73% to 82%) for all territories, with a higher concordance for the anterior wall of 84% (78% to 89%). Of the 203 patients recruited for the study, 38 (19%) had a cardiac event within 48 hours of ED presentation: 21 had acute myocardial infarction, 16 underwent an urgent revascularization procedure, and 1 died. In multivariate logistic regression models, the number of abnormal segments on CE and SPECT were significant predictors (P <.05) of cardiac events. The composite scores on CE provided 17% incremental information (P =.009, n = 203) and gated SPECT provided 23.5% additional information (P =.020, n = 163) for predicting cardiac events compared with routine demographic, clinical, and electrocardiographic variables. RF and composite evaluation was superior on SPECT compared with CE, whereas PER alone was not. CONCLUSIONS: Cardiac imaging of RF and PER at the time of ED presentation offers substantially greater diagnostic and prognostic information for early cardiac events in patients presenting to the ED with chest pain and no ST elevation than does the routine demographic, clinical, and electrocardiographic assessment.

Arbutamine stress perfusion imaging in dogs with critical coronary artery stenoses: (99m)Tc-sestamibi versus (201)Tl.

UNLABELLED: Having previously shown that dobutamine reduces (99m)Tc-methoxyisobutylisonitrile (sestamibi [MIBI]) uptake in normal myocardium by elevating intracellular calcium, we hypothesized that arbutamine, which has less inotropic effect than dobutamine, might cause less reduction in MIBI uptake, thereby improving defect contrast. In this study using a canine model, we compared the effects of arbutamine stress on myocardial blood flow, myocardial MIBI uptake, and systolic thickening in the presence of a coronary artery stenosis. METHODS: Arbutamine was infused (0.5-250 ng/kg/min) in 8 open-chest dogs with critical coronary stenoses that abolished flow reserve. At the time of peak arbutamine effect, MIBI (296 MBq), (201)Tl (27.75 MBq), and microspheres were coinjected. The dogs were killed 5 min later, and myocardial tracer activities and flow were quantified by well counting. Ex vivo imaging of heart slices was also performed. RESULTS: Arbutamine increased mean heart rate, peak positive left ventricular pressure and its first time-derivative, and normal-zone myocardial thickening. Stenotic zone flow and thickening did not increase during arbutamine infusion. MIBI uptake versus flow was significantly lower than (201)Tl uptake at the same flow values. By imaging, defect magnitude (stenotic/normal) was greater for (201)Tl than MIBI (0.57 vs. 0.77; P < 0.001) [corrected]. CONCLUSION: In the presence of coronary stenoses that abolished regional flow reserve, myocardial uptake of MIBI, compared with (201)Tl, significantly underestimated the arbutamine-induced flow heterogeneity. The attenuation of MIBI uptake and diminished defect contrast during arbutamine stress were comparable with those previously reported for dobutamine stress.

Effects of increased lipid concentration and hyperemic blood flow on the intrinsic myocardial washout kinetics of (99m)TcN-NOET.

UNLABELLED: Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a myocardial perfusion imaging agent demonstrating significant redistribution and currently in phase III clinical trials. Previous studies have suggested that (99m)TcN-NOET is bound intravascularly. Therefore, we sought to determine whether modifications in the vascular compartment would provide further insights into the mechanisms of (99m)TcN-NOET myocardial washout and redistribution. METHODS: (99m)TcN-NOET cardiac washout was studied ex vivo in 15 isolated perfused rat hearts after bolus injection (1.5 MBq) in the absence (n = 6) or presence of bovine serum albumin ([BSA] 0.03%) with (n = 5) or without (n = 4) bound lipids. The intrinsic myocardial washout of the tracer was also studied in vivo in 6 dogs after intracoronary bolus injection of the tracer (0.75 MBq) before and after hyperlipidemia induced by intravenous administration of 300 mL of 20% intralipids (n = 3) or hyperemia induced by intravenous infusion of the adenosine A(2A) receptor agonist ATL-146e (0.3 micro g/kg/min; n = 6). RESULTS: On isolated hearts, there was no significant myocardial washout of (99m)TcN-NOET with Krebs-Henseleit buffer. Addition of BSA without bound lipids resulted in a significant cardiac washout of the tracer (P < 0.001 by repeated measures ANOVA). The presence of lipids bound to BSA further accelerated the washout rate of (99m)TcN-NOET (half-life [t(1/2)], 431.5 +/- 23.2 min vs. 242.9 +/- 63.2 min; P < 0.05). In vivo in dogs, intralipid administration significantly increased the intrinsic washout rate of (99m)TcN-NOET (t(1/2), 108.0 +/- 23.9 min vs. 51.8 +/- 11.8 min; P < 0.05). In addition, vasodilatation with ATL-146e resulted in a 4.9-fold increase in coronary flow (P < 0.05 vs. baseline) and a significantly faster intrinsic (99m)TcN-NOET myocardial washout (t(1/2), 81.1 +/- 12.1 min vs. 40.7 +/- 7.3 min; P < 0.05). CONCLUSION: The myocardial washout kinetics of (99m)TcN-NOET are affected by a variety of intravascular factors, supporting the hypothesis that the tracer is most likely localized on the vascular endothelium. The potential impact of variations in circulating lipid levels among patients on clinical imaging with (99m)TcN-NOET requires further investigation.

99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats.

UNLABELLED: (99m)Tc-[bis (dimethoxypropylphosphinoethyl)-ethoxyethylamine (PNP5)]-[bis (N-ethoxyethyl)-dithiocarbamato (DBODC)] nitride (N-PNP5-DBODC or N-DBODC5) is a new monocationic myocardial perfusion tracer. We sought to compare the myocardial uptake and clearance kinetics and organ biodistribution of (99m)Tc-N-DBODC5 with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. METHODS: Seventy-five anesthetized Sprague-Dawley rats were injected intravenously with 22.2-29.6 MBq (99m)Tc-N-DBODC5 (n = 25), (99m)Tc-sestamibi (n = 25), or (99m)Tc-tetrofosmin (n = 25). Rats were euthanized at either 2, 10, 20, 30, or 60 min after injection and gamma-well counting was performed on excised organ (heart, lung, and liver) and blood samples. In 3 additional rats, serial in vivo whole-body gamma-camera imaging with each tracer was performed. RESULTS: (99m)Tc-N-DBODC5 cleared rapidly from the blood pool. At 2 min after injection, (99m)Tc-N-DBODC5 blood activity was significantly lower than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin (P < 0.01) and remained lower over 60 min. Myocardial (99m)Tc-N-DBODC5 uptake was rapid (2.9% +/- 0.1% injected dose/g at 2 min), and there was no significant clearance over 60 min, similar to (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. All 3 tracers exhibited rapid lung clearance. Importantly, (99m)Tc-N-DBODC5 cleared more rapidly from the liver than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin. As early as 30 min after injection, (99m)Tc-N-DBODC5 heart-to-liver ratio was 5.7 +/- 1.0 versus 1.6 +/- 0.1 and 2.9 +/- 0.3 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.05). By 60 min, (99m)Tc-N-DBODC5 heart-to-liver ratio further increased to 18.4 +/- 2.0 compared with 2.6 +/- 0.2 and 5.8 +/- 0.7 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.001). The rapid blood pool, lung, and liver clearance of (99m)Tc-N-DBODC5 resulted in excellent-quality myocardial images within 30 min after injection. CONCLUSION: (99m)Tc-N-DBODC5 is a promising new myocardial perfusion tracer with superior biodistribution properties. The rapid (99m)Tc-N-DBODC5 liver clearance may shorten the duration of imaging protocols by allowing earlier image acquisition and may markedly reduce the problem of photon scatter from the liver into the inferoapical wall on myocardial images.

Electromechanical mapping for detecting myocardial viability and ischemia in patients with severe ischemic cardiomyopathy.

This study was designed to evaluate several electromechanical mapping parameters for assessment of myocardial viability and inducible ischemia as defined by dipyridamole single-photon emission computed tomographic (SPECT) imaging at rest in patients with severe ischemic cardiomyopathy. Unipolar voltage, normalized unipolar voltage, bipolar voltage, and fragmentation were compared with tracer uptake at rest and reversibility on stress or rest quantitative technetium-99m sestamibi SPECT imaging in 32 patients with severe ischemic cardiomyopathy (left ventricular ejection fraction 0.24 +/- 0.08). In dysfunctional myocardial segments, logistic regression showed unipolar voltage, normalized unipolar voltage, and bipolar voltage to be predictive of viable myocardium (> or = 60% tracer uptake at rest) and was significantly higher in viable than in nonviable segments (p <0.01). A unipolar voltage of > or = 7.1 mV was the best predictor of viable myocardium. In dysfunctional viable segments, unipolar voltage was significantly higher in reversible than in fixed segments (p <0.001), and a unipolar voltage of > or = 8.5 mV had optimal power for identifying reversibility on dipyridamole SPECT imaging. We conclude that in patients with severe ischemic cardiomyopathy, unipolar voltage can identify viable from nonviable myocardium and reversible from fixed viable defects as defined by dipyridamole technetium-99m sestamibi SPECT imaging.

Prevalence and predictors of ischemia and outcomes in outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging.

Background- The prevalence of ischemia and its prediction of events are unclear in outpatients with diabetes mellitus in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of sex, stress type, and symptom status on these findings in a cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging (MPI). Methods and Results- The study cohort included 575 consecutive outpatients with diabetes mellitus who underwent quantitative, gated single-photon emission computed tomography MPI. Clinical information, stress MPI variables, and cardiac events were prospectively collected and analyzed. The study population was at intermediate risk of coronary artery disease or had known coronary artery disease (40.3%); 29% of patients were asymptomatic at the time of stress testing. Scintigraphic ischemia and significant (≥10%) left ventricular ischemia were present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of patients had early revascularization. The risk of ischemia was increased >2-fold by male sex (P<0.001), but was not impacted by pharmacological stress (P=0.15) or presence of symptoms (P=0.89). During a median 4.4 years follow-up, the rate of cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia (P<0.001). Pharmacological stress predicted a higher cardiac event rate (P<0.001) but symptoms did not (P=0.55). Conclusions- This cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography had low rates of significant ischemia and early revascularization; an initially low cardiac event rate increased after 2 years. Independent predictors of cardiac death/nonfatal myocardial infarction were known coronary artery disease, pharmacological stress, and MPI ischemia. Nearly one third of those with events had a normal MPI, indicating a need for improved risk stratification.

Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.

BACKGROUND: There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model. METHODS AND RESULTS: The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). CONCLUSIONS: The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.