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Compared with conventional coronary angiography, spiral multidetector CT (MDCT) angiography has delivered promising accuracy in the detection and validation of coronary lesions. Myocardial perfusion imaging (MPI) using SPECT is an established method for noninvasively assessing the functional significance of coronary stenoses and delivers valuable information for risk stratification. This retrospective analysis compared the accuracies of MDCT angiography and MPI in the detection of hemodynamically relevant lesions of the coronary arteries. Twenty-five patients with suspected or known coronary artery disease were studied. Electrocardiographically gated MPI and 16-MDCT angiography were performed. Myocardial perfusion images were analyzed by 2 experienced observers, and reversible and fixed perfusion defects were detected and allocated to their corresponding coronary vessels. For the evaluation of MDCT angiography, image quality was determined, and lesions > or = 50% and luminal narrowing < 50% were visually assessed and characterized by 2 independent observers unaware of the results of MPI. Ninety-nine coronary vessels were analyzed, and the quality of MDCT angiography images was assessed for 330 coronary segments. Coronary artery diameter was interpretable for 231 (70%) of 330 segments, whereas in 99 (30%) of 330 segments, vessel diameter could not be evaluated because of heavy calcifications, blurring, motion artifacts, or intracoronary stents. MDCT angiography detected stenoses > or = 50% in 15 of 100 coronary arteries. Eight (53%) of 15 stenoses > or = 50% showed reversible or fixed perfusion defects in the corresponding myocardial areas on MPI. Sensitivity, specificity, and negative and positive predictive values were 100%, 87%, 100%, and 29%, respectively, for the ability of MDCT angiography to detect reversible perfusion defects in the corresponding myocardial areas. MDCT angiography detected myocardial ischemia, as defined by reversible perfusion defects on MPI, with a positive predictive value of 29% in a nonselected study cohort. Compared with MPI alone, MDCT angiography added important morphologic information, but MPI remains mandatory for evaluating the functional relevance of coronary artery lesions.

The goal of this study was to validate the accuracy of the Emory Cardiac Tool Box (ECTB) in assessing left ventricular end-diastolic or end-systolic volume (EDV, ESV) and ejection fraction (LVEF) from gated (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT using cardiac MRI (cMRI) as a reference. Furthermore, software-specific characteristics of ECTB were analyzed in comparison with 4D-MSPECT and Quantitative Gated SPECT (QGS) results (all relative to cMRI). Seventy patients with suspected or known coronary artery disease were examined using gated (99m)Tc-MIBI SPECT (8 gates/cardiac cycle) 60 min after tracer injection at rest. EDV, ESV, and LVEF were calculated from gated (99m)Tc-MIBI SPECT using ECTB, 4D-MSPECT, and QGS. Directly before or after gated SPECT, cMRI (20 gates/cardiac cycle) was performed as a reference. EDV, ESV, and LVEF were calculated using Simpson's rule. Correlation between results of gated (99m)Tc-MIBI SPECT and cMRI was high for EDV (R = 0.90 [ECTB], R = 0.88 [4D-MSPECT], R = 0.92 [QGS]), ESV (R = 0.94 [ECTB], R = 0.96 [4D-MSPECT], R = 0.96 [QGS]), and LVEF (R = 0.85 [ECTB], R = 0.87 [4D-MSPECT], R = 0.89 [QGS]). EDV (ECTB) did not differ significantly from cMRI, whereas 4D-MSPECT and QGS underestimated EDV significantly compared with cMRI (mean +/- SD: 131 +/- 43 mL [ECTB], 127 +/- 42 mL [4D-MSPECT], 120 +/- 38 mL [QGS], 137 +/- 36 mL [cMRI]). For ESV, only ECTB yielded values that were significantly lower than cMRI. For LVEF, ECTB and 4D-MSPECT values did not differ significantly from cMRI, whereas QGS values were significantly lower than cMRI (mean +/- SD: 62.7% +/- 13.7% [ECTB], 59.0% +/- 12.7% [4DM-SPECT], 53.2% +/- 11.5% [QGS], 60.6% +/- 13.9% [cMRI]). EDV, ESV, and LVEF as determined by ECTB, 4D-MSPECT, and QGS from gated (99m)Tc-MIBI SPECT agree over a wide range of clinically relevant values with cMRI. Nevertheless, any algorithm-inherent over- or underestimation of volumes and LVEF should be accounted for and an interchangeable use of different software packages should be avoided.

We previously reported that ranolazine improves exercise myocardial perfusion. Ranolazine ameliorates myocardial ischemia by augmenting myocardial blood flow; likely by a reduction in the extravascular compression of small vessels. We hypothesized that ranolazine could improve left ventricular (LV) dyssynchrony as assessed by phase analysis of gated single photon emission computed tomographic myocardial perfusion imaging. Patients (n = 32) with known or suspected coronary artery disease and reversible perfusion defects on a clinically indicated stress myocardial perfusion imaging were restudied 4 weeks after ranolazine (500 to 1,000 mg orally twice daily) was added to their conventional treatment in an open-label trial (data previously reported). The LV systolic and diastolic dyssynchrony indexes were obtained using automated phase analysis before and after ranolazine. No significant changes were found in the heart rate or blood pressure (at rest or during stress) after treatment. The perfusion pattern improved in 13 of 18 patients who had undergone exercise testing, but in only 3 of 14 patients who had undergone vasodilator stress testing. No significant changes were seen in the LV ejection fraction or volume after treatment. The systolic and diastolic LV dyssynchrony improved after ranolazine therapy; there was a significant decrease in the systolic phase SD (21 ± 17 vs 18 ± 13, p = 0.04), systolic bandwidth (69 ± 60 vs 53 ± 38, p = 0.03), diastolic SD (29 ± 18 vs 24 ± 15, p = 0.047) and diastolic bandwidth (91 ± 61 vs 72 ± 45, p = 0.02). In conclusion, the present study is the first to show improvements in diastolic and systolic LV synchrony with ranolazine as measured by automated phase analysis of gated single photon emission computed tomographic myocardial perfusion imaging.

Obesity is a growing problem in the United States, and attenuation artifacts are more prevalent in this patient group. This study evaluated the impact of attenuation correction in patients with a high body mass index (BMI). Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99m sestamibi myocardial perfusion imaging results in 116 patients (BMI <30, n = 60; BMI ≥30, n = 56) who had coronary angiography no more than 60 days after imaging. Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected. Sensitivity, specificity, and accuracy for detection of coronary artery disease of 70% or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography (SPECT) were 86% versus 89%, 79% versus 50%, and 84% versus 79%, respectively. Sensitivity, specificity, and accuracy for attenuation-corrected versus non-attenuation-corrected SPECT for patients with BMI less than 30 were 90% versus 90%, 82% versus 64%, and 88% versus 85%, respectively. For BMI of 30 or greater, the results were 82% versus 87%, 76% versus 41%, and 80% versus 73%, respectively. There was a significant difference in specificity overall ( P = .02) and for the category of BMI of 30 or greater ( P = .03). This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging, especially in patients with BMI of 30 or greater.

The purposes of this study were (a) to assess the feasibility of diastolic function (DFx) evaluation using standard 16-frame postexercise gated (99m)Tc-sestamibi myocardial perfusion SPECT (MPS), (b) to determine the relationship of the 2 common DFx parameters, peak filling rate (PFR) and time to peak filling (TTPF), to clinical and systolic function (SFx) variables in patients with normal myocardial perfusion and SFx, and (c) to derive and validate normal limits. Ninety patients (71 men; age, 30-79 y) with normal exercise gated MPS were studied. None had hypertension, diabetes, rest electrocardiogram abnormality, or known cardiac disease. All patients reached > or = 85% of maximum predicted heart rate (HR). The population was randomized into derivation (n = 50) and validation (n = 40) groups. Univariable and multivariable approaches were deployed to assess the influence of clinical and functional variables on DFx parameters. PFR and TTPF were assessed in all patients. Mean values of PFR and TTPF in the whole study population were 2.62 +/- 0.46 end-diastolic volumes per second (EDV/s) and 164.6 +/- 21.7 ms, respectively. By applying a 2-SD cutoff to the mean values in the derivation group, the threshold for abnormal PFR and the threshold for abnormal TTPF were < 1.71 EDV/s and > 216.7 ms, respectively. The normalcy rates in the validation group for PFR and TTPF were both 100%. The PFR showed weak but significant correlations with age, EDV, end-systolic volume, left ventricular ejection fraction (LVEF), and poststress HR. However, TTPF did not correlate with these parameters. Final normal thresholds determined from the combined populations were PFR = 1.70 EDV/s and TTPF = 208 ms. Multivariable analysis showed that age, sex, LVEF, and HR are strong predictors for PFR, whereas TTPF was not influenced by any clinical or SFx variable. With a new algorithm in QGS, assessment of LV DFx is feasible using 16-frame gated MPS even without bad-beat rejection, resulting in normal limits similar to those reported with gated blood-pool studies. However, due to the dependency of PFR on SFx parameters, sex, HR, and age, TTPF appears to be a stable and more useful parameter with this approach. The clinical usefulness of these findings requires further study.

Attenuation artifact remains a substantial limitation to confident interpretation of images and reduces laboratory efficiency by requiring comparison of stress and rest image sets. Attenuation-corrected stress-only imaging has the potential to ameliorate these limitations. Ten experienced nuclear cardiologists independently interpreted 90 stress-only electrocardiography (ECG)–gated technetium 99m sestamibi images in a sequential fashion: myocardial perfusion imaging (MPI) alone, MPI plus ECG-gated data, and attenuation-corrected MPI with ECG-gated data. Images were interpreted for diagnostic certainty (normal, probably normal, equivocal, probably abnormal, abnormal, and perceived need for rest imaging). With stress MPI data alone, only 37% of studies were interpreted as definitely normal or abnormal, with a very high perceived need for rest imaging (77%). The addition of gated data did not alter the interpretations. However, attenuation-corrected data significantly increased the number of studies characterized as definitely normal or abnormal (84%, P < .005) and significantly reduced the perceived need for rest imaging (43%, P < .005). These results were confirmed by use of a nonsequential consensus interpretation of three readers. Attenuation correction applied to studies with stress-only Tc-99m ECG-gated single photon emission computed tomography images significantly increases the ability to interpret studies as definitely normal or abnormal and reduces the need for rest imaging. These findings may improve laboratory efficiency and diagnostic accuracy.

Cardiac resynchronization therapy (CRT) improves symptoms and the survival rate in patients with advanced heart failure by improving synchrony. However, CRT is not always successful, is costly, and is applied without individualization. There is no specific measure of synchrony. The goal of this study was to analyze new quantitative parameters of synchrony and compare them with established measures. Equilibrium radionuclide angiography, phase angle (Ø), and amplitude quantitate regional contraction timing and magnitude and are the basis for new synchrony ( S) and entropy ( E) parameters. S is the vector sum of all amplitudes based on the angular distribution of Ø divided by the scalar sum of the length of all vectors. Complete S equals 1, and its absence equals 0. E measures the disorder in the region of interest, is 1 with random contraction and 0 with full synchrony, and differentiates among differing contraction patterns. Left ventricular S and E were measured in 22 normal equilibrium radionuclide angiography studies, where regions of interest were drawn from the left ventricle, left atrium, and background to analyze model ventricles with normal wall motion (N), ventricles with aneurysm (An), ventricles with severe diffuse dysfunction (Diff), and ventricles with severe regional dysfunction (Reg). The new S and E parameters were highly reproducible and well differentiated among N, An, Diff, and Reg, which were not separated by SD Ø (SD of ventricular phase), which has gained popularity as a measure of synchrony. Unique scintigraphic parameters for the evaluation of ventricular synchrony were derived, and their added value was determine compared with established measures. Indications for pacemaker therapy now include the treatment of severe congestive heart failure (CHF). Atrial triggered biventricular pacemakers reduce CHF symptoms 1 and prolong life 2 in patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and increase the synchrony of ventricular activation, conduction, and contraction. CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and the need for hospitalization, 1,3 reversed ventricular remodeling, 4,5 and reduced the all-cause mortality rate 2 in CHF. However, CRT is costly, fails to improve symptoms or activity level in more than 30% of patients, 2,3,6 and is applied blindly without individualization or consideration of lead placement sight. 7 A variety of echocardiographic methods have sought to measure synchrony and its serial changes with CRT. 4,8–16 A recent study presented evidence of the poor reproducibility of several widely applied echocardiographic measurements by which to determine ventricular synchrony. 17 Magnetic resonance imaging has excellent resolution of regional wall motion and has been applied to assess ventricular synchrony and its response to pacing therapy. 18 However, these methods are complex and are not well established or widely available, and magnetic resonance imaging has not been widely applied after pacing. An accurate and reproducible method is needed by which to objectively measure regional ventricular synchrony. 19 Phase image analysis, a functional method based on the first Fourier harmonic fit of the gated blood pool time versus radioactivity curve, generates the parameters of amplitude (A), which parallels the extent of regional ventricular contraction or stroke volume, and phase angle (Ø), which represents the timing of regional contraction. It was applied early with demonstrated reproducibility 20 to show the linkage between electrical and mechanical dyssynchrony 21 and to characterize the contraction pattern in heart failure and its alteration with CRT. 22,23 The SD of ventricular Ø, applied as a marker of synchrony, has been shown to demonstrate the beneficial effects of biventricular pacing, 24 and its strong prognostic value has been shown in patients with congestive cardiomyopathy and CHF, superior to LVEF. 25 The SD Ø may not be optimal for synchrony evaluation. We sought improved, more sensitive parameters to better differentiate synchrony among the spectrum of possible patterns of dyssynergy. We derived, initially evaluated, and here present new synchrony ( S) and entropy ( E) parameters, based on the phase method, to quantitate regional and global ventricular synchrony and applied them in simulation and clinical protocols.

Ischemic left ventricular (LV) dysfunction may occur after exercise but is regarded as uncommon after vasodilator stress. We evaluated the prevalence of LV dysfunction after adenosine stress in relation to reversible perfusion defects and angiographic coronary artery disease (CAD). We studied 86 patients referred for clinically indicated adenosine dual-isotope gated single photon emission computed tomography: 43 with 1 or more reversible perfusion defects (reversible defect group) and 43 age- and sex-matched patients with no known CAD and normal LV perfusion and function (control group). Coronary angiography was performed in 36 of 43 patients (84%) in the reversible defect group. Perfusion was interpreted based on 20-segment/5-point summed rest and stress scores. The extent of reversibility was defined by the summed difference score. LV ejection fraction and volumes at rest and 60 minutes after adenosine and segmental wall thickening were quantified by QGS (Cedars-Sinai Medical Center, Los Angeles, Calif). In patients with extensive reversible perfusion defects (summed difference score ≥8), 8 of 25 (32%) demonstrated depressed post-adenosine LV ejection fraction, abnormal segmental wall thickening, end-systolic dilation, and extensive CAD. Adenosine is believed to be less likely than exercise to induce ischemia. However, myocardial stunning occurred in one third of the patients with severe reversible defects, consistent with ischemia.

Several software packages are commercially available for quantification of left ventricular ejection fraction (LVEF) and volumes from myocardial gated single-photon emission computed tomography (SPECT), all of which display a high reproducibility. However, their accuracy has been questioned in patients with a small heart. This study aimed to evaluate the performances of different software and the influence of modifications in acquisition or reconstruction parameters on LVEF and volume measurements, depending on the heart size. In 31 patients referred for gated SPECT, 64(2) and 128(2) matrix acquisitions were consecutively obtained. After reconstruction by filtered back-projection (Butterworth, 0.4, 0.5 or 0.6 cycles/cm cut-off, order 6), LVEF and volumes were computed with different software [three versions of Quantitative Gated SPECT (QGS), the Emory Cardiac Toolbox (ECT) and the Stanford University (SU-Segami) Medical School algorithm] and processing workstations. Depending upon their end-systolic volume (ESV), patients were classified into two groups: group I (ESV>30 ml, n=14) and group II (ESV<30 ml, n=17). Agreement between the different software packages and the influence of matrix size and sharpness of the filter on LVEF and volumes were evaluated in both groups. In group I, the correlation coefficients between the different methods ranged from 0.82 to 0.94 except for SU-Segami (r=0.77), and were slightly lower for volumes than for LVEF. Mean differences between the methods were not significant, except for ECT, with which LVEF values were systematically higher by more than 10%. Changes in matrix size had no significant influence on LVEF or volumes. On the other hand, a sharper filter was associated with significantly larger volume values though this did not usually result in significant changes in LVEF. In group II, many patients had an LVEF in the higher range. The correlation coefficients between the different methods ranged between 0.80 and 0.96 except for SU-Segami (r=0.49), and were slightly worse for volumes than for LVEF values. In contrast to group I, however, inter-method variability was quite large and most mean LVEF differences were significant. LVEF was systematically highest with ECT and lowest with SU-Segami. With QGS, changes in matrix size from 64(2) to 128(2) were associated with significantly larger volumes as well as lower LVEF values. Increasing the filter cut-off frequency had the same effect. With SU-Segami, a larger matrix was associated with larger end-diastolic volumes and smaller ESVs, resulting in a highly significant increase in LVEF. Increasing the filter sharpness, on the other hand, had no influence on LVEF though the measured volumes were significantly larger. In patients with a normal-sized heart, LVEF and volume estimates computed from different commercially available software packages for quantitative gated SPECT are well correlated. LVEF and volumes are only slightly sensitive to changes in matrix size. Smoothing, by contrast, is associated with significant changes in volumes but usually not in LVEF values. However, owing to the specific characteristics of each algorithm, software should not be interchanged for follow-up in an individual patient. In small hearts, on the other hand, both the used software and the matrix size or smoothing significantly influence the results of quantitative gated SPECT. LVEF values in the higher range are frequently observed with all the studied software except for SU-Segami. A larger matrix or a sharper filter could be suggested to enhance the accuracy of most commercial software, more particularly in patients with a small heart.

The prognostic value of left ventricular dyssynchrony measured by gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) and its relationship to electrical dyssynchrony measured by QRS duration are incompletely understood. The aim of this study was therefore to examine the independent and incremental prognostic value of dyssynchrony in yet the largest group of patients with coronary artery disease (CAD). Patients presenting for GSPECT- MPI between July 1993 and May 1999 in normal sinus rhythm were identified from the Duke Nuclear Cardiology Databank and the Duke Databank for Cardiovascular Disease (N = 1244). After a median of 4.2 years, 336 deaths occurred. At 8 years, the Kaplan-Meier estimates of the probability of death were 34.0% among patients with a phase bandwidth <100° and 56.8% among those with a bandwidth ≥100°. After adjustment for standard clinical variables, QRS dyssynchrony was independently associated with death (Hazard Ratio (HR), per 10°: 1.092, 95% Confidence Interval (CI) 1.048,1.139, P < .0001). Phase bandwidth was similarly associated with death after clinical adjustment (HR per 10°: 1.056, 95% CI 1.041,1.072, P < .0001). In clinically adjusted models examining QRS duration in addition to phase bandwidth, phase bandwidth had a stronger association with mortality. After accounting for left ventricular ejection fraction (LVEF), neither QRS duration nor phase bandwidth were statistically significant. Among patients with EF >35%, QRS duration and phase bandwidth together provided value above that provided by LVEF alone (P = 0.0181). When examining cardiovascular death, results were consistent with all-cause death. Among patients with CAD, mechanical left ventricular dyssynchrony measured by GSPECT MPI has a stronger relationship with outcomes than electrical dyssynchrony measured by QRS duration. After adjustment for baseline characteristics and LVEF, neither mechanical nor electrical dyssynchrony is independently associated with all-cause death or cardiac death. Among patients with EF >35%, mechanical and electrical dyssynchrony together provided prognostic value above that afforded by LVEF.