Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Quantitative diagnostic performance of myocardial perfusion SPECT with attenuation correction in women.

Attenuation correction (AC) for myocardial perfusion SPECT (MPS) had not been evaluated separately in women despite specific considerations in this group because of breast photon attenuation. We aimed to evaluate the performance of AC in women by using automated quantitative analysis of MPS to avoid any bias. METHODS: Consecutive female patients--134 with a low likelihood (LLk) of coronary artery disease (CAD) and 114 with coronary angiography performed within less than 3 mo of MPS--who were referred for rest-stress electrocardiography-gated 99mTc-sestamibi MPS with AC were considered. Imaging data were evaluated for contour quality control. An additional 50 LLk studies in women were used to create equivalent normal limits for studies with AC and with no correction (NC). An experienced technologist unaware of the angiography and other results performed the contour quality control. All other processing was performed in a fully automated manner. Quantitative analysis was performed with the Cedars-Sinai myocardial perfusion analysis package. All automated segmental analyses were performed with the 17-segment, 5-point American Heart Association model. Summed stress scores (SSS) of > or =3 were considered abnormal. RESULTS: CAD (> or =70% stenosis) was present in 69 of 114 patients (60%). The normalcy rates were 93% for both NC and AC studies. The SSS for patients with CAD and without CAD for NC versus AC were 10.0 +/- 9.0 (mean +/- SD) versus 10.2 +/- 8.5 and 1.6 +/- 2.3 versus 1.8 +/- 2.5, respectively; P was not significant (NS) for all comparisons of NC versus AC. The SSS for LLk patients for NC versus AC were 0.51 +/- 1.0 versus 0.6 +/- 1.1, respectively; P was NS. The specificity for both NC and AC was 73%. The sensitivities for NC and AC were 80% and 81%, respectively, and the accuracies for NC and AC were 77% and 78%, respectively; P was NS for both comparisons. CONCLUSION: There are no significant diagnostic differences between automated quantitative MPS analyses performed in studies processed with and without AC in women.     

Red blood cell deformability in patients with claudication after pain-free treadmill training.

OBJECTIVES: To assess the effect of pain-free treadmill training on red blood cell deformability and walking distance in patients with claudication. DESIGN: Randomized-controlled trial of exercise training. SETTING: Patients were recruited from the primary care, vascular outpatient clinic. PATIENTS: A total of 60 patients with peripheral arterial occlusive disease (stage II according to Leriche-Fontaine) were randomized into the treadmill program or a control group. Fifty-five patients completed the study (27 in the exercising group and 28 in the control group). INTERVENTIONS: Patients in the exercising group were walking on the treadmill 3 times a week for 3 months. Each session consisted of 1 hour repetitive walking [performed to 85% of the pain-free walking time (PFWT)] was supervised by a qualified physiotherapist. MAIN OUTCOME MEASUREMENTS: Changes in erythrocyte deformability and treadmill walking performance (PFWT, maximal walking time) were assessed in both groups before the study and after 3 months. RESULTS: After 3 months of treadmill training, red blood cell deformability in the exercising group significantly increased (P<0.01). No significant changes were seen in the erythrocyte deformability in the control group. PFWT was prolonged by 102% from 191+/-34 to 386+/-60 seconds (P<0.01), and maximal walking time increased by 49% from 438+/-62 to 656+/-79 seconds (P<0.01) in the exercising group, whereas these changes were insignificant in the control group. CONCLUSIONS: A significant improvement of walking ability over 3 months of pain-free treadmill training is associated with a significant increase in red cell deformability in patients with claudication.     

Sole Use of Dexmedetomidine Has Limited Utility for Conscious Sedation during Outpatient Colonoscopy

Background: This study evaluated the ability of dexmedetomidine to provide analgesia and sedation for outpatient colonoscopy, examining outcomes including cardiorespiratory variables, side effects, and discharge readiness.

Methods: Sixty-four patients were randomly assigned to one of three treatment regimens. In group D, patients received 1 [mu]g/kg dexmedetomidine over 15 min followed by an infusion of 0.2 [mu]g [middle dot] kg-1 [middle dot] h-1. Group P received meperidine (1 mg/kg) with midazolam (0.05 mg/kg), and group F received fentanyl (0.1-0.2 mg intravenous) on demand. The assessment included measurements of heart rate, blood pressure, oxygen saturation, respiratory rate, quality of sedation/analgesia, and an evaluation of the recovery time.

Results: The study was terminated before the planned 90 patients had been recruited because of adverse events in group D. In all groups, negligible hemoglobin oxygen saturation and respiratory rate variations were observed. In group D, there was a significantly larger decrease in heart rate (to approximately 40 beats/min in 2 of 19 cases) and blood pressure (to less than 50% of the initial value in 4 of 19 patients). Supplemental fentanyl was required in 47% of patients receiving dexmedetomidine to achieve a satisfactory level of analgesia (vs. 42.8% of patients in group P and 79.2% of patients in group F). Vertigo (5 patients), nausea/vomiting (5 patients), and ventricular bigeminy (1 patient) were observed only in group D. Time to home readiness was longest in group D (85 +/- 74, 39 +/- 21, and 32 +/- 13 min in groups D, P and F, respectively; P = 0.007).     

Attenuation correction in cardiac SPECT: The boy who cried wolf?

Conclusion  We would like to stress that we do not necessarily consider AC for SPECT MPI to be unfeasible or unworthy of scientific pursuit; indeed, a great deal of creative scientific effort has been poured into this area of investigation over the past 3 decades, and much of it has contributed to a better understanding of the physics, as well as the clinical aspects, of our field. However, the great variety of available AC hardware and software “flavors,” the historical pattern of commercial release of insufficiently validated AC implementations, and the increasingly clouded health care reimbursement horizon may have created an environment where the envisioned users of the technology have been desensitized and discouraged from expecting it to ever come to fruition in a standardized, validated, and costeffective form. It has been reported as recently as 2005 that the “entire base of SPECT cameras has only 5% of systems with attenuation correction.”8 Perhaps the reports of AC’s demise are exaggerated, but it certainly seems as if the people have spoken and, after readying themselves for the wolf one too many times, have come to the conclusion that “the future (of AC) ain’t what it used to be” . . .at least not yet.     

Vascular Centerline Extraction in 3D MR Angiograms for Phase Contrast MRI Blood Flow Measurement

The accuracy of 2D phase contrast (PC) magnetic resonance angiography (MRA) depends on the alignment between the vessels and the imaging plane. PC MRA imaging of blood flow is challenging when the flow in several vessels is to be evaluated with one acquisition. For this purpose, semi-automatic determination of the plane most perpendicular to several vessels is proposed based on centerlines extracted from 3D MRA. Arterial centerlines are extracted from 3D MRA based on iterative estimation-prediction, multi-scale analysis of image moments, and a second-order shape model. The optimal plane is determined by minimizing misalignment between its normal vector and the centerlines’ tangent vectors. The method was evaluated on a phantom and on 35 patients, by seeking the optimal plane for cerebral blood flow quantification simultaneously in internal carotids and vertebral arteries. In the phantom, difference of orientation and of height between known and calculated planes was 1.2° and 2.5 mm, respectively. In the patients, all but one centerline were correctly extracted and the misalignment of the plane was within 12° per artery. Semi-automatic centerline extraction simplifies and automates determination of the plane orthogonal to one vessel, thereby permitting automatic simultaneous minimization of the misalignment with several vessels in PC MRA.     

Aortic pulse wave velocity and carotid-femoral pulse wave velocity: similarities and discrepancies.

The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49+/-8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS- group. The mean values of cfPWV and aPWV were 10.65+/-2.29 m/s and 8.78+/-2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS- (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS- group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS.