Joseph A. Lodato

Real-Time Three-Dimensional Transesophageal Echocardiography of the Left Atrial Appendage: Initial Experience in the Clinical Setting

BACKGROUND The aim of this study was to determine the feasibility and accuracy of a new real-time 3-dimensional (RT3D) matrix-array transesophageal echocardiographic probe for the determination of left atrial appendage (LAA) geometry. METHODS Sixty-six consecutive patients (mean age, 53 +/- 17 years) referred for 2-dimensional (2D) transesophageal echocardiography (TEE) underwent additional RT3D TEE. The feasibility of RT3D TEE for LAA geometry was studied in the first 37 patients, and 2D and RT3D transesophageal echocardiographic quantification of the LAA were compared in the subsequent 29 patients. The LAA orifice diameter and depth were measured using biplane 2D TEE, and LAA orifice area was calculated as an ellipse. LAA orifice area and depth were measured in 3D and correlated to 2D measurement and were also correlated to 64-slice cardiac computed tomography (CT) in 8 patients. RESULTS All 66 patients underwent RT3D matrix-array TEE without complication. In the feasibility study, the LAA was well visualized in 95%. In the quantitation study, 2D TEE underestimated LAA orifice area compared with 3D imaging (3.1 +/- 1.3 vs 4.2 +/- 2.2 cm(2); r = 0.55). LAA depth by 2D and 3D imaging were well correlated (3.7 +/- 0.7 vs 3.4 +/- 0.7 cm; r = 0.77). LAA orifice area on CT was well correlated with area on 3D TEE (r = 0.98) but not with area 2D TEE (r = 0.13). Bland-Altman analysis demonstrated that 2D TEE systematically underestimated LAA orifice area compared with 3D TEE (mean bias, -1.0 cm(2), with wide limits of agreement [-4.6 to 2.6 cm(2)]). In the 8 patients who underwent both 3D TEE and CT, the mean bias was 0.15 cm(2), with narrow limits of agreement (-0.50 to 0.20 cm(2)). CONCLUSIONS RT3D TEE for the visualization and quantitative analysis of LAA orifice area is feasible and correlates well with 64-slice cardiac CT.

Feasibility of real-time three-dimensional transoesophageal echocardiography for guidance of percutaneous atrial septal defect closure

AIMS Intracardiac echocardiography (ICE) and two-dimensional transoesophageal echocardiography (2D TEE) are used in most centres for guiding transcatheter atrial septal defect (ASD) closure. ASDs have complex shapes that are not well characterized with 2D imaging. Real-time 3D TEE (RT3D TEE) provides en-face visualization of the ASD, allowing precise assessment of ASD dimensions. Accordingly, our aims were (i) to determine the feasibility of RT3D TEE to guide ASD closure and (ii) to compare ASD and balloon dimensions (BDs) using RT3D TEE vs. ICE and 2D TEE. METHODS AND RESULTS Thirteen patients with ostium secundum ASD underwent transcatheter ASD closure. 2D TEE, RT3D TEE, and ICE images were acquired sequentially. RT3D TEE was feasible in all patients. Comparing RT3D TEE and 2D imaging, the mean difference in long-axis dimension was +0.5 mm (P= NS for both), and -1.4 mm in short-axis (2D TEE, P < 0.05; ICE, P = 0.06). BD was greater with 3D TEE vs. ICE (+0.9 mm). CONCLUSION RT3D TEE can be used to guide transcatheter ASD closure with the advantages of lower cost than ICE, and ability to visualize en-face views of the ASD. ASD and BD as measured by RT3D TEE differ when compared with 2D imaging.

S100A12 Mediates Aortic Wall Remodeling and Aortic Aneurysm

Rationale: S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear. Objective: To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22&agr; promoter because S100A12 is not present in mice. Methods and Results: Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor &bgr; pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells. Conclusions: S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo.

Combined Assessment of Coronary Anatomy and Myocardial Perfusion Using Multidetector Computed Tomography for the Evaluation of Coronary Artery Disease

Multidetector computed tomography (MDCT) is increasingly used as an alternative to invasive coronary angiography. Although computed tomographic coronary angiography (CTCA) has been validated against invasive coronary angiography and nuclear myocardial perfusion imaging, the potential of MDCT to evaluate perfusion has not been fully explored. We sought to (1) develop a new technique for quantitative assessment of myocardial enhancement based on analysis of MDCT images acquired for CTCA, (2) identify the underlying causes of myocardial hypoenhancement detected by MDCT, and (3) determine the added diagnostic value of the MDCT perfusion index when combined with CTCA. We studied 84 patients undergoing clinical CTCA (64 patients with invasive coronary angiogram and a control group of 20 patients). MDCT perfusion index was calculated from x-ray attenuation measured in 16 myocardial segments. Hypoenhancement was automatically detected using comparisons with the normal range obtained in the control group, and its added value was determined against invasive coronary angiographic findings combined with known previous myocardial infarction. Myocardial hypoenhancement was detected in 29 of 64 patients in 47 vascular territories, of which 36 (77%) were abnormal by the reference technique. Of these 36 abnormalities, 10 (28%) were associated with previous myocardial infarction, whereas 26 (72%) corresponded to significant coronary stenosis. The addition of MDCT perfusion index to CTCA improved its diagnostic accuracy (sensitivity 0.87 to 0.96, accuracy 0.84 to 0.88, despite a decrease in specificity 0.79 to 0.68). In conclusion, myocardial hypoenhancement is a potentially valuable addition to MDCT evaluation of coronary artery disease without additional cost in radiation dose or contrast load.

Volumetric quantification of myocardial perfusion using analysis of multi-detector computed tomography 3D datasets: comparison with nuclear perfusion imaging

BackgroundAlthough the ability of multi-detector computed tomography (MDCT) to detect perfusion abnormalities associated with acute and chronic myocardial infarction (MI) has been demonstrated, this methodology is based on visual interpretation of selected 2D slices.ObjectivesWe sought to develop a new technique for quantitative volumetric analysis of myocardial perfusion from 3D datasets and test it against resting nuclear myocardial perfusion imaging (NMPI) reference.MethodsWe studied 44 patients undergoing CTCA: a control group of 15 patients and a study group of 29 patients. MDCT datasets acquired for CTCA were analyzed using custom software designed to: (1) generate bull’s eye display of myocardial perfusion and (2) calculate a quantitative index of extent and severity of perfusion abnormality, QH, for 16 volumetric myocardial segments. Visual interpretation of MDCT-derived bull’s eyes was compared with rest NMPI scores using kappa statistics of agreement on a coronary territory and patient basis. Quantitative MDCT perfusion data were correlated with rest NMPI summed scores and used for objective detection of perfusion defects.ResultsVisual analysis of MDCT-derived bull’s eyes accurately detected perfusion defects in agreement with NMPI (kappa = 0.70 by territory; 0.79 by patient). Quantitative data were in good agreement with NMPI, as reflected by: (1) correlation of 0.87 (territory) and 0.84 (patient) between summed QH and NMPI scores, (2) area under ROC curve 0.87 with sensitivity of 0.79–0.92, specificity 0.83–0.91, and accuracy 0.83–0.89 for objective detection of abnormalities.ConclusionsOur new technique for volumetric analysis of 3D MDCT images allows accurate objective detection of perfusion defects. This perfusion information can be obtained without additional radiation or contrast load, and may aid in elucidating the significance of coronary lesions.

Value of multidetector computed tomography evaluation of myocardial perfusion in the assessment of ischemic heart disease: comparison with nuclear perfusion imaging

MDCT-derived myocardial perfusion has not yet been validated against accepted standards. We developed a technique for quantification of myocardial perfusion from MDCT images and studied its diagnostic value against SPECT myocardial perfusion imaging (MPI). Ninety-eight patients were studied. Abnormal perfusion was detected by comparing normalized segmental x-ray attenuation against values obtained in 20 control subjects. Disagreement with resting MPI was investigated in relationship to MDCT image quality, severity of MPI abnormalities, and stress MPI findings. Resting MPI detected mild or worse abnormalities in 20/78 patients. MDCT detected abnormalities in 15/20 patients (sensitivity of 0.75). Most abnormalities missed by MDCT analysis were graded as mild on MPI. Additional abnormalities found in 16/78 patients were not confirmed on resting MPI (specificity of 0.72). However, 8 of these 16 apparently false positive MDCT perfusion tests had abnormal stress MPI; of these 8 patients, 7 had optimal MDCT image quality, while in 6/8 remaining patients, image quality was suboptimal. When compared with resting MPI, MDCT detected perfusion abnormalities with high accuracy. Moreover, half of MDCT perfusion abnormalities not confirmed by resting MPI were associated with abnormal stress MPI. Importantly, this information can be obtained without additional radiation dose or contrast agent.

Quantitative three-dimensional evaluation of myocardial perfusion during regadenoson stress using multidetector computed tomography.

Objective The ability of multidetector computed tomography (MDCT) to detect stress-induced myocardial perfusion abnormalities is of great clinical interest as a potential tool for the combined evaluation of coronary stenosis and its hemodynamic significance. We tested the hypothesis that quantitative 3-dimensional (3D) analysis of myocardial perfusion from MDCT images obtained during regadenoson stress would more accurately detect the presence of significant coronary artery disease (CAD) than identical analysis when performed on resting MDCT images. Methods We prospectively studied 50 consecutive patients referred for CT coronary angiography (CTCA) who agreed to undergo additional imaging with regadenoson (0.4 mg; Astellas). Images were acquired using prospective gating (256-channel; Philips). Custom analysis software was used to define 3D myocardial segments, and calculate for each segment an index of severity and extent of perfusion abnormality, Qh, which was compared with perfusion defects predicted by the presence and severity of coronary stenosis on CTCA. Results Three patients were excluded because of image artifacts. In the remaining 47 patients, CTCA depicted stenosis more than 50% in 23 patients in 37 of 141 coronary arteries. In segments supplied by the obstructed arteries, myocardial attenuation was slightly reduced compared with normally perfused segments at rest (mean [SD], 91 [21] vs 93 [26] Hounsfield units, not significant) and, to a larger extent, at peak stress (102 [21] vs 112 [20] Hounsfield units, P < 0.05). In contrast, index Qh was significantly increased at rest (0.40 [0.48] vs 0.26 [0.41], P < 0.05) and reached a nearly 3-fold difference at peak stress (0.66 [0.74] vs 0.28 [0.51], P < 0.05). The addition of regadenoson improved the diagnosis of CAD, as reflected by an increase in sensitivity (from 0.57 to 0.91) and improvement in accuracy (from 0.65 to 0.77). Conclusions Quantitative 3D analysis of MDCT images allows objective detection of CAD, the accuracy of which is improved by regadenoson stress.

Three-dimensional quantification of myocardial perfusion during regadenoson stress computed tomography

BACKGROUND There is no accepted methodology for CT-based vasodilator stress myocardial perfusion imaging and analysis. We developed a technique for quantitative 3D analysis of CT images, which provides several indices of myocardial perfusion. We sought to determine the ability of these indices during vasodilator stress to identify segments supplied by coronary arteries with obstructive disease and to test the accuracy of the detection of perfusion abnormalities against SPECT. METHODS We studied 93 patients referred for CT coronary angiography (CTCA) who underwent regadenoson stress. 3D analysis of stress CT images yielded segmental perfusion indices: mean X-ray attenuation, severity of defect and relative defect volume. Each index was averaged for myocardial segments, grouped by severity of stenosis: 0%, <50%, 50-70%, and >70%. Objective detection of perfusion abnormalities was optimized in 47 patients and then independently tested in the remaining 46 patients. RESULTS CTCA depicted normal coronary arteries or non-obstructive disease in 62 patients and stenosis of >50% in 31. With increasing stenosis, segmental attenuation showed a 7% decrease, defect severity increased 11%, but relative defect volume was 7-fold higher in segments with obstructive disease (p<0.001). In the test group, detection of perfusion abnormalities associated with stenosis >50% showed sensitivity 0.78, specificity 0.54, accuracy 0.59. When compared to SPECT in a subset of 21 patients (14 with abnormal SPECT), stress CT perfusion analysis showed sensitivity 0.79, specificity 0.71, accuracy 0.76. CONCLUSIONS 3D analysis of vasodilator stress CT images provides quantitative indices of myocardial perfusion, of which relative defect volume was most robust in identifying segments supplied by arteries with obstructive disease. This study may have implications on how CT stress perfusion imaging is performed and analyzed.

Quantification of myocardial perfusion using multi-detector computed tomography: Validation against invasive coronary angiography

While CT coronary angiography (CTCA) has been validated, the potential of CT to evaluate perfusion has not been explored. We sought to: (1) develop and test a technique for quantitative assessment of myocardial perfusion from CT images, (2) identify the underlying causes of perfusion abnormalities detected by CT, (3) determine the added diagnostic value of CT perfusion. We studied 84 consecutive patients undergoing clinical CTCA. Accuracy of automated detection of perfusion abnormalities was determined against invasive coronary angiography findings combined with known prior myocardial infarction (MI). Perfusion abnormalities were detected in 29/64 patients in 47 vascular territories, of which 36 were confirmed as abnormal. Of these 36, 10 were associated with prior MI, while 26 corresponded to significant stenosis. The addition of perfusion to CTCA improved its diagnostic accuracy. In conclusion, myocardial perfusion is a potentially valuable addition to CT tools for the evaluation of coronary artery disease without additional cost in radiation dose or contrast load.