Chi-Young Shim

Left Atrial Appendage Thrombi in Stroke Patients: Detection with Two-Phase Cardiac CT Angiography versus Transesophageal Echocardiography

PURPOSEnTo assess the diagnostic accuracy of two-phase 64-section cardiac computed tomographic (CT) angiography for detection of left atrial appendage (LAA) thrombi and differentiation between thrombus and circulatory stasis in patients with stroke, with transesophageal echocardiography (TEE) as the reference standard.nnnMATERIALS AND METHODSnThis study was institutional review board approved, and all patients gave written informed consent. Fifty-five consecutive patients (36 men, 19 women; mean age, 61 years) who had recently experienced a stroke, had high-risk factors for thrombus formation, and underwent both two-phase 64-section cardiac CT angiography and TEE up to 5 days apart were examined. Agreement between CT and TEE for detection of thrombus was assessed with kappa statistics. For quantitative analysis, the LAA-ascending aorta attenuation ratio (LAA/AA, in Hounsfield units) was measured on early- and late-phase CT images. The significance of differences in CT attenuation measurements were assessed by using the Student t test.nnnRESULTSnA total of 14 thrombi were detected in the 55 patients at TEE. With TEE as the reference standard, the overall sensitivity, specificity, and positive and negative predictive values of cardiac CT angiography for the detection of thrombus in the LAA were 100% (14 of 14 patients), 98% (40 of 41 patients), 93% (14 of 15 patients), and 100% (40 of 40 patients), respectively. Concordance between cardiac CT angiography and TEE for the detection of thrombus in the LAA was high (overall kappa = 0.953). Mean LAA/AA values were significantly different between thrombus (0.29 HU +/- 0.12 [standard deviation]) and circulatory stasis (0.85 HU +/- 0.12) on late-phase CT images (P < .001).nnnCONCLUSIONnTwo-phase 64-section cardiac CT angiography is a noninvasive sensitive modality for detecting LAA thrombi and differentiating thrombus from circulatory stasis in stroke patients.

Lipocalin-2 Induces Cardiomyocyte Apoptosis by Increasing Intracellular Iron Accumulation

Background: The proinflammatory adipokine lipocalin-2 is associated with obesity-related complications, such as heart failure. Results: Lipocalin-2 induces cardiomyocyte apoptosis via elevating intracellular iron levels and mediates detrimental effects on cardiac function. Conclusion: Lipocalin-2 is an important mediator of cardiac remodeling. Significance: Regulation of cardiomyocyte apoptosis by lipocalin-2, and the mechanistic role of changes in intracellular iron, may contribute to the pathogenesis of obesity-related heart failure. Our objective was to determine whether lipocalin-2 (Lcn2) regulates cardiomyocyte apoptosis, the mechanisms involved, and the functional significance. Emerging evidence suggests that Lcn2 is a proinflammatory adipokine associated with insulin resistance and obesity-related complications, such as heart failure. Here, we used both primary neonatal rat cardiomyocytes and H9c2 cells and demonstrated for the first time that Lcn2 directly induced cardiomyocyte apoptosis, an important component of cardiac remodeling leading to heart failure. This was shown by detection of DNA fragmentation using TUNEL assay, phosphatidylserine exposure using flow cytometry to detect annexin V-positive cells, caspase-3 activity using enzymatic assay and immunofluorescence, and Western blotting for the detection of cleaved caspase-3. We also observed that Lcn2 caused translocation of the proapoptotic protein Bax to mitochondria and disruption of mitochondrial membrane potential. Using transient transfection of GFP-Bax, we confirmed that Lcn2 induced co-localization of Bax with MitoTracker® dye. Importantly, we used the fluorescent probe Phen Green SK to demonstrate an increase in intracellular iron in response to Lcn2, and depleting intracellular iron using an iron chelator prevented Lcn2-induced cardiomyocyte apoptosis. Administration of recombinant Lcn2 to mice for 14 days increased cardiomyocyte apoptosis as well as an acute inflammatory response with compensatory changes in cardiac functional parameters. In conclusion, Lcn2-induced cardiomyocyte apoptosis is of physiological significance and occurs via a mechanism involving elevated intracellular iron levels and Bax translocation.

Thrombus in the Left Atrial Appendage in Stroke Patients: Detection with Cardiac CT Angiography—A Preliminary Report

PURPOSEnTo assess the diagnostic performance of 64-section cardiac computed tomographic (CT) angiography for detection of left atrial appendage (LAA) thrombi in stroke patients by using transesophageal echocardiography (TEE) as the reference standard.nnnMATERIALS AND METHODSnThis study was approved by the institutional review board. Records were reviewed from 101 consecutive patients who had experienced a recent stroke (onset within the previous 1 month) from a suspected cardioembolic source and who had undergone both 64-section cardiac CT angiography and TEE within 1 week. The numbers of thrombi in the LAA detected with cardiac CT angiography and with TEE were recorded, and the agreement between thrombus detection with CT and with TEE was assessed by using kappa statistics.nnnRESULTSnEight thrombi in the LAA were detected with TEE, and 12 were detected with cardiac CT angiography. With TEE used as the reference standard, the overall sensitivity, specificity, and accuracy of 64-section cardiac CT angiography for detecting thrombi were 100% (95% confidence interval [CI]): 63%, 100%), 95% (95% CI: 90%, 99%), and 96% (95% CI: 92%, 100%), respectively. The concordance between LAA thrombus detection with 64-section cardiac CT angiography and with TEE was high: 89 patients with no thrombus at CT or TEE; eight patients with thrombus at both CT and TEE; and four patients with thrombus at CT but not at TEE (overall kappa = 0.779 [95% CI: 0.571, 0.987]).nnnCONCLUSIONnSixty-four-section cardiac CT angiography is a noninvasive and sensitive modality for detecting thrombi in the LAA of stroke patients. Although TEE is currently considered the reference standard modality for detecting LAA thrombi, 64-section cardiac CT angiography has the potential to become a useful modality for detection of intracardiac thrombus.

RAGE and cardiovascular disease.

RAGE is pattern recognizing receptors for diverse endogenous ligands. RAGE activation by RAGE ligands is known to be associated with reactive oxygen species generation, activation of NF kappa B, as well as recruitment of proinflammatory cells. Activated endothelial cells, vascular smooth muscle cells in atherosclerotic plaques and activated inflammatory cells all have increased expression of RAGE, which with its interaction with RAGE ligands increases the secretion of proinflammatory cytokines and cell adhesion molecules. Furthermore, RAGE may have a significant role in leukocyte recruitment into the intima of the atherosclerosis. Initial insults resulting in endothelial dysfunction will result in leukocyte infiltration, oxidative stress and vascular inflammation that is amplified by RAGE activation. RAGE and its interaction with RAGE ligands may be important for initializing and maintaining the pathological processes that result in various entities of cardiovascular disease. Soluble RAGE competitively inhibits the binding of RAGE ligands to RAGE and attenuates the development of atherosclerosis in vivo. Thus RAGE may be a promising target for treatment of cardiovascular disease in the future.

Cardiac Computed Tomographic Angiography for Detection of Cardiac Sources of Embolism in Stroke Patients

Background and Purpose— We assessed the diagnostic performance of 2-phase 64-slice cardiac computed tomographic angiography (CCTA) for the detection of a cardiac source of embolism in stroke patients using transesophageal echocardiography (TEE) as the reference standard. Methods— We selected 137 patients who had experienced a recent episode of stroke and had undergone both 2-phase 64-slice CCTA and TEE within a period of 5 days. A potential cardiac source of embolism detected at both CCTA and TEE was recorded, and echocardiographic findings were categorized into high- and medium-risk sources based on the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Results— Of 137 patients, 100 abnormal findings in 91 patients were found on TEE, and 46 patients had no abnormal finding on TEE. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the 64-slice CCTA for detecting cardiac sources of embolism were 89% (95% CI, 82%, 95%), 100% (95% CI, 90%, 100%), 100% (95% CI, 95%, 100%), and 81% (95% CI, 70%, 92%), respectively. TEE detected a total of 47 high-risk sources of embolism, whereas CT detected 44 lesions. For medium-risk sources of cardiac embolic stroke, TEE detected a total of 53 abnormal findings, whereas CT detected 44 abnormal findings. Of 53 lesions, there were 8 false-negative results on CT (5 patent foramen ovale and 3 atrial septal aneurysm). Conclusions— Two-phase 64-slice CCTA is a noninvasive and useful modality for detecting high-risk cardiac sources of embolism in stroke patients.

Patent Foramen Ovale: Diagnosis with Multidetector CT—Comparison with Transesophageal Echocardiography

PURPOSEnTo evaluate the clinical feasibility and accuracy of 64-section multidetector computed tomography (CT) compared with transesophageal echocardiography (TEE) for diagnosis of a patent foramen ovale (PFO).nnnMATERIALS AND METHODSnInstitutional review board approval was obtained for this retrospective study. The study included 152 consecutive stroke patients (mean age, 61.7 years; 98 men, 54 women) who underwent both cardiac multidetector CT and TEE. Electrocardiographically gated cardiac CT was performed with a 64-section CT scanner by using a saline-chaser contrast agent injection technique. A contrast agent jet from the contrast agent-filled left atrium (LA) to the saline-filled right atrium (RA) and channel-like appearance of the interatrial septum (IAS) were evaluated on axial and oblique sagittal CT images. Two-dimensional and Doppler TEE were performed to detect PFO. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT were obtained with TEE as the reference standard.nnnRESULTSnA PFO was present in 26 patients at TEE. On CT images, a left-to-right contrast agent jet toward the inferior vena cava was noted in 21 patients (sensitivity, 73.1%; specificity, 98.4%; PPV, 90.5%; NPV, 94.7%). Channel-like appearance of the IAS was detected in 38 patients (sensitivity, 76.9%; specificity, 85.7%; PPV, 52.6%; NPV, 94.7%). Channel-like appearance of the IAS was noted in all patients who had a contrast agent jet.nnnCONCLUSIONnA contrast agent jet from LA to RA toward the inferior vena cava with channel-like appearance of the IAS on CT images confirms the presence of a PFO.

Left Ventricular Diastolic Functional Reserve during Exercise in Patients with Impaired Myocardial Relaxation at Rest

Background: Patients with similar grade diastolic dysfunction at rest may have a spectrum of alterations in diastolic function during exercise. Objective: To evaluate (a) whether exercise could unmask further diastolic abnormalities not evident during rest; (b) whether diastolic functional reserve during exercise is associated with exercise capacity. Methods: 141 subjects (77 male, mean (SD) age 62 (9)) with abnormal left ventricular (LV) relaxation (mitral E/A <0.75) and/or deceleration time >240 ms, underwent graded supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. Mitral inflow and annular velocities were measured at rest and during exercise. The LV diastolic function reserve index (DFRI) was calculated. Results: Patients were classified into two groups: group 1 (nu200a=u200a64), DFRI <13.5; group 2 (nu200a=u200a77), DFRI ⩾13.5. The ratio of E/E′ to stroke volume was used as an index of ventricular elastance (Ed). No significant differences between the groups in mitral inflow and annular velocities at rest were found. Mean (SD) Ed was not significantly different at rest between the groups (0.19 (0.07) vs 0.18 (0.06), pu200a=u200a0.29). Ed was significantly higher during exercise in group 1 than in group 2 (25 W, 0.21 (0.09) vs 0.14 (0.04), p<0.001; 50 W, 0.22 (0.10) vs 0.15 (0.04), p<0.001). Group 1 subjects had a shorter exercise duration (8.2 (2.7) vs 9.4 (3.7) min, pu200a=u200a0.04) and lower peak oxygen consumption (17.5 (4.5) vs 20.2 (5.4) ml/kg/min, pu200a=u200a0.005). Conclusions: Despite similar mitral flow and annular velocities at rest, different responses to exercise were seen in patients with abnormal LV relaxation at rest. Lower LV diastolic functional reserve was associated with higher ventricular elastance during exercise, and reduced exercise capacity.

Differential Effect of 3-Dimensional Color Doppler Echocardiography for the Quantification of Mitral Regurgitation According to the Severity and Characteristics

Background—The aim of this study is to explore the differential effect of 3-dimensional color Doppler echocardiography for the quantification of mitral regurgitation (MR). Two-dimensional color Doppler echocardiography–based MR quantification has well-documented limitations. Methods and Results—We consecutively enrolled 221 patients with MR. Adequate image quality was obtained by 2D- and 3D-color Doppler echocardiography in 211 (95.5%) patients. The quantitative differences between the MR volumes obtained by 2D- and 3D-proximal isovelocity surface area (PISA) were analyzed in various MR subgroups. In the validation cohort (n=52), MR volume obtained by 3D-PISA showed a better agreement with phase-contrast cardiac MRI than 2D-PISA (r=0.97 versus 0.84). In all 211 patients, 2D-PISA underestimated the MR volume when compared with 3D-PISA (52.4±19.6 versus 59.5±25.6 mL; P=0.005). A total of 33.3% with severe MR based on 3D-PISA were incorrectly assessed by 2D-PISA as having nonsevere MR. In the subgroup analysis, the MR severity (odds ratio, 6.96; 95% confidence interval, 3.04–15.94; P<0.001) and having an asymmetrical orifice (odds ratio, 11.48; 95% confidence interval, 3.72–35.4; P<0.001), and an eccentric jet (odds ratio, 3.82; 95% confidence interval, 1.27–11.48; P=0.017) were predictors of significant difference in MR volume (>15 mL) between 2D- and 3D-PISA methods. Conclusions—Quantification of MR by 3D-PISA method is clinically feasible and more accurate than the current 2D-PISA method. MR quantification by 2D-PISA significantly underestimated MR volume with severe, eccentric MR with an asymmetrical orifice. This article demonstrates that 3D-color Doppler echocardiography could be used as a valuable tool to confirm treatment strategy in patients with significant MR.

Differential Impact of Three-Dimensional Color Doppler Echocardiography for the Quantification of Mitral Regurgitation According to the Severity and Characteristics

Background—The aim of this study is to explore the differential effect of 3-dimensional color Doppler echocardiography for the quantification of mitral regurgitation (MR). Two-dimensional color Doppler echocardiography–based MR quantification has well-documented limitations. Methods and Results—We consecutively enrolled 221 patients with MR. Adequate image quality was obtained by 2D- and 3D-color Doppler echocardiography in 211 (95.5%) patients. The quantitative differences between the MR volumes obtained by 2D- and 3D-proximal isovelocity surface area (PISA) were analyzed in various MR subgroups. In the validation cohort (n=52), MR volume obtained by 3D-PISA showed a better agreement with phase-contrast cardiac MRI than 2D-PISA (r=0.97 versus 0.84). In all 211 patients, 2D-PISA underestimated the MR volume when compared with 3D-PISA (52.4±19.6 versus 59.5±25.6 mL; P=0.005). A total of 33.3% with severe MR based on 3D-PISA were incorrectly assessed by 2D-PISA as having nonsevere MR. In the subgroup analysis, the MR severity (odds ratio, 6.96; 95% confidence interval, 3.04–15.94; P<0.001) and having an asymmetrical orifice (odds ratio, 11.48; 95% confidence interval, 3.72–35.4; P<0.001), and an eccentric jet (odds ratio, 3.82; 95% confidence interval, 1.27–11.48; P=0.017) were predictors of significant difference in MR volume (>15 mL) between 2D- and 3D-PISA methods. Conclusions—Quantification of MR by 3D-PISA method is clinically feasible and more accurate than the current 2D-PISA method. MR quantification by 2D-PISA significantly underestimated MR volume with severe, eccentric MR with an asymmetrical orifice. This article demonstrates that 3D-color Doppler echocardiography could be used as a valuable tool to confirm treatment strategy in patients with significant MR.

Diverse left ventricular morphology and predictors of short-term outcome in patients with stress-induced cardiomyopathy.

BACKGROUNDnThere is paucity of data with regard to the clinical spectrum according to left ventricle (LV) morphological variation in stress-induced cardiomyopathy (SCMP) patients, and still there is controversy in terms of prognosis since some people believe that the published in-hospital mortality data of patients with SCMP are underestimated. Therefore, we sought to investigate the morphological features of LV and in-hospital outcome of patients with SCMP and explored predictors of short-term prognosis.nnnMETHODSnThis was a multicenter, observational study of 208 SCMP patients. Morphological features of LV were determined by echocardiography and were divided into typical (apical) and atypical ballooning types, which were subcategorized into mid-LV ballooning and basal inverted ballooning type. All-cause mortality of patients with SCMP during hospitalization was recorded.nnnRESULTSnThe apical ballooning type was most common (67.3%) in SCMP followed by the mid-LV ballooning type (28.3%), and the basal inverted ballooning type (4.3%). There were no differences in stressor types and in-hospital mortality between patients with typical and atypical SCMP. Notably, all the in-hospital mortality of SCMP patients occurred in patients with physical stressors, where age, shock, and LV ejection fraction were the independent risk factors for predicting in-hospital mortality.nnnCONCLUSIONSnSCMP patients showed diverse patterns of LV morphology, but there were no definite differences on clinical spectrum among SCMP patients presenting various LV morphological patterns. In terms of short-term prognosis, underlying physical conditions combined with old age, hemodynamic compromise, and low LV systolic function might be the most important factors in SCMP patients.