To 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. This 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. A 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). Two-phase 64-section cardiac CT angiography is a noninvasive sensitive modality for detecting LAA thrombi and differentiating thrombus from circulatory stasis in stroke patients.
1 February 2012 in Journal of Biological Chemistry
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.
Background—: Recent evolution of cardiac computed tomography (CT) provides useful information about valvular and perivalvular structures. We compared the diagnostic performance of CT and transesophageal echocardiography (TEE) with applications of 3-dimensional reconstruction in detecting vegetation and intracardiac complications in patients with infective endocarditis (IE). Methods and Results—: Seventy-five patients (53 men; age, 58±15 years) with definite IE who underwent TEE and CT with 3-dimensional reconstruction within 3 days were analyzed. The diagnostic performances of the 2 modalities for vegetation and IE-related intracardiac complications (valve perforation, valve aneurysm, perivalvular abscess, pseudoaneurysm, fistula, and prosthetic valve dehiscence) were compared. The detection rate of vegetation in TEE and CT was 97.3% and 72.0%, respectively. The maximum sizes of vegetation identified by TEE and CT were well correlated ( r =0.593; P <0.001), especially in patients with large vegetation (≥10 mm), suggestive of a high risk of systemic embolism ( r =0.608; P <0.001). However, small vegetation (<10 mm) was underdiagnosed by CT (52.8%) compared with TEE (94.4%), and the sizes of the 2 modalities were poorly correlated ( r =0.187; P =0.445). Both modalities showed fair diagnostic performance for detecting IE-related intracardiac complications with excellent agreement. TEE was more useful for diagnosing valve perforation and intracardiac fistula, whereas CT was better for diagnosing perivalvular abscess. Conclusions—: Cardiac CT shows a comparable diagnostic performance with TEE for large vegetation and several IE-related complications. TEE is better for detecting small vegetation, valve perforation, and intracardiac fistula, whereas CT is more useful for detecting perivalvular abscess and coronary artery disease.