ABSTRACT
PURPOSE: To test the potential of magnetic resonance imaging (MRI) in early detection of left ventricular (LV) dysfunction in patients with pulmonary regurgitation and normal LV ejection fraction after repair of tetralogy of Fallot. MATERIALS AND METHODS: Patients (n = 18) with repaired tetralogy of Fallot and pulmonary regurgitation were prospectively recruited. Healthy volunteers (n = 10) were used as control. Tagging MR images were acquired at the base, mid, and apical LV levels for assessing segmental rotation and circumferential strain. Cine MR images and velocity-encoded MR images were also acquired for assessment of biventricular volumes and biventricular function and pulmonary regurgitant fraction, respectively. Mean values were compared between groups using unpaired Student's t-test. RESULTS: Patients presented with preserved global LV function (LVEF of 59 ± 5%). A significant decrease in LV peak circumferential strain was seen in patients compared with normal volunteers at the basilar (-15.6 ± 4.5% vs. -17.6 ± 4.4%; P < 0.01) and apical (-14.4± 6.1% vs. -17.3± 5.1%, P < 0.01) slices. LV peak rotation was also delayed in patients compared with volunteers at the basilar (6.1 ± 2.6° vs. 4.2 ± 0.6°; P < 0.01) and mid (8.0 ± 1.7° vs. 4.9 ± 1.0°; P < 0.01) slices. CONCLUSION: MRI can detect early regional LV dysfunction in patients with preserved LVEF after repair of tetralogy of Fallot. MR may be a useful technique for guiding clinical decisions in these patients in order to prevent future global LV deterioration.
Subject(s)
Magnetic Resonance Imaging/methods , Tetralogy of Fallot/surgery , Ventricular Dysfunction, Left/diagnosis , Adult , Cardiology/methods , Contrast Media/pharmacology , Exercise Test , Female , Heart Ventricles/pathology , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged , Tetralogy of Fallot/physiopathology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
Aortic arch (AA) atheroma is a common source of artery-to-artery embolism. Identification of AA atherosclerotic disease is an important component of the embolic stroke workup. Transesophageal echocardiography (TEE) is the gold standard for AA evaluation, but it has associated risks and is not always readily available. Computed tomography angiography (CTA) is a rapid and noninvasive alternative. This study was conducted to compare the sensitivity and specificity of CTA and TEE for detecting AA disease. We performed a retrospective review of 250 consecutive patients at a tertiary stroke center who underwent both TEE and CTA within a 90-day period. We compared the presence and characteristics of AA plaques using a predetermined grading system for plaques in the ascending, transverse, and descending arch for both modalities (grades 1-4). Out of 750 AA segments (ascending, transverse, and descending AA in 250 patients), 494 were adequately imaged by CTA and TEE. The sensitivity of CTA in detecting grade 1-4 AA atheromas was 53%, and the specificity was 89%. For only high-grade atheromas, the specificity improved to 99%, but the sensitivity decreased to 23%. The negative predictive value of CTA for detection of AA atheromas was 60% (range 54%-65%) for all grades and 95% (range 92%-96%) for high-grade atheromas. CTA has a high negative predictive value for AA atheromas, especially for higher-grade atheromas, and thus may be a useful screening tool to exclude high-grade plaques, indicating a possible complementary role for CTA in detecting AA atheromas.
Subject(s)
Aorta, Thoracic/diagnostic imaging , Aortic Diseases/diagnosis , Aortography/methods , Atherosclerosis/diagnosis , Echocardiography, Transesophageal , Tomography, X-Ray Computed , Aortic Diseases/diagnostic imaging , Atherosclerosis/diagnostic imaging , Humans , Predictive Value of Tests , Retrospective Studies , San Francisco , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
The recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride-induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis. Complete ablation of thrombin signaling would be difficult to achieve in human beings because human platelets have 2 thrombin receptors that are each capable of mediating transmembrane signaling. However, it is possible that complete ablation of thrombin signaling in platelets is not necessary for an antithrombotic effect. In mouse platelets, PAR3 functions as a cofactor that binds thrombin and promotes productive cleavage of PAR4, and thrombin responses are decreased but not absent in Par3(-/-) platelets. We now report that Par3(-/-) mice were protected against ferric chloride-induced thrombosis of mesenteric arterioles and against thromboplastin-induced pulmonary embolism. Surprisingly, Par3(-/-) and Par4(-/-) mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times. Thus, even a partial decrease in mouse platelet responsiveness to thrombin protected against thrombosis and impaired hemostasis in some settings. These results demonstrate the importance of PAR3's unusual cofactor function and underscore the relative importance of thrombin's actions on platelets in vivo. They also suggest that PAR inhibition might be explored for the prevention or treatment of thrombosis in human beings.
Subject(s)
Mesentery/blood supply , Platelet Activation/physiology , Pulmonary Embolism/prevention & control , Receptors, Thrombin/physiology , Thrombosis/prevention & control , Animals , Arterioles , Bleeding Time , Chlorides , Enzyme Activation , Female , Ferric Compounds/toxicity , Genotype , Lung/blood supply , Mice , Mice, Inbred C57BL , Mice, Knockout , Platelet Activation/genetics , Pulmonary Embolism/chemically induced , Receptors, Thrombin/deficiency , Receptors, Thrombin/genetics , Single-Blind Method , Thrombin/metabolism , Thromboplastin/toxicity , Thrombosis/chemically inducedABSTRACT
The coagulation protease Factor Xa (Xa)(1) triggers a variety of cellular responses that may be important for inflammatory reactions to tissue injury. Protease-activated receptors (PAR1, PAR2, and PAR4) can mediate Xa signaling in heterologous expression systems. However, other candidate Xa receptors have been described, and the extent to which one or more PARs account for Xa signaling in relevant differentiated cells is unknown. We examined Xa signaling in endothelial cells from wild-type and PAR-deficient mice. Wild-type endothelial cells responded to agonists for PAR1, PAR2, and PAR4. Relative to wild-type, Xa-triggered phosphoinositide hydrolysis was reduced by 60-75% in Par2 -/- endothelial cells, by 20-30% in Par1 -/- endothelial cells, and by approximately 90% in Par2 -/- endothelial cells treated with a PAR1 antagonist. Similar results were obtained when ERK1/2 phosphorylation was used to assess Xa signaling. Thus PAR2 is the main endogenous Xa receptor in these endothelial cell preparations and, together, PAR2 and PAR1 appear to account for approximately 90% of endothelial Xa signaling. By contrast, in fibroblasts, PAR1 by itself accounted for virtually all Xa-induced phosphoinositide hydrolysis. This information is critical for the design and interpretation of knockout mouse studies to probe the possible roles of Xa signaling in vivo.
