F-Amplitude,left atrial appendage velocity,and thromboembolic risk in nonrheumatic atrial fibrillation

Background: Reduced left atrial appendage velocity (LAAV) has been identified as a marker for thromboembolism in patients with atrial fibrillation. Hypothesis: It was postulated that electrocardiographic (ECG) F-wave amplitude would correlate with LAAV, and inversely with the risk of thromboembolism in patients with atrial fibrillation. Methods: In all, 53 patients with nonrheumatic (NRAF) and 7 patients with rheumatic (RAF) atrial fibrillation underwent assessment of maximum LAAV, which was correlated to the maximum ECG F-wave voltage from lead V¹ (Fmax). In 450 NRAF patients on neither aspirin nor warfarin, the relationship between Fmax and thromboembolic risk was assessed over an average follow-up of 1.3 years. Results: Fmax did not correlate with LAAV (r = 0.2, p = 0.07). Patients with intermittent atrial fibrillation (n = 123) had smaller Fmax amplitude than patients with constant atrial fibrillation (n = 327) (mean 0.73 vs. 0.88 mV^?1, p = 0.001). Fmax amplitude was not related to a history of hypertension, systolic blood pressure, duration of NRAF, abnormal transthoracic echocardiographic left ventricular (LV) systolic function or left atrial (LA) diameter. There was a strong trend for increased LV mass being related to smaller Fmax amplitude after adjusting for body surface area (p = 0.06). Fmax amplitude was not correlated with risk of embolic events, including only those events presumed by a panel of case-blinded neurologists to be cardioembolic. Conclusion: Fmax amplitude in NRAF is smaller in patients with intermittent versus constant AF. It does not correlate with LAAV, LA size, increased LV mass, or systolic dysfunction, hypertension, or risk of embolism. Therefore, Fmax amplitude may not be used as a surrogate for LAAV, or as a measure of thromboembolic risk in NRAF.     

Use of the bioMérieux VIDAS troponin I ultra assay for the diagnosis of myocardial infarction and detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome

BACKGROUND: We demonstrate the performance of the bioMérieux VIDAS Troponin I Ultra assay for diagnostic accuracy for detection of myocardial infarction (MI) and risk stratification. METHOD: cTnI was measured in 545 patients from 2 clinical centers with symptoms suggestive of ACS at admission, with an additional specimen at 4-12 h (453 patients). The 99th percentile value (0.01 microg/l) was used to assess clinical accuracy for diagnosis of acute MI. Primary endpoint for risk stratification was first of cardiac event or death in 302 patients (one center) followed for 60 days. RESULTS: 157 (28.8%) patients ruled in for an MI during index hospitalization. Sensitivities and specificities were 88.1% (95% CI 81.9 to 92.4%) and 79.9% (CI 75.5 to 83.6%) for baseline and 100% (CI 96.5 to 100%) and 79.4% (CI 74.4 to 83.4%) for follow-up specimens. ROC curve areas increased from 0.912 (CI 0.879 to 0.944) at baseline to 0.994 (CI 0.988 to 0.999) at second sampling (n=453, p<0.01); with no differences between sites. Primary endpoint rate for the 223 patients (74%) with normal cTnI on presentation was lower than the 79 patients (26%) with cTnI>0.01 ug/l (5.9% vs. 42.3%, p<0.0001). The relative risk for the >0.01 ug/l group was 8.9 (CI 4.6 to 17). CONCLUSION: The VIDAS cTnI assay is a sensitive diagnostic method for the early detection of MI and predicts increased risk for adverse events in patients with symptoms suggestive of ACS.     

Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction in atrial fibrillation

OBJECTIVES: We evaluated left atrial appendage obliteration in high-risk patients with atrial fibrillation (AF). BACKGROUND: Left atrial appendage thrombosis and embolization is the principal mechanism of stroke in AF. Anticoagulation is underutilized and often contraindicated. METHODS: Thoracoscopic Left Appendage, Total Obliteration, No cardiac Invasion (LAPTONI) was undertaken with a loop snare in eight patients and a stapler in seven patients, median age 71 years, with clinical risk factors for stroke and with an absolute contraindication to or failure of prior thrombosis prevention with warfarin. Eleven patients had a history of prior thromboembolism. One patient took sustained warfarin during follow-up. RESULTS: The LAPTONI procedure was completed in 14 of 15 patients, and 1 patient required urgent conversion to open thoracotomy because of bleeding. Patients have been followed up for 8 to 60 months, mean 42 +/- 14 months. One fatal stroke occurred 55 months after surgery, and one non-disabling stroke three months after surgery. Two other deaths occurred, one after coronary bypass surgery and the other from hepatic failure. The subgroup of 11 patients with prior thromboembolism had an annualized rate of stroke of 5.2% per year (95% confidence interval [CI] 1.3 to 21) after LAPTONI, which compares to a rate of 13% per year (95% CI 9.0 to 19) for similar aspirin-treated patients from the Stroke Prevention in Atrial Fibrillation trials (p = 0.15). CONCLUSIONS: The LAPTONI procedure appears technically feasible without immediate disabling neurologic morbidity or mortality, and it demonstrates low post-operative event rates and a statistical trend toward thromboembolic risk reduction in high-risk AF patients.     

A unique Rab GTPase, EhRabA, is involved in motility and polarization of Entamoeba histolytica cells

Entamoeba histolytica, an enteric protozoan parasite, infects 10% of the world's population leading to 50 million cases of invasive amoebiasis annually. Motility, which requires cell polarization, is important to the virulence of this pathogen, as it may result in destruction of host tissues and invasion. To gain insight into these processes in Entamoeba, a unique Rab GTPase, EhRabA, which localizes to the leading edge of cells, was characterized. Cell lines expressing a dominant negative version of EhRabA (EhRabA-DN) were generated. These mutant cells exhibited alterations in cell shape, polarity, and motility, supporting a role for this Rab in the regulation of these processes. Consistent with the notion that a dynamic actin cytoskeleton is crucial to cell polarity and motility, these mutants also exhibited alterations in the actin cytoskeleton. Cells expressing EhRabA-DN also displayed defects in several virulence functions including the ability to adhere to host cells, destroy host cells, and release cysteine proteases. Mislocalization of a prominent adhesion molecule, the galactose/N-acetylgalactosamine (Gal/GalNAc) adherence lectin and reorganization of ordered lipid domains, known as lipid rafts, also accompanied expression of EhRabA-DN. Interestingly, several endocytic processes were unaffected by expression of EhRabA-DN. Together, these data suggest that EhRabA may be involved in the regulation of polarization, motility and actin cytoskeletal dynamics: functions that participate in the pathogenicity of Entamoeba.     

Involvement of raft-like plasma membrane domains of Entamoeba histolytica in pinocytosis and adhesion

Lipid rafts are highly ordered, cholesterol-rich, and detergent-resistant microdomains found in the plasma membrane of many eukaryotic cells. These domains play important roles in endocytosis, secretion, and adhesion in a variety of cell types. The parasitic protozoan Entamoeba histolytica, the causative agent of amoebic dysentery, was determined to have raft-like plasma membrane domains by use of fluorescent lipid analogs that specifically partition into raft and nonraft regions of the membrane. Disruption of raft-like membrane domains in Entamoeba with the cholesterol-binding agents filipin and methyl-beta-cyclodextrin resulted in the inhibition of several important virulence functions, fluid-phase pinocytosis, and adhesion to host cell monolayers. However, disruption of raft-like domains did not inhibit constitutive secretion of cysteine proteases, another important virulence function of Entamoeba. Flotation of the cold Triton X-100-insoluble portion of membranes on sucrose gradients revealed that the heavy, intermediate, and light subunits of the galactose-N-acetylgalactosamine-inhibitible lectin, an important cell surface adhesion molecule of Entamoeba, were enriched in cholesterol-rich (raft-like) fractions, whereas EhCP5, another cell surface molecule, was not enriched in these fractions. The subunits of the lectin were also observed in high-density, actin-rich fractions of the sucrose gradient. Together, these data suggest that pinocytosis and adhesion are raft-dependent functions in this pathogen. This is the first report describing the existence and physiological relevance of raft-like membrane domains in E. histolytica.