Thrombogenic Risk in Patients With Atrial Fibrillation: Importance of Comorbid Conditions and Intracardiac Changes.

OBJECTIVES: This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. BACKGROUND: Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. METHODS: A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. RESULTS: Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). CONCLUSIONS: Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.

Effect of atrial fibrillation on atrial thrombogenesis in humans: impact of rate and rhythm.

OBJECTIVES: We sought to assess the effect of atrial fibrillation (AF) on atrial thrombogenesis in humans by determining the impact of rate and rhythm. BACKGROUND: Although AF is known to increase the risk of thromboembolic stroke from the left atrium (LA), the exact mechanisms remain poorly understood. METHODS: We studied 55 patients with AF who underwent catheter ablation while in sinus rhythm; 20 patients were induced into AF, 20 patients were atrial paced at 150 beats/min, and 15 were control patients. Blood samples were taken from the LA, right atrium, and femoral vein at baseline and at 15 min in all 3 groups. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. RESULTS: Platelet activation increased significantly in both the AF (p < 0.001) and pacing (p < 0.05) groups, but decreased in control patients (p < 0.001). Thrombin generation increased specifically in the LA compared with the periphery in both the AF (p < 0.01) and pacing (p < 0.01) groups, but decreased in control patients (p < 0.001). With AF, ADMA (p < 0.01) and sCD40L (p < 0.001) levels increased significantly at all sites, but were unchanged with pacing (ADMA, p = 0.5; sCD40L, p = 0.8) or in control patients (ADMA, p = 0.6; sCD40L, p = 0.9). CONCLUSIONS: Rapid atrial rates and AF in humans both result in increased platelet activation and thrombin generation. Prothrombotic activation occurs to a greater extent in the human LA compared with systemic circulation. AF additionally induces endothelial dysfunction and inflammation. These findings suggest that although rapid atrial rates increase the thrombogenic risk, AF may further potentiate this risk.

Increased proportion of hypermineralized osteocyte lacunae in osteoporotic and osteoarthritic human trabecular bone: implications for bone remodeling.

Hypermineralized osteocyte lacunae (micropetrosis) have received little research attention. While they are a known aspect of the aging human skeleton, no data are available for pathological bone. In this study, intertrochanteric trabecular bone cores were obtained from patients at surgery for osteoporotic (OP) femoral neck fracture (10F, 4M, 65-94 years), for hip osteoarthritis (OA; 7F, 8M, 62-87 years), and femora at autopsy (CTL; 5F, 11M, 60-84 years). Vertebral trabecular bone cores were also obtained from the vertebra of autopsy cases (CVB; 3F, 6M, 53-83 years). Specimens were resin-embedded, polished, and carbon coated for quantitative backscattered electron imaging (qBEI), energy dispersive X-ray (EDX) spectrometry, and imaging analysis. Bone mineralization (Wt %Ca) was not different between OP, OA, and CTL; but was greater in femoral CTL than in CVB. The percent of hypermineralized osteocyte lacunae relative to the total number (HL/TL) was greater in OP and OA than in CTL. However, relative to bone mineral area, OP was characterised by increased hypermineralized osteocyte lacunar number density (Hd.Lc.Dn), whereas OA was characterised by decreased osteocyte lacunar number density (Lc.Dn) and total osteocyte lacunar number density (Tt.Lc.Dn). Lc.Dn was higher in CVB than in femoral CTL. The calcium-phosphorus ratio (R(Ca/P)) was not different between hypermineralized osteocyte lacunae and bone matrix in each group. In addition, this study focused on the phenomenon of osteocyte lacunae hypermineralization using qBEI. Seven morphological types of osteocyte lacunae hypermineralization were described according to the presence of one or several hypermineralized spherites, associated or not with a hypermineralized lacunar ring. This study has described, for the first time, the morphology of hypermineralized osteocyte lacunae in OP and OA human bone. Further studies are suggested to investigate the functional influence of hypermineralized osteocyte lacunae on bone remodeling and bone biomechanical properties.