Atrial fibrillation type and renal dysfunction as important predictors of left atrial thrombus.

OBJECTIVE: We aimed to identify predictors of left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF) and to enhance the prognostic value of the CHA2DS2-VASc score. METHODS: Derivation cohort included 1033 consecutive AF patients referred for catheter ablation or direct current cardioversion, in whom transoesophageal echocardiography (TOE) was performed prior to the procedure. Logistic regression analysis was used to identify predictors of LAA thrombus on TOE. Receiver operating characteristic (ROC) curves were constructed to compare the newly developed score with the CHA2DS2 and CHA2DS2-VASc scores in the derivation and the validation (n=320) cohort. RESULTS: On TOE, LAA thrombus was present in 59 (5.7%) patients in the derivation cohort. Aside from variables encompassed by the CHA2DS2-VASc score, LAA thrombus predictors included AF type (persistent/'permanent' vs paroxysmal) and renal dysfunction. These predictors were incorporated into the CHA2DS2-VASc score. In ROC analysis, area under the curve (AUC) for the new score (CHA2DS2-VASc-RAF score) was significantly higher (0.81) than those for the CHA2DS2 and CHA2DS2-VASc scores (0.71 and 0.70, respectively). In the validation cohort, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.88) than the CHA2DS2 and CHA2DS2-VASc scores (AUC of 0.63 and 0.60, respectively). CONCLUSION: In real-world AF patients with majority on oral anticoagulation, LAA thrombus was found in approximately 6%. Two variables not included in the CHA2DS2-VASc score (AF type and renal dysfunction) proved strong, independent predictors of LAA thrombus and might improve thromboembolic risk stratification.

Comparison of different oral anticoagulant regimens in patients with atrial fibrillation undergoing ablation or cardioversion.

INTRODUCTION    Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). OBJECTIVES    The aim of the study was to assess the incidence of left atrial appendage (LAA) thrombus and dense spontaneous echo contrast (SEC), as well as to compare the clinical characteristics of patients with AF treated with different anticoagulant regimens. PATIENTS AND METHODS    We studied 1033 consecutive patients with AF, who underwent transesophageal echocardiography (TEE) before AF ablation or cardioversion. We excluded 174 patients without any prior oral anticoagulation or who underwent bridging with heparin before TEE. RESULTS    In the study group of 859 patients (median age, 61 years; men, 66%), 437 patients (50.9%) received VKAs; 191 (22.2%), dabigatran; 230 (26.8%), rivaroxaban; and 1 patient (0.1%), apixaban. There were no differences in baseline characteristics or the incidence of LAA thrombus (VKAs, 6.9%; NOACs, 5.5%; P = 0.40) and dense SEC (VKAs, 5.3%; NOACs, 3.3%; P = 0.18) between patients on VKAs and those on NOACs. Compared with patients treated with dabigatran, those on rivaroxaban more often had paroxysmal AF, higher ejection fraction, LAA emptying velocity, and platelet count, as well as lower left ventricular end­diastolic dimension and hematocrit. The frequency of LAA thrombus in patients receiving dabigatran and those receiving rivaroxaban was comparable (6.8% vs 4.4%; P = 0.29), while dense SEC occurred more often in patients treated with dabigatran (5.2% vs 1.7%; P = 0.06). In a logistic regression analysis, none of the oral anticoagulation regimens predicted LAA thrombus in TEE, whereas maximal LAA emptying velocity was the only parameter independently associated with the presence of thrombus. CONCLUSIONS    In the studied group of patients with AF, the choice of anticoagulation did not depend on thromboembolic or bleeding risk.

H2AX foci in late S/G2- and M-phase cells after hydroxyurea- and aphidicolin-induced DNA replication stress in Vicia.

Immunocytochemistry using alpha-phospho-H2AX antibodies shows that hydroxyurea (HU), an inhibitor of ribonucleotide reductase, and aphidicolin (APH), an inhibitor of DNA-polymerases alpha and delta, may promote formation of phospho-H2AX foci in late S/G2-phase cells in root meristems of Vicia faba. Although fluorescent foci spread throughout the whole area of nucleoplasm, large phospho-H2AX aggregates in HU-treated cells allocate mainly in perinucleolar regions. A strong tendency of ATR/ATM-dependent phospho-Chk1S317 kinase to focus in analogous compartments, as opposed to phospho-Chk2T68 and to both effector kinases in APH-treated cells, may suggest that selected elements of the intra-S-phase cell cycle checkpoints share overlapping locations with DNA repair factors known to concentrate in phospho-H2AX aggregates. APH-induced phosphorylation of H2AX exhibits little or no overlap with the areas positioned close to nucleoli. Following G2-M transition of the HU- and APH-pretreated cells, altered chromatin structures are still discernible as large phospho-H2AX foci in the vicinity of chromosomes. Both in HU- and APH-treated roots, immunofluorescence analysis revealed a dominant fraction of small foci and a less frequent population of large phospho-H2AX aggregates, similar to those observed in animal cells exposed to ionizing radiation. The extent of H2AX phosphorylation has been found considerably reduced in root meristem cells treated with HU and caffeine. The frequencies of phospho-H2AX foci observed during mitosis and caffeine-mediated premature chromosome condensation (PCC) suggest that there may be functional links between the checkpoint mechanisms that control genome integrity and those activities which operate throughout the unperturbed mitosis in plants.