Dimitrios I. Hatseras

Atrial Fibrillation and Hypercoagulability: Dependent on Clinical Factors or/and on Genetic Alterations?

AbstractIt is well known that atrial fibrillation is associated with high incidence of thromboembolic events, propably due to a prothrombotic or hypercoagulable state. However, it is unclear whether or not there is any difference of this prothrombotic state in the clinical subgroups of atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. From the other side the role of the arrhythmia duration on the changes of coagulative variables in atrial fibrillation patients is not clearly enough.The contribution of genetic and functional alterations in factors of the coagulation and fibrinolytic pathways (that is hemostatic risk factors) to the development of hypercoagulation state in atrial fibrillation requires clarification.We investigated therefore (1) if there are differences in the prothrombotic state between patients with different clinical status of the arrhythmia, (2) if the arrhythmia duration per se could be an independent determinant of the prothrombotic state in all atrial fibrillation patients and (3) if coexistent genetic alterations in haemostatic risk factors in patients with atrial fibrillation could contribute to the development of prothrombotic abnormalities. Methods: Over a period of 23 months, we studied 55 patients with chronic non-valvular atrial fibrillation. We recruited 18 consecutive patients (13 men, mean age 59 ± 10 years) with paroxysmal atrial fibrillation 17 patients (11 men, mean age 61 ± 7 years) with persistent atrial fibrillation who underwent elective successful DC and remained in sinus rhythm at the 3 month visit and 20 patients (14 men mean age 64 ± 9) with permanent atrial fibrillation. Blood results were compared to 17 age-sex- and race-matched controls. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P-selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). We assessed the frequencies of factor V Leiden and prothrombin variant G20210A to determine whether particular inherited haemostatic risk factors may have contribution to the development of prothrombotic state in atrial fibrillation patients. Results: Permanent atrial fibrillation was associated with significant raised levels of von Willebrand factor, fibrinogen levels and soluble P-selectin compared to matched controls (all p < 0.001) and matched patients with paroxysmal and permanent AF (all p ranged between <0.003 and <0.002). Patients with persistent atrial fibrillation had significantly elevated von Willebrand factor levels (p = 0.0064) and fibrinogen levels (p = 0.002), but not Soluble P-selectin (p = 0.509). when compared to controls. Patients with paroxysmal atrial fibrillation had significantly elevated levels of P-selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p = .0.61) compared to controls. Stepwise multiple regression analyses demonstrated that the arrhythmia duration (approximately 3 years) was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P-selectin levels. Restoration of sinus rhythm in paroxysmal atrial fibrillation subgroup and successful electrical cardioversion of patients with permanent fibrillation atrial fibrillation did not significantly alter levels of the affected factors.The frequency of factor V Leiden was 8.9 in all studied patients with atrial fibrillation, versus 2.4% in the control group (odds ratio {OR} 4.6 [95% confidence (CI) 1.4–17.5], p = 0.02). The frequency of the prothrombin variant G20210A was 6.4.% compared with control group 1.6% (OR 4.9 [95% confidence interval (CI) 1.2–2.9], p = 0.04).There was a trend towards an increased frequency of factor V Leiden and/or prothrombin variant G20210A in patients age <55 years and in patients living at a particular area of Thrace mountains. Conclusions: Our results showed that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched patients with permanent atrial fibrillation and controls in sinus rhythm.The duration of the arrhythmia (about 3 years) was an independent predictor of abnormal measured factors. We found for the first time that some genetic alterations in haemostatic risk factors could be coexist in atrial fibrillation patients and may be a contributor to the development of hypercoagulability in atrial fibrillation patients.

Anti-inflammatory cytokine profile in acute coronary syndromes: behavior of interleukin-10 in association with serum metalloproteinases and proinflammatory cytokines

BACKGROUND The anti-inflammatory cytokine interleukin-10 (IL-10) downregulates the production of metalloproteinases (MMPs) and upregulates the production of their tissue inhibitors (TIMPs). The aim of this study was to assess the levels of IL-10 in patients with acute myocardial infarction (AMI) and unstable angina (UA), as well as to investigate the relationship of circulating IL-10 with the levels of MMPs (MMP-1, -2, -9), their tissue inhibitor (TIMP-1), pro-inflammatory cytokines (IL-6, tumor necrosis factor (TNF)-alpha) and serum lipids in the same patient population. METHODS Serum MMP-1, -2, -9, TIMP-1, IL-6, TNF-alpha and IL-10 were measured by ELISA assays in 23 patients with AMI and 20 patients with UA after their hospital admission, as well as in 16 healthy controls subjects. The lipid profile was assessed by measuring the serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. RESULTS AMI patients exhibited significantly higher serum levels of IL-10 as compared with those of UA patients and healthy controls (both P=0.005). In contrast, there was no significant difference in IL-10 levels between UA patients and healthy controls. In AMI patients there was a statistically significant positive correlation of serum IL-10 with the levels of MMP-9 (rho=0.588, P=0.003), IL-6 (rho=0.502, P=0.015) and HDL-cholesterol (rho=0.697, P<0.001), as well as a significant negative correlation with the levels of triglycerides (rho=-0.417, P=0.048). CONCLUSIONS Our results suggest that UA is associated with low serum activity of IL-10, while a significant elevation of this anti-inflammatory cytokine accompanies the peripheral immune responses of AMI. This observation indicates that different patterns of inflammatory reactions are implicated in the pathophysiology of two clinical conditions.

Peripheral arterial occlusive disease as a predictor of the extent of coronary atherosclerosis in patients with coronary artery disease with and without diabetes mellitus.

We evaluated the sensitivity and specificity of a diagnosis of peripheral arterial occlusive disease (PAOD) as a predictor of the severity of coronary artery disease (CAD) in patients with and without diabetes. A total of 302 patients were assigned to groups according to the angiographic severity of their CAD and their diabetes status. Both PAOD and severe PAOD were diagnosed by measuring the ankle-brachial index (ABI) and toe-brachial index (TBI). A diagnosis of PAOD had a low sensitivity (34.3%) but a high specificity (87.0%) for detecting patients with severe CAD. Sensitivity was higher in patients with diabetes (52.4%) than without (19.5%), whereas specificity was higher in patients without diabetes (95.4%) than those with diabetes (69.8%). A diagnosis of severe PAOD had a higher specificity (96.0%), but a very low sensitivity (16.4%). We conclude that a diagnosis of PAOD among patients with CAD had a low sensitivity but a high specificity for detecting those with severe CAD, particularly in patients without diabetes.

Clotting state after cardioversion of atrial fibrillation: a haemostasis index could detect the relationship with the arrhythmia duration

BackgroundFibrin D-dimer levels have been advocated as an useful clinical marker of thrombogenesis.HypothesisWe hypothesized that i) there is a hyperclotting state after the return of atrial fibrillation to sinus rhythm, ii) the measurement of plasma D-Dimer levels might be a good screening tool of this clotting status, and iii) the duration of arrhythmia influences the haemostasis measured by plasma D-Dimer levels.MethodsForty-two patients with atrial fibrillation undergoing cardioversion were divided into two groups: in Group A (n = 24,14 male, 56 ± 11 years) the duration of atrial fibrillation was 72 hours or more (142.7 ± 103.8 hours), in Group B (n = 18, 10 male, 61 ± 13 years) the duration of atrial fibrillation was less than 72 hours (25 ± 16 hours). Plasma fibrin D-dimer levels were measured by enzyme immunoassay before, and 36 hours after, cardioversion. The change of plasma D-dimer levels 36 hours after cardioversion was calculated as delta-D-dimer.ResultsThere were no significant differences in demographic, clinical, and echocardiographic data, and the success of cardioversion between the two groups. Compared to the control, the baseline D-dimer levels were significantly higher in both groups. The delta D-dimer levels were significantly higher in Group A than in Group B (p < 0.005). Furthermore, plasma D-dimer levels 36 hours after cardioversion (r = 0.52, p = 0.0016) and delta-D-dimer levels (r = 0.73, p < 0.0001) showed significant correlations with the duration of atrial fibrillation.ConclusionThe longer duration of the atrial fibrillation episode could lead to a more prominent cardiovascular hyperclotting state after cardioversion, and the mean changes of plasma D-Dimer levels could be used as an useful clinical marker of the clotting state after atrial systole return.

Detection of Mycobacterium tuberculosis complex DNA in pericardial fluid, bone marrow and peripheral blood in a patient with pericardial tuberculosis: A case report

Definitive diagnosis of tuberculous pericarditis requires identification of bacilli in pericardial fluid or tissue. Conventional diagnostic methods are time-consuming and have a low sensitivity making bacteriological confirmation of the disease very difficult. Hereby, we report the case of molecular detection of Mycobacterium tuberculosis in pericardial fluid, bone marrow and peripheral blood from a 63-year-old woman with pericardial tuberculosis, using a nested PCR assay specific for IS6110 insertion element of M. tuberculosis complex. The patient had an excellent response to a three-drug combination anti-tuberculous regimen and 1 year later was asymptomatic, without evidence of constrictive pericarditis.