Objective-Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results-Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (PϽ0.05). Fibrin of young CAD patients was stiffer (Pϭ0.002), made of numerous (Pϭ0.002) and shorter fibers (Pϭ0.04), and lysed at a slower rate than that of controls (Pϭ0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions-This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. Key Words: acute coronary syndromes Ⅲ coagulation Ⅲ fibrinolysis Ⅲ pathophysiology Ⅲ fibrinogen Ⅲ thrombophilia T he mechanical properties of clots and their major constituent fibrin are normally finely tuned to optimize bleeding control while also minimizing their effect on atherothrombosis. 1,2 A decreased rate of fibrinolysis and increased thrombosis are generally associated with stiff clots, although such relationships are complex. 3,4 Many factors that affect clot structure have a great impact on the mechanical properties fibrin and fibrinolysis through modifications of various steps in the fibrin polymerization process and clot stabilization. 1,4,5 See page 2419Premature coronary artery disease (CAD) is associated with increased plasma levels of prothrombotic and proinflammatory biomarkers, including fibrinogen and plasminogen activator inhibitor (PAI) type 1, which are known to favor hypofibrinolysis 6 and to be independent predictors of CAD. 7,8 Epidemiological studies have also revealed a relationship between myocardial infarction (MI) and reduced permeability and increased stiffness of fibrin, especially in young post-MI patients. 9 These aspects of altered fibrin clot network architecture were not found to be attributable to classic risk factors including fibrinogen concentrations or common polymorphisms. 2 However, the relationships among premature CAD, abnormal fibrin physical properties, and hypofibrinolysis remain little explored. The lack of appropriately designed studies of the physical properties of fibrin, including simultaneous determination of viscoelastic and morphological properties o...

AimsLatent heart failure at rest can be observed in a number of patients upon exercise. Considering left atrial (LA) remodelling as the reflection of the cumulative effects of the LV filling pressure (FP) over time, our aim was to investigate whether the LA volume would predict abnormal exercise LVFP. Methods and resultsNinety patients (58.6 ± 10.8 years, 74 men) underwent exercise echocardiography. The LA maximal volume was measured by the Simpson method and indexed to body surface area. LVFP was assessed by the ratio between early peak diastolic velocities of mitral inflow and the septal annular mitral plane (E/e ′ ). Exercise E/e ′ >13 was used as a threshold to define abnormal LVFP. Indexed LA volume was correlated with E/e ′ at rest (r = 0.37, P = 0.003), but the correlation was better with exercise E/e ′ (r = 0.54, P < 0.0001). In multivariate analysis, age, LV end-diastolic volume index, LVEF, and exercise E/e ′ were the independent determinants of LA volume index (R 2 = 0.47, P < 0.0001). Eleven patients had exercise E/e ′ >13; compared with the rest of the population, these patients were older and achieved a milder effort. LA volume index >33 mL/m 2 predicted an abnormal exercise LVFP with a 91% sensitivity and a 78% specificity. None of the patients with an LA volume index <26 mL/m 2 (n = 31, 34%) had an exercise E/e ′ >13.

The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities.

Mortality after angioplasty remains high in people > or =75 years with cardiogenic shock despite all the advances in the management of myocardial infarction. These disappointing results should encourage us to assess the role of surgical revascularisation and circulatory assistance.