Luc Christiaens

Resistance in vitro to low-dose aspirin is associated with platelet PlA1(GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T kozak (GP Ibα) polymorphisms

OBJECTIVES We investigated whether three platelet gene polymorphisms, Pl(A1/A2), C807T, and C-5T Kozak (encoding, respectively, for platelet membrane glycoproteins (GP) IIIa, GP Ia/IIa, GP Ibalpha), could contribute to the resistance to a low dose of aspirin (160 mg/day). BACKGROUND Aspirin antiplatelet effect is not uniform in all patients, and the mechanism by which some patients are in vitro resistant to aspirin remains to be determined. However, it has been suggested that polymorphisms of platelet membrane glycoproteins might contribute to aspirin resistance. METHODS Ninety-eight patients on aspirin (160 mg/day) for at least one month were enrolled. Aspirin resistance was measured by the platelet function analyzer (PFA)-100 analyzer; genotyping of the three polymorphisms was performed using a polymerase chain reaction-based restriction fragment-length polymorphism analysis. RESULTS Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of aspirin resistance was 29.6% (n = 29). Aspirin-resistant patients were significantly more often Pl(A1/A1) (86.2%; n = 25) than sensitive patients (59.4%; n = 41; p = 0.01). Of the 29 patients, 25 were reevaluated after having taken 300 mg/day aspirin for at least one month. Only 11 patients still have nonprolonged collagen epinephrine closure time, and these were all Pl(A1/A1). No relation was found between resistance status and C-5T Kozak or C807T genotypes. CONCLUSIONS Platelets homozygous for the Pl(A1) allele appear to be less sensitive to inhibitory action of low-dose aspirin. This differential sensitivity to aspirin may have potential clinical implications whereby specific antiplatelet therapy may be best tailored according to the patients Pl(A) genotype.

A new method for measurement of left atrial volumes using 64-slice spiral computed tomography: comparison with two-dimensional echocardiographic techniques.

BACKGROUND Left atrial (LA) volume, is related to cardiovascular morbidity. LA enlargement is usually assessed using trans-thoracic echocardiography (TTE). The association of modern multislice computed tomography (MSCT) imaging and new 3D reconstruction software, allows direct cardiac chamber volume measurement without geometrical assumptions. This study was designed to evaluate the maximal (LAmax) and minimal (LAmin) LA volumes during the cardiac cycle using MSCT and TTE approaches. METHODS We screened 26 consecutive patients referred for coronary imaging using a 64-MSCT scanner and a TTE within 12 h. Contiguous multiphase images were generated from axial MSCT data and semi-automated 3D segmentation technique was applied to generate LA volumes. Using TTE, LA volumes and LA ejection fraction (LAEF) were obtained using five assumptions methods: cubing equation, diameter-length formula, area-length formula, ellipsoidal formula and biplane Simpson rule. RESULTS Five patients were excluded for inadequate TTE visualization and one for ectopic beats during MSCT. The sample consisted in 20 patients (11 men, age: 56+/-14 years). Using MSCT, LA volumes indexed to body surface area were: LAmax=74+/-27 ml/m(2), LAmin=49+/-26 ml/m(2), with close correlations with TTE measurements and a significant underestimation by all TTE approaches. A close correlation was observed between LAEF using MSCT and TTE Simpsons method: 36+/-14% vs. 37+/-14%, r=0.99, p<0.0001. CONCLUSION Theses results suggest that the assessment of LA volumes and ejection fraction was reliable using 64-MSCT in patients referred for coronary computed tomography imaging.

Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

BACKGROUND Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin β immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. CONCLUSIONS Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function.

Real three-dimensional assessment of left atrial and left atrial appendage volumes by 64-slice spiral computed tomography in individuals with or without cardiovascular disease

CONTEXT Left atrial (LA) volume is a prognosis factor of cardiovascular morbidity in patients with cardiovascular disease (CD). Recent developments of multislice computed tomography (MSCT) have made non invasive coronary angiography reliable for selected patients and new software facilitates truly volume measurements without geometrical assumptions. OBJECTIVE To define, by using MSCT, LA and left atrial appendage (LAA) volumes in patients with or without CD. METHODS AND RESULTS In the population of patients referred to our laboratory for a conventional MSCT coronary angiography, 40 individuals without CD (Normal group) and 80 patients with CD (CD group) were prospectively selected. The CD group was constituted from 4 subgroups of patients with either coronary artery disease (n=20), idiopathic dilated cardiomyopathy (n=20), left ventricular hypertrophy (n=20) or severe mitral regurgitation (MR group, n=20). LAA and LA volumes were measured on a commercially available workstation. LA maximal and minimal volumes were lower in Normal group than in CD group, as LA ejection fraction (54+/-10 versus 67+/-20 ml/m(2), p<0.0001; 31+/-8 versus 46+/-20 ml/m(2), p<0.0001; 43+/-8% versus 33+/- 14%, p<0.001). LAA volume was larger in MR group than in Normal group (15+/-7 ml versus 9+/-3 ml, p<0.0001). CONCLUSION This MSCT study provides normal values of LA and LAA volumes for patients who underwent MSCT coronary angiography and suggests that MSCT is helpful to assess the changes of LA volumes related to various CD.

Normal Coronary Angiogram and Dobutamine‐Induced Left Ventricular Obstruction During Stress Echocardiography: A Higher Hemodynamic Responsiveness to Dobutamine

This study assessed the clinical or echographic factors predisposing to dynamic left ventricular obstruction (LVO) during dobutamine echocardiography (DE) in patients with angina‐like chest pain but without coronary artery disease (CAD). DE is an effective technique for the noninvasive diagnosis of underlying CAD. During DE, an LVO is not unusual in ischemic patients. Methods: DE (5–40 μg/kg/min) was performed in 52 consecutive patients with angina‐like chest pain and normal coronary angiogram. Mean (standard deviation) age was 61 ± 10 years (27 men, 25 women). Dobutamine‐induced LVO was defined as a new intracavitary flow acceleration of at least 3 msec in the left ventricle. Results: Dynamic LVO was observed during DE in 20 (38%) of the 52 patients and was not related to clinical or baseline echocardiographic parameters. The chronotropic response and the systolic blood pressure during DE were higher in the group with LVO (P < 0.03 and P < 0.05, respectively). Appearance of chest pain during the test was also more frequent when LVO occurred (P < 0.02). Conclusion: Dynamic LVO is common during DE in a population of patients with angina‐like chest pain without epicardial CAD and is associated with a higher hemodynamic responsiveness to dobutamine.

Major clinical vascular events and aspirin-resistance status as determined by the PFA-100 method among patients with stable coronary artery disease: a prospective study.

Aspirin inhibits platelet activation and reduces major vascular events in patients with stable coronary artery disease. The extent of platelet inhibition, denoted as aspirin resistance, however, is not always sufficient. A correlation between aspirin resistance as measured by aggregometry and adverse clinical events has been demonstrated. The point-of-care platelet function analyzer PFA-100 is usually used to detect aspirin resistance, but the relation between PFA-100 results and the vascular prognosis is not assessed. We prospectively enrolled 97 patients with stable coronary artery disease who were on aspirin (160 mg per day since 1 month or longer). Aspirin resistance was measured by the PFA-100 analyzer. Median follow-up was 2.5 years and the primary outcome was the composite of death, myocardial infarction, and ischemic cerebral infarction or acute limb ischemia. In our study, 29 patients (29.9%) showed resistance to aspirin, with a higher percentage of female patients (38 vs. 15%; P = 0.01). During the follow-up, aspirin resistance was not associated with an increased risk of death, myocardial infarction, or ischemic vascular event compared with the aspirin-sensitive patients (17 vs. 13%; P > 0.60). In this cohort of stable coronary artery disease, patients on aspirin dose of 160 mg per day, the aspirin-resistance status based on the PFA-100 results is not associated with a significant increase in major vascular clinical events.

Using a multidimensional prognostic index (MPI) based on comprehensive geriatric assessment (CGA) to predict mortality in elderly undergoing transcatheter aortic valve implantation

BACKGROUND Selection of appropriate elderly who can benefit from transcatheter aortic valve implantation (TAVI) is challenging. We evaluated the prognosis of this procedure according to the comprehensive geriatric assessment (CGA) based on the multidimensional prognostic index (MPI). METHODS Prospective observational monocentric study from January 2013 to December 2015. Consecutive patients aged ≥75 who underwent TAVI and a complete CGA were included. Baseline demographic, geriatric and cardiologic data were collected. CGA was used to calculate the MPI score that is divided in three groups according to the mortality risk. Follow up was performed until December 2016 and mortality rate was assessed at one, six and 12months. RESULTS 116 patients were included. Mean age was 86.2±4.2years, mean European system for cardiac operative risk evaluation (EuroSCORE) was 19.2±11.3%, mean MPI score was 0.39±0.13. Forty-five (38.8%) patients belonged to MPI-1 group, 68 (58.6%) to MPI-2 group and three to MPI-3 group. MPI score and Euroscore were moderately correlated (Spearman correlation coefficient rs=0.27, p=0.0035). Mortality rate was significantly different between MPI groups at six and 12months (p=0.040 and p=0.022). Kaplan Meier survival estimates at one year stratified by MPI groups was significantly different (hazard ratio HR=2.83, 95%confidence interval (CI) 1.38-5.82, p=0.004). Among variables retained to perform logistic regression analysis, the score of instrumental activities of daily living appeared the most relevant (p<0.001). CONCLUSION This study indicates that CGA based on MPI tool is accurate to predict prognosis in elderly patients undergoing TAVI procedure.

A rapid and specific whole blood HPA-1 phenotyping by flow cytometry using two commercialized monoclonal antibodies directed against GP IIIa and GP IIb-IIIa complexes

The human platelet antigen 1 (HPA‐1) system has been implicated in rare but severe diseases, such as neonatal alloimmune thrombocytopenic purpura, post‐transfusion purpura and immune platelet refractoriness. We developed a flow cytometry assay for HPA‐1 phenotyping using two commercial monoclonal antibodies, P2 and SZ21, directed against glycoprotein (GP) IIb–IIIa and GP IIIa respectively. One hundred and twenty‐seven healthy controls were studied and ratios of mean fluorescence intensity for P2 and SZ21 discriminated between HPA‐1a homozygotes and heterozygotes. These two monoclonal antibodies, coupled with flow cytometry represent a rapid and reliable tool for platelet HPA‐1 typing to aid diagnosis.

A new look at left ventricular remodeling definition by cardiac imaging

Left ventricular remodeling (LVR) typically manifests as compensatory changes in ventricular mass, composition, and volume as a response to cardiac performance inadequacy...

Apical left ventricular myocardial dysfunction is an early feature of cardiac involvement in myotonic dystrophy type 1.

Left ventricular (LV) dysfunction is a major prognostic determinant in myotonic dystrophy type 1 (DM1). Therefore, markers of early‐stage LV impairment may be useful. The aim of this study was to evaluate 2D echocardiographic LV strain in a cohort of DM1 patients with preserved left ventricular ejection fraction (LVEF) and to compare the results with matched controls.