The synthesis, characterization and applications of poly[N-isopropylacrylamide-co-3-allyloxy-1,2-propanediol] grafted onto modified magnetic nanoparticles.

In this paper, a novel method is investigated for the extraction, determination, and delivery of ceftazidime in simulated gastric and real biological fluids such as serum plasma and urine in in vitro drug delivery systems. A new polymer as a nano-sorbent was synthesized by the surface grafting of [N-isopropylacrylamide-co-3-allyloxy-1,2-propanediol] onto modified magnetic nano-particles by 3-mercaptopropyltrimethoxysilane and it was characterized by FT-IR, CHN, SEM, TEM, VSM, TGA, and zeta potential analyses. The effects of main parameters such as pH, reaction time, temperature, and solvents were evaluated for ceftazidime removal. The results indicate that the newly synthesized polymer can be successfully applied for biomedical applications and drug delivery.

Left atrial catheter ablation in patients with previously implanted left atrial appendage closure devices.

AIMS: Left atrial appendage closure (LAAC) is increasingly used as an alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) patients. Feasibility and safety of left atrial (LA) catheter ablation (CA) in patients with previously implanted LAAC devices have not been well studied. We report on the feasibility, safety, and efficacy of LA CA in the presence of a previously implanted LAAC device. METHODS AND RESULTS: In this prospective cohort study consecutive patients that underwent LA CA with a previously implanted Watchman device were included. Periprocedural characteristics and long-term clinical follow-up were evaluated. Twenty-three LA CA procedures were performed in 19/162 AF patients with previously implanted Watchman devices [47% male, age 63.9 ± 6.2 years, CHA2DS2-VASc 4.0 (3.0-5.0); HASBLED 3.0 (2.0-4.0); 63% paroxysmal]. Left atrial CA was performed with irrigated radiofrequency (RF; n = 20, 87%) or phased RF (n = 3, 13%) in a mean of 18 months after LAAC implantation (range 4-80 months). Targets of CA consisted of pulmonary vein isolation (n = 19, 83%), superior vena cava isolation (n = 13, 57%), and additional linear lesions (n = 8, 35%). Procedures were carried out under vitamin K antagonist (VKA; n = 6, 26%), non-VKA OAC (NOAC; n = 8, 35%), or single antiplatelet therapy alone (n = 9, 39%). Left atrial CA was successful without any signs of interference from the device. Procedure-related complications were not observed. During a mean follow-up of 28 months, 11 patients (58%) had AF recurrence. CONCLUSION: Left atrial CA after LAAC appears to be feasible, effective, and safe in this single centre cohort. Previously implanted Watchman device should not be a reason to relinquish CA in symptomatic AF patients, even in patients on single antiplatelet therapy alone.

Increased incidence of infective endocarditis after the 2009 European Society of Cardiology guideline update: a nationwide study in the Netherlands.

Aims: After the introduction of the European Society of Cardiology (ESC) guidelines on prevention, diagnosis, and treatment of infective endocarditis (IE) in 2009, prophylaxis for patients at risk became less strict. We hypothesize that there will be a rise in IE after the introduction of the guideline update. Methods and Results: We performed a nationwide retrospective trend study using segmented regression analysis of the interrupted time series. The patient data were obtained via the national healthcare insurance database, which collects all the diagnoses nationwide. We compared the data before and after the introduction of the 2009 ESC guideline. Between 2005 and 2011, a total of 5213 patients were hospitalized with IE in the Netherlands. During this period, there was a significant increase in IE from 30.2 new cases per 1 000 000 in 2005 to 62.9 cases per 1 000 000 in 2011 (P < 0.001). In 2009, the incidence of IE increased significantly above the projected historical trend (rate ratio: 1.327, 95% CI: 1.205-1.462; P < 0.001). This coincides with the introduction of the 2009 ESC guideline. After the introduction of the ESC guideline, the streptococci-positive cultures increased significantly in the following years 2010-11 from 31.1 to 53.2% (P = 0.0031). Conclusion: This observational study shows that there has been a steady increase in the IE incidence between 2005 and 2011. After the introduction of the 2009 ESC guidelines, the incidence increased more than expected from previous historical trends. Furthermore, there was a significant increase in streptococci-related IE cases.

Glucose-dependent leucocyte activation in familial hypercholesterolemia.

BACKGROUND: Leucocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leucocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidaemia. Our study aim was to evaluate the effect of post-OGTT hyperglycaemia on leucocyte activation in patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test. Leucocyte activation markers CD11b and CD66b were determined by flow cytometry. Post-OGTT changes were calculated as area under the curve (AUC) and the incremental area under the curve corrected for baseline values (dAUC). The impact of being an FH patient and using statins on the time-dependent profile of the leucocyte activation markers was studied with repeated measurements analysis. RESULTS: Thirteen FH patients using statins, nine FH patients without statins and 14 healthy volunteers were included. FH subjects on statins had a slightly higher HbA1c than those not using these drugs or controls. Post-OGTT glucose levels were significantly higher in patients with FH when compared to healthy controls (P = 0·001). These effects were independent from the use of statins. CONCLUSIONS: Surprisingly, our study shows impaired post-OGTT glucose excursions in patients with FH compared to healthy volunteers. Post-OGTT hyperglycaemia may be related to persistent post-OGTT activation of monocytes in FH patients compared to healthy controls, and therefore, it may contribute to the development of cardiovascular disease in patients with FH.

Differential leucocyte RNA expression in the coronary arteries compared to systemic circulation discriminates between patients with and those without coronary artery disease / La expresión diferencial de ARN en leucocitos en las arterias coronarias comparada con la de leucocitos de circulación sistémica discrimina a pacientes con y sin enfermedad arterial coronaria

Aims: To test the hypothesis that the pattern of gene expression in circulating leukocytes may differ between vascular compartments, depending on the presence or absence of atherosclerosis, we evaluated the regional vascular differences in patterns of inflammatory cell activation. Methods: Patients (n = 8) with angiographically-established coronary artery disease (CAD+) and 8 without (CAD-) had blood samples taken from a peripheral vein as well as from left and right coronary arteries. Samples were pooled resulting in 4 CAD+ samples versus 4 CAD- samples and hybridised to a Whole Human Genome Microarray 4×44K. Results: CAD- patients had a similar gene expression profile across the different sites. CAD+ patients had statistically significant different gene expression patterns in venous vs. right and left coronary artery compartments. The expression pattern observed in the right coronary was where the most differences in gene expression were observed in CAD+ vs. CAD- patients. Overall, 1964 genes were differentially expressed between CAD+ and CAD−. Of these, 1052 were less expressed in CAD+ and 912 were more expressed in CAD+. Up to 12 of the 20 most differentially expressed genes appeared to reflect different phases of the atherosclerosis process: endothelial dysfunction, lipid accumulation, and smooth muscle cell proliferation. Conclusions: Gene expression of circulating leukocytes differentiates CAD+ from CAD- patients. Gene expression is significantly different between coronary arteries and the systemic circulation in CAD+ patients, but not in CAD- patients. Gene expression is significantly different between CAD+ and CAD- subjects, and appears to reflect the atherosclerosis process. These intra-individual differences may be an additional feature of established coronary artery disease

Objetivo: Para comprobar la hipótesis de que los patrones de expresión génica de leucocitos en circulación pueden ser diferentes entre los compartimentos vasculares dependiendo de la presencia o ausencia de arteriosclerosis, hemos evaluado en distintas regiones vasculares las diferencias entre los patrones de expresión y la activación de células inflamatorias. Métodos: Se extrajeron muestras de sangre de venas periféricas y de las arterias coronarias (derecha e izquierda) de pacientes con (n=8; CAD+) y sin (n=8; CAD−) enfermedad arterial coronaria establecida angiográficamente. Las muestras fueron hibridadas en dos pooles de 4 muestras (CAD+ vs CAD−) mediante el kit Whole Human Genome Microarray 4×44K. Resultados: Los pacientes CAD- tenían un perfil de expresión génica similar entre los distintos compartimentos vasculares. Los pacientes CAD+ tenían patrones de expresión génica significativamente diferentes entre los compartimentos venosos y las arterias coronarias derecha e izquierda. El patrón de expresión observado en la arteria coronaria derecha fue el que presentó más diferencias entre los pacientes CAD+ vs. CAD-. En conjunto, 1.964 genes estaban expresados diferencialmente entre CAD+ y CAD-. De estos, 1.052 estaban menos expresados en CAD+ i 912 estaban más expresados en CAD+. Hasta 12 de los 20 genes más diferencialmente expresados estaban relacionados con las diferentes fases del proceso arteriosclerótico: disfunción endotelial, acumulación lipídica y proliferación de células musculares lisas. Conclusiones: La expresión génica de leucocitos circulantes diferencia pacientes CAD+ de CAD-. La expresión genética es significativamente diferente entre arterias coronarias y circulación sistémica en pacientes CAD+, pero no en pacientes CAD-. Estas diferencias intraindividuales podrían ser una característica adicional en el diagnóstico de la enfermedad arterial coronaria

Novel stroke risk reduction in atrial fibrillation: left atrial appendage occlusion with a focus on the Watchman closure device.

Atrial fibrillation (AF) remains an important clinical problem with severe complications such as stroke, which especially harms those with risk factors as calculated by the CHADS2 or CHA2DS2-VASc. Until now, no therapy has proven 100% effective against AF. Since the left atrial appendage (LAA) is the most prominent nonvalvular AF-related thromboembolic source and (novel) oral anticoagulant [(N)OAC] carries the hazard of bleeding, LAA occlusion may be an alternative, especially in patients who are ineligible for (N)OAC therapy. In this review, we discuss several LAA occlusion techniques with a focus on the Watchman device since this device is the most thoroughly studied device of all.

Differential leucocyte RNA expression in the coronary arteries compared to systemic circulation discriminates between patients with and those without coronary artery disease.

AIMS: To test the hypothesis that the pattern of gene expression in circulating leukocytes may differ between vascular compartments, depending on the presence or absence of atherosclerosis, we evaluated the regional vascular differences in patterns of inflammatory cell activation. METHODS: Patients (n=8) with angiographically-established coronary artery disease (CAD+) and 8 without (CAD-) had blood samples taken from a peripheral vein as well as from left and right coronary arteries. Samples were pooled resulting in 4 CAD+ samples versus 4 CAD- samples and hybridised to a Whole Human Genome Microarray 4×44K. RESULTS: CAD- patients had a similar gene expression profile across the different sites. CAD+ patients had statistically significant different gene expression patterns in venous vs. right and left coronary artery compartments. The expression pattern observed in the right coronary was where the most differences in gene expression were observed in CAD+ vs. CAD- patients. Overall, 1964 genes were differentially expressed between CAD+ and CAD-. Of these, 1052 were less expressed in CAD+ and 912 were more expressed in CAD+. Up to 12 of the 20 most differentially expressed genes appeared to reflect different phases of the atherosclerosis process: endothelial dysfunction, lipid accumulation, and smooth muscle cell proliferation. CONCLUSIONS: Gene expression of circulating leukocytes differentiates CAD+ from CAD- patients. Gene expression is significantly different between coronary arteries and the systemic circulation in CAD+ patients, but not in CAD- patients. Gene expression is significantly different between CAD+ and CAD- subjects, and appears to reflect the atherosclerosis process. These intra-individual differences may be an additional feature of established coronary artery disease.

Percutaneous left atrial appendage closure devices: safety, efficacy, and clinical utility.

Atrial fibrillation (AF) is the most common arrhythmia treated in the clinical practice. One of the major complications of AF is a thromboembolic cerebral ischemic event. Up to 20% of all strokes are caused by AF. Thromboembolic cerebral ischemic event in patients with AF occurs due to atrial thrombi, mainly from the left atrial appendage (LAA). Prevention of clot formation with antiplatelet agents and especially oral anticoagulants (vitamin K antagonists or newer oral anticoagulants) has been shown to be effective in reducing the stroke risk in patients with AF but has several drawbacks with (major) bleedings as the most important disadvantage. Therefore, physical elimination of the LAA, which excludes the site of clot formation by surgical or percutaneous techniques, might be a good alternative. In this review, we discuss the safety, efficacy, and clinical utility of the Watchman™ LAA closure device.

Coronary leukocyte activation in relation to progression of coronary artery disease.

Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease (CAD) of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CD11b, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase (MPO) in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion (26 patients had single-vessel disease, 18 patients had twovessel disease and 26 patients had three-vessel disease). The median follow-up duration was 2242 days (interquartile range: 2142-2358). During follow-up, 13 patients (13%) developed progression of CAD. Monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO do not predict the risk of progression of CAD.

In vivo evidence for chylomicrons as mediators of postprandial inflammation.

BACKGROUND AND AIMS: The postprandial situation is a pro-inflammatory condition most likely linked to the development of atherosclerosis. We evaluated the relationship between apolipoprotein (apo) B48 and fasting and postprandial leukocyte activation markers. METHODS: Leukocyte activation markers and apo B48 were determined in 80 subjects with and without coronary artery disease (CAD). Twelve healthy subjects underwent an oral fat loading test (up to 8 h). RESULTS: Fasting apo B48 was significantly higher in patients with CAD (n = 47, 8.1 ± 5.2 mg/L) than in subjects without CAD (n = 33, 5.9 ± 3.9 mg/L, p = 0.022). Fasting apo B48 and triglycerides correlated positively with fasting monocyte CD11b and neutrophil CD66b expression. Plasma apo B48 and leukocyte activation markers increased after an oral fat load. No correlations were found between fasting or postprandial triglycerides and postprandial leukocyte activation markers. We observed no correlations between postprandial apo B48 and postprandial neutrophil CD11b or CD66b expression. CONCLUSION: This study suggests that chylomicron remnants may be responsible for postprandial leukocyte activation in the circulation. The postprandial chylomicron response may be a stronger mediator of postprandial inflammation than postprandial triglyceridemia.

Ablation for Atrial Fibrillation Combined With Left Atrial Appendage Closure.

OBJECTIVES: The study sought to determine long-term clinical effects of combining catheter ablation (CA) and left atrial appendage (LAA) occlusion (LAAO) in a single procedure. BACKGROUND: CA relieves symptoms in atrial fibrillation (AF), but freedom from AF is not assured. Thus, oral anticoagulation (OAC) remains necessary in high stroke risk patients. LAAO has proved a viable alternative for preventing thromboembolic complications. METHODS: Symptomatic patients with drug-refractory AF (CHADS2 ≥1) and indications for LAAO were included. Transesophageal echocardiography was performed to assess LAA size/anatomy/thrombus. After CA, LAAO was performed using the Watchman device (Atritech, Inc., Plymouth, Minnesota, Minnesota). At 3 months, OAC was switched to aspirin/clopidogrel if LAAO criteria were met. RESULTS: From September 2009 to October 2013, 62 patients (22 female, 64 ± 8 years of age, CHADS2 2.5) underwent combined procedures. Indications for LAAO included history of stroke despite OAC (29.0%), contraindications for OAC (24.2%), high stroke risk (24.2%), and miscellaneous reasons (22.6%). LAAO resulted in complete acute closure in all, with a median number of 1 device. After a median follow-up of 38 (range: 25 to 45) months, 95% of the patients met the criteria for successful sealing and 78% could discontinue OAC, while recurrence of AF was documented in 42%. During long-term follow-up, 3 ischemic strokes were observed with an annual stroke risk of 1.7%, which is lower than the expected annual risk of 6.5%. CONCLUSIONS: LAAO combined with CA for AF can be performed successfully and safely in a single procedure, with a lower than expected stroke rate. Further studies are necessary to determine which patients benefit most from the combined therapy.

Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls.

BACKGROUND: Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on leukocyte activation in patients with a wide range of insulin sensitivity. METHODS: Leukocyte activation was determined after ingestion of 75 gram glucose in subjects with T2DM, familial combined hyperlipidemia (FCH) and healthy controls. Leukocyte activation markers were measured by flow cytometry. Postprandial changes were calculated as the area under the curve (AUC), and the incremental area under the curve corrected for baseline values (dAUC). RESULTS: 51 Subjects (20 T2DM, 17 FCH and 14 controls) were included. Fasting neutrophil CD66b expression and CD66b-AUC were respectively 36% and 39% higher in T2DM patients than in controls (p=0.004 and p=0.003). Fasting neutrophil CD66b expression correlated positively with glucose-AUC (Spearman's rho 0.481, p<0.001) and HbA1c (rho 0.433, p=0.002). Although fasting monocyte CD11b expression was not significantly different between subjects, monocyte CD11b-AUC was 26% higher in T2DM than in controls (p=0.006). Similar trends were observed for FCH patients. Monocyte CD11b-dAUC correlated positively with glucose-AUC (rho 0.322, p=0.022) and HbA1c (rho 0.319, p=0.023). CONCLUSIONS: These data suggest that both acute and chronic hyperglycemia, associated with insulin resistance as seen in T2DM and FCH, are involved in the increased fasting and postprandial leukocyte activation observed in these conditions.

Survival of transcatheter mitral valve repair compared with surgical and conservative treatment in high-surgical-risk patients.

OBJECTIVES: The goal of this study was to compare survival between transcatheter mitral valve (MV) repair using MitraClip system (Abbott Vascular, Santa Clara, California), MV-surgery, and conservative treatment in high-surgical-risk patients symptomatic with severe mitral valve regurgitation (MR). BACKGROUND: Up to 50% of patients with symptomatic severe MR are denied for surgery due to high perioperative risk. Transcatheter MV repair might be an alternative. METHODS: Consecutive patients (n = 139) treated with transcatheter MV repair were included. Comparator surgically (n = 53) and conservatively (n = 59) treated patients were identified retrospectively. Surgical risk was based on the logistic European System for Cardiac Operative Risk Evaluation (log EuroSCORE) or the presence of relevant risk factors, as judged by the heart team. RESULTS: The log EuroSCORE was higher in the transcatheter MV repair group (23.9 ± 16.1%) than in the surgically (14.2 ± 8.9%) and conservatively (18.7 ± 13.2%, p < 0.0001) treated patients. Left ventricular ejection fraction was higher in surgical patients (43.9 ± 14.4%, p = 0.003), with similar values for the transcatheter MV repair (36.8 ± 15.3%) and conservatively treated (34.5 ± 16.5%) groups. After 1 year of follow-up, the transcatheter MV repair and surgery groups showed similar survival rates (85.8% and 85.2%, respectively), whereas 67.7% of conservatively treated patients survived. The same trend was observed after the second and third years. After weighting for propensity score and controlling for risk factors, both the transcatheter MV repair (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.22 to 0.78, p = 0.006) and surgical (HR: 0.52, 95% CI: 0.30 to 0.88, p = 0.014) groups showed better survival than the conservatively treated group. The transcatheter MV repair and surgical groups did not differ (HR: 1.25, 95% CI: 0.72 to 2.16, p = 0.430). CONCLUSIONS: Despite a higher log EuroSCORE, high-surgical-risk patients with symptomatic severe MR treated with transcatheter MV repair show similar survival rates compared with surgically treated patients, with both displaying survival benefit compared with conservative treatment.

Trans-vessel gradient of myeloperoxidase in coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) may reflect generalized inflammation. We evaluated leucocyte activation in subjects with and without CAD in different vascular compartments. MATERIALS AND METHODS: Patients were divided in two groups; subjects without CAD (controls; n = 25) and with stable CAD (n = 52) based on coronary angiography. After blood sampling from vessels, cardiovascular risk factors and leucocyte activation markers CD11b, CD66b and cytoplasmatic myeloperoxidase (MPO) were determined by flow cytometry. RESULTS: Myeloperoxidase (MPO) was higher in patients with CAD at all sites compared with controls (188 ± 7 vs. 210 ± 12 au for venous (P < 0.05), 178 ± 7 vs. 212 ± 12 au for femoral artery (P = 0.08), 166 ± 7 vs. 195 ± 12 au for abdominal artery (P < 0.05), 166 ± 6 vs. 189 ± 14 au for left coronary (P = 0.08) and 163 ± 6 vs. 193 ± 12 au for the right coronary artery (P < 0.05)). Other markers did not differ between the groups. A gradient of inflammation from peripheral vessels to the coronaries was found by differences in MPO in both groups; from 210 ± 12 au in the venous compartments towards 189 ± 14 and 193 ± 12 au, in the left and right coronaries, respectively, for the controls (P = 0.001), and from 188 ± 7 au in the venous compartment towards 166 ± 6 and 163 ± 6 au in the left and right coronaries, respectively, for the patients (P = 0.007). Other leucocyte activation markers did not show such a gradient. CONCLUSIONS: There is a generalized inflammatory neutrophil gradient for MPO from peripheral vessels towards the coronaries in both patients with CAD and controls. However, patients with CAD show a higher degree of inflammation, mostly in the coronaries. These data strengthen the role of activated neutrophils in CAD.

Catheter ablation in combination with left atrial appendage closure for atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope. Patients with AF have a five-fold higher risk of stroke. Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64%. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug. The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers. CA is a well-established treatment for AF symptoms, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy. Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes). This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy. Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding or other warfarin-associated problems. The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Exploring the value of apoB48 as a marker for atherosclerosis in clinical practice.

BACKGROUND: Postprandial accumulation of atherogenic remnants has been described in patients with type 2 diabetes mellitus (T2DM), familial combined hyperlipidaemia (FCH), familial hypercholesterolaemia (FH) and coronary artery disease (CAD). Scarce data are available on fasting plasma apolipoprotein (apo) B48 levels in relation to these conditions and atherosclerosis. DESIGN: Treated patients with FCH (18), FH (20), T2DM (26), CAD (65), T2DM with CAD (T2DM/CAD) (28) and 33 healthy controls were included. Intima-media thickness (IMT) measurements were carried out to investigate subclinical atherosclerosis. RESULTS: LDL-C and total apoB were lowest in patients with T2DM/CAD owing to the more frequent use of lipid-lowering medication. Fasting plasma apoB48 was elevated in patients with FCH (11·38 ± 1·50 mg/L) and T2DM/CAD (9·65 ± 1·14 mg/L) compared with the other groups (anova, P < 0·01). CAD patients (8·09 ± 0·57 mg/L) had higher apoB48 levels than controls (5·74 ± 0·55 mg/L) and FH patients (5·40 ± 0·51 mg/L) (P = 0·02). IMT was highest in subjects with T2DM/CAD (0·77 ± 0·03 mm) (P < 0·01). The lowest IMT was measured in controls (0·56 ± 0·02 mm) and FCH patients (0·60 ± 0·03 mm). In the total group, the best association for apoB48 was found with fasting triglyceride (Pearson's r = 0·72, P < 0·001). In the subjects not using statins (n = 74), the best correlation was found with IMT (r = 0·52; P < 0·001), whereas total apoB was not associated with IMT (r = 0·20, P = 0·12). CONCLUSIONS: ApoB48 concentrations are highest in patients with FCH and in atherosclerotic subjects with T2DM. In patients not using statins, the surrogate atherosclerosis marker IMT correlates best with apoB48, suggesting that fasting apoB48 may help to detect subjects at risk.

Erythrocyte-associated apolipoprotein B and its relationship with clinical and subclinical atherosclerosis.

BACKGROUND: Apolipoprotein (apo) B-containing lipoproteins are closely linked to atherogenesis. These lipoproteins are transported in plasma and are also associated with blood leucocytes. Our aim was to investigate whether apoB-containing lipoproteins are also present on the surface of erythrocytes and investigate the relationship with the presence of atherosclerosis in a cross-sectional study. MATERIALS AND METHODS: Erythrocyte-bound apoB (ery-apoB) was measured by flowcytometry in subjects with (CAD+) and without coronary artery disease (CAD-), based on coronary angiography or on a history of cardiovascular disease. Intima media thickness (IMT) measurements were carried out using B-mode ultrasound. The relationship between ery-apoB and clinical and subclinical atherosclerosis was evaluated with binary logistic regression. RESULTS: A total of 166 subjects were included (40 CAD+ and 126 CAD-). ApoB was detected on freshly isolated erythrocytes (range: 0·1-5·5 au; mean ± SEM 0·86 ± 0·09 au) in all but nine subjects (four CAD+ and five CAD-). Ery-apoB was lower in CAD+ (0·62 ± 0·09 au) compared to CAD- (1·18 ± 0·10 au; P < 0·001). Higher ery-apoB was associated with a lower risk of CAD (adjusted OR: 0·003 (95% CI: 0·001-0·08; P < 0·001), but the protective effect was diminished with increasing age (adjusted OR: 1·10 (95% CI: 1·04-1·16; P < 0·001). IMT was increased in CAD+ subjects (0·77 ± 0·13 mm) compared to CAD- (0·57 ± 0·14 mm; P < 0·001). A significant negative association was found between ery-apoB and IMT (ß = -0·214: 95% CI -0·284 to -0·145; P < 0·001). There was no association between ery-apoB and plasma apoB (Pearson's r = -0·45; P = 0·57). CONCLUSIONS: Human erythrocytes carry apoB-containing lipoproteins. Subjects with atherosclerosis have lower ery-apoB. High ery-apoB may be protective against atherosclerosis and may reflect an alternative blood cell-mediated lipoprotein transport system in the circulation, in which these lipoproteins less likely interact with the endothelium.

Mannose binding lectin 2 haplotypes do not affect the progression of coronary atherosclerosis in men with proven coronary artery disease treated with pravastatin.

OBJECTIVE: Mannose binding lectin (MBL) is one of the three initiators of complement activation. Polymorphisms of the MBL2 gene and its promoter, and especially haplotypes, determine MBL plasma levels. MBL deficiency has been associated with the development of atherosclerosis. We evaluated whether the rate of angiographic progression of coronary atherosclerosis during pravastatin treatment was associated with MBL2 haplotypes in REGRESS, a placebo-controlled 2 years intervention study. METHODS: Three polymorphic sites in exon 1 (rs1800450, rs1800451 and rs5030737) of the MBL2 gene and 2 sites (rs7096206 and rs11003125) in the promoter region were genotyped in 398 subjects. Genotyping was performed using Applied Biosystems® TaqMan® Genotyping Assays. We divided the group in high, intermediate and low MBL2 secretor haplotypes. Quantitative coronary angiography was performed. Endpoints were mean segment diameter (MSD) and minimum obstruction diameter (MOD) established by quantitative coronary angiography. RESULTS: At inclusion, 50.1, 31.7 and 17.6% of the patients in the REGRESS cohort carried the high, intermediate and low MBL2 secretor haplotypes, respectively. In 0.6% of the patients, the haplotype was not informative. There were no baseline differences between the MBL2 haplotypes for age, BMI, lipid levels, leukocyte counts, CRP, MSD and MOD. The intermediate MBL2 placebo group showed the greatest increase in MSD compared to the low MBL2 group (P=0.03). No difference was found for the change in MOD. No significant interaction between MBL2 haplotype groups and pravastatin therapy was observed. CONCLUSION: In men with proven coronary artery disease, MBL2 secretor haplotypes are not associated to the rate of progression of coronary sclerosis nor does pravastatin treatment influence progression based on MBL2 haplotypes.