Development of endovascular stent-grafts based on a nanocomposite polymer

Objective: To use a novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane with superior bio-mimetic properties in the development of endovascular stent-grafts. Methods: A self-expanding and sutureless aortic stent-graft was developed using nanocomposite polymer bonded to Nitinol. A new aortic model was designed for physiological assessment of stent-grafts and compliance and viscoelasticity were measured and compared with porcine aortas as control. The stent-grafts (n=4) were fatigue tested using in vitro accelerated model for 400-million cycles equivalent to 10-years in human body and compared with zero-cycled control. A curved and conformable stent-graft was developed for thoracic aorta and aortic arch. Compliance and stiffness index of the thoracic stent-graft were measured in vitro and compared to FDA-approved Gore TagTM stent-graft based on ePTFE (expanded polytetrafluoroethylene). MRI compatibility of the thoracic stent-graft was assessed by analysing signal attenuation and velocity measurements (flux) and compared to FDA-approved Medtronic ValiantTM. Results: The stent-graft had expanded diameter of 31.1 mm and was successfully collapsed to 6.5 mm to achieve delivery profile similar to current devices. The thoracic stent-graft had uniform graft thickness of 150.7±6.6 µg and conformed to the curvature of aortic arch. The new aortic model was significantly more compliant than porcine aortas with no significant difference in elastic stiffness. All the stent-grafts successfully completed accelerated pulsatile fatigue testing. Scanning electron microscopy images confirmed uniform surface topography. There was no loss of tensile strength, or compliance and no evidence of thermo-mechanical degradation in the nanocomposite polymer. Compliance of the thoracic stent-graft was significantly better compared with ePTFE stent-graft (3.3±0.61 vs. 2.3±0.95 %/mm Hg x 10-2; P=0.0003). On MRI, there was no significant signal attenuation and no significant difference in flux between Valiant and nanocomposite polymer stent-grafts (102±2.27 vs. 99.8±2.4 ml/sec; P=0.33). Conclusions: A new endovascular stent-graft based on novel design and nanocomposite polymer with properties of compliance, viscoelasticity, anti-thrombogenicity and MRI compatibility has been developed. Sutureless technology with new biocompatible material bonded to Nitinol stents proved to be robust with no separation over accelerated 10-year cycle. These stent-grafts have the potential to address poor long-term durability, thrombogenicity, and compliance mismatch associated with present generation devices and reduce reintervention rate

Application of Quantitative MRI Techniques in Ischemic and Congenital Heart Disease image-guided therapy

It is estimated that each year, 30,000 people in the Netherlands suffer from myocardial infarction, and is in fact a major public health care burden. Next to ischaemic heart disease (IHD), thanks to modern medicine, more and more patients with congenital heart disease (CHD) reach adulthood, but nonetheless require lifelong professional care. Imaging techniques are essential in these two groups of patients for establishing diagnosis, guiding therapy and predicting outcomes. This thesis investigated the application of cardiac MRI in patients with IHD and CHD and evaluated novel non-invasive MRI techniques in both humans and in a porcine model. In this thesis we showed that cardiac MRI is an excellent tool for the evaluation of atherosclerotic and congenital cardiovascular disease. It is an excellent tool in predicting outcome after STEM! in patients undergoing primary percutaneous coronary intervention. Furthermore, studied in this thesis, the incidence of per procedural complications in patients with CHD seems higher than in the general population suggesting that placement of a pacemaker device might be challenging in this group of patients

Computational studies of oxygen transport in arterio-venous fistulae

Arterio-venous-fistulae (AVF) are surgically-formed connections between an artery and a vein and are regarded as the “gold standard” method of vascular access, for haemodialysis. Nonetheless, up to 60% fail within three months of creation. Their principal failure mechanism is intimal hyperplasia (IH), an adverse inflammatory process causing AVF to block and fail. Evidence suggests that IH is a multifactorial process, attributable to an altered vascular environment, including increased metabolic stress, flow disturbances, mechanical stress, and wall hypoxia (low oxygen levels). The present work focuses on studying wall hypoxia in idealised AVF. Vascular walls are oxygenated by transport from both luminal oxygenated blood and adventitial vasa vasorum (VV), the microvascular network supplying large vessels. Luminal oxygen supply is affected by the altered AVF haemodynamics, while altered wall-mechanics can prevent adequate VV perfusion. The aim of this thesis is to ascertain what is most important in determining wall-oxygen levels: (i) modified luminal flow field; (ii) mechanically-modified VV perfusion. Hence, a model of oxygen transport, capable of accounting for VV damage/hypoperfusion, was developed. Geometries and VV perfusion fields obtained from mechanical simulations were used to provide the oxygen transport model with a VV oxygen source. Results suggest that for a given set of wall parameters, the local wall-oxygen levels are governed by the flow field, while spatial distributions of mechanically-modified VV perfusion are shown to have negligible effects on the local wall-oxygen levels. However, overall wall-oxygen levels are highly sensitive to changes in bulk wall parameters, particularly oxygen consumption rates. Finally, these results were used to develop a simplified oxygen transport model, that is combined with a mesh-adaptive-direct-search approach to identify an optimal AVF configuration with reduced hypoxia levels. The configuration features a non-planar anastomosis and a helical shaped vein.Open Acces

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes