Cleverballoon: An integrated approach for developing a drug-coated balloon with everolimus.

Coronary artery disease (CAD) is a chronic disease associated with high mortality and morbidity. Although treatment with drug-eluting stents is the most frequent interventional approach for coronary artery disease, drug-coated balloons (DCBs) constitute an innovative alternative, especially in the presence of certain anatomical conditions in the local coronary vasculature. DCBs allow the fast and homogenous transfer of drugs into the arterial wall, during the balloon inflation. Their use has been established for treating in-stent restenosis caused by stent implantation, while recent clinical trials have shown a satisfactory efficacy in de novo small-vessel disease. Several factors affect DCBs performance including the catheter design, the drug dose and formulation. Cleverballoon focuses on the design and development of an innovative DCB with everolimus. For the realization of the development of this new DCB, an integrated approach, including in- vivo, in-vitro studies and in-silico modelling towards the DCB optimization, is presented.Clinical Relevance-The proposed study introduces the integration of in- vivo, in-vitro and in silico approaches in the design and development process of a new DCB, following the principles of 3R's for the replacement, reduction, and refinement of animal and clinical studies.

Investigation of crimping effects on the stent deployment through in silico modeling.

Atherosclerosis is one of the most mortal diseases that affects the arterial vessels, due to accumulation of plaque, altering the hemodynamic environment of the artery by preventing the sufficient delivery of blood to other organs. Stents are expandable tubular wires, used as a treatment option. In silico studies have been extensively exploited towards examining the performance of such devices by employing Finite Element Modeling. This study models the crimping stage during stent implantation to examine the effect of inclusion of pre-stress state of the stent. The results show that modeling of the crimping stress state of the stent prior to the deployment results in under-expansion of the stent, due to the indirect inclusion of strain-induced hardening effects. As a result, it is evident that the compressive stent stress configuration is important to be considered in the computational modeling approaches of stent deployment.

Investigation of Drug Eluting Stents performance in human atherosclerotic artery through in silico modeling.

Atherosclerosis is a chronic inflammatory disease associated with heart attack and stroke. It causes the growth of atherosclerotic plaques inside the arterial vessels, which in turn results to the reduction of the blood flow to the different organs. Drug-Eluting Stents (DES) are mesh-like wires, carrying pharmaceutical coating, designed to dilate and support the arterial vessel, restore blood flow and through the controlled local drug delivery inhibit neo-intimal thickening. In silico modeling is an efficient method of accurately predicting and assessing the performance of the stenting procedure. The present in silico study investigates the performance of two different stents (Bare Metal Stent, Drug-Eluting Stent) in a patient-specific coronary artery and assesses the effect of stent coating, considering that the same procedural approach is followed by the interventional cardiologist. The results demonstrate that even if small differences are obtained in the two models, the incorporation of the stent coatings (in DES) does not significantly affect the outcomes of the stent deployment, the stresses and strains in the scaffold and the arterial tissue. Nevertheless, it is suggested that regarding the DES expansion, higher pressure should be applied at the inner surface of the stent.

A multiscale approach for modeling atherosclerosis progression.

Progression of atherosclerotic process constitutes a serious and quite common condition due to accumulation of fatty materials in the arterial wall, consequently posing serious cardiovascular complications. In this paper, we assemble and analyze a multitude of heterogeneous data in order to model the progression of atherosclerosis (ATS) in coronary vessels. The patient's medical record, biochemical analytes, monocyte information, adhesion molecules, and therapy-related data comprise the input for the subsequent analysis. As indicator of coronary lesion progression, two consecutive coronary computed tomography angiographies have been evaluated in the same patient. To this end, a set of 39 patients is studied using a twofold approach, namely, baseline analysis and temporal analysis. The former approach employs baseline information in order to predict the future state of the patient (in terms of progression of ATS). The latter is based on an approach encompassing dynamic Bayesian networks whereby snapshots of the patient's status over the follow-up are analyzed in order to model the evolvement of ATS, taking into account the temporal dimension of the disease. The quantitative assessment of our work has resulted in 93.3% accuracy for the case of baseline analysis, and 83% overall accuracy for the temporal analysis, in terms of modeling and predicting the evolvement of ATS. It should be noted that the application of the SMOTE algorithm for handling class imbalance and the subsequent evaluation procedure might have introduced an overestimation of the performance metrics, due to the employment of synthesized instances. The most prominent features found to play a substantial role in the progression of the disease are: diabetes, cholesterol and cholesterol/HDL. Among novel markers, the CD11b marker of leukocyte integrin complex is associated with coronary plaque progression.

A quasi-lumped model for the peripheral distortion of the arterial pulse.

As blood circulates through the arterial tree, the flow and pressure pulse distort. Principal factors to this distortion are reflections form arterial bifurcations and the viscous character of the flow of the blood. Both of them are expounded in the literature and included in our analysis. The nonlinearities of inertial effects are usually taken into account in numerical simulations, based on Navier-Stokes like equations. Nevertheless, there isn't any qualitative, analytical formula, which examines the role of blood's inertia on the distortion of the pulse. We derive such an analytical nonlinear formula. It emanates from a generalized Bernoulli's equation for an an-harmonic, linear, viscoelastic, Maxwell fluid flow in a linear, viscoelastic, Kelvin-Voigt, thin, cylindrical vessel. We report that close to the heart, convection effects related to the change in the magnitude of the velocity of blood dominate the alteration of the shape of the pressure pulse, while at remote sites of the vascular tree, convection of vorticity, related to the change in the direction of the velocity of blood with respect to a mean axial flow, prevails. A quantitative comparison between the an-harmonic theory and related pressure measurements is also performed.

Anterior aortic reimplantation of anomalous left coronary artery from the pulmonary artery (ALCAPA) originating from the nonfacing sinus in an adult.

We report successful repair of a rare type of anomalous origin left main coronary artery from the nonfacing pulmonary artery sinus in an adult patient presenting with cardiac arrest as first symptom. Intraoperative findings and surgical technique are discussed.

Ventricular arrhythmias and antioxidative medication: experimental study.

INTRODUCTION: Reperfusion arrhythmias could be due to free radicals, while contraction excitation feedback is the cause of arrhythmias generated by blood pressure elevation (BPE). The aim of this study was to test the antiarrhythmic effects of an antioxidant (vitamin C [vit C], 1.5 g), an iron-binding agent (deferoxamine [Def], 1 g), and their combination in an experimental model of arrhythmia based on these 2 mechanisms. METHODS: Thirty anaesthetised sheep were divided into 4 groups, depending on the infused agent: saline (8 sheep), combination of vit C and Def (8), Def (6), and vit C (8). Induction of ventricular arrhythmias was attempted in all animals using both ischaemia-reperfusion (phase I) and a combination of ischaemia and BPE (phase II). In all cases ischaemia was caused by ligating the left anterior descending coronary artery distally to the origin of the 1st diagonal artery, while reperfusion was achieved by releasing the ligation 45 min later. BPE was achieved by obstructing the ascending aorta or by administering intravenous metaraminol. All agents were infused intravenously for 15 min and their administration was started 30 min after the first ligation. Phases I and II lasted 50 and 20 min, respectively. RESULTS: Ventricular tachycardia/fibrillation (VT/VF) was induced in all animals in the control group (8/8) and in the Def group (6/6). VT/VF appeared in 6/8 of the animals in the vit C group (75%) and in only 3/8 of the animals in the combination therapy group (37.5%). The difference between the combination and control groups was statistically significant (p < 0.03). CONCLUSIONS: The intravenous administration of vit C and Def in combination protects against VT/VF induced by ischaemia-reperfusion and/or BPE. Administration of Def alone does not appear to help, while the action of vit C alone is not clear.

Transient intraventricular conduction delay associated with concurrent intake of propafenone and antineoplastic agents.

An 82-year old man was admitted with acute pulmonary edema. Myocardial ischemia and electrolyte abnormalities were excluded and he responded promptly to frusemide, nitrates and morphine. On admission, the duration of the QRS interval was markedly abnormal at 240 ms with a nonspecific intraventricular conduction defect pattern, of left bundle branch block type. This finding was not present three weeks prior to his admission, and was felt to be the result of drug interaction between propafenone and antineoplastic agents, as evidenced by resolution of the clinical and electrocardiographic picture after discontinuation of these agents.

Mapping the binding domains of the alpha(IIb) subunit. A study performed on the activated form of the platelet integrin alpha(IIb)beta(3).

alpha(IIb)beta(3), a member of the integrin family of adhesive protein receptors, is the most abundant glycoprotein on platelet plasma-membranes and binds to adhesive proteins via the recognition of short amino acid sequences, for example the ubiquitous RGD motif. However, elucidation of the ligand-binding domains of the receptor remains controversial, mainly owing to the fact that integrins are conformationally labile during purification and storage. In this study, a detailed mapping of the extracellular region of the alpha(IIb) subunit is presented, using overlapping 20-peptides, in order to identify the binding sites of alpha(IIb) potentially involved in the platelet-aggregation event. Regions alpha(IIb) 313-332, alpha(IIb) 265-284 and alpha(IIb) 57-64 of alpha(IIb)beta(3) were identified as putative fibrinogen-binding domains because the corresponding peptides inhibited platelet aggregation and antagonized fibrinogen association, possibly by interacting with this ligand. The latter is further supported by the finding that the above peptides did not interfere with the binding of PAC-1 to the activated form of alpha(IIb)beta(3). Furthermore, alpha(IIb) 313-332 was found to bind to fibrinogen in a solid-phase binding assay. It should be emphasized that all the experiments in this study were carried out on activated platelets and consequently on the activated form of this integrin receptor. We hypothesize that RAD and RAE adhesive motifs, encompassed in alpha(IIb) 313-332, 265-284 and 57-64, are capable of recognizing complementary domains of fibrinogen, thus inhibiting the binding of this ligand to platelets.

Aortic dissection with aorto-left atrial fistula formation soon after aortic valve replacement: A lethal complication diagnosed by transthoracic and transesophageal echocardiography.

Fistulas between the aorta and left atrium are a rare manifestation of aortic dissection and are infrequently diagnosed premortem. We report the case of a 70-year-old man who exhibited this condition soon after aortic valve replacement and eventually died from rapidly developing refractory congestive heart failure. The diagnosis was indicated by transthoracic echocardiography and was ultimately made with transesophageal echocardiography and color flow Doppler imaging. Transesophageal echocardiography is the procedure of choice for establishing the correct diagnosis and leading to prompt surgical repair of this lethal condition.

Alarming atrioventricular block and mitral valve prolapse in the Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution mtDNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. The same deletion of mitochondrial DNA present in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed with the KSS was admitted to our hospital because of an upper respiratory tract infection and dysphagia. ECG showed cardiac conduction defects. The patient had no history of syncope. At her surface ECG there was a complete RBBB (QRS duration approximately 130 ms), a clockwise rotation with an axis of approximately 90 degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse with thickening and degeneration of both mitral valve leaflets but without mitral regurgitation. The patient was started on a diet rich in potassium and pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly improved biochemical profile but apparent clinical improvement. Urgent pacemaker implantation was decided but unfortunately the patient died due to acute cardiac arrest 10 days later.