A Proof of Concept for Computational Fluid Dynamic Analysis of the Left Atrium in Atrial Fibrillation on a Patient-Specific Basis.

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of cerebrovascular events, being responsible of 15-18% of all strokes. The morphological and functional remodeling of the left atrium (LA) caused by AF favors blood stasis and, consequently, stroke risk. In this context, several clinical studies suggest that the stroke risk stratification could be improved by using hemodynamic information on the LA and the left atrial appendage (LAA). The goal of this study was to develop a personalized computational fluid dynamics (CFD) model of the LA which could clarify the hemodynamic implications of AF on a patient-specific basis. In this paper, we present the developed model and its application to two AF patients as a preliminary advancement toward an optimized stroke risk stratification pipeline.

Automatic management of atrial and ventricular stimulation in a contemporary unselected population of pacemaker recipients: the ESSENTIAL Registry.

AIMS: We investigated the applicability of the Ventricular Capture Control (VCC) and Atrial Capture Control (ACC) algorithms for automatic management of cardiac stimulation featured by Biotronik pacemakers in a broad, unselected population of pacemaker recipients. METHODS AND RESULTS: Ventricular Capture Control and Atrial Capture Control were programmed to work at a maximum adapted output voltage as 4.8 V in consecutive recipients of Biotronik pacemakers. Ambulatory threshold measurements were made 1 and 12 months after pacemaker implant/replacement in all possible pacing/sensing configurations, and were compared with manual measurements. Among 542 patients aged 80 (73-85) years, 382 had a pacemaker implant and 160 a pacemaker replacement. Ventricular Capture Control could work at long term in 97% of patients irrespectively of pacing indication, lead type, and lead service life, performance being superior with discordant pacing/sensing configurations. Atrial Capture Control could work in 93% of patients at 4.8 V maximum adapted voltage and at any pulse width, regardless of pacing indication, lead type, and service life. At 12-month follow-up, a ventricular threshold increase ≥1.5 V had occurred in 4.4% of patients uneventfully owing to VCC functioning. Projected pacemaker longevity at 1 month was strongly correlated with the 12-month estimate, and exceeded 13 years in >60% of patients. CONCLUSION: These algorithms for automatic management of pacing output ensure patient safety in the event of a huge increase of pacing threshold, while enabling maximization of battery longevity. Their applicability is quite broad in an unselected pacemaker population irrespectively of lead choice and service of life.

Synthesis, structure, and magnetism of a family of heterometallic {Cu2Ln7} and {Cu4Ln12} (Ln = Gd, Tb, and Dy) complexes: the Gd analogues exhibiting a large magnetocaloric effect.

The syntheses, structures, and magnetic properties of two heterometallic Cu(II)-Ln(III) (Ln(III) = Gd, Tb, and Dy) families, utilizing triethanolamine and carboxylate ligands, are reported. The first structural motif displays a nonanuclear {Cu(II)2Ln(III)7} metallic core, while the second reveals a hexadecanuclear {Cu(II)4Ln(III)12} core. The differing nuclearities of the two families stem from the choice of carboxylic acid used in the synthesis. Magnetic studies show that the most impressive features are displayed by the {Cu(II)2Gd(III)7} and {Cu(II)4Gd(III)12} complexes, which display a large magnetocaloric effect, with entropy changes -ΔSm = 34.6 and 33.0 J kg(-1) K(-1) at T = 2.7 and 2.9 K, respectively, for a 9 T applied field change. It is also found that the {Cu(II)4Dy(III)12} complex displays single-molecule magnet behavior, with an anisotropy barrier to magnetization reversal of 10.1 K.

Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. FROM THE CLINICAL EDITOR: Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies.

Patient-specific left atrium contraction quantification associated with atrial fibrillation: A region-based approach.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is a widespread cardiac arrhythmia that significantly impacts heart function. AF disrupts atrial mechanical contraction, leading to irregular, uncoordinated, and slow blood flow inside the atria which favors the formation of clots, primarily within the left atrium (LA). A standardized region-based analysis of the LA is missing, and there is not even any consensus about how to define the LA regions. In this study we propose an automatic approach for regionalizing the LA into segments to provide a comprehensive 3D region-based LA contraction assessment. LA global and regional contraction were quantified in control subjects and in AF patients to describe mechanical abnormalities associated with AF. METHODS: The proposed automatic approach for LA regionalization was tested in thirteen control subjects and seventeen AF patients. After dividing LA into standard regions, we evaluated the global and regional mechanical function by measuring LA contraction parameters, such as regional volume, global and regional strains, regional wall motion and regional shortening fraction. RESULTS: LA regionalization was successful in all study subjects. In the AF group compared with control subjects, results showed: a global impairment of LA contraction which appeared more pronounced along radial and circumferential direction; a regional impairment of radial strain which was more pronounced in septal, inferior, and lateral regions suggesting a greater reduction in mechanical efficiency in these regions in comparison to the posterior and anterior ones. CONCLUSION: An automatic approach for LA regionalization was proposed. The regionalization method was proved to be robust with several LA anatomical variations and able to characterize contraction changes associated with AF.

Ablation of CTI-dependent flutter using different ablation technologies: acute and long-term outcome from the LEONARDO study.

BACKGROUND: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. METHODS: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). RESULTS: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. CONCLUSIONS: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. CLINICAL TRIAL REGISTRATION: Atrial Flutter Ablation in a Real World Population. (LEONARDO). CLINICALTRIALS: gov Identifier: NCT02591875.

Elastocaloric Properties of Polycrystalline Samples of NiMnGaCu Ferromagnetic Shape Memory Alloy under Compression: Effect of Improvement of Thermoelastic Martensitic Transformation.

Shape memory alloys (SMAs) and ferromagnetic shape memory alloys (FeSMAs) have recently attracted interest for solid state refrigeration applications. Among NiMnGa-based quaternary systems, NiMnGaCu exhibits an interesting giant magnetocaloric effect thanks to the overlapping of the temperatures related to the magnetic transition and the thermoelastic martensitic transformation (TMT); in particular, for compositions with Cu content of approximately 6 at%. In the present work, we investigated the improvement effect of TMT on the total entropy change (ΔS) in the elastocaloric performances of polycrystalline Ni50Mn18.5Cu6.5Ga25 at% alloy samples, just above room temperature. We report an extensive calorimetric and thermomechanical characterization to explore correlations between microstructural properties induced by the selected thermal treatment and elastocaloric response, aiming at providing the basis to develop more efficient materials based on this quaternary system. Both ΔT and ΔS values obtained from mechanical curves at different temperatures and strain recovery tests under fixed load vs. T were considered. Maximum values of ΔS = 55.9 J/KgK and ΔT = 4.5 K were attained with, respectively, a stress of 65 MPa and strain of 4%. The evaluation of the coefficient of performance (COP) was carried out from a cyclic test.

[Changes in cardiac implantable electronic device follow-up induced by the COVID-19 pandemic in 2020: report of a single-centre experience]. / Variazioni del follow-up dei dispositivi elettronici cardiaci impiantabili indotte dalla pandemia COVID-19 nel 2020: esperienza di un singolo centro.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has greatly modified outpatient follow-ups. The aim of this retrospective study was to evaluate the organizational modalities and clinical effects of rearrangements of pacemaker (PM) and implantable cardioverter-defibrillator (ICD) outpatient visits performed in our centers at Ravenna and Lugo Hospitals, Italy, during the pandemic outbreak in 2020. METHODS: All scheduled in-person device follow-up visits in March-December 2020 have been considered. On the basis of documented past functioning of each device and of remote monitoring (RM) capabilities, in-person visits were either performed or postponed at variable times. The characteristics of the follow-ups and the device-related clinically relevant events were analyzed, the latter being further divided into serious malfunction and problems to be corrected by device reprogramming. RESULTS: Overall, 27% of in-person visits were postponed (n = 576) (36% of ICDs and 25% of PMs), peaking 62% in March-May 2020. RM compensated nearly all hold-ups in ICDs and just 63% of postponements in PMs. The postponement-caused delay between in-person visits was 5.6 ± 1.1 months for ICDs and 4.7 ± 1.2 months for PMs; in 24% of ICDs the time interval between in-person visits was ≥18 months. Clinically relevant events were 56 (18 [4.4%] in ICDs, 38 [2.1%] in PMs), with no deaths and 21 serious malfunctions (4 [1%] in ICDs, 15 [0.8%] in PMs). RM identified all ICD malfunctions, while it was not available in the affected PMs. In comparison with the year 2019, serious malfunctions increased, though the difference was not significant. Monthly RM transmissions increased by 2.3 fold. CONCLUSIONS: In our single-center experience during the COVID-19 pandemic, numerous in-person PM/ICD follow-up visits were postponed, and delays were well beyond the previously recommended time limits. However, device-related malfunctions did not increase, notably, when RM capabilities were used.

Computational Analysis of Mapping Catheter Geometry and Contact Quality Effects on Rotor Detection in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and catheter mapping has been proved to be an effective approach for detecting AF drivers to be targeted by ablation. Among drivers, the so-called rotors have gained the most attention: their identification and spatial location could help to understand which patient-specific mechanisms are acting, and thus to guide the ablation execution. Since rotor detection by multi-electrode catheters may be influenced by several structural parameters including inter-electrode spacing, catheter coverage, and endocardium-catheter distance, in this study we proposed a tool for testing the ability of different catheter shapes to detect rotors in different conditions. An approach based on the solution of the monodomain equations coupled with a modified Courtemanche ionic atrial model, that considers an electrical remodeling, was applied to simulate spiral wave dynamics on a 2D model for 7.75 s. The developed framework allowed the acquisition of unipolar signals at 2 KHz. Two high-density multipolar catheters were simulated (Advisor™ HD Grid and PentaRay®) and placed in a 2D region in which the simulated spiral wave persists longer. The configuration of the catheters was then modified by changing the number of electrodes, inter-electrodes distance, position, and atrial-wall distance for assessing how they would affect the rotor detection. In contact with the wall and at 1 mm distance from it, all the configurations detected the rotor correctly, irrespective of geometry, coverage, and inter-electrode distance. In the HDGrid-like geometry, the increase of the inter-electrode distance from 3 to 6 mm caused rotor detection failure at 2 mm distance from the LA wall. In the PentaRay-like configuration, regardless of inter-electrode distance, rotor detection failed at 3 mm endocardium-catheter distance. The asymmetry of this catheter resulted in rotation-dependent rotor detection. To conclude, the computational framework we developed is based on realistic catheter shapes designed with parameter configurations which resemble clinical settings. Results showed it is well suited to investigate how mapping catheter geometry and location affect AF driver detection, therefore it is a reliable tool to design and test new mapping catheters.

Left atrial appendage thrombosis in a patient with Friedreich Ataxia-related cardiomyopathy, left ventricular systolic dysfunction, and atrial fibrillation.

Friedreich ataxia is the most common form of hereditary ataxia. Heart involvement in Friedreich ataxia is common and can include increased left ventricular wall thickness, atrial fibrillation, and in the later stages, a reduction of left ventricular ejection fraction. We present the case of a 45-year-old man with a history of paroxysmal atrial fibrillation and a congestive heart failure, hypertension, age ⩾ 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, and female sex (CHA2DS2-VASc) score of only 1 (because of reduced left ventricular ejection fraction) who presented with pneumonia and was also found to have atrial fibrillation with a rapid ventricular response. Despite already being on long-term therapy with a non-vitamin K-antagonist oral anticoagulant, a transesophageal echocardiogram showed a mobile floating thrombus in the left atrial appendage. In accordance with previous necropsy evidence of thrombosis and thromboembolism in Friedreich ataxia subjects who likely have had only non-sex-related CHA2DS2-VASc score ⩽1, this case suggests that the risk of thromboembolism in Friedreich ataxia subjects with atrial fibrillation may not be adequately predicted by the sole CHA2DS2-VASc score.

Impedance mapping with constant contact force on 3D electroanatomic map to characterize tissues at pulmonary veno-atrial junction.

PURPOSE: Generator impedance (Im) mapping with constant contact force (CF) by tip catheter at PV isolation (PVI) was assessed for a proposal of tissue characterization at PV-LA junction (PV-LAJ). METHODS: In this observational, prospective, single-center study, Im mapping at constant CF = 10 g (± 2 g) was performed before PVI at PV-LAJ. PV in-vein, PV ostium (PVos), and antrum (PVan) contours were manually traced based on the 3D electroanatomic map (3DEAM) integrating intracardiac echocardiography and computerized tomography. PVan contour-methods based on Im mapping was defined on 3DEAM as the atrial-like Im contour closest to PVos, and its distance from anatomical PVan contour > 5 mm was assumed as the non-concordance marker between contour and methods. RESULTS: Sixty-two patients (62 ± 9 years; 43 males) were enrolled, and 244 PV-LAJ were assessed. From in-vein PV to LA and, less prominently, from PVos to PVan and LA, Im showed a unidirectional decrease with highly variable individual-specific distribution and values. PVan non-concordance was found in 59/665 segments (8.8%), 18% of PV-LAJs, and 53% of pts; it prevailed in superior PV-LAJ and measured on average 7.2 ± 1.1 mm. Im decrease patterns and non-concordance were not associated with any clinical or anatomical feature, including PV dimensions and shape. CONCLUSIONS: Im mapping of LA-PVJ at constant CF added to 3DEAM may consistently track the tissue transition from PV to LA. PVan identified by Im was often located more toward LA than the 3D anatomical PVan, particularly in LSPV, suggesting the potential advantage of avoiding ablation of venous-like tissue. Im mapping can deserve further investigation for target characterization at LA-PVJ.

Heart failure hospitalizations and costs in ICD/CRT-D recipients following replacement or upgrade: the DECODE registry.

AIMS: The aim of this study is to report heart failure hospitalization (HFH) rates and associated costs within 12 months following implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) device replacement or upgrade from ICD to CRT-D. METHODS AND RESULTS: The DEtect long-term COmplications after icD rEplacement (DECODE) was a prospective, single-arm, multicentre cohort study that explored complications in ICD/CRT-D recipients. All clinical and survival data at 12 months were prospectively analysed. For each adjudicated HFH, admission and discharge dates and ICD-9-CM diagnosis and procedure codes were recorded. The reimbursement for each HFH was calculated for each diagnosis-related group code. Between 2013 and 2015, 983 patients (mean age 71 years, male 76%, mean left ventricular ejection fraction 35%, and New York Heart Association Class I/II 75.6%) were enrolled. Patients underwent device replacement (900; 91.6%, 446 ICD/454 CRT-D) or ICD upgrade to CRT-D (83; 8.4%). Post-replacement hospitalizations occurred in 220 patients, with the primary discharge diagnosis identifying cardiovascular causes in 175 patients (80%). Fifty-five (5.6%) patients experienced at least one HFH. Overall, 91 HFH events occurred (9.6% event rate, 95% confidence interval: 7.7-11.7) in 70 patients; 66 (6.7%) patients died, 40 (60.6%) of cardiovascular causes. The HFH rate was significantly higher following upgrades, and the occurrence of HFH was associated with an 11-fold increased mortality risk (95% confidence interval: 5.9-20.5, P < 0.0001). Medical diagnosis-related group accounted for 91.2% of HFH; the mean cost per HFH was €5662 ± 9497, and the mean cost per patient was €9369 ± 12 687. On multivariate analysis, predictors of HFH were atrial fibrillation, chronic kidney disease, and all-cause hospitalization within 30 days prior to the procedure. CONCLUSIONS: In the DECODE registry, HFH and mortality rates in the year following ICD/CRT-D replacement or upgrade were low. In this particular subset, underlying cardiac disease was the main driver of HFH, mortality, and higher healthcare expenditures.

Is electrocardiography a reliable tool for identifying patients with isthmus-dependent atrial flutter?

AIMS: To verify the reliability of the surface ECG to discriminate between cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) and non-CTI-AFL. METHODS AND RESULTS: We reviewed the ECGs of 186 consecutive patients who underwent catheter ablation of AFL between January 2004 and January 2008. The ECG pattern was defined typical for CTI-AFL, if F-waves were: (i) dominantly negative in the inferior leads and positive in V1 (CCW) or (ii) dominantly positive in the inferior leads and negative in V1 (CW). At the electrophysiological study (EPS), 138 patients (74.2%) had a CTI-AFL and 48 patients (25.8%) had a non-CTI-AFL. A CTI-AFL was found not only in 90.5% of patients having a typical ECG, but also in 40% of patients having an atypical ECG. Thus, a typical AFL ECG showed a sensitivity of 0.83 and a specificity of 0.75 to predict a CTI-AFL, with a positive predictive value of 90.5% and a negative predictive value of 60%. CONCLUSION: Typical AFL ECG is a good predictor of CTI-AFL, and in this case, an ablation procedure can be recommended. On the contrary, an atypical AFL ECG does not rule out a CTI-AFL; so, even in this group of patients, an EPS should not be denied when indicated by the clinical circumstances.

The Impact of Left Atrium Appendage Morphology on Stroke Risk Assessment in Atrial Fibrillation: A Computational Fluid Dynamics Study.

Atrial fibrillation (AF) carries out a 5-fold increase in stroke risk, related to embolization of thrombi clotting in left atrium (LA). Left atrial appendage (LAA) is the site with the highest blood stasis which causes thrombus formation. About 90 % of the intracardiac thrombi in patients with cardioembolic events originally develop in the LAA. Recent studies have been focused on the association between LAA anatomical features and stroke risk and provided conflicting results. Haemodynamic and fluid dynamic information on the LA and mostly on the LAA may improve stroke risk stratification. Therefore, the aim of this study was the design and development of a workflow to quantitatively define the influence of the LAA morphology on LA hemodynamics. Five 3D LA anatomical models, obtained from real clinical data, which were clearly different as regard to LAA morphology were used. For each LAA we identified and computed several parameters describing its geometry. Then, one LA chamber model was chosen and a framework was developed to connect the different LAAs belonging to the other four patients to this model. These new anatomical models represented the computational domain for the computational fluid dynamics (CFD) study; simulations of the hemodynamics within the LA and LAA were performed in order to evaluate the interplay of the LAA shape on the blood flow characteristics in AF condition. CFD simulations were carried out for five cardiac cycles. Blood velocity, vorticity, LAA orifice velocity, residence time computed in the five models were compared and correlated with LAA morphologies. Results showed that not only complex morphologies were characterized by low velocities, low vorticity and consequently could carry a higher thrombogenic risk; even qualitatively simple morphologies showed a thrombogenic risk equal, or even higher, than more complex auricles. CFD results supported the hypothesis that LAA geometric characteristics plays a key-role in defining thromboembolic risk. LAA geometric parameters could be considered, coupled with the morphological characteristics, for a comprehensive evaluation of the regional blood stasis. The proposed procedure might address the development of a tool for patient-specific stroke risk assessment and preventive treatment in AF patients, relying on morpho-functional defintion of each LAA type.

Impact of pacemaker longevity on expected device replacement rates: Results from computer simulations based on a multicenter registry (ESSENTIAL).

BACKGROUND: The rate of device replacement in pacemaker recipients has not been investigated in detail. HYPOTHESIS: Current pacemakers with automatic management of atrial and ventricular pacing output provide sufficient longevity to minimize replacement rate. METHODS: We considered a cohort of 542 pacemaker patients (age 78 ± 9 years, 60% male, 71% de-novo implants) and combined 1-month projected device longevity with survival data and late complication rate in a 3-state Markov model tested in several Monte Carlo computer simulations. Predetermined subgroups were: age < or ≥ 70; gender; primary indication to cardiac pacing. RESULTS: At the 1-month follow-up the reported projected device longevity was 153 ± 45 months. With these values the proportion of patients expected to undergo a device replacement due to battery depletion was higher in patients aged <70 (49.9%, range 32.1%-61.9%) than in age ≥70 (24.5%, range 19.9%-28.8%); in women (39.9%, range 30.8%-48.1%) than in men (32.0%, range 24.7%-37.5%); in sinus node dysfunction (41.5%, range 30.2%-53.0%) than in atrio-ventricular block (33.5%, range 27.1-38.8%) or atrial fibrillation with bradycardia (27.9%, range 18.5%-37.0%). The expected replacement rate was inversely related to the assumed device longevity and depended on age class: a 50% increase in battery longevity implied a 5% reduction of replacement rates in patients aged ≥80. CONCLUSIONS: With current device technology 1/4 of pacemaker recipients aged ≥70 are expected to receive a second device in their life. Replacement rate depends on age, gender, and primary indication owing to differences in patients' survival expectancy. Additional improvements in device service time may modestly impact expected replacement rates especially in patients ≥80 years.

An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery.

The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-copolyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1-97.5%), and span values of particle size distribution (1.03-1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone.

Cardiac device therapy in patients with left ventricular dysfunction and heart failure: 'real-world' data on long-term outcomes (mortality, hospitalizations, days alive and out of hospital).

BACKGROUND: The impact on long-term outcomes of implantable cardioverter defibrillators (ICDs) and biventricular defibrillators for cardiac resynchronization (CRT-D) devices in 'real world' patients with heart failure (HF) needs to be assessed in terms of clinical effectiveness. METHODS AND RESULTS: A registry including consecutive HF patients who underwent a first implant of an ICD (891 patients) or a CRT-D device (709 patients) in 2006-2010 was followed (median 1487 days and 1516 days, respectively), collecting administrative data on survival, all-cause hospitalizations, cardiovascular or HF hospitalizations, and days alive and out of hospital (DAOH). Survival free from death/cardiac transplant was 61.9% and 63.8% at 5 years for ICD and CRT-D patients, respectively. Associated comorbidities (Charlson Comorbidity Index) had a significant impact on death/cardiac transplant, as well as on hospitalizations. The median values of DAOH% were 97.4% for ICD and 97.7% for CRT-D patients, but data were highly skewed, with the lower quartile of DAOH% values including values ranging between 0% and 52.8% for ICD and between 0% and 56.1% for CRT-D patients. Charlson Comorbidity Index was a very strong predictor of DAOH%. CONCLUSIONS: Patients who were implanted in 'real world' clinical practice with an ICD or a CRT-D device have, on average, a relatively favourable outcome, with a survival of around 62-64% at 5 years, but with an important burden of hospitalizations. Comorbidities, as evaluated by means of the Charlson Comorbidity Index, have a significant impact on outcomes in terms of mortality/heart transplant, hospitalizations and days spent alive and out of hospital.

Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation.

We tested the hypothesis that left ventricular (LV) pacing is superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. The potential benefit of LV over RV pacing needs to be evaluated without the confounding effect of other variables that can influence cardiac performance. An acute intrapatient comparison of the QRS width and echocardiographic parameters between RV versus LV pacing was performed within 24 h after ablation in 44 patients. Both modes of pacing were also compared with pre-implantation values. Compared with RV pacing, LV pacing caused a 5.7% increase in the ejection fraction (EF) and a 16.7% decrease in the mitral regurgitation (MR) score; the QRS width was 4.8% shorter with LV pacing. Similar results were observed in patients with or without systolic dysfunction and/or native left bundle branch block, except for a greater improvement in MR in the latter group. Compared with pre-ablation measures, the EF increased by 11.2% and 17.6% with RV and LV pacing, respectively; the MR score decreased by 0% and 16.7%; and the diastolic filling time increased by 12.7% and 15.6%.Rhythm regularization achieved with AV junction ablation improved EF with both RV and LV pacing; LV pacing provided an additional modest but favorable hemodynamic effect, as reflected by a further increase of EF and reduction of MR. The effect seems to be equal in patients with both depressed and preserved systolic functions and in those with and without native left bundle branch block.

Fractal nanochannels as the basis of the ionic transport in AgI-based glasses.

We propose a new model to explain the transport properties of AgI-based fast ion conducting glasses. The main factor affecting the ionic conductivity is the mobility of the Ag+ carriers, that is controlled by the Ag local environment. We model the ionic conductivity in terms of a percolation between a low-conducting phase (purely oxygen-coordinated sites), and a high-conducting one (iodine/oxygen, I/O, coordinated sites). The percolation takes place along pathways with fractal structure. The nature of the glass network, and namely its connectivity and dimensionality, plays a significant role only for low I/O values, originating the transport and thermal anomalies observed in borate and phosphate glasses.

Marbles in the façade of the "Certosa di Pavia": a physico-chemical study.

In the framework of an interdisciplinary research project on the well known monastery "Certosa di Pavia", the thermal and structural properties of marbles employed in the construction of the façade of the basilica were investigated in order to detect the main decomposition phenomena occurring on the monument surface. The results obtained by means of thermogravimetric and differential thermal analyses, as well as by means of X-ray diffraction and IR spectroscopy, allowed one to characterize samples taken from various sculptures of the façade and to bring out the degradation phenomena occurring in some of them, in particular the formation of "black crusts" with a high content in gypsum. The present findings are in fair agreement with those reported by other research groups which also studied with different techniques the construction materials of this monument.