Cost, efficiency, and outcomes of pulsed field ablation vs thermal ablation for atrial fibrillation: A real-world study.

BACKGROUND: With the exponential growth of catheter ablation for atrial fibrillation (AF), there is increasing interest in associated health care costs. Pulsed field ablation (PFA) using a single-shot pentaspline multielectrode catheter has been shown to be safe and effective for AF ablation, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. OBJECTIVE: The purpose of this study was to compare cost, efficiency, effectiveness, and safety between PFA, CB, and RF for AF ablation. METHODS: We studied 707 consecutive patients (PFA: 208 [46.0%]; CB: 325 [29.4%]; RF: 174 [24.6%]) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, laboratory use, and hospital stay, and compared between ablation modalities, as were effectiveness and safety. RESULTS: Skin-to-skin times and catheter laboratory times were significantly shorter with PFA (68 and 102 minutes, respectively) than with CB (91 and 122 minutes) and RF (89 and 123 minutes) (P < .001). General anesthesia use differed across modalities (PFA 100%; CB 10.2%; RF 61.5%) (P < .001). Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and laboratory costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) than with CB (£8106) and RF (£8949) (P < .001). CONCLUSION: In this contemporary real-world study of the 3 major AF ablation modalities used concurrently, PFA had shorter skin-to-skin and catheter laboratory times than did CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely because of higher equipment cost.

NIR-Emitting Gold Nanoclusters Encapsulated in PS-b-PEG Polymer Micelles.

Gold nanoclusters (AuNCs) are an emerging type of luminescent probe, featuring good biocompatibility, high photostability, and large Stoke shifts. Their lack of colloidal stability is, however, a drawback for many applications. Here, we report the stabilization of AuNCs emitting in the NIR by a thiol-terminated polystyrene chain (Mn = 5000 g mol-1). The optical properties of this nanocomposite remain invariant for 2 years in THF. To use the PS5k-AuNCs in an aqueous environment, these were encapsulated into polymer micelles using a polystyrene-b-poly(ethylene glycol) copolymer. The resulting hierarchical constructs, with diameters of ca. 125 to 215 nm, have promising properties for applications as luminescent probes such as contrast agents for biomedical imaging.

Waterborne Polymer Coatings with Bright Noniridescent Structural Colors.

Structural color pigments offer an efficient, sustainable, and environmentally friendly approach to obtain waterborne polymer coatings. We developed polymer-based spherical photonic pigments to incorporate in aqueous dispersions of polymer nanoparticles used to obtain waterborne polymer films. Our spherical photonic pigments are assembled from polymer nanoparticles and are highly stable in water dispersion, maintaining their optical properties in the final polymer films. Unlike conventional dyes and pigments, which are prone to photobleaching because they are based on the absorption of light, photonic pigments rely on the selective reflection of light by their nanostructure and therefore are not photodegraded. Furthermore, different colors can be obtained from the same materials, changing only their nanostructure, in this case, the size of the polymer nanoparticles. Our novel spherical photonic pigments are noniridescent and can be incorporated in aqueous polymer nanoparticle dispersions without deteriorating their structure to produce waterborne polymer coatings with structural color. This approach for structural colored waterborne polymer coatings is efficient, simple, and environmentally friendly, offering excellent prospects for application in paints and coatings.

Multifunctional Nanoparticles with Superparamagnetic Mn(II) Ferrite and Luminescent Gold Nanoclusters for Multimodal Imaging.

Gold nanoclusters (AuNCs) with fluorescence in the Near Infrared (NIR) by both one- and two-photon electronic excitation were incorporated in mesoporous silica nanoparticles (MSNs) using a novel one-pot synthesis procedure where the condensation polymerization of alkoxysilane monomers in the presence of the AuNCs and a surfactant produced hybrid MSNs of 49 nm diameter. This method was further developed to prepare 30 nm diameter nanocomposite particles with simultaneous NIR fluorescence and superparamagnetic properties, with a core composed of superparamagnetic manganese (II) ferrite nanoparticles (MnFe2O4) coated with a thin silica layer, and a shell of mesoporous silica decorated with AuNCs. The nanocomposite particles feature NIR-photoluminescence with 0.6% quantum yield and large Stokes shift (290 nm), and superparamagnetic response at 300 K, with a saturation magnetization of 13.4 emu g-1. The conjugation of NIR photoluminescence and superparamagnetic properties in the biocompatible nanocomposite has high potential for application in multimodal bioimaging.

Integrated FRET Polymers Spatially Reveal Micro- to Nanostructure and Irregularities in Electrospun Microfibers.

A spatial view of macroscopic polymer material properties, in terms of nanostructure and irregularities, can help to better understand engineering processes such as when materials may fail. However, bridging the gap between the molecular-scale arrangement of polymer chains and the spatially resolved macroscopic properties of a material poses numerous difficulties. Herein, an integrated messenger material that can report on the material micro- to nanostructure and its processes is introduced. It is based on polymer chains labeled with fluorescent dyes that feature Förster resonance energy transfer (FRET) dependent on chain conformation and concentration within a host polymer material. These FRET materials are integrated within electrospun polystyrene microfibers, and the FRET is analyzed by confocal laser scanning microscopy (CLSM). Importantly, the use of CLSM allows a spatial view of material nanostructure and irregularities within the microfibers, where changes in FRET are significant when differences in fiber geometries and regularities exist. Furthermore, changes in FRET observed in damaged regions of the fibers indicate changes in polymer conformation and/or concentration as the material changes during compression. The system promises high utility for applications where nano-to-macro communication is needed for a better understanding of material processes.

Bright and Stable Nanomaterials for Imaging and Sensing.

This review covers strategies to prepare high-performance emissive polymer nanomaterials, combining very high brightness and photostability, to respond to the drive for better imaging quality and lower detection limits in fluorescence imaging and sensing applications. The more common approaches to obtaining high-brightness nanomaterials consist of designing polymer nanomaterials carrying a large number of fluorescent dyes, either by attaching the dyes to individual polymer chains or by encapsulating the dyes in nanoparticles. In both cases, the dyes can be covalently linked to the polymer during polymerization (by using monomers functionalized with fluorescent groups), or they can be incorporated post-synthesis, using polymers with reactive groups, or encapsulating the unmodified dyes. Silica nanoparticles in particular, obtained by the condensation polymerization of silicon alcoxides, provide highly crosslinked environments that protect the dyes from photodegradation and offer excellent chemical modification flexibility. An alternative and less explored strategy is to increase the brightness of each individual dye. This can be achieved by using nanostructures that couple dyes to plasmonic nanoparticles so that the plasmon resonance can act as an electromagnetic field concentrator to increase the dye excitation efficiency and/or interact with the dye to increase its emission quantum yield.

Understanding Fenofibrate Release from Bare and Modified Mesoporous Silica Nanoparticles.

To investigate the impact of the surface functionalization of mesoporous silica nanoparticle (MSN) carriers in the physical state, molecular mobility and the release of Fenofibrate (FNB) MSNs with ordered cylindrical pores were prepared. The surface of the MSNs was modified with either (3-aminopropyl) triethoxysilane (APTES) or trimethoxy(phenyl)silane (TMPS), and the density of the grafted functional groups was quantified via 1H-NMR. The incorporation in the ~3 nm pores of the MSNs promoted FNB amorphization, as evidenced via FTIR, DSC and dielectric analysis, showing no tendency to undergo recrystallization in opposition to the neat drug. Moreover, the onset of the glass transition was slightly shifted to lower temperatures when the drug was loaded in unmodified MSNs, and MSNs modified with APTES composite, while it increased in the case of TMPS-modified MSNs. Dielectric studies have confirmed these changes and allowed researchers to disclose the broad glass transition in multiple relaxations associated with different FNB populations. Moreover, DRS showed relaxation processes in dehydrated composites associated with surface-anchored FNB molecules whose mobility showed a correlation with the observed drug release profiles.

Online Monitoring of Sensor Calibration Status to Support Condition-Based Maintenance.

Condition-Based Maintenance (CBM), based on sensors, can only be reliable if the data used to extract information are also reliable. Industrial metrology plays a major role in ensuring the quality of the data collected by the sensors. To guarantee that the values collected by the sensors are reliable, it is necessary to have metrological traceability made by successive calibrations from higher standards to the sensors used in the factories. To ensure the reliability of the data, a calibration strategy must be put in place. Usually, sensors are only calibrated on a periodic basis; so, they often go for calibration without it being necessary or collect data inaccurately. In addition, the sensors are checked often, increasing the need for manpower, and sensor errors are frequently overlooked when the redundant sensor has a drift in the same direction. It is necessary to acquire a calibration strategy based on the sensor condition. Through online monitoring of sensor calibration status (OLM), it is possible to perform calibrations only when it is really necessary. To reach this end, this paper aims to provide a strategy to classify the health status of the production equipment and of the reading equipment that uses the same dataset. A measurement signal from four sensors was simulated, for which Artificial Intelligence and Machine Learning with unsupervised algorithms were used. This paper demonstrates how, through the same dataset, it is possible to obtain distinct information. Because of this, we have a very important feature creation process, followed by Principal Component Analysis (PCA), K-means clustering, and classification based on Hidden Markov Models (HMM). Through three hidden states of the HMM, which represent the health states of the production equipment, we will first detect, through correlations, the features of its status. After that, an HMM filter is used to eliminate those errors from the original signal. Next, an equal methodology is conducted for each sensor individually and using statistical features in the time domain where we can obtain, through HMM, the failures of each sensor.

Frequent premature atrial contractions as a signalling marker of atrial cardiomyopathy, incident atrial fibrillation, and stroke.

Premature atrial contractions are a common cardiac phenomenon. Although previously considered a benign electrocardiographic finding, they have now been associated with a higher risk of incident atrial fibrillation (AF) and other adverse outcomes such as stroke and all-cause mortality. Since premature atrial contractions can be associated with these adverse clinical outcomes independently of AF occurrence, different explanations have being proposed. The concept of atrial cardiomyopathy, where AF would be an epiphenomenon outside the causal pathway between premature atrial contractions and stroke has received traction recently. This concept suggests that structural, functional, and biochemical changes in the atria lead to arrhythmia occurrence and thromboembolic events. Some consensus about diagnosis and treatment of this condition have been published, but this is based on scarce evidence, highlighting the need for a clear definition of excessive premature atrial contractions and for prospective studies regarding antiarrhythmic therapies, anticoagulation or molecular targets in this group of patients.

Optically traceable PLGA-silica nanoparticles for cell-triggered doxorubicin delivery.

Fluorescent silica nanoparticles with a polymer shell of poly (D, L-lactide-co-glycolide) (PLGA) can provide traceable cell-triggered delivery of the anticancer drug doxorubicin (DOX), protecting the cargo while in transit and releasing it only intracellularly. PLGA with 50:50 lactide:glycolide ratio was grown by surface-initiated ring-opening polymerization (ROP) from silica nanoparticles of ca. 50 nm diameter, doped with a perylenediimide (PDI) fluorescent dye anchored to the silica structure. After loading DOX, release from the core-shell particles was evaluated in solution at physiological pH (7.4), and in human breast cancer cells (MCF-7) after internalization. The hybrid silica-PLGA nanoparticles can accommodate a large cargo of DOX, and the release in solution (PBS) due to PLGA hydrolysis is negligible for at least 72 h. However, once internalized in MCF-7 cells, the nanoparticles release the DOX cargo by degradation of the PLGA. Accumulation of DOX in the nucleus causes cell apoptosis, with the drug-loaded nanoparticles found to be as potent as free DOX. Our fluorescently traceable hybrid silica-PLGA nanoparticles with cell-triggered cargo release offer excellent prospects for the controlled delivery of anticancer drugs, protecting the cargo while in transit and efficiently releasing the drug once inside the cell.

Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model.

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2'-bipy-4,4'-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3-14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy.

Molecular Transport within Polymer Brushes: A FRET View at Aqueous Interfaces.

Molecular permeability through polymer brush chains is implicated in surface lubrication, wettability, and solute capture and release. Probing molecular transport through polymer brushes can reveal information on the polymer nanostructure, with a permeability that is dependent on chain conformation and grafting density. Herein, we introduce a brush system to study the molecular transport of fluorophores from an aqueous droplet into the external "dry" polymer brush with the vapour phase above. The brushes consist of a random copolymer of N-isopropylacrylamide and a Förster resonance energy transfer (FRET) donor-labelled monomer, forming ultrathin brush architectures of about 35 nm in solvated height. Aqueous droplets containing a separate FRET acceptor are placed onto the surfaces, with FRET monitored spatially around the 3-phase contact line. FRET is used to monitor the transport from the droplet to the outside brush, and the changing internal distributions with time as the droplets prepare to recede. This reveals information on the dynamics and distances involved in the molecular transport of the FRET acceptor towards and away from the droplet contact line, which are strongly dependent on the relative humidity of the system. We anticipate our system to be extremely useful for studying lubrication dynamics and surface droplet wettability processes.

A comparison of medical therapy and ablation for atrial fibrillation in patients with heart failure.

INTRODUCTION: Atrial fibrillation and heart failure frequently co-exist and the combination is associated with a worse prognosis than either condition alone. A number of pharmacological agents and invasive procedures have been shown to benefit this complex patient group. OBJECTIVE: In this review, we compare different therapeutic approaches to atrial fibrillation and heart failure, including pharmacotherapy, left atrial catheter ablation and pace-and-ablate. EXPERT OPINION: Left atrial catheter ablation is an efficacious option for restoring sinus rhythm and is most likely to provide benefit to those in whom durable sinus rhythm can be expected, and whose life expectancy is not significantly reduced by other pathologies or advanced age. A pace-and-ablate approach, particularly with physiological pacing, may provide more benefit to those with low chance of maintaining sinus rhythm. Both invasive options generally outperform pharmacotherapy, although it is important to individualize the approach for each patient through shared decision-making.

Optimizing adherence and persistence to non-vitamin K antagonist oral anticoagulant therapy in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of stroke, which can be prevented by the use of oral anticoagulation. Although non-vitamin K antagonist oral anticoagulants (NOACs) have become the first choice for stroke prevention in the majority of patients with non-valvular AF, adherence and persistence to these medications remain suboptimal, which may translate into poor health outcomes and increased healthcare costs. Factors influencing adherence and persistence have been suggested to be patient-related, physician-related, and healthcare system-related. In this review, we discuss factors influencing patient adherence and persistence to NOACs and possible problem solving strategies, especially involving an integrated care management, aiming for the improvement in patient outcomes and treatment satisfaction.

Encapsulation of gold nanoclusters: stabilization and more.

Gold nanoparticles with only a few atoms, known as gold nanoclusters (AuNCs), have dimensions below 2 nm and feature singular properties such as size dependent luminescence. AuNCs are also highly photostable and have catalytic activity, low toxicity and good biocompatibility. With these properties, they are extremely promising candidates for application in bioimaging, sensing and catalysis. However, when stabilized only with small capping ligands, their use is hindered by lack of colloidal stability. Encapsulation of the AuNCs can contribute to provide a more robust protection and even to improve their properties. Here, we review the encapsulation of AuNCs in polymers, silica and metal organic frameworks (MOFs) for applications in bioimaging, sensing and catalysis.

Reflectance Confocal Microscopy: A Powerful Tool for Large Scale Characterization of Ordered/Disordered Morphology in Colloidal Photonic Structures.

The development of appropriate methods to correlate the structure and optical properties of colloidal photonic structures is still a challenge. Structural information is mostly obtained by electron, X-ray, or optical microscopy methods and X-ray diffraction, while bulk spectroscopic methods and low resolution bright-field microscopy are used for optical characterization. Here, we describe the use of reflectance confocal microscopy as a simple and intuitive technique to provide a direct correlation between the ordered/disordered structural morphology of colloidal crystals and glasses, and their corresponding optical properties.

Prolonged Right Ventricular Outflow Tract Endocardial Activation Duration and Presence of Deceleration Zones in Patients With Idiopathic Premature Ventricular Contractions. Association With Low Voltage Areas.

BACKGROUND AND AIMS: The wavefront propagation velocity in the myocardium with fibrosis is characterized by the presence of deceleration zones and late activated zones, that are absent in the normal myocardium. Our aim was to study the right ventricular outflow tract (RVOT) endocardial activation duration in sinus rhythm, and assess the presence of deceleration zones, in patients with premature ventricular contractions (PVCs) and in controls. METHODS: We studied 29 patients with idiopathic PVCs from the outflow tract, subjected to catheter ablation that had an activation and voltage map of the RVOT in sinus rhythm. A control group of 15 patients without PVCs that underwent ablation of supraventricular arrhythmias was also studied. RVOT endocardial activation duration and number of 10 ms isochrones across the RVOT were assessed. Propagation speed was calculated at the zone with the higher number of isochrones per cm radius. Deceleration zones were defined as zones with >3 isochrones within 1 cm radius. Low voltage areas were defined as areas with local electrogram with amplitude <1.5 mV. RESULTS: The two groups did not differ in relation to age, gender or number of points in the map. RVOT endocardial activation duration and number of 10 ms isochrones were higher in the PVC group; 56 (41-66) ms vs. 39 (35-41) ms, p = 0.001 and 5 (4-8) vs. 4 (4-5), p = 0.001. Presence of deceleration zones and low voltage areas were more frequent in the PVC group; 20 (69%) vs. 0 (0%), p < 0.0001 and 21 (72%) vs. 0 (0%), p < 0.0001. The wavefront propagation speed was significantly lower in patients with PVCs than in the control group, 0.35 (0.27-0.40) vs. 0.63 (0.56-0.66) m/s, p < 0.0001. Patients with low voltage areas had longer activation duration 60 (52-67) vs. 36 (32-40) ms, p < 0.0001, more deceleration zones, 20 (95%) vs. 0 (0%), p < 0.0001, and lower wavefront propagation speed, 0.30 (0.26-0.36) vs. 0.54 (0.36-0.66) m/s, p = 0.002, than patients without low voltage areas. CONCLUSION: Right ventricular outflow tract endocardial activation duration was longer, propagation speed was lower and deceleration zones were more frequent in patients with PVCs than in controls and were associated with the presence of low voltage areas.

Anatomic guided ablation of the atrial right ganglionated plexi is enough for cardiac autonomic modulation in patients with significant bradyarrhythmias.

INTRODUCTION: Cardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe functional bradyarrhythmias, although no consensus exists on the best ablation strategy. The aim of this study was to evaluate if a simplified approach by a purely anatomical guided ablation of just the atrial right GP is enough for the treatment of these patients. METHODS: We prospectively enrolled patients with significant functional bradyarrhythmias and performed endocardial ablation purely guided by 3D electroanatomic mapping directed at the atrial right GP and accessed parameters of parasympathetic modulation and recurrence of bradyarrhythmias. RESULTS: Thirteen patients enrolled (76.9% male, median age 51, 42-63 years). After ablation, a median RR interval shortening of 28.3 (25.6-40.3)% occurred (1111, 937.5-1395.4 ms to 722.9, 652.2-882.4 ms, p = 0.0002). The AH interval also shortened (19, 10.5-35.7%) significantly after the procedure (115, 105-122 ms to 85, 71-105 ms, p = 0.0023) as well as Wenckebach cycle length (11.1, 5.9-17.8% shortening) from 450, 440-510 ms to 430, 400-460 ms, p = 0.0127. On 24-h Holter monitoring there was significant increase in heart rates (HR) of patients after ablation (minimal HR increased from 34 (26-43)bpm to 49 (43-56)bpm, p = 0,0102 and mean HR from 65 (47-72)bpm to 78 (67-87)bpm, p = 0.0004). No patients had recurrence of symptoms or significant bradyarrhythmias during a median follow-up of 8.4 months. CONCLUSIONS: A purely anatomic guided procedure directed only at the atrial right ganglionated plexi seems to be enough as a therapeutic approach for cardioneuroablation in selected patients with significant functional bradyarrhythmias.

Mesoporous Silica Nanoparticles Modified inside and out for ON:OFF pH-Modulated Cargo Release.

Highly efficient pH-modulated cargo release was achieved with a new hybrid nanocarrier composed of a mesoporous silica core with functionalized pores and a grafted pH-responsive crosslinked polymer shell of 2-(diisopropylamino)ethyl methacrylate (pKa ≈ 6.5). The retention/release performance of the system was optimized by a novel approach using selective functionalization of the silica pores to tune the carrier-cargo interaction and by tunning the amount of grafted polymer. The system features excellent retention of cationic cargo at low pH and a burst release at higher pH. This results from the expanded-collapsed conformation transition of the pH-responsive polymer shell and the simultaneous change in the interaction between the cargo and the polymer shell and the modified pore walls. At low pH, the electrostatic interaction of the cationic cargo with the protonated amine groups of the extended polymer shell retains the cargo, resulting in very low leakage (OFF state). At high pH, the electrostatic interaction with the cargo is lost (due to deprotonation of the polymer amine groups), and the polymer shell collapses, squeezing out the cargo in a burst release (ON state). Pore functionalization in combination with the stimuli-responsive polymer shell is a very promising strategy to design high-performance ON:OFF smart hybrid nanocarriers for stimuli-actuated cargo release, with great potential for application in the controlled release of drugs and other biologically active agents.

Overview of Silica-Polymer Nanostructures for Waterborne High-Performance Coatings.

Combining organic and inorganic components at a nanoscale is an effective way to obtain high performance coating materials with excellent chemical and physical properties. This review focuses on recent approaches to prepare hybrid nanostructured waterborne coating materials combining the mechanical properties and versatility of silica as the inorganic filler, with the flexural properties and ease of processing of the polymer matrix. We cover silica-polymer coupling agents used to link the organic and inorganic components, the formation of hybrid films from these silica-polymer nanostructures, and their different applications. These hybrid nanostructures can be used to prepare high performance functional coatings with different properties from optical transparency, to resistance to temperature, hydrophobicity, anti-corrosion, resistance to scratch, and antimicrobial activity.