Current status and future catheter ablation strategies in atrial fibrillation

Catheter ablation of atrial fibrillation (AF) is a highly effective therapy to achieve freedom of recurrent arrhythmia and relief from symptomatic AF. Transmural ablation of atrial tissue is crucial for success. Thus steerable sheaths and catheter design with contact measurement as an additional feature have been developed to increase success rates. New 3 dimentional (3D) mapping technologies engage clinical routine to reduce fluoroscopy time and radiation dose for patients and medical staff to a minimum. To unmask dormant pulmonary vein reconduction and to avoid early pulmonary vein reconduction administration of adenosine is useful. Future approaches aim at individualized ablation strategies taking clinical and electrophysiologic characteristics of the individual patient into account.     

Immunomodulatory Effects of Omega-3 Fatty Acids in Patients with Differentiated Thyroid Cancer Before or After Radioiodine Ablation

Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer (DTC). Methods: A total of 85 patients with DTC were allocated into two groups based on RAI dosage after thyroidectomy. Patients in each group were randomly distributed into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Fifteen healthy individuals were included as controls. Serum cytokine levels including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, TNF-α and IFN-γ were determined by cytometric bead assay. Results: IL-4, IL-6, IL-21 and IL-22 levels in patients with DTC were higher than in the healthy controls. Regardless of RAI dosage, IL-6 showed an increasing trend after RAI ablation. IL-4, IL-22, and IL-17A remained at considerably higher levels than in the healthy controls after RAI ablation. Within-group comparisons showed a significant reduction in Th1+Th17/Th2+Th22 ratio in G2 patients 1 week after RAI ablation. Between-group comparisons showed increased IL-10 levels in G3 compared with G1 patients one week after high-dose RAI ablation. In G3, Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were remarkably lesser than in G2 patients 1 month after intermediate-dose RAI ablation. Conclusion: Our results showed better anti-inflammatory effects of omega-3 when it was used therapeutically after RAI ablation in patients with DTC than when it was used prophylactically before RAI.     

Visualizing ablation gaps in vitro using a deflectable fiber optic endocardial visualization catheter

Background  The efficacy of pulmonary vein isolation for the treatment of atrial fibrillation may be limited by the ability to make continuous and transmural lesions utilizing an ablation catheter. Gaps often persist between ablation lesions leading to failed electrical isolation and thus failed ablation. Recently, a deflectable fiberoptic endocardial visualization catheter has been introduced for use in imaging the coronary sinus using light in the visible spectrum. We utilize this catheter to visualize the endocardial surface and examine radiofrequency ablation lesions in porcine endocardium to determine the presence of gaps between radiofrequency lesions. Methods  Videos were taken of the lesions and shown to two readers who were asked to identify the gaps ranging from less than 0.1 mm–9.8 mm. Results  Ninety-four lesion gaps were reviewed. The readers demonstrated a combined accuracy of 98.4% at identifying gaps. Conclusions  Gaps between ablation lesions can be accurately identified down to less than 1 mm distances in vitro using a direct visualization catheter. Further studies are warranted to confirm these finding in vivo.     

A practical guide to cardiovascular 3D printing in clinical practice: Overview and examples

The advent of more advanced 3D image processing, reconstruction, and a variety of three‐dimensional (3D) printing technologies using different materials has made rapid and fairly affordable anatomically accurate models much more achievable. These models show great promise in facilitating procedural and surgical planning for complex congenital and structural heart disease. Refinements in 3D printing technology lend itself to advanced applications in the fields of bio‐printing, hemodynamic modeling, and implantable devices. As a novel technology with a large variability in software, processing tools and printing techniques, there is not a standardized method by which a clinician can go from an imaging data‐set to a complete model. Furthermore, anatomy of interest and how the model is used can determine the most appropriate technology. In this over‐view we discuss, from the standpoint of a clinical professional, image acquisition, processing, and segmentation by which a printable file is created. We then review the various printing technologies, advantages and disadvantages when printing the completed model file, and describe clinical scenarios where 3D printing can be utilized to address therapeutic challenges.

     

Atrial fibrillation ablation complications

Atrial fibrillation (AF) is a common arrhythmia. Although significant work still needs to be done, recent advances in understanding the mechanisms of AF have led to the development of elegant catheter mapping techniques for ablation of AF, complemented by the evolution of various imaging and navigational technologies. Due to the complexity of the arrhythmia, and the significant length of time needed to successfully ablate in the left atrium, it is imperative that an acceptable risk-benefit profile be defined. Various complications, some of them serious, have been reported in the last several years. This review addresses the potential risks of AF ablation and how to avoid some of these complications.     

Three-dimensional manipulation of single cells using surface acoustic waves

The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving “acoustic tweezers” in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.The ability to precisely manipulate living cells in three dimensions, one cell at a time, offers many possible applications in regenerative medicine, tissue engineering, neuroscience, and biophysics (1–3). However, current bioprinting methods are generally hampered by the need to reconstruct and mimic 3D cell-to-cell communications and cell–environment interactions. Because of this constraint, bioprinting requires accurate reproduction of multicellular architecture (4, 5). Several approaches have been developed to produce complex cell patterns, clusters, assembled arrays, and even tissue structures. These approaches use many disparate technologies which include optics, magnetic and electrical fields, injection printing, physical or geometric constraints, or surface engineering (6–11). However, there is currently a paucity of a single method that can facilitate the formation of complex multicellular structures with high precision, high versatility, multiple dimensionality, and single-cell resolution, while maintaining cell viability, integrity, and function. As a result, there is a critical need to develop new methods that seek to overcome these limitations.“Acoustic tweezers,” which manipulate biological specimens using sound waves, offer several unique advantages (12, 13) in comparison with other techniques. First, the acoustic tweezers technology is the only active cell-manipulation method using gentle mechanical vibrations that do not alter cell characteristics. Acoustic vibrations create a pressure gradient in the medium to move suspended microobjects and cells, thereby resulting in a contamination-free, contact-less, and label-free method for cell manipulation. Sound waves are preferred for cell manipulation for the following reasons: (i) cells maintain their native state (e.g., shape, size, reflective index, charge, or polarity) in the absence of surface modification or labeling; and (ii) cells can remain in their original culture medium or extracellular matrix gel solution. Furthermore, acoustic tweezers are safe tools for biological manipulation. Acoustic tweezers involving sound waves have a power intensity that is ∼10 million times lower than that of optical tweezers. Therefore, acoustic tweezers have minimal impact on cell viability and function. Moreover, acoustic tweezers operate at a power intensity and frequency similar to the widely used medical ultrasound method that is well known as a safe technique for sensitive clinical applications such as imaging of a fetus in the mother’s womb. Finally, the acoustic tweezers platform can be constructed as a single, integrated microdevice without any moving parts or complicated setup procedures. This feature offers additional advantages for ease of use and versatility.Thus far, sound waves have been demonstrated to successfully perform many microscale functions such as the separation, alignment, enrichment, patterning, and transportation of cells and microparticles (12–17). None of these acoustic approaches, however, has hitherto demonstrated controlled 3D manipulation of single cells. The lack of these manipulation methods is mainly attributable to the limited understanding of the relationship between a 3D acoustic field and the induced acoustic streaming. Using 2D acoustic waves often results in insufficient control of a single cell in 3D space. Here, we report a standing surface acoustic wave (SSAW)-based technique that is able to create and independently manipulate an array of stable 3D trapping nodes.In this work, we illustrate the relation between the acoustic vibrations, the acoustic field produced by SSAWs, and the resulting streaming in a microfluidic chamber by recourse to both modeling and controlled experimental validation. Unlike Rayleigh streaming in bulk acoustic wave devices, the unique acoustic streaming (i.e., streaming motion caused by acoustic oscillation) pattern in a SSAW device determines how objects are lifted up from the substrate surface. By regulating the 3D distributed acoustic field and acoustic streaming, induced by two superimposed pairs of orthogonally placed SSAWs, we achieved an array of 3D trapping nodes in a microfluidic chamber. By independently tuning the relative phase angle of each SSAW or by varying the input power, the position of these 3D trapping nodes can be precisely controlled in a 3D environment. Using this concept, we demonstrate 3D trapping and three-axis manipulation of single microparticles and single biological cells. Finally, we illustrate how this 3D acoustic tweezers technique can be used for printing with live cells and for producing prescribed cell culture patterns.     

Sequential dual chamber extrastimulation: A novel pacing maneuver to identify the presence of a slowly conducting concealed accessory pathway

BACKGROUND: Transient VA block can be created in the AV node (AVN) when an atrial extrastimulus is delivered at the AVN effective refractory period (ERP) due to anterograde concealed conduction. OBJECTIVE: We hypothesized that ventricular stimulation during pacing-induced AVN refractoriness could identify concealed accessory pathways (APs) that remain hidden with standard maneuvers. METHODS: Patients undergoing electrophysiological study for supraventricular tachycardia were screened for presence of an AP using standard pacing maneuvers and/or V pacing during adenosine infusion. The dual-chamber sequential extrastimulation maneuver consisted of an 8-beat drive train of simultaneous AV pacing at 600 msec, followed by an A2 delivered at AVN ERP, followed by a V2 delivered at the drive train cycle length (600 msec). Repeat drives were then performed with decrements of 10 msec for V2 until VA block was seen. Retrograde AVN and AP ERP were recorded with standard (V1, V2) and dual-chamber extrastimulation (A1/V1, A2, V2). Patients with an AP identified with standard pacing, manifest pre-excitation, or A ERP < AVN ERP were excluded. RESULTS: Fourteen patients with and 19 patients without an AP were studied. In all patients with an AP, exclusive VA conduction over the AP, without fusion, was seen with the described pacing maneuver. In patients without an AP, retrograde AV nodal ERP was extended by a mean of 138 +/- 46 msec (range 50 to 210 msec) with the A2. Anterograde concealed conduction into the AP was also seen in some patients who showed AP conduction during standard V1V2 pacing (mean retrograde extension of ERP 12 +/- 8 msec, range 0 to 20 msec). CONCLUSION: Dual-chamber sequential extrastimulation is a useful maneuver for identifying slowly conducting APs not revealed with standard pacing maneuvers because of an ERP and conduction time similar to the AVN. The maneuver uses anterograde concealed conduction to prolong AVN refractoriness much more than that of a concealed AP, thereby allowing the AP to become manifest with the V2.     

Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction

Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiation assay in layered hydrogels to examine how these processes are affected in neurodevelopmental disorders, such as Rett syndrome. Our soft 3D system mimics the brain environment and accelerates maturation of neurons from human induced pluripotent stem cell (iPSC)-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. Using this platform, we revealed a genotype-specific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration and maturation (reduced neurite outgrowth and fewer synapses) in 3D layered hydrogels. Thus, this 3D system expands the range of neural phenotypes that can be studied in vitro to include those influenced by physical and mechanical stimuli or requiring specific arrangements of multiple cell types.Neuronal migration and maturation is a key step in brain development. Defects in this process have been implicated in many disorders, including autism (1) and schizophrenia (2). Thoroughly understanding how neural progenitor cell (NPC) migration is affected in neurodevelopmental disorders requires a means of dissecting the process using cells with genetic alterations matching those in patients. Existing in vitro assays of migration generally involve measurement of cell movement across a scratch or gap or through a membrane toward a chemoattractant in 2D culture systems. Although widely used, such assays may not accurately reveal in vivo differences, as neuronal migration is tightly regulated by physical and chemical cues in the extracellular matrix (ECM) that NPCs encounter as they migrate.In vitro 3D culture systems offer a solution to these limitations (3–7). Compared with 2D culture, a 3D arrangement allows neuronal cells to interact with many more cells (4); this similarity to the in vivo setting has been shown to lengthen viability, enhance survival, and allow formation of longer neurites and more dense networks in primary neurons in uniform matrices or aggregate culture (8, 9). Indeed, 3D culture systems have been used to study nerve regeneration, neuronal and glial development (10–12), and amyloid-β and tau pathology (13). Thus, measuring neuronal migration through a soft 3D matrix would continue this trend toward using 3D systems to study neuronal development and pathology.We sought to develop a 3D assay to examine potential migration and neuronal maturation defects in Rett syndrome (RTT), a genetic neurodevelopmental disorder that affects 1 in 10,000 children in the United States and is caused by mutations in the X-linked methyl-CpG-binding protein-2 (MECP2) gene (14). Studies using induced pluripotent stem cells (iPSCs) from RTT patients in traditional 2D adherent culture have revealed reduced neurite outgrowth and synapse number, as well as altered calcium transients and spontaneous postsynaptic currents (1). However, 2D migration assays seemed unlikely to reveal inherent defects in this developmental process, which could be affected because MeCP2 regulates multiple developmental related genes (15). Migration of RTT iPSC-derived NPCs has not previously been studied.Using a previously unidentified 3D tissue culture system that allows creation of layered architectures, we studied differences in migration of MeCP2-mutant iPSC-derived versus control iPSC-derived NPCs. This approach revealed a defect in migration of MeCP2-mutant iPSC-derived NPCs induced by either astrocytes or neurons. Further, this 3D system accelerated maturation of neurons from human iPSC-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. With mature neurons derived from RTT patients and controls, we further confirmed defective neurite outgrowth and synaptogenesis in MeCP2-mutant neurons. Thus, this 3D system enables study of morphological features accessible in 2D system as well as previously unexamined phenotypes.     

Português Registo Nacional de Eletrofisiologia Cardíaca (2015/2016)

IntroductionKnowledge of the activity performed in a country enables it to be positioned within the community of which it is part.ObjectiveWe present the results of the National Registry of Cardiac Electrophysiology of the Portuguese Association for Arrhythmology, Pacing and Electrophysiology (APAPE) for 2015 and 2016.MethodsThis is a voluntary, observational, annual registry collected retrospectively.ResultsThe data on the electrophysiological studies and ablations performed in these two years are presented.ConclusionChanges in these data over the years are analyzed and the relation of the Portuguese data in the European panorama and possible implications are discussed.     

Registration of 3D computed tomographic images with interventional systems: Implications for catheter ablation of atrial fibrillation

Despite the great promise catheter ablation offers in the treatment of complex arrhythmias such as atrial fibrillation (AF), long procedure times and somewhat suboptimal results hinder the widespread use of this technique. As fluoroscopy does not provide contrast differentiation between the area of interest and the surrounding structures, there is a lack of proper intra procedure image guidance. Segmentation of anatomical structures such as the left atrium (LA) can be performed using images obtained with modalities such as computed tomography (CT). However, unlike the cardiac mapping systems, these imaging systems do not track catheters in real time. This review addresses the evolving concept of image registration to deliver therapy in cardiac arrhythmias.     

Syndrome de Brugada asymptomatique : diagnostic,pronostic, nouvelles stratégies thérapeutiques

Brugada syndrome management may be a difficult question. This article reviews diagnosis, prognosis evaluation, current and investigated treatments.     

活体超声心肌消融的生物学效应

目的 探讨超声消副活体心肌的效应特征,提供导管超声用以治疗心律失常的实验基础。方法 用１０．４ＭＨｚ的超声导管消融１０只活体犬心肌,观察消融深度、形态和温度变化及其与射频消融心肌效应的差异。结果 超声在活体犬可产生深达１０ｍｍ的心肌消融,消融深度与消融时间呈良好相关且边界清晰;其熟中心在心肌内部。而射频消融不祺明显低于超声,其热中心在消融的心肌表面。结论 超声可产生边界清晰且深入的心肌消融,消融深