Tissue Contact Research Articles

Abstract 12390: Differences in the Impact of Use of Contact Force Sensing Catheters on Subsequent Rates of Pulmonary Vein Reconnection Detected Between Men and Women During Repeat Ablation of Atrial Fibrillation

Background: Radiofrequency catheter ablation (CA) is an effective treatment for atrial fibrillation (AF). Contact force (CF) sensing catheters permit tissue contact monitoring that may lead to durable pulmonary vein (PV) isolation. Objective: To assess the impact of CF-sensing catheters on PV reconnection rates at repeat AF ablation and whether there are sex-based differences. Methods: We conducted a retrospective study of patients who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Patients were divided into 2 groups: Group 1 (non-CF sensing catheters) and Group 2 (CF-sensing catheters). Results: One hundred sixty-one patients were included in the study (76 in Group 1 and 85 in Group 2, 32% female, 70 ± 10 years old). Initial use of CF-sensing catheters at index ablation was associated with a lower PV reconnection rate at repeat ablation (60% for Group 2 vs 87% for Group 1; P = 0.001). There were no significant differences in locations of PV reconnection between Group 1 and Group 2. When stratified by sex, there were significantly lower rates of PV reconnection in male patients with use of CF-sensing catheters (92% for Group 1 vs 67% for Group 2; p=0.001) but not for female patients (71% for Group 1 vs 50% for Group 2; p=0.23). On multivariable logistic regression analysis, use of CF-sensing catheters at index ablation (adjusted odds ratio [aOR]: 0.28, 95% CI: 0.12 to 0.65; p=0.003) and female sex (aOR: 0.38, 95% CI: 0.17 to 0.86; p=0.02) were associated with significantly lower rates of PV reconnection found at repeat ablation. Conclusion: Use of CF sensing catheters reduced PV reconnection rate found at repeat AF ablation. Females have lower rates of PV reconnection identified at repeat ablation which suggest that non-PV triggers may be a more common cause of recurrent AF, thereby blunting the impact of CF-sensing catheters on reducing recurrent AF in females.

Study of the Thermal and Mechanical Properties of the Hydrophilic Blend Material Polyhydroxyethyl Methacrylate/Polyethylene Glycol: Hydrogen Bonding Analysis

A hydrophilic blend material is a material that can take up an important quantity of water, which makes it useful in various applications such as tissue engineering, contact lenses, and drug delivery. In this study, the polymeric blend material polyhydroxyethyl methacrylate/polyethylene glycol (pHEMA/PEG) was prepared through a UV photo-polymerization reaction; hexanediol diacrylate (HDDA) and Darocur 1,173 were used, respectively, as a cross-linking agent and a photoinitiator. The main objective of this investigation was to evaluate the impact of the PEG content on the thermal and mechanical properties of the crosslinked pHEMA/HDDA. Many analytical techniques, including Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA), were used, to analyze the bonding vibrations, the glass transition temperature (Tg), and the elastic and loss moduli, respectively. The complex viscosity was analyzed by a rheometer. The swelling and deswelling behavior of the crosslinked pHEMA/PEG in distilled water were studied over time. It was found that the PEG increased the polymerization rate of the HEMA monomer, and a significant decrease in the glass transition temperature was observed with increasing PEG quantity in the blend material, confirming its plasticizing effect. The mechanical, swelling kinetics, and rheology results showed a threshold effect at 1 wt.% for PEG. The docking analysis showed that there was more hydrogen bonding between the pure pHEMA’s chains, but the integration of PEG decreased the number of hydrogen bonds, which gave flexibility to the blend material, hence; this theoretical conclusion well agreed with the experimental results.

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy

BackgroundThree-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. ObjectiveTo investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. MethodsEndocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. ResultsARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5–3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5–4 vs. 4.3,IQR:2.9–6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59–78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75–0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = −0.370, p < 0.001) was found. ConclusionsEAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC.

Catheter navigation by intracardiac echocardiography enables zero-fluoroscopy linear lesion formation and bidirectional cavotricuspid isthmus block in patients with typical atrial flutter

IntroductionOne of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL).Methods and resultsThirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration.ConclusionsZero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure.Graphical

Ultrasonic Aspirator for Tissue Contact Detection: An Online Classification on Time-Series.

The goal of neurosurgical tumor surgery is to remove the tumor completely without damaging healthy brain structures and thereby impairing the patient's neurological functions. This requires careful planning and execution of the operation by experienced neurosurgeons using the latest intraoperative technologies to achieve safe and rapid tumor reduction without harming the patient. To achieve this goal, a standard ultrasonic aspirator designed for tissue removal is equipped with additional intraoperative tissue detection using machine learning methods.Since decision-making in a clinical context must be fast, online contact detection is critical. Data are generated on three types of artificial tissue models in a CNC machine-controlled environment with four different ultrasonic aspirator settings. Contact classification on artificial tissue models is evaluated on four classification algorithms: change point detection (CPD), random forest (RF), recurrent neural network (RNN) and temporal convolutional network (TCN). Data preprocessing steps are applied, and their impacts are investigated. All methods are evaluated on five-fold cross-validation and provide generally good results with a performance of up to 0.977±0.007 in mean F1-score. Preprocessing the data has a positive effect on the classification processes for all methods and consistently improves the metrics. Thus, this work indicates in a first step that contact classification is feasible in an online context for an ultrasonic aspirator. Further research is necessary on different tissue types, as well as hand-held use to more closely resemble the intraoperative clinical conditions.

Loss of Ephaptic Contacts in the Murine Thalamus during Osmotic Demyelination Syndrome

ABSTRACT Background and aim A murine model mimicking osmotic demyelination syndrome (ODS) revealed with histology in the relay posterolateral (VPL) and ventral posteromedial (VPM) thalamic nuclei adjoined nerve cell bodies in chronic hyponatremia, amongst the damaged 12 h and 48 h after reinstatement of osmolality. This report aims to verify and complement with ultrastructure other neurophysiology, immunohistochemistry, and molecular biochemistry data to assess the connexin-36 protein, as part of those hinted close contacts. This ODS investigation included four groups of mice: Sham (NN; n = 13), hyponatremic (HN; n = 11), those sacrificed 12 h after a fast restoration of normal natremia (ODS12h; n = 6) and mice sacrificed 48 h afterward, or ODS48 h (n = 9). Out of these, thalamic zones samples included NN (n = 2), HN (n = 2), ODS12h (n = 3) and ODS48h (n = 3). Results Ultrastructure illustrated junctions between nerve cell bodies that were immunolabeled with connexin36 (Cx36) with light microscopy and Western blots. These cell’s junctions were reminiscent of low resistance junctions characterized in other regions of the CNS with electrophysiology. Contiguous neurons showed neurolemma contacts in intact and damaged tissues according to their location in the ODS zones, at 12 h and 48 h post correction along with other demyelinating alterations. Neurons and ephaptic contact measurements indicated the highest alterations, including nerve cell necrosis in the ODS epicenter and damages decreased toward the outskirts of the demyelinated zone. Conclusion Ephapses contained C × 36between intact or ODS injured neurons in the thalamus appeared to be resilient beyond the core degraded tissue injuries. These could maintain intercellular ionic and metabolite exchanges between these lesser injured regions and, thus, would partake to some brain plasticity repairs.

Sodium alginate/polycaprolactone co-axial wet-spun microfibers modified with N-carboxymethyl chitosan and the peptide AAPV for Staphylococcus aureus and human neutrophil elastase inhibition in potential chronic wound scenarios

In chronic wound (CW) scenarios, Staphylococcus aureus-induced infections are very prevalent. This leads to abnormal inflammatory processes, in which proteolytic enzymes, such as human neutrophil elastase (HNE), become highly expressed. Alanine-Alanine-Proline-Valine (AAPV) is an antimicrobial tetrapeptide capable of suppressing the HNE activity, restoring its expression to standard rates. Here, we proposed the incorporation of the peptide AAPV within an innovative co-axial drug delivery system, in which the peptide liberation was controlled by N-carboxymethyl chitosan (NCMC) solubilization, a pH-sensitive antimicrobial polymer effective against Staphylococcus aureus. The microfibers' core was composed of polycaprolactone (PCL), a mechanically resilient polymer, and AAPV, while the shell was made of the highly hydrated and absorbent sodium alginate (SA) and NCMC, responsive to neutral-basic pH (characteristic of CW). NCMC was loaded at twice its minimum bactericidal concentration (6.144 mg/mL) against S. aureus, while AAPV was loaded at its maximum inhibitory concentration against HNE (50 μg/mL), and the production of fibers with a core-shell structure, in which all components could be detected (directly or indirectly), was confirmed. Core-shell fibers were characterized as flexible and mechanically resilient, and structurally stable after 28-days of immersion in physiological-like environments. Time-kill kinetics evaluations revealed the effective action of NCMC against S. aureus, while elastase inhibitory activity examinations proved the ability of AAPV to reduce HNE levels. Cell biology testing confirmed the safety of the engineered fiber system for human tissue contact, with fibroblast-like cells and human keratinocytes maintaining their morphology while in contact with the produced fibers. Data confirmed the engineered drug delivery platform as potentially effective for applications in CW care.

Determinants of left atrial local impedance: relationships with contact force, atrial fibrosis and rhythm

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific Background The relationships between baseline tissue local impedance (LI), contact force (CF), atrial fibrosis and atrial rhythm are uninvestigated in a clinical setting. Objectives To compare the relationship of LI and CF between atrial fibrillation (AF) and sinus rhythm (SR). Establish the effects of atrial fibrosis as assessed by bipolar voltage and LI. Methods Patients undergoing persistent AF ablation were recruited. The ablation catheter was placed against the left atrial wall and CF levels varied from 1-40g. LI was recorded concurrent to changes in CF at these locations, with data collected at the same locations in AF and SR following DC cardioversion. LI values were referenced to patient blood pool, (LIr). Results 20 patients were recruited. 109 locations were sampled obtaining 1903 datapoints (SR: 966, AF: 937). CF correlated strongly with LI (repeated measures correlation = 0.64). The relationship between CF and LIr was logarithmic. Rhythm and CF had a significant main (both p &amp;lt; 0.0005) and interaction effect (p = 0.022) on tissue LI: AF demonstrated higher LIr values than SR for similar CF (Figure 1). Furthermore, AF modelled a more predictable relationship between CF and LI than SR (R2 = 0.21 vs 0.13). Bipolar voltage had no effect on the relationship of CF to LIr in either rhythm when using conventional cut-offs to determine scar (0.05mV and 0.5mV). Cut-offs for assessing scar using LIr used values of 0.5Ω and 10.5Ω based on concurrent work. Through assessing fibrosis using these values, LIr showed an interaction effect with CF for LIr in SR and AF, (SR: p &amp;lt;0.0005, AF: p = 0.01), with more fibrosis demonstrating shallower CF-LIr curves than healthier tissue, (Figure 2). Conclusions CF and rhythm significantly affect the measured LIr of LA myocardium. Optimal catheter-tissue coupling may be better achieved with higher levels of CF and in AF rather than SR. Atrial fibrosis as assessed by bipolar voltage did not affect the CF-LI relationship, but was when assessed by LIr.

Electroanatomical voltage mapping with a force-sensing technology catheter for diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Invasive three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Contact force sensing catheters (CFSC) represent the gold standard to verify adequate tissue contact during EAM. However, normal reference values for right ventricular (RV) EAM as well as substrate characterization in patients with ARVC using CFSC have not been systematically investigated, which was the aim of this prospective study. Methods EAM of the RV during sinus rhythm was performed with the Thermocool SmartTouch catheter via a long sheath in the CARTO3 system in 11 patients with definite ARVC and 5 age- and gender-matched control subjects without structural heart disease. Only points with a mean contact force of ≥4G were analyzed. To account for differences due to RV anatomy, it was divided into 5 segments: RV outflow tract (RVOT), septum, free wall, sub-tricuspid region and apex. Endocardial bipolar and unipolar voltages, signal characteristics and signal duration were analyzed. The impact of catheter orientation on endocardial signals was also assessed. Results A median of 227 (IQR:120-364) endocardial RV points were analyzed. Median bipolar voltage in healthy controls was 3.8mV (range 3.6-4.6, IQR 2.7-5.4), with lower values in the RVOT and higher values in the RV septum. ARVC patients showed significantly lower bipolar voltages as compared to controls (repeated measures ANOVA; between-subjects effect: F=6.443,p=0.024), showing significantly lower bipolar voltage values in the sub-tricuspid region (1.8±1.9vs.4.6±2.9mV,p=0.031) and in the RV apex (2.9±1.4vs.7.2±5.2mV,p=0.024), Figure 1c. Bipolar voltage values in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC62-78%,p&amp;lt;0.001 for all), with the highest performance for the sub-tricuspid region (AUC78%,95%CI0.75-0.81,p&amp;lt;0.001). A bipolar voltage value &amp;lt;1.5mV in the sub-tricuspid region yielded a sensitivity of 98% and a specificity of 53% for ARVC diagnosis (Figure 1a-b, showing the typical RV free wall "C-scar" in ARVC and normal values for the RV apex in less advanced disease stages). A positive correlation between bipolar voltage values and an orthogonal catheter orientation (46°-90°: r=0.106,p&amp;lt;0.001) as well as a higher catheter contact force (r=0.054,p=0.008), and a negative correlation between bipolar voltage values and QRS duration (r=-0.370,p&amp;lt;0.001) was found. Conclusions For the first time a systematic analysis of RV endocardial low voltage areas in ARVC patients as compared to controls by using CFSC was performed, and confirmed that RV voltages are generally lower in ARVC as compared to controls, with the sub-tricuspid area showing the lowest values and highest discriminatory power vs controls.

P104 LASER BALLOON APPROACH FOR PULMONARY VEIN ISOLATION IN MARFAN SYNDROME

Abstract Background Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue and it’s associated with an increased incidence of atrial fibrillation (AF), due to scar–mediated processes and sites of atrial ectopy. Limited data exist regarding ablation techniques in these patients. The frailty of atrial walls correlated to connective disease makes the ablation challenging with an increased risk of complications. Laser–balloon (LB) approach for pulmonary vein isolation (PVI) could be a promising strategy due to the possibility to ablate a large volume of tissue with a single application of energy, short procedure times, and real–time monitoring of balloon–tissue contact. We present a case in which LB technology was applied for PVI in an MFS patient Clinical case A 44–year–old woman with MFS and paroxysmal AF underwent PVI. The echocardiographic examination showed mild aortic and mitral valve regurgitation, the first due to a slight dilation of the aortic root, the latter associated with mitral valve prolapse. Atrial volume was normal. No other comorbidities were present. The procedure was executed in general anesthesia. A decapolar catheter was inserted in the coronary sinus and used later to stimulate the phrenic nerve during the ablation of the right pulmonary veins (Fig.1C). Left atria (LA) was reached after an ultrasound–guided transeptal puncture. High–density mapping of the LA was performed to assess the number and geometry of PVs (Fig.1A). A LB catheter was used to perform laser ablation at the level of PV antrum, delivering 13 W in automatic rapid mode in regions with optimal contact and 5.5 W in areas with more represented blood–tissue interface. LA mapping after ablation assessed the effective isolation of pulmonary veins (Fig.1B). No complications occurred during the procedure. Conclusion a laser–balloon approach for PVI in MFS patients seems feasible and safe. To our knowledge, this is the first application of this technology on MFS patients. Larger data are needed to confirm our findings.

PO-02-095 UTILITY OF LOCAL IMPEDANCE MONITORING TO GUIDE HIGH-POWER SHORT-DURATION RADIOFREQUENCY ABLATION FOR ATRIAL FIBRILLATION

Local impedance (LI) measurement can predict tissue heating during RF ablation. To evaluate the utility of prespecified target LI to prospectively guide high power, short-duration (HPSD) RF ablation for PV isolation. This is a single-center prospective study of 44 consecutive patients who underwent initial PV isolation for AF. Circumferential ablation around the antrum of each PV was performed using using a 4 mm tip open irrigation RF ablation catheter with an LI sensor. RF energy was applied at each site at power output of 50 W. Adequacy of each RF application was solely guided by LI measured from the ablation catheter. PV electrograms were not monitored during RF ablation. Annotation of RF ablation applications was based on predefined parameters: the: (1) catheter stability <3 mm; (2) LI drops by >5 Ω (regardless of baseline LI) within the first 5 seconds; and (3) RF application duration of >5 seconds. Each tagged RF application was continued for a total duration of 6-10 seconds for the LA posterior wall and 10-15 seconds for other LA regions. If the LI failed to drop quickly (>5-Ω decrease within the first 5 seconds energy delivery), RF application was interrupted and ablation catheter adjusted to achieve better tissue contact, and RF was reapplied. RF application was stopped if esophageal temperature rose to >40°C or LI dropped by >30 Ω. Ultrahigh-density mapping was performed after first pass encircling of all PVs with inter-lesion distance of 4 mm. First-pass PV isolation was achieved in 163 of 175 PVs (93.1%) in 34/44 patients (77.3%). In 5 PVs (in 5 patients), high-density mapping identified 11 LA-PV conduction gaps at sites where RF applications did not meet annotation criteria (due to catheter instability, esophageal heating, or lack of sufficient LI drop). In 7 other PVs (in 7 Patients), 10 conduction gaps were identified at sites where RF applications did satisfy our ablation protocol. Compared to sites with tagged ablation points with conduction gaps, sites without gaps (suggestive of acutely effective ablation lesions) exhibited significantly larger absolute LI drop (16.4 ± 6.7 Ω vs. 12.2 ± 4.6 Ω, p=0.01) and % change in LI (14.8% ± 5.1% vs. 10.9% ± 4%, p=0.013) during RF energy delivery. The anatomical distribution of conduction gaps is shown in Figure. No steam pops or major complications occurred during or after the procedures. Our prespecified LI target drop magnitude may be used prospectively to guide safe and successful HPSD ablation for AF.

AB-452675-2 PULMONARY VEIN ISOLATION USING A NOVEL MAP-AND-ABLATE SPHERICAL ARRAY PULSED FIELD ABLATION CATHETER: THE PULSE-EU PAROXYSMAL AF COHORT

Despite the promise of pulsed field ablation (PFA), there is much about the biophysics of this novel energy technology that remains to be understood. Preclinical studies have shown that close electrode-tissue proximity increases the likelihood of achieving transmural PFA lesions by maximizing the electric field penetration into the target tissue. The current single-shot PFA catheters are capable of performing pulmonary vein isolation (PVI), but cannot reliably confirm tissue contact. To report the clinical outcomes using a novel Map-and-Ablate spherical array multielectrode catheter that is able to verify tissue contact and deliver single-shot PFA. In the first-in-human PULSE-EU study, paroxysmal AF pts underwent PVI using the spherical array PFA catheter (Globe; Kardium Inc., Canada) using a 16Fr deflectable sheath under general anesthesia and ICE-guidance. Using a custom mapping system integrated with the PFA catheter (GPS; Kardium Inc.) the array catheter rendered contact and voltage anatomic maps. The spherical array was positioned at each PV ostia and PF applications (1.7 kV/lesion, ungated, micro-second scale pulses) were delivered after verifying tissue contact (Figure). Follow-up included post-procedure EGD and plans for protocol-mandated invasive remapping at 2-3 mo after the index procedure. A total of 24 pts (age 59.9±10.8 years; gender women-37.5%; LA 42.5±3.7 mm; LVEF 62.6±8.0%%) underwent PVI with a total procedure duration of 71.5±22.9 min. All PVs (96 of 96 PVs) were acutely isolated, typically with a single application. There were no acute reconnections. The total pulse delivery time and LA catheter dwell time were 42.2±7.6 sec and 36.8±13.7 min, respectively. There were no serious procedure or device related adverse events including no stroke/TIA, pericardial effusion, phrenic nerve injury, or esophageal complications. One patient had pericarditis which was treated medically. Post-procedure EGD revealed no thermal injury in 21 of 21 pts. PV remapping has thus far been performed in 6 pts, and revealed durable PVI in all 24 of 24 (100%) PVs. [Remapping data on the remaining cohort will be available by May 2023.] In this first-in-human PULSE-EU clinical study, the spherical array PFA catheter was able to render atrial anatomy, isolate PVs (with initial data indicating 100% durability), and perform pre-/post- electrical mapping.

PO-05-232 SAFETY AND EFFICACY OF ATRIOVENTRICULAR NODAL REENTRY TACHYCARDIA ABLATION USING AN IRRIGATED CONTACT FORCE CATHETER

Atrioventricular Nodal Reentry Tachycardia (AVNRT) ablation is a common procedure in contemporary electrophysiology practice. Traditionally ablation for AVNRT has been performed with non-irrigated catheters, guided by fluoroscopy and intracardiac electrograms. Increasingly electroanatomic mapping systems are utilized to allow for low or zero fluoroscopy procedures. Contact force catheters can provide information on tissue contact and stability that can be helpful in patients with challenging anatomy. Available contact force catheters are irrigated and concern has existed for using irrigated tip ablation catheters for AVNRT ablation due to the potential to create lesions that are too deep and could increase the risk for AV block. To describe the safety and efficacy for the use of irrigated contact force catheters for ablation of AVNRT Review of procedural data from patients undergoing radiofrequency ablation for AVNRT using electroanatomical mapping combined with irrigated contact force catheter. Fifty patients from 4 regions across Australia were included. Procedures were performed by 9 experienced electrophysiologists. No periprocedural complications occurred. Procedural success was achieved in 96%. Median lesion contact force (25-75 centile) was 4.0(2-6)g. Peak power was set at 50W, median baseline irrigation was at 2ml/min and 6ml/min during ablation. Median number of lesions was 9(4.5-17.5); with total ablation time of 203(95-366) seconds. 60% of the cases were performed without fluoroscopy. Ablation of AVNRT using an irrigated contact force catheter on low irrigation setting is safe and effective. Contact force catheters using low irrigation settings may safely improve success rates in AVNRT with challenging anatomy or ablation of other substrate in close proximity to vital structures.

PO-04-077 EPICARDIAL ABLATION OF A PREVIOUSLY FAILED RIGHT LATERAL ACCESSORY PATHWAY

Catheter ablation is a potentially curative treatment for accessory pathways. However, ablation of right lateral accessory pathways is challenging and has a lower procedural success rate and high recurrence rate due to catheter instability and difficulty in catheter manipulation, inadequate tissue contact and structural heart disease like Ebstein's anomaly. We describe a challenging case of WPW syndrome with right lateral accessory pathway, where the pathway was located epicardially. N/A N/A A 23-year-old female with history of recurrent palpitations was evaluated and diagnosed as a case of WPW syndrome with right free wall pathway with structurally normal heart and normal biventricular function and failed ablation twice in 2018 and 2020. In view of recurrent symptoms, patient was started on anti-arrhythmic therapy. As the patient was refractory to flecainide, sotalol and amiodarone , she was referred to our center for a repeat ablation. Baseline ECG showed manifest pre-excitation. A standard electrophysiology study was performed under general anaesthesia with sequential endocardial and epicardial mapping approach. Retrograde ERP (effective refractory period) of the pathway was 240 ms whereas antegrade ERP was 340 ms (on amiodarone and general anaesthesia). Orthodromic atrio-ventricular reciprocating tachycardia was easily induced by programmed stimulation with a tachycardia cycle length of 470 ms with earliest atrial electrogram noted in the lateral right atrium. However, despite extensive mapping of the tricuspid annulus, ablation at the earliest endocardial site failed to terminate the tachycardia. Hence, epicardial access was obtained using Sosa’s tenchique and mapping along the tricuspid annulus was performed. At lateral tricuspid annulus epicardially, fused atrial and ventricular signals were obtained with local ventricular signal preceding the surface delta wave by 35 ms. Right coronary angiography revealed safe distance between the right coronary artery and the site of ablation. Epicardial ablation at this site led to loss of accessory pathway conduction within 5 seconds. Post ablation, no tachycardia was inducible despite aggressive pacing protocols and bidirectional AV block was demonstrated using intravenous adenosine. At 1-year follow-up, patient is asymptomatic with no evidence of accessory pathway conduction. Epicardial mapping and ablation should be considered in previously failed cases of endocardial ablation of right lateral accessory pathways.

PO-02-094 ALL PULMONARY VEIN ISOLATION STRATEGIES ARE EQUALLY EFFECTIVE IN REDUCING THE RECURRENCE OF ATRIAL ARRHYTHMIAS

Ostial and antral pulmonary vein isolation techniques have different properties. In addition, there are differences between radiofrequency and cryoballoon ablation based on tissue contact characteristics. Finally, posterior wall isolation (PWI) has been proposed as an adjuvant to PVI because of embryological origin similarities. We examine the results of ostial and antral RF ablation, cryoballoon PVI and PWI adjunction in the DECAAF-II trial with regard to the recurrence of atrial arrhythmias after ablation. Patients with persistent AF from the DECAAF-II trial who underwent PVI only or PVI + PWI were included. All patients underwent LGE-MRI before ablation and 3 months after ablation. The electroanatomic maps at time of procedure displaying the location of ablation lesions were merged with baseline LGE-MRI images, and two reviewers analyzed and classified the resulting reconstructions. PVI were classified as ostial if the lesions were in the immediate proximity of the pulmonary veins’ ostium and as antral if the lesions included a portion of the antrum around the pulmonary veins. Patients with PVI + PWI were extracted as a separate group. Patients were followed up for a total of 18 months using daily single-lead smartphone ECG strips. The primary outcome of this analysis was recurrence of atrial arrhythmias after the 90-day blanking period. A total of 367 patients were considered for analysis. 211 patients underwent ostial PVI, 81 antral PVI, 31 had PVI + PWI, and 44 underwent cryoablation. Baseline characteristics were comparable in terms of age, sex, fibrosis percentage, comorbidity profile (hypertension, diabetes, hyperlipidemia, CAD, history of stroke), and medication history, except for a significant difference in history of heart failure (10.4% vs. 18.5% vs. 29% vs. 27.3%, p = 0.004) and prior AAD use (46.9% vs. 44.4% vs. 64.5% vs. 29.5%, p = 0.026). Recurrence rates were comparable among the four groups: 91 (43%) patients had recurrence in the ostial PVI group, 39 (48%) in the antral PVI group, 12 (39%) in the PWI group, and 22 (50%) in the cryoablation group (log rank P=0.76). In patients with persistent AF, all PVI techniques show equal efficacy in terms of atrial arrhythmia recurrence. Isolation of the posterior wall during ablation in persistent AF has no procedural advantage.

108 A Novel Robotic-Assisted Platform for Spinal Decompression Procedures

INTRODUCTION: Removal of pathologic tissue during degenerative spinal surgery cases near a bone-nerve interface presents a challenge during spinal decompression, especially in minimally invasive procedures. Robotic systems for spinal surgeries can potentially offer greater accuracy than manual operations. However, today’s robotic systems are designed only for placement of fusion hardware and lack the ability to work in-situ and in proximity to neural structures. METHODS: In the proposed approach, the surgeon utilizes a 6-degrees-of-freedom joystick to control an industrial grade robotic arm connected to curved-at-the-tip high-speed, shielded drilling end-effectors to perform various bone removal tasks. Live visual feedback is displayed from top-view and endoscopic camera views. Force readouts, correlated to the force exerted on the end-effector through tissue contact, provide real time visual feedback. Additional safety restrictions are designed into the system to prevent excessive force. System orientation training was conducted on vertebral models. Initially, three spine surgeons used the system to perform ipsilateral decompression and foraminotomy in four surgeries in a live pig model. Next, six surgeons used the system to perform ipsilateral decompression on two human cadavers. All surgeons completed questionnaires assessing procedure efficacy and system usability. RESULTS: Animal studies: Required decompression was achieved in all cases, with no complications and minimum-to-moderate bleeding. Intuitive usability and acceptable kinematic range of motion of the robotic system was confirmed. Cadaver study: Questionnaire results demonstrated high scores of confidence in the technique (4.7/5), overall satisfaction (4.4/5) and achievement of adequate decompression (3.9/5). All neural structures remained intact. CONCLUSIONS: This preliminary data indicates that the proposed robotic system can facilitate safe and precise decompression through removal of sufficient tissue removal at the bone/nerve interface. Further studies with a medical grade robotic arm are planned.

Coupled thermal-hemodynamics computational modeling of cryoballoon ablation for pulmonary vein isolation

Cryoballoon ablation (CBA) is a cryo-energy based minimally invasive treatment procedure for patients suffering from left atrial (LA) fibrillation. Although this technique has proved to be effective, it is prone to reoccurrences and some serious thermal complications. Also, the factors affecting thermal distribution at the pulmonary vein-antrum junction that are critical to the treatment success is poorly understood. Computer modeling of CBA can resolve this issue and help understand the factors affecting this treatment. To do so, however, numerical challenges associated with the simulation of advection-dominant transport process must be resolved. Here, we describe the development of a thermal-hemodynamics computational framework to simulate incomplete occlusion in a patient-specific LA geometry during CBA. The modeling framework uses the finite element method to predict hemodynamics, thermal distribution, and lesion formation during CBA. An incremental pressure correction scheme is used to decouple velocity and pressure in the Navier-Stokes equation, whereas several stabilization techniques are also applied to overcome numerical instabilities. The framework was implemented using an open-source FE library (FEniCS). We show that model predictions of the hemodynamics in a realistic human LA geometry match well with measurements. The effects of cryoballoon position, pulmonary vein blood velocity and mitral regurgitation on lesion formation during CBA was investigated. For a −700C cryoballoon temperature, the model predicts lesion formation for gaps less than 2.5 mm and increasing efficiency of CBA for higher balloon tissue contact areas. The simulations also predict that lesion formation is not sensitive to variation in pulmonary vein blood velocity and mitral regurgitation. The framework can be applied to optimize CBA in patients for future clinical studies.

Comparative study of cyclosporine A liposomes and emulsions for ophthalmic drug delivery: Process optimization through response surface methodology (RSM) and biocompatibility evaluation

Herein, cyclosporine A loaded liposomes (CsA-Lips) were fabricated aimed at improving the biocompatibility of the ophthalmic formulation and getting rid of the direct contact of ocular tissues with irritant excipients. Response surface methodology was exploited in order to investigate the influence of miscellaneous factors on the key characteristics of CsA-Lips. Ratio of EPC:CsA, ratio of EPC:Chol, and stirring speed were selected as the independent variables, while size, drug-loading content (DL), and drug-loading content (DL) loss rate were applied as the response variables. In case of the maximal lack-of-fit p-value and minimum sequential p-value, quadratic model was regarded as the fittest model to analyze the data. The correlation of independent variables with response variables was described by three-dimension surface figures. Optimized formulation for CsA-Lips was obtained with ratio of EPC:CsA set as 15, ratio of EPC:Chol set as 2, and stirring speed set as 800 rpm. The particle size of CsA-Lips was 129.2 nm after optimalization while their TEM images exhibited spherical unilamellar vesicles with clearly shell-core structure. CsA released more rapidly from CsA-Lips in comparison with self-made emulsion and Restasis®. Besides, minimum cytotoxicity of CsA-Lips was perceived via both MTT method and LDH method, indicating the excellent compatibility of the ophthalmic formulation. Simultaneously, CsA-Lips showed enhanced nonspecific internalization in the cytoplasm with a time-dose-dependent manner. In conclusion, CsA-Lips could be adhibited as the hopeful ophthalmic drug delivery system clinically for dry eye syndrome (DES).

Determination of arterial invasion in pancreatic ductal adenocarcinoma: what is the best diagnostic criterion on CT?

To investigate the diagnostic performance and interobserver variability in the determination of arterial invasion in pancreatic ductal adenocarcinoma (PDAC) and determine the best CT imaging criterion. We retrospectively evaluated 128 patients with PDAC (73 men and 55 women) who underwent preoperative contrast-enhanced CT. Five board-certified radiologists (expert) and four fellows (non-expert]) independently assessed the arterial invasion (celiac, superior mesenteric, splenic, and common hepatic arteries) using a 6-point score: 1, no tumor contact; 2, hazy attenuation ≤ 180°; 3, hazy attenuation > 180°; 4, solid soft tissue contact ≤ 180°; 5, solid soft tissue contact > 180°; and 6, contour irregularity. ROC analysis was performed to evaluate the diagnostic performance and determine the best diagnostic criterion for arterial invasion, with pathological or surgical findings as references. Interobserver variability was assessed using Fleiss's ĸ statistics. Among the 128 patients, 35.2% (n = 45/128) received neoadjuvant treatment (NTx). Solid soft tissue contact ≤ 180° was the best diagnostic criterion for arterial invasion as defined by the Youden Index both in patients who did and did not receive NTx (sensitivity, 100% vs. 100%; specificity, 90% vs. 93%; and AUC, 0.96 vs. 0.98, respectively). Interobserver variability among the non-expert was not inferior to that among the expert (ĸ = 0.61 vs 0.61; p = .39 and ĸ = 0.59 vs 0.51; p < .001 in patients treated with and without NTx, respectively). Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasion in PDAC. Considerable interobserver variability was seen among the radiologists. • Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasionin pancreatic ductal adenocarcinoma. • Interobserver agreement among non-expert radiologists was almost comparable to that among expert radiologists.

Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study.

Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men. This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test. Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged. TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.