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Water disinfection is an essential process that provides safe water by inactivating pathogens that cause waterborne diseases. However, disinfectants react with organic matter naturally present in water, leading to the formation of disinfection by-products (DBPs). Multi-analyte methods based on mass spectrometry (MS) are preferred to quantify multiple DBP classes at once however, most require extensive sample pre-treatment and significant resources. In this study, two analytical methods were developed for the quantification of 32 regulated and unregulated DBPs. A purge and trap (PT) coupled with gas chromatography mass spectrometry (GC-MS) method was optimized that automated sample pre-treatment and analyzed volatile and semi-volatile compounds, including trihalomethanes (THMs), iodinated trihalomethanes (I-THMs), haloacetonitriles (HANs), haloketones (HKTs) and halonitromethanes (HNMs). LOQs were between 0.02-0.4 µg/L for most DBPs except for 8 analytes that were in the low µg/L range. A second method with liquid chromatography (LC) tandem mass spectrometry (MS/MS) was developed for the quantification of 10 haloacetic acids (HAAs) with a simple clean-up and direct injection. The LC-MS/MS direct injection method has the lowest detection limits reported (0.2-0.5 µg/L). Both methods have a simple sample pre-treatment, which make it possible for routine analysis. Hyperchlorination and uniform formation conditions (UFC) formation potential tests with chlorine were evaluated with water samples containing high and low TOC. Hyperchlorination formation potential test maximized THMs and HAAs while UFC maximized HANs. Ascorbic acid was found to be an appropriate quencher for both analytical methods. Disinfected drinking water from four water utilities in Alberta, Canada were also evaluated.

Funding Acknowledgements Type of funding sources: None. Background Conducting systematic annotation and ablation of evoked delayed potentials (EDP) in response to short coupled right ventricular extra-stimuli (RV-ES) has improved ablation outcome of post myocardial infarction (MI) ventricular tachycardia (VT). The reported short radiofrequency catheter ablation (RFCA) times suggests the presence of predilection areas for these functional substrates. Purpose To evaluate the electroanatomical characteristics and distribution of EDPs in post-MI patients referred for RFCA of VT. Methods Electroanatomical mapping (EAM) data of 48 post-MI patients (69 ± 9 years, 39 male, LV ejection fraction 36 ± 10%, anterior MI 20 [42%], inferior MI 28 [58%]), who underwent functional substrate mapping and ablation were analyzed. Pre-procedural cardiac CTs of 16 patients (8 anterior, 8 inferior MI) were integrated with EAM data. Infarct extension (defined as bipolar voltage [BV] Results RV-ES was performed during mapping at 2180 LV sites (median 46 per patient, range 8-81) and EDPs were observed at 631 (29%) sites. Patients had a median of 11 (range 1-37) EDP sites. Compared to no-EDP sites, EDP sites had lower BV (median 0.57 mV vs. 0.77 mV, P 3.0 mV, respectively. In the 16 patients with CT image integration, a total of 124/272 segments showed EA scar with a median (IQR, range) of 8 (6-9, 4-12) segments per patient. Any EDP was identified in 71/124 (57%) of segments with EA scar. Of note, 73% of all EDPs in inferior MIs and 64% of all EDPs in anterior MI were located in 4 AHA segments, namely 3,4, 9,10 and 7,8,13,14, respectively, close to the inferior or anterior RV insertion. Such a cluster of EDP sites around the RV insertion was found in 6 (75%) patients with inferior MI and in 7 (88%) patients with anterior MI. Conclusion About 10% of EDPs are identified at sites with BV of ≥1.5mV and

Funding Acknowledgements Type of funding sources: None. Background Patients with repaired tetralogy of Fallot (rTOF) remain at risk for monomorphic ventricular tachycardia (MVT) and sudden cardiac death. Primary prevention ICD implantation studies report annualized rates of appropriate ICD therapy of ≈7% mainly for MVT. Slow conducting anatomical isthmus (SCAI) is the dominant MVT substrate, and SCAI transection by ablation has been associated with favorable long-term outcomes. Electroanatomical mapping (EAM) is the gold standard to identify SCAI. The impact of a systematic approach of EAM and ablation of SCAI on patient selection for ICD implantation is unknown. Objective The study aimed to evaluate the long-term arrhythmic outcome of rTOF patients who underwent EAM and ablation for primary and secondary prevention of MVT. Methods Consecutive patients with rTOF who underwent EAM for VT substrate identification between 2005 and 2020 were included. Indication for EAM were (A) spontaneous VT/cardiac arrest or (B) before re-valving or for risk stratification. In patients with SCAI, catheter or surgical transection was attempted. The risk score for VT/SCD proposed by Khairy et. al was calculated. After successful ablation of SCAI, ICD implantation was offered but subject to shared decision making. Patients were followed for VT and all-cause mortality. Results A total of 125 pts (Group A=28; Group B=97) were included (37±17 years, 62% men, QRS 155±32ms, preserved/mildly reduced LV and RV function 96% and 81%, respectively). A SCAI was present in 59 patients (47%) (A=26, B=33). In 45 patients, 67 MVTs were induced (CL 271±54 ms), of which 63 (94%) were related to SCAI. In 44/61 patients (72%) who underwent ablation, procedural success could be achieved (A 16/27, B 28/34). During a median follow-up of 58 (IQR 27-105) months (36 pts with ICDs), 7 patients died (5 heart failure; 2 non-cardiac cause), and 13 had VT (A=9, B=4). In 12/13 pts with VT, SCAI could not be transected (A=8, B=4), and the remaining patient, who had impaired LV/RV function, recurred with a different VT. In patients without SCAI or successful SCAI transection and preserved/mildly reduced function, no VT occurred (figure). According to the risk score, 22, 27, and 48 of group B patients were classified as high (predicted annualized VT 0%), intermediate (3.8%), and low risk (17.5%). Accordingly, 77/125 (62%) (all 28 pts of group A and 49 patients [intermediate or high risk] of group B) would have been considered candidates for ICD. After implementing the EAM-based approach, 39 patients (18 patients in group A and 21 patients in group B) may remain candidates for ICD implantation, indicating a potential 49% reduction in ICD implantation. Conclusion Patients with successful transection of SCAI had excellent long-term outcome. EAM-based risk stratification and (preventive) ablation targeting SCAI may significantly reduce ICD implantation rates for primary and secondary preventions in rTOF.

Funding Acknowledgements Type of funding sources: None. Introduction Patients with ischemic cardiomyopathy (ICM) and monomorphic, sustained ventricular tachycardia (VT) are considered to be at risk for arrhythmia-related sudden cardiac death (SCD). Prior studies have suggested that patients with well-tolerated VTs and preserved or moderately reduced left ventricular ejection fraction (LVEF) and successful VT ablation may not benefit from cardioverter defibrillator implantation (ICD Current guidelines indicate that in selected patients catheter ablation should be considered instead of ICD, but supporting evidence is limited. Aim This study aims to analyze arrhythmia outcomes of ICM patients referred for VT ablation without prior ICD implantation according to LVEF, hemodynamical stability during VT and ablation outcome. Methods ICM patients without prior ICD implantation undergoing VT ablation in a tertiary center between 2009 and 2022 were included. Patients who presented with a first episode of tolerated VT and w a LVEF≥35% were offered catheter ablation (CA) as first-line therapy. Patients were categorized according to (1) LVEF, (2) clinical presentation (hemodynamically tolerated/non-tolerated VT) and (3) acute ablation outcome. According to the institutional protocol, ICD was offered to all patients after ablation, but was subject to shared decision making, explaining the available evidence supporting ICDs for the different categories. Results Eighty-six ICM patients without ICD underwent ablation for VT. Mean age was 69±9 years and 72 (84%) were men, mean LVEF was 41±9% and 34 patients (28%) were using anti-arrhythmic drugs (AAD). The median VT cycle length (VTCL) at presentation was 323ms [300 – 375] and VT was tolerated in 58 (67%) patients (median tolerated VTCL 325ms [300 – 371]). In 66 (77%) patients, the LVEF was ≥35% of which 51 had well-tolerated VT. Of these 51 patients, 37 (73%) were rendered non-inducible after ablation and in 14 patients non-clinical VTs remained inducible (median remaining VTCL 238ms [203-288]). In 5/37 non-inducible and in 11/14 inducible patients, an ICD was implanted. Of the 35 patients who had LVEF During a median follow-up of 35 [22 – 53] months, 10 patients (12%) had VT-recurrence and one patient with an ICD had SCD. Mortality was 22%. In the 37 patients with LVEF≥35%, tolerated VT and non-inducibility post procedure, no SCD or VT-recurrence was observed. Also, in this group no patient was using AAD for VT at last follow-up. In the 14 remaining patients with LVEF≥35% and tolerated VT who were still inducible after ablation, no SCD occurred but VT recurred in 29% (median VTCL 303ms [200-374]) with AAD-use for VT in 29%. Conclusion This study supports that ICM patients without prior ICD and LVEF≥35% who present with hemodynamically well-tolerated VT and are non-inducible after ablation have an excellent prognosis. Successful CA without ICD implantation seems to be safe in these selected patients.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research lnitiative: An initiative with support of the Dutch Heart Foundation and Hartekind. Background Patients with repaired tetralogy of Fallot (rTOF) have a time-dependent increase in risk of ventricular tachycardia (VT) after the age of 30 years (Y), with slow conducting anatomical isthmus (SCAI) 3, located between the pulmonary annulus and the ventricular septal defect (VSD) patch, as dominant VT substrate (1-4). However, SCAI may be already present before 30Y. Purpose To assess (1) the prevalence of SCAI, (2) the associated factors in SCAI development, and (3) the occurrence of clinical VT, in rTOF patients Methods From a database of 146 patients with rTOF or related lesions who underwent electroanatomical mapping (EAM) and programmed electrical stimulation (PES) between 2007 and 2022 for treatment of ventricular arrhythmias (VA), risk stratification or before pulmonary valve replacement (PVR), those aged Results Of 146 rTOF patients, 55 (38%) were In 16/55 (29%) SCAI 3 could be identified; no other SCAI (1,2,4) was present. Of note, 9/16 (56%) of patients with SCAI 3 had initial RV-PA conduit repair/early PVR, in comparison with only 3/39 (8%) of patients without SCAI. In univariable analysis complex TOF (OR 6.8 [95% CI 1.8-26.4]), ventriculotomy (OR 5.3 [95% CI 1.2-22.3]), any prior PVR (OR 4.8 [95% CI 1.4-16.7]), and initial RV-PA conduit/early PVR (OR 15.4 [95% CI 3.3-71.8]) were significantly associated with SCAI 3. In multivariable analysis initial RV-PA conduit/early PVR remained the only independent predictor of SCAI 3 (OR 13.0 [95% CI 1.2-142.4]). Conclusions A SCAI 3 is present in 29% of rTOF patients

Funding Acknowledgements Type of funding sources: None. Introduction The dominant mechanism of ventricular tachycardia (VT) in patients with non-ischemic cardiomyopathy (NICM) is re-entry related to fibrosis. Fibrosis in NICM is fundamentally different from post-infarct scars. Fibrosis does not equal VT substrate. The amount and characteristics of fibrosis related to VT in NICM are unknown. Aim To describe histological characteristics associated with VT substrate in patients with NICM using integration of electroanatomical mapping (EAM) data and whole human heart histology. Methods EAM data of 10 patients with NICM who died or underwent heart transplantation after catheter ablation (CA) for VT were reviewed. VT related sites were categorized as class I (entrainment response/VT termination during CA), or class II (other ablation target sites). Explanted hearts were sliced and stained. Ablation lesions were identified and excluded from histological analysis. EAM and whole heart histology were integrated and class I/II sites projected onto the slices using reversed registration and assigned to a segment (32 segment model). VT exit sites (based on 12 lead VT-ECG) were indicated on a 16-segment model (fig 1). The amount and homogeneity of fibrosis was determined. A new method to measure pattern and inhomogeneity of fibrosis was developed with scores between 0 (inhomogeneous confluent) and 0.5 (homogeneous diffuse). Results In 10 patients (9 with a class IV/V mutation) a median of 11 (range 3-18) VTs were induced. A total of 37 class I sites could be identified and 182/320 segments contained class II sites. After exclusion of ablation lesions, the LV had a median of 24.7% fibrosis (range 11.3-39.3%). Higher percentages of fibrosis were found in the basal anteroseptal ring which also contained the majority of class 1 (21/37) sites. In contrast, VT exit areas were clustered in the apico-septal and basal anterolateral segments. Class 1 VT related site segments contained more fibrosis (median 35.3% IQR [29.1-48.7] vs 22.1% [13.2-32.8], p31% fibrosis for the identification of class I VT related sites (AUC: 0.75, sensitivity 72% specificity 72%). Of note, in segments with Conclusion In human hearts with NICM and VT, fibrosis clusters in the basal anteroseptal ring. The majority of VT related sites are located in segments with >31% fibrosis and a higher degree of inhomogeneity but they are also found in segments with less fibrosis, but with inhomogeneous confluent fibrosis. This data suggest that location, amount and inhomogeneous confluence of fibrosis contribute to arrhythmogeneity.

Tumor-specific CD8+ T cells play a pivotal role in anti-tumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stem-like CD8+ T cells give rise to their cytotoxic progeny – Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated. We herein show that terminally differentiated CD8+ T cells can be generated within tumor-draining lymph nodes (TDLNs) and that CD69 expression on tumor-specific CD8+ T cells controls its differentiation process through regulating the expression of the transcription factor TOX. In TDLNs, CD69 deficiency diminished TOX expression in tumor-specific CD8+ T cells, and consequently promoted generation of functional terminally differentiated CD8+ T cells. Anti-CD69 administration promoted the generation of terminally differentiated CD8+ T cells, and the combined use of anti-CD69 and anti-PD-1 showed an efficient anti-tumor effect. Thus, CD69 is an attractive target for cancer immunotherapy that synergizes with immune checkpoint blockade.

Wastewater effluents are complex mixtures that may potentially contain thousands of compounds that are not well removed from conventional wastewater treatment. There are more than 350,000 chemicals registered for production or use that can potentially end up in the environment. Quantification of emerging contaminants by target analysis has been extensively applied however, these methods are often limited by the availability of analytical standards and resources. The total organic halogen (TOX) method is a comprehensive evaluation of the total halogen content in water including emerging halogenated contaminants and disinfection by-products. In this study, an analytical method was developed to simultaneously quantify TOX as total organic fluorine (TOF), total organic chlorine (TOCl), total organic bromine (TOBr), and total organic iodine (TOI). Halophenol recovery experiments were performed in secondary wastewater effluents for TOF, TOCl, TOBr, and TOI with recoveries between 61-105%. Also, nine halogenated contaminants were spiked into ultrapure water with recoveries between 19-107%. The TOX method was used to evaluate four secondary wastewater effluents prior to disinfection across 2 cities in Alberta, Canada. It was observed that TOF, TOCl, and TOBr ranged from 4.9 - 10.5 µg/L, 67.5 - 80.0 µg/L, and 5.0 – 9.0 µg/L, respectively whereas TOI was only detected in two samples at 1.8 and 6.1 µg/L. A sample was analyzed for 196 emerging contaminants to characterize and identify TOX in wastewater for the first time. Target analysis with liquid chromatography tandem mass spectrometry only identified 1.5% of TOX which underlines the severe limitations of target analysis in wastewater samples. These results highlight the applicability of the TOX method in wastewater analysis.

Background Sports injuries are strongly associated with the impact loading at landing. The abilities to produce force and adjust timing are simultaneously required to absorb impact loading. Aims Hence, we aimed to examine the hypothesis that the ability to produce an explosive force at the right timing is related to the ability to absorb the impact loading at landing. Methods Twenty-nine healthy young men volunteered to participate in the study. We proposed a new test to measure the rate of force development (RFD) in accordance with the countdown signal. To evaluate the ability to produce explosive force at the right time, we measured the rate of change between the RFD at the standard start signal and the RFD at the countdown signal. Furthermore, to evaluate the ability to land from a jump, we measured the loading rate at single-leg drop landing (20 cm). Results We divided the participants into two groups based on the timing effect: the positive group (participants with increased RFD at the countdown signal, n = 11) and the negative group (participants with decreased RFD at the countdown signal, n = 18). The loading rate was significantly greater (P Conclusions Participants with increased RFD at the countdown signal had a lower loading rate at landing. Our results suggest that the ability to produce a timely explosive force may be a determinant of safe landing ability.

IntroductionKawasaki disease (KD) is an acute systemic vasculitis that predominantly afflicts children. KD development is known to be associated with an aberrant immune response and abnormal platelet activation, however its etiology is still largely unknown. Myosin light chain 9 (Myl9) is known to regulate cellular contractility of both non-muscle and smooth muscle cells, and can be released from platelets, whereas any relations of Myl9 expression to KD vasculitis have not been examined.MethodsPlasma Myl9 concentrations in KD patients and children with febrile illness were measured and associated with KD clinical course and prognosis. Myl9 release from platelets in KD patients was also evaluated in vitro. Myl9 expression was determined in coronary arteries from Lactobacillus casei cell wall extract (LCWE)-injected mice that develop experimental KD vasculitis, as well as in cardiac tissues obtained at autopsy from KD patients.Results and discussionPlasma Myl9 levels were significantly higher in KD patients during the acute phase compared with healthy controls or patients with other febrile illnesses, declined following IVIG therapy in IVIG-responders but not in non-responders. In vitro, platelets from KD patients released Myl9 independently of thrombin stimulation. In the LCWE-injected mice, Myl9 was detected in cardiac tissue at an early stage before inflammatory cell infiltration was observed. In tissues obtained at autopsy from KD patients, the highest Myl9 expression was observed in thrombi during the acute phase and in the intima and adventitia of coronary arteries during the chronic phase. Thus, our studies show that Myl9 expression is significantly increased during KD vasculitis and that Myl9 levels may be a useful biomarker to estimate inflammation and IVIG responsiveness to KD.

Background Intestinal ultrasound (IUS) is non-invasive and can assess all segments of the colon even in severe ulcerative colitis (UC). While IUS can estimate the endoscopic findings of UC, in terms of the Treat to Target strategy, it remains a crucial clinical question whether the changes in IUS findings with therapeutic interventions can predict the treatment efficacy and the patient prognosis. Here, we investigated if comparing IUS findings at baseline and 3 months after starting a molecular-targeted medication (MTM) can predict the steroid-free clinical remission (SFCR) of UC at 6 months. Methods Inclusion criteria were (1) patients with UC who started an MTM as the induction therapy by March 2022 in Kyorin University Hospital, (2) IUS was performed at baseline and 3 months after starting the medication, and (3) patients could be tracked until 6 months after starting the medication. SFCR was defined as Lichtiger index Results In total 18 cases (ustekinumab: 7, infliximab: 5, vedolizumab: 4, adalimumab: 1, and tofacitinib: 1) were analyzed. IUS was performed at 0 and 88.5 days (median) after starting the molecular-target medications. Fourteen subjects achieved SFCR at 6 months (SFCR+ group). ΔBWT was significantly better in the SFCR+ group (-1.41±2.90) compared to the SFCR- group (1.20±1.31) (p=0.023). The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of ΔBWT for SFCR at 6 months was 0.875. ΔBWT% showed a similar predicting capacity. Apparent sonographic improvements, (1) BWS became intact, (2) i-fat disappeared, and (3) haustration became normal, were observed only in the SFCR+ group. MUC and UII decreased more in the SFCR+ group compared to the SFCR- group, but not statistically significant in the present analysis. Conclusion Assessing BWT over time at baseline and 3 months can be a promising index to predict the efficacy of the molecular-targeted medications at 6 months.

CD4+ T cells not only direct immune responses against infectious micro-organisms but are also involved in the pathogenesis of inflammatory diseases. In the last two to three decades, various researchers have identified and characterized several functional CD4+ T-cell subsets, including T-helper 1 (Th1), Th2, Th9 and Th17 cells and regulatory T (Treg) cells. In this mini-review, we introduce the concept of pathogenic Th cells that induce inflammatory diseases with a model of disease induction by a population of pathogenic Th cells: the ‘pathogenic Th population disease-induction model’. We will focus on Th2 cells that induce allergic airway inflammation—pathogenic Th2 cells (Tpath2 cells)—and discuss the nature of Tpath2 cells that shape the pathology of chronic inflammatory diseases. Various Tpath2-cell subsets have been identified and their unique features are summarized in mouse and human systems. Second, we will discuss how Th cells migrate and are maintained in chronic inflammatory lesions. We propose a model known as the ‘CD69–Myl9 system’. CD69 is a cell surface molecule expressed on activated T cells and interaction with its ligand myosin light chain 9 (Myl9) is required for the induction of inflammatory diseases. Myl9 molecules in the small vessels of inflamed lungs may play a crucial role in the migration of activated T cells into inflammatory lesions. Emerging evidence may provide new insight into the pathogenesis of chronic inflammatory diseases and contribute to the development of new therapeutic strategies for intractable inflammatory disorders.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide–bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu’s parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection–triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1–expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)–containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

This article presents a method to experimentally estimate the direct and cross-coupled dynamic coefficients of tilting-pad journal bearings of vertical hydro-generators and other similar rotating machinery for damage detection purposes. Based on a simplified second-order model of a journal bearing in the state-space, the method employs only the usually monitored vibrations, the shaft radial relative, and the bearing radial absolute vibrations originated by the hydro-generator residual unbalance or by hydraulic excitations in the turbine rotor. This article shows that the method was successfully tested using the shaft and bearing vibration signals synthesized by a mathematical model of a 700 MW hydro-generator, even when these signals are contaminated with random noise. This article also shows the method’s performance when applied to real vibration signals acquired from the modeled hydro-generator. Finally, it discusses the possible measures to improve the method’s efficiency.

Funding Acknowledgements Type of funding sources: None. Background Patients with repaired tetralogy of Fallot (rTOF) remain at risk of sudden cardiac death due to reentrant sustained monomorphic ventricular tachycardia (SMVT). Slow conducting anatomical isthmuses (SCAI), in particular SCAI3 at the outlet septum, bordered by the pulmonary annulus and the ventricular septal defect patch, are the dominant substrate for SMVT. Electroanatomical mapping (EAM) is the invasive gold standard to identify SCAIs, and transection of SCAI by catheter ablation has been correlated with favorable long-term outcome. Non-invasive identification of SCAI for risk stratification and treatment planning is needed but has not been established yet. Three-dimensional (3D) late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) facilitates accurate visualization of morphologically complex hearts with high-spatial resolution. Objective The study thought to determine whether 3D LGE-CMR can identify SCAIs. Methods Consecutive patients with rTOF who underwent right ventricular (RV) EAM and 3D LGE-CMR were included. LGE-CMR-derived 3D RV reconstructions were created (ADAS-3D) and merged with 3D RV EAM data. Mapping points were superimposed on the CMR-derived 3D reconstruction allowing for direct comparison of EAM data and local signal intensity (SI). The optimal SI cut-off to identify low bipolar voltage (LBV, BV Results Forty-eight rTOF patients (34±16 years, 58% male) were included. At EAM, 21 patients had normal AI, and 20 and 7 had a SCAI ( A total of 9240 points were analyzed, showing a significant correlation between BV and SI (R=0.4, P Conclusion 3D LGE-CMR can identify SCAI with 100% sensitivity and may identify diseased AI3 even before critical conduction delay occurs. This technique may allow for non-invasive risk stratification of VT and can refine patient selection for invasive EAM.

Background In patients with VT after myocardial infarction (MI), substrate-based ablation is superior to approaches that target clinical and tolerated VTs only. Different substrate modification strategies have been reported. However, proposed ablation targets are prone to operator interpretation (e.g. abnormal electrograms). Accordingly, ablation results can also be operator dependent. Evoked delayed potentials (EDP) are a well-defined target. Elimination of EDP has been effective to prevent VT recurrence in a retrospective, single center cohort. Aim (1)To evaluate the outcome of EDP ablation in a prospective cohort of patients included on an intention-to-treat principle and (2)to assess the outcome of EDP ablation following one uniform protocol when performed in centers without prior experience with this strategy. Methods Consecutive patients referred for post-MI VT ablation were prospectively enrolled in one center with extensive experience in EDP ablation and 5 centers with no prior experience. Substrate mapping focused on EDP identification followed a uniform protocol across all centers. In brief, all electrograms located within the infarct area were analyzed during sinus rhythm, RV pacing at a fixed rate and during the application of one short-coupled RV extra-stimulus (S2). Sites showing low-voltage, nearfield electrograms with >10ms delay or block in response to S2 were categorized as EDP and targeted for ablation. After ablation, re-mapping to confirm EDP elimination and a complete stimulation protocol (up to 4 extra's from RV and LV) were performed. Patients were followed for VT recurrence and mortality. Results 130 patients (69±10 years, 87% men, 42% anterior MI, LVEF 34% (IQR 24–43), 71% NYHA II–III, 42% on amiodarone, 52% ≥1 ICD shock, 22% with electrical storm or incessant VT) were included. The extra-stimulation protocol was systematically conducted in 127 (98%) patients and in 121 (93%), EDPs were identified. EDPs were successfully eliminated in 117/121 (97%) patients. After 23 (IQR 14–35) min of RF, 102 (78%) patients were rendered non-inducible. Median procedural duration was 212 (IQR 179–262) min. During follow-up of 14 (IQR 8–18) months, 36 (28%) patients had VT recurrence and 13 (10%) died or received a LVAD. VT-free survival was 79% (95% CI: 72–86) and 72% (95% CI: 63–80) at 6 and 12 months follow-up. Of note, VT-free survival at 12 month was not significantly different between patients undergoing the procedure in centers with and without prior experience in EDP ablation (76% (95% CI: 61–90) vs. 70% (95% CI: 59–81); P=0.269). Conclusion In a large prospective cohort of patients with post-MI VT, substrate ablation based on EDP elimination resulted in excellent long-term outcome. Of importance, procedural outcomes were similar in centers with or without experience in EDP ablation, indicating that this approach can be easily reproduced by operators previously not familiar with the technique. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Patients with ischemic cardiomyopathy (ICM) referred for catheter ablation (CA) of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodeling of the left ventricle (LV). Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV mapping derived parameter that corrects for oversampling of the infarct area may reflect the total amount of remaining LV viable myocardium. Objective To evaluate if the newly proposed parameter, `area weighted unipolar voltage’ (awUV), can predict HF related death/LVAD/Heart transplant (HFD) in ICM. Methods Voltage maps from consecutive patients with ICM referred for CA of VT, were transferred to Paraview after valve area removal. AwUV was calculated by mathematically interpolating all mapping points weighted for relative distances divided by the LV endocardial surface. Unipolar low voltage areas (ULVA, UV Results Eighty-nine patients in the study group (age 68±8; LVEF 33% [IQR 24-40%]; ULVA 64% [IQR 46-86%]; awUV 7.01 [IQR 5.01-8.52]) and 69 patients in the validation group (age 68±9; LVEF 39% [IQR 29-44%]; ULVA 59% [IQR 43-77%]; awUV 7.60 [IQR 6.16-8.69]) were included. Follow-up was 32±17 months in the study group, 28±17 months in the validation group. HFD was 20% in the study group, 10% in the validation cohort. Patients with HFD had lower LVEF and awUV, and larger ULVA than patients without HFD (LVEF 23±10% vs. 35±11%; awUV: 5.12±1.92 vs. 7.75±2.64; LVA 86±21% vs. 60±23%, all P Conclusion The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at risk for HFD.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): the research grant D2 from Kansai Medical University Objectives Angiopoietin-like protein 2 (ANGPTL2) is a protein, whose structure is similar to that of angiopoietin, but binds to a different receptor. Overexpression of ANGPTL2 promotes chronic inflammation and relates to the development of aging-related diseases. ANGPTL2 has been reported to be mainly secreted by adipose tissue. Although ANGPTL2 has been implicated in the pathogenesis of heart failure, there are no studies about serum ANGPTL2 levels in patients with heart failure participating in cardiac rehabilitation program. The aim of this study was to investigate the characteristics, related factors and changes of ANGPTL2 in patients with chronic heart failure during phase III of cardiac rehabilitation program. Methods The subjects included 57 patients (70.1 ± 10.2 years old; 46 men) with chronic heart failure whose serum ANGPTL2 levels were measured during the maintenance phase of cardiac rehabilitation program. Furthermore, we classified 25 patients (70.6 ± 7.5 years old; 23 men) from the 6-month course into a reduced group and an unchanged group to characterize change in ANGPTL2. We excluded patients who were admitted or discharged within 3 months of the evaluation of serum ANGPTL2. We evaluated exercise tolerance using the cardiopulmonary exercise test, grip strength, body composition using a body composition analyzer, blood examinations, and echocardiography. Serum ANGPTL2 was measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Results The median value of ANGPTL2 was 4.05 ng/ml. ANGPTL2 was positively correlated with body weight, body mass index, body fat mass, body fat percentage, C-reactive protein (CRP) and total protein (TP) levels, and negatively correlated with skeletal muscle mass percentage and anaerobic threshold (AT). From the result of the logistic regression analysis, AT (OR=0.68, 95% CI:0.47-0.97and TP (OR=20.1, 95% CI:2.52-160.63) were extracted as independent factors related to the level of ANGPTL2. In addition, overall serum ANGPTL2 levels decreased significantly after 6 months. Changes in ANGPTL2 in the reduced group showed a positive correlation between baseline peak VO2, left ventricular ejection fraction and skeletal muscle rate, and a negative correlation with baseline ANGPTL2, CRP, body fat mass. In an unchanged group, HbA1c increased, but no significant change was observed in other factors. Conclusions Exercise tolerance in patients with chronic heart failure during maintenance phase might be related to the inflammation marker ANGPTL2. Serum ANGPTL2 levels with stable chronic heart failure patients decreased significantly 6 months after continued cardiac rehabilitation.

Funding Acknowledgements Type of funding sources: None. [Purpose] Phase angle (PhA) by BIA was studied as muscle function in various diseases. However the effects of nutrition states to phase angle is unclear especially in cardiac patients. This study examined the relationship between PhA, physical function and nutritional index in patients with heart disease. Methods PhA was measured using InBody770 for 33 heart disease patients (age: 71.6 ± 13.4 years, EF: 58.6 + 11.0%) who underwent cardiac rehabilitation during hospitalization. Short Physical Performance Battery (SPPB) was performed for physical function evaluation, and ALB, eGFR, and NT-ProBNP were evaluated for blood tests. calorie intake and GNRI were calculated as nutritional assessments. Results PhA was 4.1 ± 0.9 °. PhA has a positive correlation with SMI (r = 0.62), chair rise time (r = 0.62), dietary calorie intake (r = 0.49), GNRI (r = 0.50), NT-ProBNP (r = -0.631), ECW A negative correlation was found with / TBW (r = -0.91). As a result of multiple regression analysis with PhA as the dependent variable, ECW / TBW (β = -0.73), SMI (β = 0.33), and chair rise time (β = 0.10) were extracted as significant independent factors (β = -0.13). r² = 0.96). [Conclusion] PhA in patients with heart disease was correlated with physical function and nutritional index, and a significant independent factor was physical function. In particular, lower limb muscle strength was extracted independently of extracellular water ratio and muscle mass. These results suggest that PhA may be a comprehensive index of physical function in cardiac patients.

Cancer immunotherapy utilizes our immune system to attack cancer cells and is an extremely promising strategy for cancer treatment. Although immune-checkpoint blockade, such as anti-PD-1 (programmed cell death 1) antibody, has demonstrated significant enhancement of anti-tumor immunity and has induced notable clinical outcomes, its response rates remain low, and adverse effects are always a matter of concern; therefore, new targets for cancer immunotherapy are always desired. In this situation, new concepts are needed to fuel the investigation of new target molecules for cancer immunotherapy. We propose that CD69 is one such target molecule. CD69 is known to be an activation marker of leukocytes and is also considered a crucial regulator of various immune responses through its interacting proteins. CD69 promotes T-cell retention in lymphoid tissues via sphingosine-1-phosphate receptor 1 (S1P1) internalization and also plays roles in the pathogenesis of inflammatory disorders through interacting with its functional ligands Myl9/12 (myosin light chains 9, 12a and 12b). In anti-tumor immunity, CD69 is known to be expressed on T cells in the tumor microenvironment (TME) and tumor-draining lymph nodes (TDLNs). We revealed that CD69 negatively regulates the effector function of intratumoral T cells and importantly controls the ‘exhaustion’ of CD8 T cells. In addition, we and others showed that either CD69 deficiency or the administration of anti-CD69 monoclonal antibody enhances anti-tumor immunity. Thus, CD69 is an attractive target for cancer immunotherapy.