bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and additive manufacturing of bionic hybrid structure inspired by cuttlebone to achieve superior mechanical properties and shape memory function
Authors: Yuan Luhao , Gu Dongdong , Liu Xin , Shi Keyu , Lin Kaijie , Liu He , Zhang Han , Dai Donghua , Sun Jianfeng , Chen Wenxin , Wang Jie
Published: May 2024

Lightweight porous materials with high load-bearing, damage tolerance and energy absorption (EA) as well as intelligence of shape recovery after material deformation are beneficial and critical for many applications, e.g. aerospace, automobiles, electronics, etc. Cuttlebone produced in the cuttlefish has evolved vertical walls with the optimal corrugation gradient, enabling stress homogenization, significant load bearing, and damage tolerance to protect the organism from high external pressures in the deep sea. This work illustrated that the complex hybrid wave shape in cuttlebone walls, becoming more tortuous from bottom to top, creates a lightweight, load-bearing structure with progressive failure. By mimicking the cuttlebone, a novel bionic hybrid structure (BHS) was proposed, and as a comparison, a regular corrugated structure and a straight wall structure were designed. Three types of designed structures have been successfully manufactured by laser powder bed fusion (LPBF) with NiTi powder. The LPBF-processed BHS exhibited a total porosity of 0.042% and a good dimensional accuracy with a peak deviation of 17.4 μm. Microstructural analysis indicated that the LPBF-processed BHS had a strong (001) crystallographic orientation and an average size of 9.85 μm. Mechanical analysis revealed the LPBF-processed BHS could withstand over 25 000 times its weight without significant deformation and had the highest specific EA value (5.32 J·g−1) due to the absence of stress concentration and progressive wall failure during compression. Cyclic compression testing showed that LPBF-processed BHS possessed superior viscoelastic and elasticity energy dissipation capacity. Importantly, the uniform reversible phase transition from martensite to austenite in the walls enables the structure to largely recover its pre-deformation shape when heated (over 99% recovery rate). These design strategies can serve as valuable references for the development of intelligent components that possess high mechanical efficiency and shape memory capabilities.
Calibration and measurement capability evaluation for 1 MN hydraulic force standard machine newly installed at NMIJ
Authors: Hasegawa Akira , Hayashi Toshiyuki
Published: May 2024

Social safety is predicated on accurately evaluated force standards and a system for force traceability. National Metrology Institute of Japan, the body responsible for managing Japan’s national force standards, has implemented a new 1 MN hydraulic force standard machine. In this paper, we assess the calibration and measurement capability of this new force standard machine using five different force measuring instruments. Our findings confirm that its capability is less than 1 × 10−4 relative, demonstrating its adequate performance as one of the national force standards.
Biomimetic artificial islet model with vascularized microcapsule structures for durable glycemic control
Authors: Li Jingbo , Fang Yile , Wu Zhuhao , Shang Luoran , Li Ling
Published: May 2024

Islet transplantation is a promising strategy for diabetes mellitus treatment as it can recapitulate endogenous insulin secretion and provide long-term glycemic control. Islet models constructed in biomaterial scaffolds that reproduce biological characteristics of native islets is a feasible option to circumvent the dilemma of donor shortage and the requirement of chronic immunosuppression. Herein, we developed bioinspired artificial microcapsule-based islet models with microvessels for glycemic control using microfluidic electrospray strategy. Microfluidic electrospray can generate uniform hydrogel microcapsules with core-shell structure for encapsulating islet cells. The cell-laden microcapsules enabled the efficient transportation of nutrient, oxygen, and insulin; as well as the incorporation with microvessels for prompting glucose responsiveness and molecular exchange. We demonstrated by in vivo experiments that the blood glucose, food intake, and body weight of diabetic mouse models were alleviated, and the glucose tolerance was promoted after the engraftment of islet microcapsules. We further demonstrated the improved functionality of transplanted islet model in insulin secretion, immune escape, and microcirculation using standard histological and molecular analysis. These results indicated that the microcapsules with microvessels are promising artificial islet models and are valuable for treating diabetes.
Compositional sparsity of learnable functions
Authors: Poggio Tomaso , Fraser Maia
Published: May 2024

Neural networks have demonstrated impressive success in various domains, raising the question of what fundamental principles underlie the effectiveness of the best AI systems and quite possibly of human intelligence. This perspective argues that compositional sparsity, or the property that a compositional function have “few” constituent functions, each depending on only a small subset of inputs, is a key principle underlying successful learning architectures. Surprisingly, all functions that are efficiently Turing computable have a compositional sparse representation. Furthermore, deep networks that are also sparse can exploit this general property to avoid the “curse of dimensionality”. This framework suggests interesting implications about the role that machine learning may play in mathematics.
Poincaré on the value of reasoning machines
Authors: McLarty Colin
Published: May 2024

Hilbert’s Foundations of Geometry in 1899 made Poincaré think of “reasoning machines” before Hilbert did. Poincaré found the idea “deadly for teaching, and desiccating for researchers” but indispensable for telling when intuitions have been fully expressed. A machine will use stated axioms without the vague intuitions Poincaré considered vital to learning and research. Years of famously intuitive creativity, plus boundless faith in technology, as well as the impact of Hilbert, led Poincaré to see that machines could aid human intuition but not replace it, precisely because machines have no intuition. This relates to recent machine achievements in Lean and HoTT, and to the issues in Akshay Venkatesh’s essay.
Proofs for a price: Tomorrow’s ultra-rigorous mathematical culture
Authors: De Toffoli Silvia
Published: May 2024

Computational tools might tempt us to renounce complete certainty. By forgoing of rigorous proof, we could get (very) probable results for a fraction of the cost. But is it really true that proofs (as we know and love them) can lead us to certainty? Maybe not. Proofs do not wear their correctness on their sleeve, and we are not infallible in checking them. This suggests that we need help to check our results. When our fellow mathematicians will be too tired or too busy to scrutinize our putative proofs, computer proof assistants could help. But feeding a mathematical argument to a computer is hard. Still, we might be willing to undertake the endeavor in view of the extra perks that formalization may bring—chiefly among them, an enhanced mathematical understanding.
Statistics of Extremes and Records in Random Sequences
Authors: Majumdar Satya N , Schehr Grégory
Published: May 2024

Extreme value statistics (EVS) and the statistics of records in a random sequence are truly interdisciplinary topics, spanning statistics and mathematics on one side to the physics of disordered systems on the other. They have important practical applications in a wide variety of fields, such as climate science, finance, spin-glasses, random matrices. One of the basic questions in EVS is how the maximum or minimum of a time series fluctuates from one sample to another. This is well understood when the time series entries are independent and identically distributed (IID), which is the subject of the classical theory of EVS. However, more recently, EVS started to play a very important role in statistical physics. It turns out that in many physical systems the entries of the underlying time series are actually strongly correlated and the classical theory is no longer applicable, which has led to a plethora of activities in the statistical physics and mathematics communities. What is currently missing is a pedagogical book with examples illustrating the basic tools and techniques. The purpose of this book is to provide an introductory monograph on this subject with a style adapted for a graduate student who only has a basic knowledge of probability theory and statistical mechanics. We present the basic ideas and tools using two simple models of time series: an IID sequence, where there is no correlation between the entries, and a random walk sequence, where the entries are strongly correlated. The EVS and related observables can be computed exactly for both models, as we illustrate with several examples and exercises.
Records
Authors: Majumdar Satya N , Schehr Grégory
Published: May 2024

We discuss the statistics of records in the two basic models, along with several applications. The universality of record statistics is also discussed.
The Mexican Constitution of 1917
Authors: Alterio Ana Micaela , Ortega Roberto Niembro
Published: May 2024

The chapter addresses the Mexican Constitution as a canonical constitution for comparative constitutional law. This is because of two main characteristics. On the one hand, it was the first constitution in the world to recognize social rights, and it did so within a hyper-presidential structure. This combination has been a canonical model for Latin American constitutionalism until today. On the other hand, the rigid formula of the Mexican Constitution through a “permanent constituent power” has allowed more than 700 amendments since its origin in 1917. This second feature is considered more as an anticanon for constitutional stability. The chapter critically reviews the development of these characteristics.
The Hollow Canon of Transnational Constitutional Engagement
Authors: Perju Vlad
Published: May 2024

This chapter analyses the rise and fall of transnational constitutional engagement in judicial decisions. Around the turn of the twenty-first century, constitutional courts around the world started using foreign law in new and creative ways. Yet, within two decades, those practices diminished considerably and, in some jurisdictions such as the United States, abruptly came to a halt. This chapter starts by tracing that evolution through canonical cases involving the constitutionality of criminal punishments—death penalty and life imprisonment—in South Africa and the United States. It then turns to theories in support of the legitimacy of the use of foreign law in the constitutional context. While the use of foreign law challenges core normative presuppositions in modern constitutionalism, few if any normative accounts match in theory the boldness of the constitutional practice. Lacking a theory to stabilize, legitimize, and ultimately entrench the practice, the use of foreign law became victim to changes in the political and historical factors that brought it into existence in the first place. The chapter argues that the use of foreign law in constitutional interpretation imploded not only under the political and ideological pressure of its fierce critics, but also under the weak and unimaginative defenses of its supporters.
British Conversation is Changing: Resonance and Engagement in the BNC1994 and the BNC2014
Authors: Tantucci Vittorio , Wang Aiqing
Published: May 2024

This applied study assesses the degree to which speakers re-use and acknowledge parts of one another’s utterances. This form of alignment is called resonance (DuBois 2014; Tantucci and Wang 2021), and is a decisive indicator of creativity and verbal engagement. Consistent absence of resonance indicates interactional detachment, which is distinctive of autistic speech (Tantucci and Wang 2023). We analysed resonance in naturalistic interaction among British speakers in the demographically sampled sections of the British National Corpora of English: the BNC1994 and the BNC2014. We controlled for creativity, age, class, gender, context, dialect, and intra-generational speech for 1,600 turns of informal speech. We discovered that upper-class people from the corporate world and neighbouring sectors mutually resonated much more in 2014 than they used to in 1994. This may be due to the dramatic change in corporate and institutional communication in the 2000s, involving a new turn towards corporate social responsibility, participatory frameworks in higher education, and the enactment of ideologies such as inclusivity, engagement, and equality in higher social grades of British society. This plausibly affected not only the system of values of those communities but also their interactional behaviour, now increasingly geared towards overt acknowledgement of other people’s talk.
WGCCRR: a web-based tool for genome-wide screening of convergent indels and substitutions of amino acids
Authors: Dong Zheng , Wang Chen , Qu Qingming
Published: May 2024

Genome-wide analyses of proteincoding gene sequences are being employed to examine the genetic basis of adaptive evolution in many organismal groups. Previous studies have revealed that convergent/parallel adaptive evolution may be caused by convergent/parallel amino acid changes. Similarly, detailed analysis of lineage-specific amino acid changes has shown correlations with certain lineage-specific traits. However, experimental validation remains the ultimate measure of causality. With the increasing availability of genomic data, a streamlined tool for such analyses would facilitate and expedite the screening of genetic loci that hold potential for adaptive evolution, while alleviating the bioinformatic burden for experimental biologists. In this study, we present a user-friendly web-based tool called WGCCRR (Whole Genome Comparative Coding Region Read) designed to screen both convergent/parallel and lineage-specific amino acid changes on a genome-wide scale. Our tool allows users to replicate previous analyses with just a few clicks, and the exported results are straightforward to interpret. In addition, we have also included amino acid indels that are usually neglected in previous work. Our website provides an efficient platform for screening candidate loci for downstream experimental tests.

Availability and Implementation

The tool is available at: https://fishevo.xmu.edu.cn/.
TARO: tree-aggregated factor regression for microbiome data integration
Authors: Mishra Aditya K , Mahmud Iqbal , Lorenzi Philip L , Jenq Robert R , Wargo Jennifer A , Ajami Nadim J , Peterson Christine B
Published: May 2024

Motivation

Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.

Results

We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the taxonomic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.

Availability and implementation

The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package.
SWGTS—a platform for stream-based host DNA depletion
Authors: Spohr Philipp , Ried Max , Kühle Laura , Dilthey Alexander
Published: May 2024

Motivation

Microbial sequencing data from clinical samples is often contaminated with human sequences, which have to be removed prior to sharing. Existing methods for human read removal, however, are applicable only after the target dataset has been retrieved in its entirety, putting the recipient at least temporarily in control of a potentially identifiable genetic dataset with potential implications under regulatory frameworks such as the GDPR. In some instances, the ability to carry out stream-based host depletion as part of the data transfer process may be preferable.

Results

We present SWGTS, a client–server application for the transfer and stream-based host depletion of sequencing reads. SWGTS enforces a robust upper bound on the maximum amount of human genetic data from any one client held in memory at any point in time by storing all incoming sequencing data in a limited-size, client-specific intermediate processing buffer, and by throttling the rate of incoming data if it exceeds the speed of host depletion carried out on the SWGTS server in the background. SWGTS exposes a HTTP–REST interface, is implemented using docker-compose, Redis and traefik, and requires less than 8 Gb of RAM for deployment. We demonstrate high filtering accuracy of SWGTS; incoming data transfer rates of up to 1.65 megabases per second in a conservative configuration; and mitigation of re-identification risks by the ability to limit the number of SNPs present on a popular population-scale genotyping array covered by reads in the SWGTS buffer to a low user-defined number, such as 10 or 100.

Availability and implementation

SWGTS is available on GitHub: https://github.com/AlBi-HHU/swgts (https://doi.org/10.5281/zenodo.10891052). The repository also contains a jupyter notebook that can be used to reproduce all the benchmarks used in this article. All datasets used for benchmarking are publicly available.
tstrait: a quantitative trait simulator for ancestral recombination graphs
Authors: Tagami Daiki , Bisschop Gertjan , Kelleher Jerome
Published: May 2024

Ancestral recombination graphs (ARGs) encode the ensemble of correlated genealogical trees arising from recombination in a compact and efficient structure and are of fundamental importance in population and statistical genetics. Recent breakthroughs have made it possible to simulate and infer ARGs at biobank scale, and there is now intense interest in using ARG-based methods across a broad range of applications, particularly in genome-wide association studies (GWAS). Sophisticated methods exist to simulate ARGs using population genetics models, but there is currently no software to simulate quantitative traits directly from these ARGs. To apply existing quantitative trait simulators users must export genotype data, losing important information about ancestral processes and producing prohibitively large files when applied to the biobank-scale datasets currently of interest in GWAS. We present tstrait, an open-source Python library to simulate quantitative traits on ARGs, and show how this user-friendly software can quickly simulate phenotypes for biobank-scale datasets on a laptop computer.

Availability and implementation

tstrait is available for download on the Python Package Index. Full documentation with examples and workflow templates is available on https://tskit.dev/tstrait/docs/, and the development version is maintained on GitHub (https://github.com/tskit-dev/tstrait).
Heterogenous atrial conduction in patients with hypertrophic cardiomyopathy and atrial fibrillation
Authors: Klis M , Gharaviri A , Vigneswaran V , Sim I , Bodagh N , Niederer S , O'neill M , Williams S E
Published: May 2024

Background/Introduction

Hypertrophic cardiomyopathy (HCM) is characterised by myocardial thickening, fibrosis, and disarray, affecting both ventricles and atria. This pathology extends to atrial tissue, potentially influencing conductivity and contributing to arrhythmias, notably atrial fibrillation (AF). Pulmonary vein isolation to treat AF in HCM patients yields less satisfactory results compared to other patient groups. Improved understanding of the pathophysiology of AF in HCM patients could improve treatment stratification and delivery.

Purpose

This study aims to analyse atrial conduction properties in HCM patients with AF, compared to age, body mass index and sex-matched control patients.

Methods

Pre-ablation electroanatomic mapping data from 10 HCM patients and a matched control group of patients with structurally normal hearts undergoing AF ablation was retrospectively analysed. All patients underwent pre-ablation electroanatomic mapping during proximal coronary sinus pacing. This data was analysed using OpenEP software to quantify voltage mapping, conduction velocity and wave collision points. Conduction velocity was calculated using both plane fitting and triangulation methods. Wave collisions were identified by calculating the percentage of points with conduction velocity field divergence values less than -1.5.

Results

HCM patients exhibited significantly reduced mean left atrial bipolar voltage and greater low voltage burden <0.5mV than matched control patients (1.43mV vs. 2.14mV, p=0.0177; and 38.28% vs. 15.68%, p<0.0001), (Figure 1A and B). Wave collision points were significantly more prevalent in the HCM group (5.4% vs. 1.6%, p=0.0004), indicating more heterogeneous conduction (Figure 1C). Figure 2 shows example of divergence map with local electrograms around wave collision points. Both methods of quantifying conduction velocity showed comparable results. While average conduction velocity showed no statistically significant difference (plane fitting method - 0.61m/s in HCM group vs. 0.64m/s in control group, p = 0.465; triangulation method - 0.61m/s in HCM group, 0.64m/s in control group, p=0.393), a trend toward lower velocities in HCM patients was observed (Figure 1D and 1E).

Conclusion

HCM patients demonstrate significantly lower bipolar voltage and significantly greater low voltage areas than matched control patients. Atrial conduction in patients with HCM is significantly more heterogenous than matched control patients. These findings highlight marked conduction abnormalities in HCM patients which are likely to contribute to AF pathogenesis.
Whole exome sequencing in young atrial fibrillation patients
Authors: Rudaka I , Vilne B , Kalejs O , Rots D , Trusinskis K , Gailite L
Published: May 2024

Background

Up to 10% of atrial fibrillation (Afib) patients develop the condition in the young age and in the absence of any related risk factors. Recent publications emphasized the importance of genetic testing in this population. However, the yield of the investigation is highly variable and ranges from 1 to 24% precents.

Purpose

The purpose of this study is to evaluate the prevalence of causative genetic variants in young Afib patients without risk factors and evaluate any structural changes of the heart.

Methods

We performed whole exome sequencing in 54 young (age of Afib onset less than 65 years) Afib patients without any Afib related risk factors (original cohort). Using ACMG guidelines we performed analysis of 349 previously described cardiomyopathy and arrhythmia associated genes. If a pathogenic (P) or likely pathogenic (LP) variant was found, a cardiac magnetic resonance imaging (CMR) was performed to exclude any structural abnormalities of the heart. We also extracted 107 young Afib patients without any risk factors from UK Biobank (UK Biobank cohort) and performed analysis of the same genes in the subgroup.

Results

The prevalence of P and LP variants was 24% (13 cases) in the original cohort and 8% (9 cases) in the UK Biobank cohort (p=0.006). We observed variants in cardiac structural and developmental genes only in both cohorts (Table 1 and 2). In the original cohort there were nine (17%) patients with P and LP variant in TTN gene. Moreover, five patients were positive for the same TTN variant NM_001267550.2:c.13696C>T p.(Gln4566Ter). In six (46%) original cohort patients we observed structural changes of the heart on CMR – in five patients there was dilation of one or both ventricles and in one there was increased T1 mapping intensity of septal wall segments.

Conclusions

1. There is a high prevalence of pathogenic and likely pathogenic causative genetic variants in young atrial fibrillation patients without any risk factors. 2. All variants are localized in cardiac structural or developmental genes only. 3. There is a high grade of structural changes of the heart observed on cardiac magnetic resonance imaging in patients with monogenic atrial fibrillation.Table 1.WES data in original cohortTable 2.WES data in UK Biobank cohort
Obesity paradox in atrial fibrillation patients on oral anticoagulation therapy: a Korean nationwide cohort study
Authors: Lee K N , Soh M S , Park B H , Kim D Y , Roh S Y
Published: May 2024

Background

The obesity paradox is a phenomenon that has been observed in specific pathological conditions, wherein individuals who are overweight or obese exhibit a survival advantage over those with a normal weight. This phenomenon has also been noted in patients diagnosed with atrial fibrillation (AF), although the impact of body mass index (BMI) on clinical outcomes in AF patients undergoing oral anticoagulant (OAC) therapy remains uncertain.

Purpose

The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with AF who were receiving OAC.

Methods

We utilized administrative claims data from the Korean National Health Insurance Service and the combined health check-up database of the National Health Insurance Corporation to conduct a retrospective national cohort study spanning from 2013 to 2020. The patients newly prescribed OAC for AF were included, between January 2015 and December 2019. We followed up with patients from their index date until each outcome event or the end of the study period. BMI was categorized into 5 groups based on the World Health Organization's recommended criteria for Asian populations. The predefined clinical outcomes included thromboembolism, major bleeding, all-cause death, and the composite outcome.

Results

A total of 35,333 patients were included in the study. The mean age was 69 ± 10 years, and 37.1% were female. During a median follow-up of 2.0 years (IQR, 0.4–3.3), there were 11,634 thromboembolic events, 1,521 major bleeding events, and 2,586 deaths. The adjusted hazard ratio (HR) for thromboembolism, major bleeding, all-cause death, and a composite outcome were lower in obese II group (HR 0.79, 95% CI 0.73–0.86; HR 0.99, 95% CI 0.79–1.24; HR 0.75, 95% CI 0.62–0.91; HR 0.81, 95% CI 0.75–0.88) compared to the normal range BMI group.

Conclusions

In AF patients undergoing OAC therapy, individuals classified as obese exhibited a reduced risk of thromboembolism, major bleeding, all-cause mortality, and composite outcome compared to patients with normal weight.Adjusted hazard ratio of outcomes by BMI
Clinical significance of new-onset atrial fibrillation in patients with coronary artery or peripheral artery disease: results from the COMPASS trial
Authors: Benz A P , Alings M , Bosch J , Avezum A , Bhatt D L , Healey J S , Johnson L S , Mcintyre W F , Widimsky P , Yusuf S , Connolly S J , Eikelboom J W
Published: May 2024

Background

The COMPASS trial enrolled patients with coronary artery or peripheral artery disease, but excluded patients requiring oral anticoagulation. Compared to aspirin alone, rivaroxaban in addition to aspirin reduced a composite of cardiovascular death, stroke or myocardial infarction.

Purpose

This study aimed to explore the clinical significance of a new diagnosis of atrial fibrillation (AF) during follow-up.

Methods

New AF was identified from unplanned hospitalization, study drug discontinuation and adverse event reports. The associations between new-onset AF, clinical characteristics and outcomes in COMPASS participants were studied using time-updated regression modeling. Event rates were reported as per 100 patient-years (following a new diagnosis of AF vs. from randomization until the end-follow-up or new AF, whichever came first).

Results

During a mean follow-up of 23 months, 655 of 27,395 participants (2.4%) were newly diagnosed with AF. Advanced age, male sex, white race, higher body mass index, higher systolic blood pressure, heart failure and prior myocardial infarction were independently associated with new-onset AF. The rates of permanent discontinuation of study drug were 83.8% following a new diagnosis of AF, compared to 17.5% in participants without/before new AF. Compared to participants without/before a new diagnosis of AF, participants with new-onset AF were at increased risk of a composite of cardiovascular death, stroke or myocardial infarction (8.9 vs. 2.5 per 100 patient-years, hazard ratio [HR] 4.49, 95% confidence interval [CI] 3.37-6.00) (Figure 1). Risk increases with new-onset AF were also observed for hospitalization for heart failure (9.1 vs. 1.1 per 100 patient-years, HR 6.35, 95% CI 4.59-8.80) (Figure 2) and major bleeding (4.1 vs. 1.3 per 100 patient-years, HR 2.93, 95% CI 1.99-4.33).

Conclusion

In COMPASS, a new diagnosis of AF during trial follow-up was associated with a marked increase in risk of adverse outcomes.Composite outcome after new-onset AFHeart failure after new-onset AF
Atrial fibrillation after transcatheter tricuspid valve repair: rhythm control strategies and outcomes
Authors: Schipper J , Woermann J , Van Den Bruck J , Filipovic K , Dittrich S , Scheurlen C , Erlhoefer S , Pavel F , Iliadis C , Pfister R , Sultan A , Lueker J , Steven D
Published: May 2024

Background

Transcatheter tricuspid valve (TV) repair emerged as a viable treatment option in patients with severe tricuspid regurgitation and high operative risk. Although atrial fibrillation (AF) is common in these patients, the prognostic value of maintenance of sinus rhythm (SR) after transcatheter TV repair is unknown.

Purpose

We sought to assess the prevalence and efficacy of rhythm control strategies and impacts of maintenance of sinus rhythm on outcomes after transcatheter TV repair.

Methods

All patients undergoing transcatheter TV repair in our center between April 2017 and December 2022 were included in this single-center retrospective analysis. Patients who maintained SR throughout the follow-up (FU) were compared to patients who did not. The composite study endpoint included death from any cause, heart failure (HF) hospitalization and repeat TV repair. Furthermore, prevalence and efficacy of rhythm control strategies were evaluated.

Results

A total of 203 patients (mean age 78 ± 7 years, 145 (68 %) female) after transcatheter TV repair was analyzed. After a median follow-up of 12 months (IQR 4-20), 21 patients (10 %) did maintain SR. AF was present in 183 patients (90 %), of whom 134 had permanent AF. In the AF group, direct-current cardioversion (DCCV) was performed in 6 patients (3 %). Following DCCV, SR was restored in 4 patients (75 %), of whom 3 patients (75 %) presented in SR 30 days after DCCV. 2 patients (1 %) underwent AF ablation. After a case-control matching including 38 patients (SR vs. AF), during a median follow-up of 8 months (IQR 1-20) the study endpoint occurred in 7 of 19 patients (37 %) in the SR group and 12 of 19 patients (63 %) in the AF group (HR 0.70, p = 0.43).

Conclusions

The incidence of AF among patients undergoing transcatheter TV repair is high. In the present patient cohort, there was a trend towards a higher likelihood of death from any cause, HF hospitalization and repeat transcatheter TV repair in patients with AF. Further randomized studies are needed to evaluate the impact of rhythm control in patient undergoing TV repair.
Effects of sodium glucose co-transporter-2 inhibitor on atrial tachyarrhythmia burden in patients with cardiovascular implantable electronic device
Authors: Nantsupawat T , Apaijai N , Prommintikul A , Prasertwitayakij N , Chattipakorn S , Chattipakorn N , Wongcharoen W
Published: May 2024

Introduction

Previous studies showed that sodium glucose co-transporter-2 inhibitors (SGLT2i) were associated with a lower atrial fibrillation (AF) incidence.

Purpose

Since mitochondrial dysfunction has been linked with AF, we aimed to examine the effects of SGLT2i on AF burden and mitochondrial function in patients with cardiovascular implantable electronic device (CIED).

Methods

Patients with CIED were randomly assigned to receive either dapagliflozin 10 mg daily or placebo for 3 months. The AF burden was measured as atrial high-rate episodes (AHRE) via CIED interrogations, and data were collected at baseline and 3-months post-treatment. Oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs).

Results

The study enrolled 54 CIED patients. There were 9 (16.7%) patients with diabetes mellitus and 36 (66.7%) patients with history of clinical AF. The changes of AHRE burden after 3-month treatments did not differ between dapagliflozin and placebo groups. However, in those with clinical AF, dapagliflozin significantly decreased the number of AHRE per month as compared to placebo (-2.2 vs. +0.6 episodes per month, p=0.048) (Table 1). Mitochondrial spare respiratory capacity (SRC) percentage was significantly increased after treatment with dapagliflozin (162.1% to 203.2%, p=0.003), whereas this was not found in the placebo group (Figure 1). In the subgroup analysis of patients with clinical AF, dapagliflozin showed significant improvement in both the SRC percentage (165.7 to 201.7%, p=0.016) and a reduction in cellular oxidative stress (26,840.5 to 18,164.0 arbitrary unit, p=0.049).

Conclusions

Dapagliflozin significantly reduced the number of AHRE per month in patients with history of clinical AF. The improvement in PBMC’s mitochondrial function and reduced cellular oxidative stress among dapagliflozin users could be the mechanisms responsible for its anti-atrial arrhythmic effect.Table 1Figure 1
Presence and predictors of atrial low voltage zones in patients with non cardiovertable atrial fibrillation
Authors: Bergt I , Richter S R , Ebert M E , Mayer J M , Zedda A Z , Ulbrich S U , Dindane Z D , Richter U R , Gaspar T G
Published: May 2024

Background

Interventional treatment of persistent atrial fibrillation (pAF) presents a challenge due to the lack of clear evidence on adjunctive strategies beyond pulmonary vein isolation (PVI). One promising approach is ablation of left atrial low voltage zones, which has been shown to improve outcomes in patients with pAF. However, reliable assessment of left atrial endocardial voltage requires sinus rhythm (SR). In a significant proportion of patients with persistent atrial fibrillation (pAF) however, restoration of sinus rhythm (SR) cannot be achieved. These may lead to extensive ablations such as defragmentation or empirical isolation of the posterior wall of the left atrium. This study aims to investigate the potential of unsuccessful cardioversion prior ablation as a predictor for the presence of low voltage zones (LVZ) in the left atrium.

Methods

This retrospective, single-centre study was conducted on 264 patients (31,8% female; age: 67±10 years; mean AF duration: 1-2 years) diagnosed with pAF who underwent catheter ablation for pAF between 01/2017 and 01/2020. All patients underwent electrical cardioversion (CV) before ablation. If restoration of SR was achieved, high-density contact mapping was performed in sinus rhythm before pulmonary vein isolation (PVI), in case of unsuccessful initial cardioversion, high-density contact mapping was performed after repeated CV followed the PVI, respectively.

Results

Initial cardioversion was unsuccessful in 53 out of 264 (19.7%) patients. Subsequent to pulmonary vein isolation, cardioversion was successful in 47 out of 53 (81%) patients initially considered non-cardiovertible. In 32 out of 53 (60.4%) patients who had an initial unsuccessful cardioversion, no left atrial low voltage was identified. Amongst patients who underwent a successful initial cardioversion, left atrial low voltage zones were apparent in 77 out of 211 patients (36.5%). There is no significant difference in the the presence of left atrial low voltage between patients who had initially successful and unsuccessful CV (χ²(1) = 0.178, p = 0.673, φ = 0.026). According to the ROC analysis, the success of CV does not have any predictive value for LVZ (AUC 0.511).

Conclusion

Cardioversion failure before pulmonary vein isolation does not predict left atrial low-voltage zones (LVZ). PVI alone may be adequate even in patient with clinically "end stage" non-cardiovertible atrial fibrillation. Ablation beyond pulmonary vein isolation have the potential to overtreat this specific patient group, resulting in an increase in secondary arrhythmias. These findings indicate that even single-shot devices such as balloon-based techniques may be a considerable ablation strategy in these patient cohort.
Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial
Authors: Rillig A , Eckardt L , Borof K , Camm A J , Crijns J G M , Goette A , Metzner A , Schotten U , Wegscheider K , Zapf A , Heidbuchel H , Willems S , Schnabel R , Magnussen C , Kirchhof P
Published: May 2024

Background

Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease.

Purpose

SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4.

Methods

We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and primary efficacy outcome (cardiovascular death, stroke and hospitalization for worsening of heart failure or acute coronary syndrome) during SCB-intake for ERC patients (n=1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy.

Results

Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI and 26 with left ventricular hypertrophy >15mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p<0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) patient-years, adjusted p=0.015). Sinus rhythm at 2 years was similar between groups (SCB 537/610 (88); SCBnever 472/579 (82)).

Conclusion

Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including selected patients with stable cardiovascular disease such as coronary artery disease and stable heart failure.
Characterization of conduction recovery and atrial electrophysiological properties after pulmonary vein isolation using pulsed field ablation
Authors: Scharfe F , Karolyi L , Spitzer S , Langbein A
Published: May 2024

Background

Pulsed field ablation (PFA) is a relatively new technology for isolation of pulmonary veins in patients with atrial fibrillation (AF). Data addressing reasons for recurrent atrial fibrillation despite primarily successful pulmonary vein isolation (PVI) using PFA are scarce, due to an up to date limited number of patients treated this way.

Objective

The aim of this study was to analyze electrophysiological characteristics of reconduction and / or left atrial substrate of patients referred to our center for Re-Do procedures for recurrent AF after an initial PVI using PFA.

Methods

90 patients (mean age 66±9 years, 69 male (77%)) had been treated in our center from November 2021 to July 2023 with PVI using PFA. 9 (10%) of these patients were referred for Re-Do procedures. These were performed by radiofrequency ablation (RFA) using Carto system including high density mapping and high power / short duration (HPSD) ablation. We analyzed location of PV reconnection and low voltage areas (LVA) in the left atria.

Results

7 out of 9 patients (77%) presented with reconnections of pulmonary veins. In one patient a single vein showed reconduction (RSPV), in 5 patients 2 veins were conducting (1x LSPV, 3x LIPV, 1 left sided common os (LCo), 1x RSPV, 3x RIPV). None of the patients showed 3 or 4 reconnected veins. Areas of reconduction in each vein were: LSPV 1x ridge, 1x posterior; LIPV 1x posterior, 1x anterior and posterior; LCo 1x posterior, RSPV 1x anterior, 2x carina, 1x anterior and posterior; RIPV 1x complete, 2x carina. In 7 patients a fibrotic atrial cardiomyopathy (FACM) was diagnosed via high density mapping of LVA’s. In 2 of these patients all 4 pulmonary veins were chronically isolated after the initial PVI. All patients except one (very small anterior LVA) with FACM ≥1 were treated with additional linear or encircling lesions according to the individual extent of the fibrotic areas. 2 patients had no LVA’s detectable. In one of those 2 patients 2 veins had reconnected. The other patient had chronically isolated veins (no proof of dormant conduction with adenosine) and no detectable non-PV-triggers under isoprenaline.

Conclusion

In the population of patients undergoing PVI using PFA in our center, only 10% had clinically relevant recurrences leading to the necessity of a Re-Do procedure. Most patients (77%) in this setting had reconnections of pulmonary veins. There is a tendency of posterior reconnections of the left pulmonary veins and reconnections of the carina of the right pulmonary veins, but the number of patients is too small to clearly define predilection sites that have to be paid attention to when using PFA. Additionally, left atrial substrate is an important problem in patients with recurrent AF despite primarily successful PVI and has to be considered and thoroughly addressed in Re-Do procedures.Reconnection of LSPV and anterior LVAAblation of RSPV and LSPV (posterior)
The contribution of pulmonary veins to the mechanism of persistent AF is dependent on their extent of electrical connection
Authors: Marchetti M , Haddad C , Luca A , Gentil P , Le Bloa M , Teres C , Domenichini G , Pia-Porretta A , Herrera C , Pruvot E , Pascale P
Published: May 2024

Introduction

Success rate of pulmonary vein isolation (PVI) is lower in patients with persistent AF (peAF) compared to paroxysmal AF. The indiscriminate use of adjunctive catheter ablation (CA) strategies beyond PVI involve potential risks and new areas of iatrogenic arrhythmogenesis. Thus, distinguishing patients with peAF who may be cured with PVI-only from those who need CA beyond PVI would allow a more efficient patient-tailored CA strategy.

Purpose

We aimed to evaluate whether the circumferential extent of PV electrical connection assessed during pre-ablation mapping predicts the success rate of a PVI-only CA strategy.

Methods

Consecutive patients with peAF undergoing first CA consisting of a PVI-only CA were included. The extent of PV electrical connection was assessed using a circular mapping catheter placed within the PVs prior to ablation. Based on their follow-up (FU), patients were considered: a) PVI-responders, in the absence of AF or atrial flutter recurrence ≥ 12 months off-anti-arrhythmic drugs, b) PVI-non responders, in case of AF recurrence despite absence of any PV reconnection at reintervention, or despite one reintervention consisting of stand-alone residual PV connection ablation, c) PVI response was considered as indeterminate for all other instances (eg. Sinus rhythm maintenance on-AAD, shorter FU, etc).

Results

148 patients were included (mean age 64 ± 9.7 years, mean peAF duration 7.3 ± 7 months). After a mean FU of 18 months after last PVI, we identified 60 PVI-responders and 25 PVI- non responders. In the remaining 63 patients, PVI response was indeterminate. In PVI-responders, the median percentage of the PV circumference displaying PVs potentials was significantly higher compared to PVI-non responders (68% vs. 60%, respectively; p=0.035).

Conclusions

The circumferential extent of PVs connection is correlated to the success rate of a stand-alone PVI CA strategy in patients with peAF. It may be a marker of the contribution of PVs to AF. Patients with poorly connected PVs during index CA ablation may warrant additional ablation strategies beyond PVI.
Very-high power short duration radiofrequency ablation (90W/4seconds) under mild conscious sedation: lesion metrics and 12-month outcomes
Authors: Mills M , Calvert P , Koniari I , Ashrafi R , Snowdon R , Gupta D , Luther V
Published: May 2024

Background

Pulmonary vein isolation (PVI) is often performed under general anaesthesia (GA) or deep sedation. Anaesthetic availability is limited in many centres across Europe, and deep sedation is prohibited in some countries without anaesthetic support. Very high-power short duration (vHPSD – 90W/4sec) PVI using the Q-Dot catheter is well tolerated under mild conscious sedation (MCS) administered by nurses under physician direction. Here, we present lesion metrics and 12-month freedom from atrial arrhythmia with this approach.

Methods

Our approach to radiofrequency (RF) PVI under MCS is standardised and includes a single catheter approach with a steerable sheath (Figure 1). We identified patients who had undergone Q-Dot RF PVI between March 2021 and December 2022 in our centre, comparing those undergoing vHPSD ablation under MCS (90W/MCS) against those undergoing 50W ablation under GA (50W/GA). Data were extracted from the CARTO system and electronic clinical records.

Results

83 patients were included in our analysis (51 90W/MCS; 32 50W/GA). Despite shorter ablation times (353 vs 886 sec; p<0.001), the 90W/MCS group received more lesions (median 87 vs 58, p<0.001), resulting in similar procedure times (120 vs 123 min; p=0.705) (Figure 2). PVI was achieved in all cases, and first pass isolation rates were similar (left WACA 82.4% vs 87.5%, p=0.758; right WACA 74.5% vs 78.1%, p=0.796; 90W/MCS vs 50W/GA respectively). Analysis of 6,647 ablation lesions found similar mean impedance drops (10.0 ± 1.9 Ω vs 10.0 ± 2.2 Ω; p=0.989) and mean contact force (14.6 ± 2.0 g vs 15.1 ± 1.6 g; p=0.248). Similar percentages of lesions achieved >10Ω impedance drop in each arm (48.5 ± 23.1% vs 42.6 ± 17.4%; p=0.224). Only a median 2.5% of lesions in the 90W/MCS arm failed to achieve impedance drop ≥5Ω, compared with 13.7% in the 50W/GA arm (p<0.001). In the 90W/MCS group, there were no procedural related complications. Across median 12-month follow-up, freedom from atrial arrhythmia was observed in 78.4% of patients in the 90W/MCS group, compared with 68.8% in the 50W/GA group (p=0.437), the difference likely being accounted for by the higher prevalence of persistent AF, hypertension and significant left atrial enlargement in the 50W/GA group. Redo ablation was required in 3 (5.9%) of the 90W/MCS group vs 2 (6.2%) of the 50W/GA group (p>0.999) during 12-month follow-up.

Conclusion

vHPSD PVI can be performed under nurse-administered MCS safely and effectively to achieve adequate rates of 12-month arrhythmia freedom. The mean contact force and impedance drop of a 90W/MCS lesion is similar to a 50W/GA lesion. Whilst more lesions may be required using 90W/MCS to achieve FPI, total ablation duration is significantly shorter and procedural times are similar when compared to 50W/GA. This provides a compelling option for centres with limited anaesthetic support.Figure 1Figure 2