bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability
Authors: Cao Yunlong , Bai Yali , Yuan Tianjiao , Song Liyang , Fan Yu , Ren Liuhao , Song Weiliang , Peng Jiahui , An Ran , Gu Qingqing , Zheng Yinghui , Xie Xiaoliang Sunney
Published: November 2023

Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status. Using Cabernet, we revealed the 5mC, hemi-5mC and 5hmC dynamics during early mouse embryo development, uncovering genomic regions exclusively governed by active or passive demethylation. We show that hemi-methylation status can be used to distinguish between pre- and post-replication cells, enabling more efficient cell grouping when integrated with 5mC profiles. The property of Tn5 naturally enables Cabernet to achieve high-throughput single-cell methylome profiling, where we probed mouse cortical neurons and embryonic day 7.5 (E7.5) embryos, and constructed the library for thousands of single cells at high efficiency, demonstrating its potential for analyzing complex tissues at substantially low cost. Together, we present a way of high-throughput methylome and hydroxymethylome detection at single-cell resolution, enabling efficient analysis of the epigenetic status of biological systems with complicated nature such as neurons and cancer cells.
How visualisations with typography are used in Persian and English corporate identity logos
Authors: Pormehr Yabandeh AmirHossein , Abeddoost Hossein , Kazempoor Ziba
Published: November 2023

Typography simplifies and facilitates the information transfer process, and establishes a quick and
straightforward connection between text and audience. Combining writing with images provides the basis for creating symbolic
relationships in typography. This study intends to define the paradigmatic relationships between visual signs and writing in
integrated Persian typographies and English logotypes. In this study Persian and English logotype samples are compared. It is
observed that in the Persian sample, logotype letters are often affected by the visual elements; however, only one letter is
usually replaced with an image in the English samples.
Time-frequency enhanced characterization method based on asymmetric image reconstruction autoencoder
Authors: Han Ruiyu , Mao Zhiwei , Zhang Zhenjing , Zhang Jinjie
Published: November 2023

The vibration signals of mechanical equipment are subject to the influence of complex and variable working conditions, often exhibiting non-smooth and non-linear characteristics. The conventional time-frequency (TF) analysis (TFA) method, which relies on energy concentration, is susceptible to noise and impact, making it challenging to accurately extract fault characteristics. To overcome these limitations, this paper proposes an innovative approach. In this paper, we introduce an asymmetric image reconstruction autoencoder model, which is based on two well-known TFA methods, namely, short-time Fourier transform (STFT) and synchroextracting transform (SET), effectively reducing noise and improving the TF energy concentration process through learning the mapping relationship between STFT and SET. To address the clarity issue in the reconstructed TF images, the paper incorporates a channel attention mechanism known as SE Block into the encoding-decoding structure. Additionally, a skip connection structure is introduced to aid in restoring the structural details of the reconstructed TF images. Moreover, an improved weighted joint loss function is proposed to adaptively enhance various types of TF distribution features. This enhancement ensures that different characteristics of TF distribution are adequately addressed during the reconstruction process. The proposed method is put to the test using both simulated signals and experimental signals from gearbox rolling bearing faults. The results demonstrate that compared to traditional TFA and post-processing methods, the proposed model exhibits superior capabilities in enhancing the TF characterization of multi-source time-varying signals. Furthermore, it demonstrates remarkable robustness to noise and can accurately extract instantaneous frequency. These findings point to the promising potential of this method for mechanical fault identification and diagnosis applications.
Statistical features of systems driven by non-Gaussian processes: theory & practice
Authors: Lucente Dario , Puglisi Andrea , Viale Massimiliano , Vulpiani Angelo
Published: November 2023

Nowadays many tools, e.g. fluctuation relations, are available to characterize the statistical properties of non-equilibrium systems. However, most of these tools rely on the assumption that the driving noise is normally distributed. Here we consider a class of Markov processes described by Langevin equations driven by a mixture of Gaussian and Poissonian noises, focusing on their non-equilibrium properties. In particular, we prove that detailed balance does not hold even when correlation functions are symmetric under time reversal. In such cases, a breakdown of the time reversal symmetry can be highlighted by considering higher order correlation functions. Furthermore, the entropy production may be different from zero even for vanishing currents. We provide analytical expressions for the average entropy production rate in several cases. We also introduce a scale dependent estimate for entropy production, suitable for inference from experimental signals. The empirical entropy production allows us to discuss the role of spatial and temporal resolutions in characterizing non-equilibrium features. Finally, we revisit the Brownian gyrator introducing an additional Poissonian noise showing that it behaves as a two dimensional linear ratchet. It has also the property that when Onsager relations are satisfied its entropy production is positive although it is minimal. We conclude discussing estimates of entropy production for partially accessible systems, comparing our results with the lower bound provided by the thermodynamic uncertainty relations.
Regularity and numerical approximation of fractional elliptic differential equations on compact metric graphs
Authors: Bolin David , Kovács Mihály , Kumar Vivek , Simas Alexandre
Published: November 2023

The fractional differential equation

L
β

u
=
f

L^\beta u = f

posed on a compact metric graph is considered, where

β
>
0

\beta >0

and

L
=

κ
2

−
∇
(
a
∇
)

L = \kappa ^2 - \nabla (a\nabla )

is a second-order elliptic operator equipped with certain vertex conditions and sufficiently smooth and positive coefficients

κ
,
a

\kappa ,a

. We demonstrate the existence of a unique solution for a general class of vertex conditions and derive the regularity of the solution in the specific case of Kirchhoff vertex conditions. These results are extended to the stochastic setting when

f
f

is replaced by Gaussian white noise. For the deterministic and stochastic settings under generalized Kirchhoff vertex conditions, we propose a numerical solution based on a finite element approximation combined with a rational approximation of the fractional power

L

−
β

L^{-\beta }

. For the resulting approximation, the strong error is analyzed in the deterministic case, and the strong mean squared error as well as the

L
2

(
Γ
×
Γ
)

L_2(\Gamma \times \Gamma )

-error of the covariance function of the solution are analyzed in the stochastic setting. Explicit rates of convergences are derived for all cases. Numerical experiments for

L
=

κ
2

−
Δ
,
κ
>
0

{L = \kappa ^2 - \Delta , \kappa >0}

are performed to illustrate the results.
𝐶^{1,1-𝜖} isometric embeddings
Authors: Martínez Ángel
Published: November 2023

In this paper we use the convex integration technique enhanced by an extra iteration originally due to Källén and revisited by Kröner to provide a local

h
h

-principle for isometric embeddings in the class

C

1
,
1
−
ε

C^{1,1-\varepsilon }

for

n
n

-dimensional manifolds in codimension

1
2

n
(
n
+
1
)

\frac {1}{2}n(n+1)

.
The connectivity of the human frontal pole cortex, and a theory of its involvement in exploit versus explore
Authors: Rolls Edmund T , Deco Gustavo , Huang Chu-Chung , Feng Jianfeng
Published: November 2023

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system. There is also connectivity with temporal lobe, inferior parietal, and posterior cingulate regions. Given this new connectivity evidence, and evidence from activations and damage, it is proposed that the frontal pole cortex contains autoassociation attractor networks that are normally stable in a short-term memory state, and maintain stability in the other prefrontal networks during stable exploitation of goals and strategies. However, if an input from the orbitofrontal or anterior cingulate cortex that expected reward, non-reward, or punishment is received, this destabilizes the frontal pole and thereby other prefrontal networks to enable exploration of competing alternative goals and strategies. The frontal pole connectivity with reward systems may be key in exploit versus explore.
Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors
Authors: Li Yu-Lin , Wu Jia-Jia , Li Wei-Kai , Gao Xin , Wei Dong , Xue Xin , Hua Xu-Yun , Zheng Mou-Xiong , Xu Jian-Guang
Published: November 2023

Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen–Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl’s gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.
Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered With Seasonal Inactivated Influenza Vaccine in Older Adults
Authors: Athan Eugene , Baber James , Quan Karen , Scott Robert J , Jaques Anna , Jiang Qin , Li Wen , Cooper David , Cutler Mark W , Kalinina Elena V , Anderson Annaliesa S , Swanson Kena A , Gruber William C , Gurtman Alejandra , Schmoele-Thoma Beate ,   for the Study C3671006 Investigator Group, Argent Christopher , Arya Mark , Athan Eugene , Bird Paul , Bloch Mark , Bull Sheetal , Colquhoun David , De Silva Gustinna , Deshmukh Sachin , Eizenberg Peter , Gilfillan Christopher , Gunner Elizabeth , Hiew Valerie , Leah Amber , Leelasena Indika , Lickliter Jason , McGirr Anthony , Mohan Rahul , Morbey Claire , Murdoch Louise , Nelson Mark , Neville A Munro , O'Sullivan Matthew , Rook Christopher , Russo Marc , Ryan Philip , Scott Robert , Tai Sze , Tiong Florence , Voloshyna Olga , Wark Peter
Published: November 2023

Background

Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines.

Methods

The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy adults aged ≥65 years in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein–based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% confidence interval >.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data.

Results

Of 1403 participants randomized, 1399 received vaccinations (median age, 70; range, 65‒91 years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin.

Conclusions

The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older-adult population.

Clinical Trials Registration

https://clinicaltrials.gov/study/NCT05301322.
Opportunistic Treatment of Hepatitis C Infection Among Hospitalized People Who Inject Drugs (OPPORTUNI-C): A Stepped Wedge Cluster Randomized Trial
Authors: Midgard Håvard , Malme Kristian Braathen , Pihl Charlotte Meinich , Berg-Pedersen Riikka Mari , Tanum Lars , Klundby Ingvild , Haug Anne , Tveter Ida , Bjørnestad Ronny , Olsen Inge Christoffer , Finbråten Ane-Kristine , Dalgard Olav
Published: November 2023

Background

We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID).

Methods

We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment.

Results

A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2–77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1–45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0–46.2]; risk ratio 1.9 [95% CI: 1.4–2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8–12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5–6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8–70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6–73.9]) during control conditions.

Conclusions

An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation.

Clinical Trials Registration. NCT04220645
Deep-learning based analysis of intracoronary optical coherence tomography images: detection and characterization of lipid plaques
Authors: Volleberg R H J A , Rodgriguez Esteban G , Mol J H Q , Quax S , Isgum I , Sanchez C I , Van Ginneken B , Thannhauser J , Van Royen N
Published: November 2023

Background

Intracoronary optical coherence tomography (OCT) enables in vivo detection and characterization of atherosclerotic disease. However, manual assessment of OCT images is time-consuming and subject to intra- and interobserver variability. Therefore, automated and trustworthy methods for plaque assessment are warranted.

Purpose

To develop and validate an artificial intelligence based algorithm for detection and characterization of lipid plaques on OCT images.

Methods

From the prospective, observational PECTUS-obs study, we studied a representative subset of OCT pullbacks performed in fractional flow reserve-negative non-culprit lesions in patients presenting with myocardial infarction. Manual segmentation of cross-sectional frames (e.g. lumen, tunica intima including the fibrous cap, tunica media and lipid pools) was performed by trained experts. Pullbacks were randomly divided into a training and test set. For automated segmentation and analysis, a two-dimensional no-new U-shaped neural network (nnUNet) was constructed with 5-fold cross validation. To test the diagnostic performance of the nnUnet for detection of lipid plaques, sensitivity, specificity and Cohen’s kappa were calculated. As for plaque characterization, the lipid arc and minimal fibrous cap thickness were measured manually in the test set on each frame containing a lipid plaque. Values of lipid arc and minimal fibrous cap thickness obtained following automated assessment were compared to manual analysis using the intraclass correlation coefficient (ICC) for absolute agreement.

Results

In total, 1215 frames were used for training and 162 frames for testing of the nnUNet. Lipid plaques were present in 77 frames (47.5%) in the test set. Substantial agreement (κ=0.79) for detection of a lipid plaque was achieved with a sensitivity and specificity of 96.1% and 83.5%, respectively. As for plaque characterization, we found good reliability for lipid arc assessment (ICC 0.88, mean difference 6±32º) and moderate reliability for assessment of the minimal fibrous cap thickness (ICC 0.54, mean difference 23±140µm).

Conclusion

We developed a deep learning algorithm for automated analysis of intracoronary OCT images, that was able to accurately detect lipid plaques. Moreover, the algorithm showed promising results in terms of plaque characterization. With further refinements, the developed algorithm has the potential to reduce the time required for OCT interpretation, ultimately enabling more efficient, real-time use of this imaging modality in clinical practice.
Gender-related differences in absolute coronary flow and microvascular resistance in patients with angina and non-obstructed coronary arteries (ANOCA)
Authors: Belmonte M , Gallinoro E , Bertolone D , Paolisso P , Viscusi M M , Storozhenko T , Sakai K , Botti G , Barbato E , Vanderheyden M M , Collet C , De Bruyne B
Published: November 2023

Background

Women with angina more often have non-obstructive coronary artery disease (ANOCA) compared to males. Coronary microvascular dysfunction (CMD) is responsible for angina in a sizable proportion of ANOCA patients. Intracoronary continuous thermodilution allows direct quantification of absolute coronary flow (Q) and microvascular resistance (Rµ).

Purpose

To evaluate gender-related differences in the prevalence and pattern of CMD assessed with intracoronary continuous thermodilution in ANOCA patients. Specifically, we assessed resting and hyperemic Q (Qrest and Qhyper), R (Rµ,rest and Rµ,hyper), coronary flow reverse (CFR), and microvascular resistance reserve (MRR) in ANOCA patients stratified by gender.

Methods

Single-center, prospective study of patients with ANOCA. CMD was invasively assessed by intracoronary continuous thermodilution in the left anterior descending artery (LAD) and defined as CFR<2.5.

Results

A total of 118 patients (n=49 females and n= 69 males) were enrolled. The mean patient age was 65 years. The mean fractional flow reserve (FFR) was 0.85±0.04, with no difference between the 2 genders. There was no difference in Rµ,rest, Qrest and Qhyper between the two genders. However, Rµ,hyper were higher in females compared to males (p=0.003). Among patients with ANOCA, CMD was more prevalent in females (28% vs 22%, p=0.014). Yet, in both females and males with CMD, a higher Qrest was observed compared to patients without CMD. In male patients, also Qhyper was lower in CMD patients versus those without CMD.

Conclusion

Among patients with ANOCA and investigated with intracoronary continuous thermodilution, CMD appeared more prevalent in females compared to males. Females had higher microvascular Rµ,hyper compared to males. In both genders, CMD was characterized by higher Qrest, suggestive of functional rather than structural CMD.
Mechanisms of very late stent thrombosis assessed by optical coherence tomographyin japanese patients
Authors: Mori H
Published: November 2023

Background

Although very late stent thrombosis (VLST) remains an important concern, the underlying etiology and clinical characteristics are not fully elucidated in Japanese patients who daily undergo intravascular imaging-guided percutaneous coronary intervention (PCI).

Objectives

The aim of this study was to explore the mechanisms of VLST in bare metal stents (BMSs) and drug eluting stents (DESs) in Japanese patients.

Methods

We identified 50 VLST lesions (BMS [n=16], 1ST generation DES [n=14], newer generation DES [n=20]) in patients managed in our institutes. The underlying mechanism of VLST was assessed by optical coherence tomography (OCT) and the major etiology of each lesion was determined.

Results

The median duration following stent implantation was 10 (range 1–20) years. The most frequent etiology of VLST was neoatherosclerotic rupture (44%) followed by neointimal erosion (24%). Edge disease (10%) and evagination (10%) were similarly observed. Malapposition (8%) was mostly acquired late by going back to the index procedure. Uncovered strut (2%) and in-stent calcified nodule (2%) were the least frequent etiologies. Regardless of etiology, signs of neoatherosclerosis were present in most (82%) lesions. Most patients received single (68%) or dual (8%) antiplatelet therapy or oral anticoagulation alone (4%), whereas considerable proportion of patients stopped any medication (20%). Regarding the treatment strategy, drug-coated balloon was the most frequent strategy (56%), followed by newer DES implantation (34%).

Conclusion

The mechanisms underlying VLST in Japanese patients were unique, with neoathersclerotic rupture and neointimal erosion accounting for two-thirds of cases of VLST. In these patients, biological responses seemed to be more relevant rather than index procedure-related factors.
Cost effectiveness analysis of drug coated balloon only angioplasty for de novo coronary artery disease intervention
Authors: Merinopoulos I , Gunawardena T , Corballis N , Tsampasian V , Vassiliou V , Eccleshall S , Ryding A , Xydopoulos G
Published: November 2023

Background

DCB angioplasty is an emergent technology for the treatment of coronary artery disease. There is lack of data regarding the cost-effectiveness of DCB-only angioplasty for treatment of de novo coronary artery disease as compared with 2nd DES. We aimed to perform a cost analysis of drug coated balloon (DCB)-only angioplasty versus drug eluting stent (DES), for de novo disease of all vessel sizes and all clinical indications.

Methods

We compared total costs of patients treated with DCB or DES for first presentation of ST elevation myocardial infarction, non-ST elevation myocardial infarction or stable angina due to de novo disease between 1st January 2018 and 15th November 2019. The health economics analysis was undertaken from the National Health Service perspective, using the national annually published resource, the Personal Social Services Research Unit (PSSRU) and Unit Costs of Health and Social Care 2022. We defined total cost as the sum of 1) procedural devices-cost 2) procedural staff-cost 3) post-PCI hospital stay cost 4) antiplatelet regime cost. A cost minimisation analysis was performed to compare the costs of DCB and DES.

Results

We present 1952 all-comer, consecutive patients; 902 (1064 lesions) treated with DCB and 1050 (1186 lesions) treated with DES for de novo coronary artery disease. There were very few differences in terms of baseline clinical characteristics. The DCB group had more patients with history of stroke or heart failure while the DES group had more patients with history of smoking or chronic obstructive pulmonary disease. More scoring balloons were used in the DCB group while more intravascular imaging was used in the DES group. The average procedural duration was slightly shortened in the DCB group. The cost per patient was estimated to be £9.02 more expensive in the DCB group (£3153.00 versus £3143.98) (Fig 1). However, the cost per lesion treated was calculated to be £44.29 cheaper in the DCB group (£3007.56 versus £3051.85) (Fig 2). The results were consistent irrespective of duration of long-term antiplatelet medications. Apart from the deterministic analysis, the probabilistic sensitivity analysis showed that in terms of cost per lesion, DCB presents a 92.3% probability of being cost saving.

Conclusion

We have demonstrated for the first time that DCB-only angioplasty has similar cost to DES per patient and is cost-effective compared to DES in de novo coronary artery disease at the lesion level.DCB vs DES cost per patientDCB vs DES cost per lesion
NT-pro-BNP pre TAVI and relationship with long-term outcomes
Authors: Soerensen L M , Petersen J K , Strange J E , Schou M , Koeber L , De Backer O , Fosbol E
Published: November 2023

Background

Blood levels of NT-proBNP correlates with aortic valve stenosis and has been suggested as a future target for intervention or selection of patients for aortic valve replacement.

Purpose

To examine how levels of NT-proBNP pre-TAVI relates to risk of one-year rates of heart failure admission and mortality in patients undergoing TAVI.

Methods

With Danish nationwide registries, we identified all patients undergoing TAVI from 2014–2021 who had available pre-TAVI NT-pro-BNP measured up to one year prior to TAVI. According to NT-proBNP blood samples, patients were classified according to quartiles of pre-TAVI NT-proBNP levels. The quartiles were then converted into two final groups: Q1-3 including patients with NT-proBNP< 420 pmol/L and Q4 including patients with a NT-proBNP ≥ 420 pmol/L. Groups were compared using cumulative incidence curves of post-TAVI heart failure admissions and Kaplan-Meier estimates to assess comparative all-cause mortality. Adjusted rates of outcomes were assessed, using multivariable Cox analysis, with patients with NT-proBNP< 420 pmol/L serving as reference.

Results

We identified 1,140 patients undergoing a first-time TAVI procedure (53.1% male, median age 81 year) with an availabel NT-pro-BNP (19.5% of the national chohort of TAVI patients). Of these, 846 (74.21%) patients had a NT-proBNP < 420 pmol/L (55.0% male, median age 81 year) and 294 (25.79%) patients with NT-proBNP ≥ 420 pmol/L (53.1% male, median age 82 year). The one-year cumulative incidence of heart failure was 9.1% and 23.1% for patients with a NT-proBNP <420 pmol/L and ≥ 420 pmol/L, respectively (p<0.001) (Figure 1). This corresponded to an adjusted hazard ratio of 1.91 (95% CI: 1.33–2.74). The one-year cumulative incidence of all-cause mortality was 6.0% and 14.6% for patients with a NT-proBNP <420 pmol/L and ≥ 420 pmol/L, respectively (p<0.001) (Figure 1). This corresponded to an adjusted hazard ratio of 1.85 (95% CI: 1.17-2.92).

Conclusion

In patients undergoing TAVI, a baseline NT-proBNP ≥ 420 pmol/L was associated with increased one-year rates of heart failure admissions and mortality post-TAVI. The results suggest that NT-proBNP is associated with adverse outcomes on the long-term and that this could be a target for intervention.Figure 1:HF admission and mortality
Long-term structural right heart remodeling following transcatheter annuloplasty for treating severe tricuspid regurgitation assessed by CT scan
Authors: Pardo Sanz A , Salido Tahoces L , Gonzalez Martin S , Hinojar Baydes R , Garcia Martin A , Gonzalez Gomez A , Garcia Sebastian C , Sanroman Guerrero M A , Fernandez-Golfin Loban C , Mestre Barcelo J L , Arteagoitia Bolumburu A , Gonzalez Leal A , Zamorano Gomez J L , Sanchez Recalde A
Published: November 2023

Background

Transcatheter tricuspid annuloplasty has emerged as an attractive percutaneous therapy for patients with severe symptomatic tricuspid regurgitation. Cardioband (Edwards) was the first dedicated CE marked percutaneous device for tricuspid regurgitation. Despite mid-long-term clinical safety and efficacy demonstrated in early feasibility trials and registries, there is no data about its impact on right heart structural remodeling using computed tomography (CT). Our aim was to assess right heart remodeling and changes in the tricuspid annulus (TA) one year after Cardioband implantation.

Methods

A total of 30 patients were prospectively included in the study; 21 of them had baseline and at least 1-year follow-up CT analysis. The average time from the basal CT scan and the procedure was 118±136 days, and from the intervention to follow-up CT scan was 468±251 days. 2D and 3D analyses were performed with 3mensio version 10.3 at baseline and at least 12 months after Cardioband implantation.

Results

There was a significant decrease in right ventricular dimensions at follow-up (right ventricular basal diameter was 53.65 ± 8.45 mm at baseline Vs 48.54 ± 9.12 mm at 1-year follow-up; right ventricular mid cavity diameter was 40.30 ± 9.10 mm at baseline Vs 34.22 ± 9.22 at the end of follow-up, and right ventricular longitudinal diameter was 75.43 ± 9.85 mm at baseline Vs 69.95 ± 9.96 mm at the end of follow-up, all of them were statistically significant). A reduction in right atrial dimension was also observed (longitudinal diameter 66.86 ± 7.63 mm at baseline Vs 64.89 ± 9.99 mm at the end of follow-up; transverse diameter of 61.62 ± 8.38 mm at baseline Vs 60.59 ± 8.3 mm at the end of follow-up, p<0.001). There was a significant decrease in the area and diameters of the dilated TA (area at baseline 16.51 ± 3.06 cm2 vs 8.90 ± 2.71 cm2 at the end of follow-up, p=0.02; septolateral diameter 45.42 ± 5.02 mm at baseline vs 33.87 ± 5.09 mm at the end of follow-up, p=0.01).

Conclusions

Long-term favorable right ventricular chambers and TA remodeling was observed following Cardioband implantation assessed by CT scan. This finding could explain the long-term clinical benefit demonstrated in feasibility studies.Right heart remodeling after Cardioband
Timing on patent foramen ovale closure: early versus delayed closure
Authors: Jeronimo A , Nombela-Franco L , Freixa X , Tomassini F , Lopez-Tejero S , Ojeda S , Veiga G , Goncalves-Ramirez L , Garcia-Blas S , Salinas P
Published: November 2023

Introduction

Pivotal randomized clinical trials showed benefit in patent foramen ovale closure (PFOC) up to 9 months after a cryptogenic stroke or transient ischemic attack (TIA) [1-4]. It might be sensible to indicate PFOC also in non-recent cryptogenic strokes, but evidence is lacking.

Purpose

We aimed to compare the effectiveness of PFOC according to the time elapsed from the patient’s last episode of cryptogenic cerebrovascular event (CVE) or systemic embolism (SE).

Methods

A retrospective, international, multicentre, cohort study was performed to compare the outcomes of an early closure (EC, <9 months) or delayed closure (DC, ≥9 months) of patent foramen ovale (PFO) as secondary prevention after the index event. The primary end-point was recurrence of CVE or SE after PFOC.

Results

A total of 325 and 171 patients were classified in the EC and DC groups, with a median time to PFOC of 3.4 (IQR 1.9-5.5) and 17.5 (IQR 12.2-33.4) months, respectively. No significant differences were observed regarding the type of event indicating PFOC (stroke was the most frequent (77.8% in EC group vs 79.0% in DC group), followed by TIA (19.4% vs 18.7%)); neither about neuroanatomic localization of the lesions, nor contrast transcranial Doppler patterns, nor Risk of Paradoxical Embolism (RoPE) score (7 (IQR 5-8) vs 6 (IQR 5-7), p=0.077). Echocardiographic PFO characteristics of both groups were similar, except for a larger defect size (tunnel width) in the DC group (6 (IQR 4-14) vs 12 (IQR 6-16) mm, p=0.005)). PFOC device, procedural success (99.4 in EC vs 98.8% in DC group) and periprocedural complications (2.1 vs 0.8%) were comparable in both groups. Median follow-up was 2.0 (IQR 1.3-3.8) years in the EC group and 2.2 (IQR 1.2-4.9) in the DC group (p=0.721). No significant differences were observed concerning recurrence of stroke, TIA or SE (3.9% vs 2.6%, p=0.443), time from PFOC to recurrence (0.9 (IQR 0-2.1) vs 6.1 (2.5-8.8) years, p=0.090), death (1.4% vs 1.0%, p=0.697), residual shunt 12 months after PFOC, or antithrombotic treatment during follow-up (Figure 1). Moreover, a subanalysis considering those patients with a very delayed PFOC (≥24 months) after the index event also showed no differences in recurrence rate during follow-up compared to the earlier procedures (4.2% in the <24-month group vs 3.4% ≥24-month group, p=0.770).

Conclusions

No differences were observed regarding recurrences of CVE/SE in patients undergoing PFOC before and after 9 months from the index event. Despite the absence of evidence from randomized trials, this study suggests that the preventive benefit of PFOC after a cryptogenic CVE/SE may be extended beyond 9 months after the last event.Figure 1:Incidence of recurre
Feasibility and accuracy of real-time 3D-holographic graft length measurement, a sub-study of the FAST-TRACK CABG trial
Authors: Tsai T , Kageyama S , He X C , Onuma Y , Pompilio G , Andreini D , La Meir M , De Mey J , Puskas J , Narula J
Published: November 2023

Background

3D Hologram is an emerging tool for intuitively manipulating and visualizing CT images. Mixed reality (MR) technology can display high-definition 3D holograms while preserving situational awareness. The new MR software offers the possibility to measure 3D objects using hand gestures and voice commands. However, these measurements made on 3D holograms have not been validated.

Purpose

We aimed to assess the feasibility and accuracy of using CT-derived 3D holograms for bypass graft length measurement.

Methods

Twenty-seven consecutive cases in the FAST TRACK CABG trial were included. The post-operative CT images performed at 30 days follow-up were analyzed in an independent core lab. Two analysts blinded to clinical information performed Holographic reconstruction and measurement using the CanaLife Holo software (Medapp, Krakow, Poland). (Figure 1) Inter-observer agreement was assessed in the first 20 cases. Another analyst with full access to clinical information performed the validation measurements on the CardIQ W8 system (GE Healthcare, Milwaukee, Wisconsin). (Figure 1)

Results

A total of 62 grafts (27 left internal mammary artery grafts, 27 saphenous vein grafts, and 8 right internal mammary artery grafts) were measured. There was an excellent inter-observer agreement between the analysts in the first 47 grafts analyzed (interclass correlation 0.9879 [0.9783-0.9933]). (Figure 2A, 2B) On average, holographic reconstruction and measurement of a case took 3 minutes and 36 seconds± 50.74 seconds compared to around 10 minutes per vessel on the traditional CT system. There was no significant difference between the graft length measured by hologram and CT (188.59±51.63 mm vs. 183.95±50.93 mm, p=0.616). The length measured by hologram and CT were similar across different graft types. The measurements of hologram and CT are highly correlated (r=0.973, p <0.001) with an excellent agreement (interclass correlation 0.9928 [0.9880-0.9957]). (Figure2C, 2D)

Conclusion

Holographic vessel length measurement is feasible, fast, and accurate even for tortuous coronary bypass grafts. This new methodology can empower surgeons to visualize and measure the results of their work by themselves and may provide insights for procedure evaluation. 3D Holograms can eventually empower surgeons to plan the precise length of the arterial and venous grafts to be harvested for every individual case.
Ten years follow-up after aortic valve replacement with bioprosthesis trifecta: a single center retrospective cohort
Authors: Goncalves C , Cerqueira R , Araujo J , Moreira S , Palma P , Almeida J , Amorim M J , Pinho P , Diaz S O , Barros A S , Lourenco A P , Saraiva F , Leite- Moreira A
Published: November 2023

Introduction

St. Jude’s Trifecta (TF) bioprosthesis were adopted at most centers due to their unique design and hemodynamic performance. However, concerns regarding durability have been raised and long-term follow-up studies (≥10 years) are scarce.

Purpose

To report hemodynamic performance as well as early and long-term results of TF valve.

Material and Methods

In this longitudinal, single-center study, consecutive patients that underwent surgical aortic valve replacement with TF, from July 2011 to June 2019 were included. Pre-, intra- and post-operative data, including routine and first outpatient ambulatory postoperative transthoracic echocardiogram (TTE) (median 4 months) were collected. Hospital mortality was defined as in-hospital or within the first 30 days after surgery. Survival and need for reoperation were accessed in December 2021. Median follow-up was 4 years and maximum was 10,5 years. Kaplan-Meier method was used for time-to-event outcomes (all-causes mortality and need for reoperation).

Results

We included 1084 patients, 54% being male, with a mean age of 74±8 years. Surgery priority was elective in 840 (78%) of cases. Most patients received a TF prothesis of size 23 (35%), followed by size 21 (30%). There were 563 (52%) multiple procedures, mostly coronary artery bypass grafting (46% within the multiple procedures). Bypass and clamping times were 86±31 minutes and 62±22 minutes, respectively for isolated procedures, and 143±27 minutes and 100±40 minutes, respectively, for multiple procedures. Hospital mortality was 6%. Excluding these patients, cumulative survival at 1-, 3-, 5- and 10-years, were, respectively, 96%, 89%, 78% and 52%. There were 27 patients who needed reoperation: 16 due to endocarditis, 5 due to structural valve deterioration (SVD) and 6 due to non-structural valve dysfunction. Freedom from reoperation at 1-, 3-, 5- and 10- years were of 99%, 98%, 98% and 95%, respectively. At follow-up TTE (n=995), transvalvular mean gradient was 11±4 mmHg and the effective orifice area mean was 2.1±0.5cm2. Patient-prosthesis mismatch occurred in 79 (9.1%), being severe in 8 (0,9%) cases.

Conclusion

Our findings confirm the satisfactory hemodynamics and safety profile of TF bioprosthesis. Long-term results are comparable with published TF series and there seems to be no particular sign of adverse valve-related events in our population.
Should women have lower thresholds for hypertension? Severe ultrastructural abnormalities in systemic arterioles of normotensive and hypertensive women
Authors: Brewster L M , Perrotta I D , Taherzadeh Z , Van Montfrans G E R T
Published: November 2023

Background

Hypertension in women is increasingly recognized to originate in the pre-menopause, but the factors that may affect the greater blood pressure increments observed in premenopausal women compared to age-matched men are understudied.

Uterine fibroids, occurring in 30-50% of all women, are a strong sex-specific factor associated with hypertension and early cardiovascular events, but the nature of this association is not known. To assess a possible shared pathology of smooth muscle, we studied the ultrastructure of systemic resistance arteries of women with fibroids.

Methods

Resistance-sized arteries (200 to 400 μm) were harvested from omental samples obtained during fibroid surgery. Transmission electron microscopic images were taken at different magnifications and locations of the vessel wall to assess qualitative and morphological characteristics. Mean blood pressure was calculated as DBP+1/3(SBP-DBP).

Results

Resistance arteries of 17 women (8 hypertensive, 4 treated), mean age 42 (SE 1) y, were available for analysis. None had a history of cardiovascular disease. Mean blood pressure was 91.4 mm Hg in normotensives and 119.4 in hypertensives.

The endothelium showed mitochondrial and endoplasmic reticulum stress in normotensives (Figure, Panel A), to necrosis and sloughing in hypertensives (B).

Myocyte-like cells were observed to migrate across the internal elastic lamina, forming small aggregates of subendothelial myocytes in normotensives (C), and larger subendothelial myo-intimal "cushions" in hypertensives (D).

Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria and myofilament loss involving focal areas or entire cells (E, clinically considered normotensive).

Untreated hypertensives had a significantly higher intima-media thickness-to-lumen ratio (%) than normotensives and treated hypertensives as expected, respectively 15.9 (1.8), 12.5 (1.6) and 13.4 (2.1).

Conclusion

To our knowledge the first ultrastructure data of systemic resistance-sized arteries in women with fibroids, show that young premenopausal women considered clinically normotensive already have severe microvascular abnormalities that may cause or reflect perturbations in microvascular function and predispose to early end organ damage.

While there is abundant clinical evidence that the association between blood pressure and cardiovascular events is stronger in women, hypertension in women is understudied. In particular women-specific risk factors are ill-understood.

Our observations are relevant to the current discussion regarding whether the clinical threshold for hypertension treatment is too high for women and whether earlier management of cardiovascular risk is needed. Further studies are warranted in a woman-specific research agenda on cardiovascular risk factors in younger premenopausal women.Figure
Improved health-related quality of life after renal denervation in patients with resistant hypertension: 3-year outcomes in the global symplicity registry
Authors: Mahfoud F , Weil J , Mancia G , Schmieder R E , Ruilope L , Schlaich M , Narkiewicz K , Williams B , Fahy M , Bohm M
Published: November 2023

Background

Hypertension is associated with increased mental anxiety and depression. Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled, resistant hypertension (rHTN). The Global SYMPLICITY Registry (GSR) DEFINE is a prospective, open-label, single-arm, all-comer worldwide study, enrolling patients to undergo RDN. Whether BP reductions after RDN improve patients’ self-reported health and quality of life through long-term follow-up remains elusive.

Purpose

To evaluate changes in self-reported health and quality of life of rHTN patients following radiofrequency RDN.

Methods

GSR DEFINE patients completed the EuroQoL five-dimensions three-level (EQ-5D) questionnaire to assess their own health state on a visual analog scale (VAS: 0 to 100, with 0 being ‘worst possible’ and 100 being ‘best possible'). Patients were also asked to assess five dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, anxiety/depression at 3 levels: no problems (score: 0), some problems (1), severe problems (2). Patients answered the questionnaire at 6, 12, 24, and 36-month follow-up after the RDN procedure. Categorical measures from the pooled results of the questionnaire between subgroups were compared using the Kruskal-Wallis test. Here we assess the self-reported health state and quality of life measures among patients with rHTN (office systolic BP ≥150 mmHg and on ≥3 antihypertensive drugs) at baseline through 36 months.

Results

At baseline, GSR patients with rHTN (n=2051) had an office systolic blood pressure (OSBP) of 175.2 ± 19.8 mmHg and a 24-h ambulatory systolic blood pressure (ASBP) of 157.4 ± 18.6 mmHg. At 36 months after RDN, rHTN patients had significant reductions in OSBP (-23.5 ± 27.0 mmHg; n=906; p<0.001) and ASBP (-10.3 ± 20.9 mmHg; n=329; p<0.001), respectively. Antihypertensive medication remained unchanged through 36 months. Correspondingly, patients with rHTN reported a significant improvement in the self-reported health state from baseline after RDN at each follow-up through 36 months (Figure). At baseline (n=1813), patients with rHTN reported a 0.86 ± 0.20 EQ-5D quality of life score. At 36 months (n=839), patients with rHTN reported an improved quality of life with a 0.85 ± 0.21 score which was a statistically significant change from baseline (p=0.0024).

Conclusion

Following RDN, self-reported health state and quality of life data from a large population of rHTN patients improved from baseline through 36-months. These results suggest that BP reductions following radiofrequency RDN may alleviate mental anxiety and depression associated with hypertension.