bluuebunny/crossref_metadata_2025 huggingface dataset:
Computing eigenvalues of the Laplacian on rough domains
Authors: Rösler Frank , Stepanenko Alexei
Published: January 2023

We prove a general Mosco convergence theorem for bounded Euclidean domains satisfying a set of mild geometric hypotheses. For bounded domains, this notion implies norm-resolvent convergence for the Dirichlet Laplacian which in turn ensures spectral convergence. A key element of the proof is the development of a novel, explicit Poincaré-type inequality. These results allow us to construct a universal algorithm capable of computing the eigenvalues of the Dirichlet Laplacian on a wide class of rough domains. Many domains with fractal boundaries, such as the Koch snowflake and certain filled Julia sets, are included among this class. Conversely, we construct a counterexample showing that there does not exist a universal algorithm of the same type capable of computing the eigenvalues of the Dirichlet Laplacian on an arbitrary bounded domain.
The interior penalty virtual element method for the biharmonic problem
Authors: Zhao Jikun , Mao Shipeng , Zhang Bei , Wang Fei
Published: January 2023

In this paper, an interior penalty virtual element method (IPVEM) is developed for solving the biharmonic problem on polygonal meshes. By modifying the existing

H
2

H^2

-conforming virtual element, an

H
1

H^1

-nonconforming virtual element is obtained with the same degrees of freedom as the usual

H
1

H^1

-conforming virtual element, such that it locally has

H
2

H^2

-regularity on each polygon in meshes. To enforce the

C
1

C^1

continuity of the solution, an interior penalty formulation is adopted. Hence, this new numerical scheme can be regarded as a combination of the virtual element space and discontinuous Galerkin scheme. Compared with the existing methods, this approach has some advantages in reducing the degree of freedom and capability of handling hanging nodes. The well-posedness and optimal convergence of the IPVEM are proven in a mesh-dependent norm. We also derive a sharp estimate of the condition number of the linear system associated with IPVEM. Some numerical results are presented to verify the optimal convergence of the IPVEM and the sharp estimate of the condition number of the discrete problem. Besides, in the numerical test, the IPVEM has a good performance in computational accuracy by contrast with the other VEMs solving the biharmonic problem.
Random orthonormal polynomials: Local universality and expected number of real roots
Authors: Do Yen , Nguyen Oanh , Vu Van
Published: January 2023

We consider random orthonormal polynomials

F

n

(
x
)
=

∑

i
=
0

n

ξ

i

p

i

(
x
)
,

\begin{equation*} F_{n}(x)=\sum _{i=0}^{n}\xi _{i}p_{i}(x), \end{equation*}

where

ξ

0

\xi _{0}

, …,

ξ

n

\xi _{n}

are independent random variables with zero mean, unit variance and uniformly bounded

(
2
+
ε
)

(2+\varepsilon )

moments, and

(

p
n

)

n
=
0

∞

(p_n)_{n=0}^{\infty }

is the system of orthonormal polynomials with respect to a fixed compactly supported measure on the real line.

Under mild technical assumptions satisfied by many classes of classical polynomial systems, we establish universality for the leading asymptotics of the average number of real roots of

F
n

F_n

, both globally and locally.

Prior to this paper, these results were known only for random orthonormal polynomials with Gaussian coefficients (see D. D. Lubinsky, I. E. Pritsker, and X. Xie [Proc. Amer. Math. Soc. 144 (2016), pp. 1631–1642]) using the Kac-Rice formula, a method that does not extend to the generality of our paper.
A novel tool for the unbiased characterization of epithelial monolayer development in culture
Authors: Dawney Nicole S. , Cammarota Christian , Jia Qingyuan , Shipley Alicia , Glichowski Joseph A. , Vasandani Muskaan , Finegan Tara M. , Bergstralh Dan T.
Published: January 2023

A novel tool, ALAn (Automated Layer Analysis), is developed to classify the architecture of epithelial cell layers in three dimensions. The rearrangement of MDCK cells in the apical-basal axis is dependent on substrate availability, and the lack of substrate leads to disorganization.
Hannah Arendt: A Very Short Introduction
Authors: Villa Dana
Published: January 2023

The book provides an overview of Hannah Arendt’s (1906‒75) contributions to political thought and philosophy, along with a sketch of her dramatic life story. A German-Jewish refugee from Hitler’s Germany, Arendt escaped to America and became one of its most respected political thinkers and public intellectuals. The book provides summary and discussion of Arendt’s primary works, including The Origins of Totalitarianism, Eichmann in Jerusalem, The Human Condition, On Revolution, and the posthumously published The Life of the Mind. It also examines criticisms of her work, and dispels some common but surprisingly widespread misinterpretations.
Judging, thinking, and willing
Authors: Villa Dana
Published: January 2023

This chapter examines Arendt’s theory of political and moral judgment, which is the “other side” of her theory of political action. It describes how her interest in the nature of judgment was piqued by the trial of Adolf Eichmann in Jerusalem. Eichmann’s thoughtlessness and his failure to judge spurred Arendt to investigate this all-important faculty, and to suggest that the activity of thinking as such helps condition us against evil-doing. The chapter also describes how Arendt’s interest in the mental activity of thinking or reflection led her to juxtapose it to willing, our faculty for the future and for spontaneous beginning.
308 Tralokinumab provides other clinically meaningful improvements in adolescents with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16
Authors: Paller Amy , Blauvelt Andrew , Soong Weily , Hong Chih-ho , Schuttelaar Marie L A , Schneider Shannon  , Moerch Marie Holst , Simpson Eric 
Published: January 2023

In the monotherapy phase 3 trial (ECZTRA 6, NCT03526861) in adolescents with moderate-to-severe atopic dermatitis (AD) treated with tralokinumab, IGA of clear/almost clear skin (IGA 0/1) at week 16 was a primary endpoint. IGA 0/1 can be a high standard to achieve for patients with moderate-to-severe AD and may not fully reflect achievement of other clinically meaningful parameters, such as improvement in signs, symptoms and/or quality-of-life (QoL). To assess the impact of tralokinumab (150 or 300 mg) vs. placebo on other clinically meaningful parameters at week 16 in the subset of patients who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Adolescents (12–17 years) were randomized to subcutaneous tralokinumab 150 or 300 mg, or placebo, every 2 weeks. Patients who did not achieve IGA 0/1 at week 16 and/or utilized rescue therapy were included in this post-hoc analysis. Non-responder imputation was used for patients who utilized rescue therapy or had missing data. Clinically meaningful responses were defined as EASI-50, ≥ 3-point improvement in pruritus NRS, or ≥6-point improvement in CDLQI. At week 16, 78.6% and 82.5% of tralokinumab-treated patients (150 mg/300 mg) vs. 95.7% (placebo) exhibited IGA > 1 and/or used rescue therapy. 36.4% (150 mg) and 52.5% (300 mg) of patients with IGA > 1 in the tralokinumab arms, compared to 21.1% (placebo), achieved clinically meaningful responses in at least one measure: EASI-50, pruritus NRS, or CDLQI. Greater proportions of tralokinumab-treated patients (150/300 mg vs. placebo) achieved EASI-50 (31.2%/41.3% vs. 10.0%) and ≥3-point improvement in pruritus NRS (21.6%/22.8% vs. 8.0%). A greater proportion of tralokinumab 300 mg patients vs. placebo (35.2% vs. 15.0%) achieved ≥6-point improvement in CDLQI. Many tralokinumab-treated adolescents who did not achieve IGA 0/1 at week 16 and/or used rescue therapy still achieved clinically meaningful improvements in AD signs, symptoms, and/or QoL.
319 Effects of omega-3 fatty acid supplementation on atopic dermatitis
Authors: Abdelnour Alyssa M , Shareef Sarah J , Kreuser Kaitlin , Ashack Kurt
Published: January 2023

Oral supplements are commonly used by patients to enhance skin health for aesthetic purposes and in response to cutaneous disorders. Currently, the Food and Drug Administration (FDA) is not authorized to approve the efficacy or safety of dietary supplements prior to public marketing. Therefore, evidence-based medicine is needed for dermatologists to better counsel patients regarding oral supplementation. Physicians must take this into consideration while treating patients with chronic conditions, such as atopic dermatitis (AD). AD is the most common cutaneous inflammatory disease affecting individuals from infancy through adulthood. Prevention and management are focused on avoiding environmental triggers, daily skin care with emollients and/or topical steroids, and decreasing systemic inflammation. Patients with AD use various treatment options and over-the-counter supplements throughout their lifetime. Interestingly, omega-3 fatty acids (O3FA) are marketed for their anti-inflammatory effects and have been widely studied to understand health benefits. To our knowledge, the effects of oral supplementation of O3FA (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) for AD are not summarized in the literature. Thus, this study was conducted to examine O3FA’s impact on AD and ultimately, to determine if supplementation is an effective therapy for the prevention and/or treatment of AD. A comprehensive electronic search with EPA and DHA for atopic dermatitis in PubMed/MEDLINE, Cochrane Central, Embase, and Google Scholar yielded 45 articles. Duplicate, non-English articles and irrelevant articles were excluded. These parameters resulted in 38 articles being excluded as they did not meet study qualifications. Therefore, seven articles are included in this review. Of the included articles, 2/7 studies discussed an improvement in skin inflammation with O3FA supplementation, while 5/7 did not find a significant difference in the prevention of allergic disease. On the other hand, one trial resulted in a significant decline in the prevalence of eczema and another indicated significant clinical improvement compared to baseline, but not in comparison to the placebo. O3FA supplementation is not effective in preventing allergic symptoms, but may decrease the prevalence of AD and provide clinical improvement. Further evaluation is needed to characterize the efficacy of O3FA supplementation in the prevention and treatment of AD.
353 Amlitelimab reduces serum IL-13 in a phase 2a clinical trial in atopic dermatitis without impacting T-cell expansion in a T-cell recall assay
Authors: Weidinger Stephan , Cork Michael , Reich Adam  , Bieber Thomas , Lucchesi Davide  , Rynkiewicz Natalie  , Sainson Richard C A   , Chen Ron  , Prandi Francesca , van Krinks Cassandra  , Stebegg Marisa , Porter-Brown Ben 
Published: January 2023

Amlitelimab (SAR445229), a fully human non-depleting, non-cytotoxic, monoclonal antibody, binds to OX40Ligand (OX40L) on antigen-presenting cells (APC) to block OX40-OX40L interactions. In a 16-week, double-blind, Phase 2a trial (NCT03754309), amlitelimab induced clinically meaningful disease activity improvement in patients with moderate-to-severe atopic dermatitis (AD). To assess the effects of amlitelimab on interleukin (IL)-13 and T-cell recall responses. In the trial, 89 patients were randomized to amlitelimab low dose (LD; 200 mg loading/100 mg maintenance every 4 weeks [Q4W]), high dose (HD; 500 mg loading/250 mg maintenance Q4W), or placebo. Serum IL-13 levels were assessed by single molecule immunoassay (259 samples). Using human peripheral blood mononuclear cells from five healthy donors, a T-cell recall assay was performed. At baseline in the trial, IL-13 levels significantly correlated with disease severity (Eczema Area and Severity Index; r = 0.4784, P < 0.0001). Week 16 IL-13 levels were significantly reduced with amlitelimab vs. baseline but not placebo (median fold change [95% confidence interval, CI] from baseline to week 16 with P-values based on two-way Analysis of Variance [ANOVA] of log10-transformed fold change for patients with a complete dataset at week 16: LD 0.345 [0.23–0.44], P < 0.0001; HD 0.390 [0.30–0.63], P = 0.0002; placebo 0.835 [0.34–1.12], P = 0.1544). In a T-cell recall assay, amlitelimab significantly reduced IL-13 protein levels at days 3 and 6 without negatively impacting T-cell expansion, based on the percentage of proliferating CD4+ T-cells vs. isotype control. Amlitelimab decreased IL-13 levels in patients with AD and in a T-cell recall assay without negative effects on T-cell expansion, thus reducing inflammation without blocking T-cell proliferation during recall responses.
Perspectives on Adherence From the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach With 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment
Authors: Sowah Leonard A , Smeaton Laura , Brates Irena , Bhattacharya Debika , Linas Benjamin , Kreter Bruce , Wagner-Cardoso Sandra , Solomon Sunil , Sulkowski Mark , Robbins Gregory K
Published: January 2023

Background

With the advent of efficacious oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial.

Methods

ACTG A5360 enrolled HCV treatment-naive persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression.

Results

In total, 400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24. Median age was 47 years with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% confidence interval [CI] [94.1%, 97.9%]) vs 77.8% (95% CI [59.2%, 89.4%]) P value < .001. In the multivariate model age <30 years and being a US participant were independently associated with early sub-optimal adherence. Participants <30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts.

Conclusions

Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals <30 years may also be prioritized for additional adherence support.

Clinical Trials Registration. NCT03512210.
Structure Fault Tolerance of Exchanged Hypercube
Authors: Liu Heqin , Cheng Dongqin
Published: January 2023

The undirected graph, exchanged hypercube $EH(s,t)$, is a variant of hypercube proposed by Loh et al. It is obtained by removing some links from $(s+t+1)$-dimensional hypercube. It retains many excellent properties, so many people have studied its reliability and fault tolerance. In this paper, combining the structure connectivity and substructure connectivity of graphs proposed not long ago, we obtain its $P_k$-path, $C_{2l}$-cycle and $K_{1,r}$-star structure connectivity and substructure connectivity where $2\le k,r\le s-1\le t-1$ and $6\le 2l\le s-1\le t-1$; we also establish $\kappa ^s(EH(s,t);C_4)$ for $5\le s\le t$ and the upper bound of $\kappa (EH(s,t);C_4)$ for $4\le s\le t$.
The nature of losses from cyber-related events: risk categories and business sectors
Authors: Shevchenko Pavel V , Jang Jiwook , Malavasi Matteo , Peters Gareth W , Sofronov Georgy , Trück Stefan
Published: January 2023

In this study, we examine the nature of losses from cyber-related events across different risk categories and business sectors. Using a leading industry dataset of cyber events, we evaluate the relationship between the frequency and severity of individual cyber-related events and the number of affected records. We find that the frequency of reported cyber-related events has substantially increased between 2008 and 2016. Furthermore, the frequency and severity of losses depend on the business sector and type of cyber threat: the most significant cyber loss event categories, by number of events, were related to data breaches and the unauthorized disclosure of data, while cyber extortion, phishing, spoofing, and other social engineering practices showed substantial growth rates. Interestingly, we do not find a distinct pattern between the frequency of events, the loss severity, and the number of affected records as often alluded to in the literature. We also analyse the severity distribution of cyber-related events across all risk categories and business sectors. This analysis reveals that cyber risks are heavy-tailed, i.e. cyber risk events have a higher probability to produce extreme losses than events whose severity follows an exponential distribution. Furthermore, we find that the frequency and severity of cyber-related losses exhibit a very dynamic and time-varying nature.
Contribution Threat Perception, School Climate and Prejudice as Mediator to Student’s Cyber Aggression
Authors: Mardianto Mardianto , Hartati Niken , Aulia Farah , Fikry Zulian , Utami Rahayu Hardianti , Magistarina Elrisfa
Published: January 2023

This study aims to test students’ cyber aggression models based on previous studies, especially those related to high school students’ Cyber Aggression behavior. Following the stages of adolescent development, this research uses the socio-ecological theoretical perspective of the cyber context. This study determines several predictive variables as risk factors and protective factors that have the most potential to influence student cyber aggression, such as perceived threats, school climate, and prejudice. The model tested in this study is the role of the perceived threat and school climate on students’ Cyber Aggression behavior mediated by prejudice. This study uses a quantitative approach with structural equation modeling analysis, namely the structural equation model (SEM). The sampling technique used in this study is purposive sampling. The subjects of this study are high school students who actively use social media every day, with 1118 students as respondents from several cities in Indonesia. The result shows that the theoretical model of students’ Cyber Aggression behavior as per the empirical conditions in the field has met the goodness of fit model standard, meaning that the perception of threats and the school climate-mediated by prejudice were simultaneously proven to play a role as predictors of student Cyber Aggression
Electrocardiographic predictors of disease severity, mortality, and advanced ventilatory support among hospitalized covid-19 patients: a two year single center retrospective, cohort study
Authors: Vista G , Vestal M
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

For detecting myocardial injury in severe and critical COVID-19, the electrocardiogram (ECG) is neither sensitive nor specific; but in a resource-poor environment, it remains relevant. Changes in the ECG can be a potential marker of severe and critical COVID-19 to be used for predicting not only disease severity but also the prognosis for recovery.

Methods

The admitting and interval ECGs of 1,333 COVID-19 patients were reviewed in a two-year, single-center, retrospective cohort study. Each was evaluated for 29 pre-defined ECG patterns under the categories of rhythm, rate, McGinn-White and RV overload patterns, axis and QRS abnormalities, ischemia/infarct patterns, and AV blocks before univariate and multivariate regression analyses for correlation with disease severity; need for advanced ventilatory support; and in-hospital mortality.

Results

Of the 29 ECG patterns, 18 showed a significant association with the dependent variables on univariate analysis. Multivariate analysis revealed that atrial fibrillation, HR >100 bpm, low QRS voltage, QTc >500msec, diffuse nonspecific T-wave changes, and "any AMI" ECG patterns correlate with disease severity; need for advanced ventilatory support and in-hospital mortality. S1Q3 and S1Q3T3 increased the odds of critical disease and need for high oxygen requirement by 2.5-3 fold. Fractionated QRS increased odds of advanced ventilatory support.

Conclusion

The ECG can be useful for predicting the severity and outcome of more than moderate COVID-19. Their use can facilitate rapid triage, predict disease trajectory, and prompt a decision to intensify therapy early in the disease to make a positive impact on clinical outcomes.
Demographic, clinical, and echocardiographic factors predicting maintenance of sinus rhythm following first elective cardioversion
Authors: Plant A , Hooks D , Larsen P
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background/Introduction

Atrial fibrillation is common. Cardioversion to restore sinus rhythm is successful in over 90% of cases, but reversion to atrial fibrillation within a year occurs in the majority. Although predictors of maintenance of sinus rhythm following cardioversion have been described, to our knowledge no study has looked specifically at the population of patients undergoing first elective cardioversion for atrial fibrillation.

Purpose

We aimed to examine the demographic, clinical, and echocardiographic parameters that predict the maintenance of sinus rhythm to one year following first elective cardioversion, with the goal of generating a prediction tool to aid patient selection for the procedure.

Methods

Coding data was used to identify all patients who had undergone elective cardioversion at two centres in central New Zealand over a five-year period. Those with previous cardioversion were excluded. A range of demographic, clinical, and echocardiographic variables were collated, and univariate followed by multivariate analysis conducted to identify predictors of maintained sinus rhythm at one year, evidenced by documented recurrence of arrhythmia in the clinical record.

Results

287 patients underwent first elective cardioversion across both sites, restoring sinus rhythm in 86% with 39% in sinus rhythm at one year. Atrial flutter (66 patients) had higher rates of successful cardioversion (96%), and maintained sinus rhythm (64%) than atrial fibrillation (83% and 32%), whilst cardioversion in one centre (52% vs. 31%) and the absence of paroxysmal symptoms (41% vs. 26%) were both associated with higher likelihood of maintained sinus rhythm at one year. Only the presence of atrial flutter (OR 1.34, P<0.001), and cardioversion in one of the centres (OR 1.19, P=0.002) increased the odds of maintained sinus rhythm at one year in multivariate analysis.

A range of other demographic (age, gender, BMI), clinical (duration of symptoms, antiarrhythmics, renal function), and echocardiographic (left atrial volume, left ventricular ejection fraction, mitral valve dysfunction) variables failed to predict restoration and maintenance of sinus rhythm.

Conclusion

In patients undergoing first elective cardioversion, the presence of atrial flutter and site of cardioversion both predict maintained sinus rhythm at one year. A range of other demographic, clinical, and echocardiographic variables shown elsewhere to predict sinus rhythm after cardioversion fail to do so in this study. This negative outcome likely reflects low numbers of patients in sinus rhythm at one year following first cardioversion, significant population heterogeneity, and small effect size of contributor variables. Overcoming this would require a substantially larger dataset, something that could be overcome through the use of a national dataset for patients undergoing cardioversion.
Frequent need for apixaban dose adjustment for atrial fibrillation in an unselected acute medical admission population during the COVID 19 pandemic
Authors: Kyaw K K K , Menown I B
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

During the COVID-19 pandemic, systematic switching patients of eligible patients with atrial fibrillation from warfarin to direct oral anticoagulants (DOACs) was encouraged to simplify drug dosing and obviate the need for regular monitoring. Regional exclusions to switching included mechanical heart valves, moderate to severe mitral stenosis and stage 5 chronic kidney disease (estimated glomerular filtration rate [eGFR]< 15ml/min/1.73m2). However, each DOAC requires dose adjustment depending on renal function and other patient factors.

Purpose

Failure to dose reduce when indicated leads to excessive serum drug concentration and increased risk of major haemorrhage, particularly in patients who are acutely unwell. We thus quantified the likelihood of need for dose adjustment in an unselected acute medical admission population.

Methods

While on call, a single investigator prospectively identified all patients admitted on the acute medical or cardiology take-in between 1/12/21 and 1/2/22 who were taking apixaban for atrial fibrillation. Apixaban was selected as the study DOAC as it was the most commonly used DOAC but had the most complex dose adjustment algorithm and hence risk of dose error. In order to determine the appropriate drug dosage, patient age, weight, serum creatinine and eGFR were recorded. Dose reduction to 2.5mg was required if the patient meet 2 of the following 3 criteria of [age>80 years, weight <60kg, serum creatinine >133umol/l], or a single criterion, had an eGFR <30ml/min/1.73m2. Drug discontinuation was required if eGFR was <15ml/min/1.73m2.

Results

All patients identified (n=50) had a CHA2DS2-VASc score of ≥2. Patients with active COVID-19 infection were excluded. Mean age was 77.2 years (range 46-102). Mean weight was 78kg (range 52-101). Mean serum creatinine was 212umol/l (range 62-595). Mean eGFR was 33ml/min/1.73m2 (range 8 to >60). Of the 50 patients, 24 (48%) were taking the appropriate apixaban dose on admission which did not require dose adjustment (18 of whom were appropriately taking 5mg bd and 6 were taking 2.5mg bd). Dose reduction from 5mg bd to 2.5mg bd was required in 17 (34%) patients. Stopping treatment, at least temporarily due to eGFR<15ml/min/1.73m2, was indicated in 9 (18%) of patients. No patient required an increase in drug dose. (Graph 1)

Conclusion

Over half of acute medical or cardiology patients admitted within a COVID-19 setting and taking apixaban for atrial fibrillation required at least temporary drug dose adjustment or discontinuation. Clinicians should expect that adjustment of apixaban dose may be required during acute admission.
Influence of non-apical permanent pacing on left ventricular systolic impairment
Authors: Baimbetov A , Jukenova A , Yakupova I , Bizhanov K , Tursunkhanov Z H , Bigeldiyev N , Azatkhanova N
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Right ventricular apical (RVA) pacing deleterious effects on left ventricular ejection fraction (LVEF) had been demonstrated. Non-apical pacing, such as right ventricular mid-septal (RVMS) and His Bundle pacing, appear as practical alternatives. Our purpose is to evaluate the effect of alternate sites of right ventricular (RV) pacing on left ventricular (LV) function and hemodynamics in patients with bradyarrhythmias.

Methods

We observed 118 patients (age 58±27 years, 64% men) with AV block III, who underwent permanent dual chamber pacemaker implantation. To 72 patients RV lead has implanted the middle area of RV septum (RVMS) and 46 patients’ RV lead has been implanted traditionally to the right ventricular apex (RVA). Color tissue velocity imaging was performed to analyze time to peak systolic velocity (Ts) in a 12 segment model of the LV for each pacing site. Measurements included standard deviation of time to peak systolic velocity (SD-Ts) for all segments, the maximal difference in Ts between any 2/6 basal (Ts-B), any 2/6 mid segments (Ts-M) and maximal Ts difference between any 2/12 segments (Ts-12). Stroke volume was estimated using Doppler velocity time integral (TVI) in the left ventricular outflow tract (LVOT). QRS width for each site was recorded. Measurements were observed by transthoracic echocardiography and electrocardiography before and 12 months after implantation.

Results

Ts-12 was significantly higher with RVA - pacing (107 ms, p=0.003) compared to RVMS - pacing (81 ms) sites. SD-Ts were significantly higher with RVA - pacing (38.5 ms, p=0.01) than RVMS - pacing (28.7 ms). QRS duration was the longest for RVA - pacing (157 ms) while significantly shorter RVMS - pacing (115 ms, p<0.001). LVOT VTI was significantly higher for RVMS - pacing than for RVA (p=0.0014) pacing.

Conclusions

Right ventricular mid-septal pacing may reduce electro-mechanical dyssynchrony compared to RVA pacing and RVMS – pacing to effect better LV function and hemodynamics than RVA pacing in patients with permanent pacemaker implantation.
Advantages of leadless pacemakers compared to conventional pacemakers
Authors: Baimbetov A , Bizhanov K , Yakupova I , Bozshagulov T , Tursunkhanov Z H , Bigeldiyev N , Jukenova A
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Leadless pacemakers (L-PM) are a new safe alternative technology for pacing the right ventricle. However, not enough information is available on their potential benefits for quality of life (QoL) in patients with L-PM. The purpose of the study was the quality of life comparison of patients with L-PM and conventional pacemakers (C-PM).

Methods

The study included patients who underwent implantation of a single-chamber pacemaker from December 2018 to March 2022. We used the SF-36 Questionnaire to assess quality of life at baseline and after 6 and 12 months of follow-up. We also used a questionnaire consisting of 10 specific questions related to the implantation procedure.

Results

Total of 32 patients were included (16 L-PM; 16 C-PM). There were no differences in baseline characteristics between groups (L-PM vs. C-PM), except for age (47.5 vs. 57.3 years; P = 0.012) and diabetes 28% vs. 21%; P = 0.021). Baseline SF-36 did not differ between groups. After 6 months of follow-up, patients in the L-PM group showed significantly higher scores on physical function (47 vs 32; P<0.001), physical role (53 vs 37; P=0.004) and mental health (67 vs 52; P=0.017), even after adjusting for covariates. Pacemaker-related discomfort and physical limitations were significantly lower in the L-PM group.

Conclusion

L-PM is associated with a better quality of life than C-PM, both in terms of physical and mental health. Patients who underwent L-PM implantation reported less procedure-related discomfort, physical limitations, and anxiety.
A retrospective study of characteristics and burden of heart failure in Thailand: an interim analysis
Authors: Jiampo P , Boonyapiphat T , Torpongpun A , Senthong V , Pongmesa T , Taepanich N , Tangkittikasem T
Published: January 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Novartis (Thailand) Limited

Background/Introduction

Heart failure (HF) is a major health problem due to its significant prevalence, disease burden and cost, mainly driven by high rates of hospitalization and mortality. Although numerous studies have demonstrated HF burden in western countries, data on current burden of HF in Thailand are limited.

Purpose

To describe characteristics and burden of HF, in terms of HF subgroups, hospital visits/hospitalization from HF and mortality, in participating hospitals in Thailand in 2019.

Methods

We retrospectively reviewed hospital profiles and medical records of HF adult patients at the five study sites which located in different regions across Thailand. All patients were diagnosed (newly and existing) with HF during 2018-2019, as identified by the International Classification of Diseases (ICD)-10 coding "I50". The interim data cutoff was scheduled when 4,000 patients were included. Hospital burden and the patients’ clinical and outcome data were collected and analyzed with descriptive statistics.

Results

From 4,000 patients, a total of 2,826 patients had follow-up visits in 2019 and then included in this analysis. Most of them were female (51.8%) and the overall patients’ mean (SD) age was 67.6 (15.0). Among 1,668 patients with available baseline left ventricular ejection fraction (LVEF), HF with preserved EF (HFpEF) was the most common subgroup (47.3%), followed by HF with reduced EF (HFrEF (39.0%) and HF with mid-range EF (HFmrEF) (13.7%). Of the total hospital visits from HF, 11.5% (95% CI 10.8-12.3) were from unscheduled visits to emergency or outpatient departments. HFpEF accounted for the highest number of hospital visits for HF, both scheduled and unplanned visits (46.4%, 48.9%), followed by HFrEF (39.0%, 41.5%) and HFmrEF (14.6, 9.6%), respectively. Among these 2,826 HF patients, the numbers of hospitalizations and rehospitalization from HF were 2,553 and 447. The total rate of HF rehospitalization was highest at 30 days (39.1%, 95% CI 34.6-43.7), followed by at 180 days (26.8%, 95% CI 22.7, 30.9), and 60 days (23.5%, 95% CI 19.6-27.4), respectively. The rates of all-cause and CV deaths within identified HF patients were 8.6% (95% CI 7.6-9.7) and 7.2% (95% CI 6.3-8.2). HFrEF accounted for the highest proportions of both (re) hospitalization and deaths (all-cause and CV) while HFpEF had the highest number of total beds.

Conclusion

Among the studied patients, HFpEF was the most common form of HF and HF was associated with a substantial healthcare burden in Thailand. The hospitalization rates from HF were especially high during the first 30 days after discharge, with a number of visits being unplanned or emergency visits leading to high hospital resource utilization.
Effects of SGLT2 inhibitors on heart failure symptoms, quality of life and exercise capacity in patients with heart failure and preserved ejection fraction: A meta-analysis
Authors: Merin L R C , Inso C A
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Patients with HFpEF usually have severe exercise intolerance which leads to poor quality of life. While SGLT2 inhibitors in HFrEF patients have been proven beneficial, with HFpEF it remains uncertain. This meta-analysis aimed to determine the outcomes of heart failure symptoms, exercise capacity, and quality of life in patients on SGLT2 inhibitors.

Methods

The studies included only RCTs. Eligible studies were appraised using the CASP RCT Standard Checklist. Outcomes expressed as mean difference (MD) between placebo group and SGLT-2 inhibitors group after 12 weeks in the Kansas City Cardiomyopathy Questionnaire Total Summary Score (KCCQ-TSS), Clinical Symptoms score (KCCQ-CS), Overall symptoms score (KCCQ-OS) and 6-minute walk test distance (6MWTD) were the main effect measures.

Results

Three RCTs with a total of 6,617 HFpEF patients were included in this meta-analysis. The patients on SGLT2-inhibitors showed improvement of HF symptoms and Quality of life based on KCCQ-TSS 2.68 (95% CI 0.78, 4.57), KCCQ-CS MD 2.60 (95%, CI 1.56, 3.63), KCCQ-OS MD 2.18 (95% CI 0.56, 3.8) and exercise capacity assessed by the 6-MWTD with MD 17.47 (95% CI 6.46, 28.48).

Conclusion

This meta-analysis showed that there was significant improvement in the heart failure symptoms, Quality of life and exercise capacity in patients taking SGLT2 inhibitors.
Real-world comparison of intracoronary imaging and fractional flow reserve measurements on outcomes of semi-urgent and elective percutaneous coronary intervention in a multi-ethnic asian population
Authors: Soh Y H R , Teo Y N , Teo Y H , Djohan A H , Ho S Y J , Sukmawati I , Chan K A , Sim H W , Yeo T C , Tan H C , Chan Y Y M , Sia C H
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Intracoronary imaging and fractional flow reserve measurements (FFR) are helpful in optimisation of percutaneous coronary intervention (PCI) for patients with stable coronary artery disease, but their comparative efficacy is not well described. Furthermore, few studies involve Asian patients in a real-world context.

Purpose

This study aims to compare the use of intracoronary imaging and fractional flow reserve measurements on the outcomes of semi-urgent and elective PCI in a multi-ethnic Asian population.

Methods

This was a retrospective database study of patients who underwent semi-urgent and elective PCI from 1st Jan 2014 to 31st Dec 2015 at a tertiary academic centre. The patients were split into 2 groups – imaging-guided (IG) consisting of intravascular ultrasound guided PCI or optical coherence tomography guided PCI and physiology-guided (PG) which included FFR-guided PCI. Patients who underwent both IG PCI and PG PCI were excluded. Incidence rates of major adverse cardiovascular events (MACE) (Subsequent myocardial infarction, congestive cardiac failure, all-cause mortality) and major adverse cardiovascular and cerebrovascular events (MACCE) (Subsequent myocardial infarction, congestive cardiac failure, stroke or transient ischemic attack and all-cause mortality) were compared between the two groups. One-to-one propensity score matching (PSM) was performed to control for potential bias.

Results

Of 1,732 patients studied, the median age was 61.0 years (IQR 53.0 to 68.0) and 336 were female (19.4%). There were 266 patients (15.4%) in IG and 186 (10.7%) in PG. The patients were followed up for 33 ±37 months. A total of 133 pairs were matched. In the unmatched cohort, there was no statistical difference between the IG and PG group in the incidence of MACE (24.2% vs 15.5%, p= 0.099) and MACCE (26.6% vs 17.7%, p= 0.112). Baseline and procedural characteristics were balanced between the IG and PG groups. In the matched cohort, the incidence rates of MACE (11.3% vs 7.5%, p= 0.383) and MACCE (15.8% vs 12.8%, p=0.596) did not differ significantly between the two groups.

Conclusion

In a real-world multi-ethnic Asian registry of semi-urgent and elective PCI patients, there was no difference in outcomes whether patients underwent the use of intracoronary imaging or fractional flow reserve measurements during PCI.
Association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with acute myocardial infarction
Authors: Tran Cong D , Le Gia Hoang L , Do Duc M , Thai Thanh T , Hoang Van S , Truong Quang B
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Acute myocardial infarction (AMI) remains a public health issue with high morbidity and mortality rates and significantly reduces patients' health-related quality of life. The identification of factors influencing coronary artery lesion characteristics in patients with AMI can contribute to the strategy of primary and secondary prevention for AMI.

Purpose

This study was aimed to investigate the ACE I/D genotype rate and its relationship with coronary artery lesion characteristics in AMI patients.

Methods

This study was conducted with the prospective cross-sectional method among AMI patients admitted to the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital from January 1, 2020 to June 30, 2021. The minimum sample size of this study was 163 patients. The ACE I/D genotype was determined at the Center for Molecular Biomedicine.

Results

During the study period, a total of 522 AMI patients were recruited at the Department of General Cardiology and Department of Interventional Cardiology. The mean age of the AMI patients was 63.9±11.7 and the age group 45-64 accounted for the most (46.4%). Males were predominant (71.5%). The patients' median Gensini score was 34.3. The II, ID and DD genotype rates of ACE I/D polymorphism were 48.9%, 36.4%, and 14.7% respectively. The ACE DD genotype was not associated with the location and number of diseased coronary arteries but was associated with the severity of coronary artery disease. Multivariable linear regression analysis showed that along with the Killip class, the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotype.

Conclusions

This has been the first study in Vietnam demonstrated the association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with AMI. The ACE I/D gene polymorphism may be considered for testing to contribute to the comprehensive assessment and aggressive treatment of AMI patients.
Association between body mass index (BMI) and severity of coronary artery disease in young onset acute coronary syndrome (ACS)
Authors: Moniruzzaman M , Koli A , Malik F , Islam S
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

A high body mass index (BMI) is seems to be associated with an increased incidence of coronary artery disease. If the affected person is young, the consequences are more tragic. There are variable information on the relation of incidence and severity of coronary artery disease in high BMI populations. We have examined the association between BMI and severity of coronary artery disease in young onset Acute Coronary Syndrome (ACS).

Methods

In this prospective observational study a total number of 150 patients, aged ≤45 years presented with acute coronary syndrome were enrolled to analyze association between Body Mass Index (BMI) and severity of coronary artery disease.

Results

The mean BMI in male was 24.6±3.6 and the mean BMI in female was 25.4±3.3. Among the 150 patients, 2(1.3%) was underweight, 78(52%) was normal, 60(40%) was overweight & 10(6.7%) was obese. All underweighted patients were diagnosed as STEMI. Among the normal BMI patients, 18(23.1%) had UA, 12(15.4%) had NSTEMI & 48 (61.5%) had STEMI. Among the overweight patients, 23(38.3%) had UA, 9(15%) had NSTEMI & 28(46.7%) had STEMI. And among the obese patients, 4(40%) had UA, 1 (10%) had NSTEMI & 5(50%) had STEMI. Considering involving coronary artery, left main coronary artery involvement was 0(0%), 6 (7.7%), 5 (8.3%) & 0(0%) in underweight, normal, overweight & obese patients respectively. Left anterior descending coronary artery involvement was 2(100%), 54 (69%), 45 (75%) & 7 (70%) in underweight, normal, overweight & obese patients respectively. Left circumflex coronary artery involvement was 1(50%), 33 (42%), 25 (41.7%) & 1 (9%) in underweight, normal, overweight & obese patients respectively. And right coronary artery involvement was 1(50%), 35 (44.9%), 31 (51.7%) & 5 (50%) in underweight, normal, overweight & obese patients respectively. In underweight patients 1(50%) had SVD and 1 (50%) had TVD. In normal BMI patients 40 (51.3%) had SVD, 11(14.1%) had DVD and 19 (24.4%) had TVD. In overweight patients 27 (45%) had SVD, 15 (25%) had DVD and 13 (21.7%) had TVD. And in obese patients 5 (50%) had SVD, 3(30%) had DVD and 0 (0%) had TVD. In all BMI group SVD was more common.

Conclusion

There is no statistically significant differences in severity of coronary artery in respect to body mass index (BMI), in patients presented with acute coronary syndrome.
Preliminary results of whole exome sequencing in a clinical hypertrophic cardiomyopathy cohort in India
Authors: Chockalingam P , Thenral S G , Ramprasad V , Anantharaman R
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Hypertrophic cardiomyopathy (HCM), characterized by unexplained left ventricular hypertrophy and outcomes ranging from normal life expectancy to heart failure and sudden cardiac death, has a global prevalence of about 1 in 500. Genetic testing helps to improve care of patients with HCM and their family members as children of carriers have a 50% chance of inheriting the disease. However, there is limited availability, awareness and application of genetic testing modalities, particularly whole exome sequencing (WES), in the management of HCM in India.

Purpose

This study aimed to analyze the results of WES in a clinical HCM cohort in India.

Methods

Patients with unexplained moderate to severe cardiomyopathy presenting to our centre from 2017 to 2022 and consenting for genetic testing were included in the study. Following a thorough clinical diagnostic process including 3-generational family history, electrocardiogram and echocardiogram in all patients and exercise stress test, Holter monitoring and cardiac magnetic resonance imaging where applicable, pre-test counseling was provided and WES performed using genomic DNA isolated from whole blood samples. A total of 33 affected individuals including 1 affected family member from 32 families were processed for genetic testing. A multidisciplinary team comprising of cardiologist, cardiothoracic surgeon, physician with expertise in cardiogenetics, geneticist and genetic counselor carried out the study in a tertiary cardiac centre.

Results

Age of the probands (n=32) at the time of the study was 47.8±15.9 years and 24 (75%) were males. There was concomitant hypertension in 11 (34%), type 2 diabetes mellitus in 6 (19%), arrhythmias in 6 (19%) and coronary artery disease in 2 (6%) probands. Obstructive HCM was present in 2 (6%) probands. Disease-causing significant variants (Pathogenic/Likely pathogenic) were detected in 8 (25%, Table), variants of uncertain significance in 17 (53%) and no significant variants were detected in 7 cases. Cascade genetic testing of significant variants among 7 family members of 4 probands showed segregation of the pathogenic variant in 4 asymptomatic carriers.

Conclusions

The yield of whole exome sequencing in a clinical HCM cohort in India was 25%. Of note the rare variants of uncertain significance in the cardiomyopathy genes makes genetic counseling and disease management challenging. However, large-scale studies in the context of Indian population are expected to bring clarity on the role of these variants in disease manifestation. A multidisciplinary team approach incorporating genetic testing modalities such as whole exome sequencing and cascade screening is the way forward in the comprehensive management of patients with HCM and their families.