bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational risk assessment of glutaraldehyde through personal air monitoring in a hospital setting
Authors: Zambrano-Carrillo Maira Fernanda , Hernandez-Jerez Antonio F
Published: November 2023

Glutaraldehyde is a high-efficiency disinfectant that has been included in the protocols of some hospitals for controlling the spread of SARS-CoV-2, together with sodium hypochlorite and quaternary ammonium disinfectants. However, exposure has been poorly studied in workplace settings, despite the association between glutaraldehyde and respiratory diseases and skin conditions in exposed workers. This study evaluated the magnitude of exposure associated with the use of glutaraldehyde in healthcare workers across various work areas of a first level of Hospital-Based Care in Colombia. Workers were classified into similar exposure groups (SEGs) based on work areas and tasks performed, and airborne concentrations of glutaraldehyde were measured in different work areas of each SEG through direct monitoring. The 95th percentile of glutaraldehyde concentrations in all SEGs studied exceeded the TLV-C immediately after use. Cleaning workers and nurses had the highest exposures to glutaraldehyde. Results indicate that workers were overexposed and highlight the need to implement controls to reduce exposure. The high-exposure levels also raise the need to consider glutaraldehyde substitution and adequate use of personal protective equipment (PPE).
Responses of a common tropical epiphyte,Asplenium nidus, to changes in water and nutrient availability
Authors: Chen Xiao-Zhen , Hogan J Aaron , Wang Chiao-Ping , Wang Pei-Ling , Lin Teng-Chiu
Published: November 2023

Epiphytes are highly dependent on atmospheric inputs of water and nutrients. Reductions in water availability associated with warming and climate change and continual atmospheric nitrogen (N) deposition can affect plant growth but few studies have evaluated the effects of changes in both water and nutrient availabilities on epiphytes. We experimentally tested whether epiphyte growth is more water- or nutrient-limited, if nutrient limitation was stronger for nitrogen or phosphorus, and whether nutrient limitation interacts with water availability. We applied watering (high and low) and nutrient addition (control, +N, +P, +N+P) treatments to greenhouse-grown Asplenium nidus, a common epiphytic fern found in many tropical and subtropical wet forests. We measured leaf area production and leaf elemental concentrations to assess how A. nidus growth and physiology respond to changes in water and nutrient availabilities. We found that leaf growth of A. nidus was more affected by water availability than nutrient addition and the effect of adding nutrients was not fully realized under low-water availability. Among the different nutrient treatments, +N+P had the greatest effects on A. nidus growth and physiology in both watering treatments. Watering treatment changed leaf elemental concentrations but not their ratios (i.e. C:N and N:P). Nutrient addition altered C:N and N:P ratios and increased the concentration of the added elements in leaves, with more pronounced increases in the high-watering treatment. We conclude that the growth of A. nidus is more water- than nutrient-limited. When nutrient limitation occurs (i.e. under high-water availability), nutrient co-limitation is stronger than limitation by N or P alone. This result taken together with studies of other epiphytes suggests greater water than nutrient limitation is likely widespread among epiphytic plants. The limited effects of nutrient addition in the low-water treatment suggest that the effect of atmospheric N deposition on epiphyte growth will be limited when water availability is low.
Are Textbooks Authentic From a Developmental Perspective? A Corpus Analysis of Word Use in Chinese Textbooks in US Universities
Authors: Yan Xun , Lei Yuyun , Shih Chilin
Published: November 2023

There is a prevailing belief that second language (L2) textbooks should strive for authenticity, aiming to accurately and reliably represent natural language use. However, assessing the authenticity of language textbooks is not a straightforward task, as it requires both a comparison between instructional texts and real-world language use and a consideration of the comparison within the broader context of language development. This study employs a corpus-based approach to examine word use in 31 widely used commercial textbooks across different proficiency levels, which serve as the primary resource for teaching, learning, and assessment in Chinese language programs at US universities. Using hierarchical cluster analysis, Zipf’s law analysis, and descriptive statistics, we found supportive evidence for the authenticity of word use in Chinese textbooks from a developmental perspective. Specifically, our findings reveal a nuanced gradation in the distribution of words across proficiency levels within these Chinese textbooks. Moreover, as proficiency levels increase, there is a discernible register shift in word use from spoken to written discourse. These observations carry significant implications for the utility of textbooks in Chinese language programs, particularly in the realms of instruction and assessment.
Normative Data Estimation in Neuropsychological Tests: A Systematic Review
Authors: delCacho-Tena Ana , Christ Bryan R , Arango-Lasprilla Juan Carlos , Perrin Paul B , Rivera Diego , Olabarrieta-Landa Laiene
Published: November 2023

Objective

To quantify the evolution, impact, and importance of normative data (ND) calculation by identifying trends in the research literature and what approaches need improvement.

Methods

A PRISMA-guideline systematic review was performed on literature from 2000 to 2022 in PubMed, Pub-Psych, and Web of Science. Inclusion criteria included scientific articles about ND in neuropsychological tests with clear data analysis, published in any country, and written in English or Spanish. Cross-sectional and longitudinal studies were included. Bibliometric analysis was used to examine the growth, productivity, journal dispersion, and impact of the topic. VOSViewer compared keyword co-occurrence networks between 1952–1999 and 2000–2022.

Results

Four hundred twelve articles met inclusion and exclusion criteria. The most studied predictors were age, education, and sex. There were a greater number of studies/projects focusing on adults than children. The Verbal Fluency Test (12.7%) was the most studied test, and the most frequently used variable selection strategy was linear regression (49.5%). Regression-based approaches were widely used, whereas the traditional approach was still used. ND were presented mostly in percentiles (44.2%). Bibliometrics showed exponential growth in publications. Three journals (2.41%) were in the Core Zone. VOSViewer results showed small nodes, long distances, and four ND-related topics from 1952 to 1999, and there were larger nodes with short connections from 2000 to 2022, indicating topic spread.

Conclusions

Future studies should be conducted on children’s ND, and alternative statistical methods should be used over the widely used regression approaches to address limitations and support growth of the field.
The nucleolar protein NIFK accelerates the progression of colorectal cancer via activating MYC pathway
Authors: Xia Tingting , Wang Bin , Sun Lingling
Published: November 2023

This study aimed to explore the function of nucleolar protein interacting with the FHA domain of MKI67 (NIFK) on colorectal cancer (CRC) and its associated molecular mechanisms. NIFK was upregulated in CRC tissues and cells. NIFK silencing resulted in reduced cell growth and metastasis, as well as in promoted apoptosis in CRC cells. Moreover, NIFK silencing was also confirmed to inhibit lipid accumulation and decrease fatty acid synthesis via downregulating lipogenic enzymes in CRC cells. Gene set enrichment analysis and western blot co-verified that NIFK silencing inhibited MYC proto-oncogene, bHLH transcription factor (MYC) pathway in CRC cells. In addition, we also revealed that NIFK silencing function on cell growth, apoptosis, metastasis, and fatty acid metabolism in CRC might be cancelled after c-MYC overexpression. Silencing NIFK could inhibit cell growth and metastasis, and promoted apoptosis, as well as regulated fatty acid metabolism by inhibiting MYC pathway in CRC.
PEDL+: protein-centered relation extraction from PubMed at your fingertip
Authors: Weber Leon , Barth Fabio , Lorenz Leonie , Konrath Fabian , Huska Kirsten , Wolf Jana , Leser Ulf
Published: November 2023

Relation extraction (RE) from large text collections is an important tool for database curation, pathway reconstruction, or functional omics data analysis. In practice, RE often is part of a complex data analysis pipeline requiring specific adaptations like restricting the types of relations or the set of proteins to be considered. However, current systems are either non-programmable web sites or research code with fixed functionality. We present PEDL+, a user-friendly tool for extracting protein–protein and protein–chemical associations from PubMed articles. PEDL+ combines state-of-the-art NLP technology with adaptable ranking and filtering options and can easily be integrated into analysis pipelines. We evaluated PEDL+ in two pathway curation projects and found that 59% to 80% of its extractions were helpful.

Availability and implementation

PEDL+ is freely available at https://github.com/leonweber/pedl.
PhasiHunter: a robust phased siRNA regulatory cascade mining tool based on multiple reference sequences
Authors: Feng Zerong , Feng Jiejie , Zhang Baoyi , Fei Yuhan , Zhang Hongsheng , Huang Ji
Published: November 2023

In recent years, phased small interfering RNA has been found to play crucial roles in many biological processes in plants. However, efficiently predicting phasiRNA regulatory cascades with computational methods is still challenging. Here, we introduce PhasiHunter, a phasiRNA regulatory network prediction tool that has several distinctive features compared to existing tools: (i) PhasiHunter employs two major phasiRNA prediction algorithms, namely phase score and hypergeometric distribution-based methods, to ensure the integrity and accuracy of prediction; (ii) PhasiHunter can identify phasiRNAs and their regulatory networks based on multiple reference sequences and the predicted results can be automatically integrated; (iii) PhasiHunter can efficiently identify the phasiRNAs generated through alternative splicing events; and (iv) the excellent data structure and parallel computing architecture allow PhasiHunter to predict phasiRNAs and their regulatory pathways with high efficiency.

Availability and implementation

PhasiHunter is an open-source tool that is available at https://github.com/HuangLab-CBI/PhasiHunter.
Updated epidemiology of alopecia areata in Germany: the data tell a lot but hide a lot
Authors: Kinoshita-Ise Misaki
Published: November 2023

This commentary briefly introduces the outcomes of the epidemiological study in Germany with potential biases the readers need to pay attention to.
Congenital myasthenic syndromes: a retrospective natural history study of respiratory outcomes in a single centre
Authors: Poulos Jordan , Samuels Martin , Palace Jacqueline , Beeson David , Robb Stephanie , Ramdas Sithara , Chan Samantha , Munot Pinki
Published: November 2023

Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes, a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood and progressive respiratory failure requiring ventilation are features of certain genotypes of congenital myasthenic syndromes. Robb et al. published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there are little published longitudinal natural history data on respiratory outcomes of these disorders. We report a retrospective, single-centre study on respiratory outcomes in a cohort of 40 well characterized genetically confirmed cases of congenital myasthenic syndromes, including 10 distinct subtypes (DOK7, COLQ, RAPSN, CHAT, CHRNA1, CHRNG, COL13A1, CHRNE, CHRNE fast channel syndrome and CHRNA1 slow channel syndrome), with many followed up over 20 years in our centre. A quantitative and longitudinal analysis of key spirometry and sleep study parameters, as well as a description of historical hospital admissions for respiratory decompensation, provides a snapshot of the respiratory trajectory of congenital myasthenic syndrome patients based on genotype.
Long non-coding RNA NRAV in the 12q24.31 risk locus drives gastric cancer development through glucose metabolism reprogramming
Authors: Zhang Yan , Gao Yun , Li Fengyuan , Qi Qi , Li Qian , Gu Yuanliang , Zheng Zhonghua , Hu Beiping , Wang Tianpei , Zhang Erbao , Xu Hao , Liu Li , Tian Tian , Jin Guangfu , Yan Caiwang
Published: November 2023

Long non-coding RNAs (lncRNAs) serve as vital candidates to mediate cancer risk. Here, we aimed to identify the risk single-nucleotide polymorphisms (SNPs)-induced lncRNAs and to investigate their roles in gastric cancer (GC) development. Through integrating the differential expression analysis of lncRNAs in GC tissues and expression quantitative trait loci analysis in normal stomach tissues and GC tissues, as well as genetic association analysis based on GC genome-wide association studies and an independent validation study, we identified four lncRNA-related SNPs consistently associated with GC risk, including SNHG7 [odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.09–1.23], NRAV (OR = 1.11, 95% CI: 1.05–1.17), LINC01082 (OR = 1.16, 95% CI: 1.08–1.22) and FENDRR (OR = 1.16, 95% CI: 1.07–1.25). We further found that a functional SNP rs6489786 at 12q24.31 increases binding of MEOX1 or MEOX2 at a distal enhancer and results in up-regulation of NRAV. The functional assays revealed that NRAV accelerates GC cell proliferation while inhibits GC cell apoptosis. Mechanistically, NRAV decreases the expression of key subunit genes through the electron transport chain, thereby driving the glucose metabolism reprogramming from aerobic respiration to glycolysis. These findings suggest that regulating lncRNA expression is a crucial mechanism for risk-associated variants in promoting GC development.
A relapsing–remitting rash with associated neurological symptoms
Authors: Thomas Lianne , Bajwa Dalvir S , Desai Prachi , Chapman James , Bajaj Vrinda
Published: November 2023

We report a case of a 46-year-old woman who presented with erythematous annular plaques on her upper extremities. She subsequently went on to develop multiple neurological symptoms over a 3-year period. We discuss how the combination of a skin biopsy and neurological investigations helped lead to a diagnosis, and provide an overview of this rare condition.
Sex- and age-based differences in fetal and early childhood hippocampus maturation: a cross-sectional and longitudinal analysis
Authors: Nichols Emily S , Grace Michael , Correa Susana , de Vrijer Barbra , Eagleson Roy , McKenzie Charles A , de Ribaupierre Sandrine , Duerden Emma G
Published: November 2023

The hippocampus, essential for cognitive and affective processes, develops exponentially with differential trajectories seen in girls and boys, yet less is known about its development during early fetal life until early childhood. In a cross-sectional and longitudinal study, we examined the sex-, age-, and laterality-related developmental trajectories of hippocampal volumes in fetuses, infants, and toddlers associated with age. Third trimester fetuses (27–38 weeks’ gestational age), newborns (0–4 weeks’ postnatal age), infants (5–50 weeks’ postnatal age), and toddlers (2–3 years postnatal age) were scanned with magnetic resonance imaging. A total of 133 datasets (62 female, postmenstrual age [weeks] M = 69.38, SD = 51.39, range = 27.6–195.3) were processed using semiautomatic segmentation methods. Hippocampal volumes increased exponentially during the third trimester and the first year of life, beginning to slow at approximately 2 years. Overall, boys had larger hippocampal volumes than girls. Lateralization differences were evident, with left hippocampal growth beginning to plateau sooner than the right. This period of rapid growth from the third trimester, continuing through the first year of life, may support the development of cognitive and affective function during this period.
Prognostic impact of acute decompensated heart failure in patients with heart failure with mildly reduced ejection fraction
Authors: Schmitt Alexander , Schupp Tobias , Reinhardt Marielen , Abel Noah , Lau Felix , Forner Jan , Ayoub Mohamed , Mashayekhi Kambis , Weiß Christel , Akin Ibrahim , Behnes Michael
Published: November 2023

Aims

This study sought to determine the prognostic impact of acute decompensated heart failure (ADHF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). ADHF is a major complication in patients with heart failure (HF). However, the prognostic impact of ADHF in patients with HFmrEF has not yet been clarified.

Methods and results

Consecutive patients hospitalized with HFmrEF (i.e. left ventricular ejection fraction 41–49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognosis of patients with ADHF was compared with those without (i.e. non-ADHF). The primary endpoint was long-term all-cause mortality. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related re-hospitalization. Kaplan–Meier, multivariable Cox proportional regression, and propensity score matched analyses were performed for statistics. Long-term follow-up was set at 30 months. A total of 2184 patients with HFmrEF were included, ADHF was present in 22%. The primary endpoint was higher in ADHF compared to non-ADHF patients with HFmrEF [50% vs. 26%; hazard ratio (HR) = 2.269; 95% confidence interval (CI) 1.939–2.656; P = 0.001]. Accordingly, the secondary endpoint of long-term HF-related re-hospitalization was significantly higher (27% vs. 10%; HR = 3.250; 95% CI 2.565–4.118; P = 0.001). A history of previous ADHF before the index hospitalization was associated with higher rates of long-term HF-related re-hospitalization (42% vs. 23%; HR = 2.073; 95% CI 1.420–3.027; P = 0.001), but not with long-term all-cause mortality (P = 0.264).

Conclusion

ADHF is a common finding in patients with HFmrEF associated with an adverse impact on long-term prognosis.
Echocardiographic estimation of pulmonary artery wedge pressure: invasive derivation, validation, and prognostic association beyond diastolic dysfunction grading
Authors: Lindow Thomas , Manouras Aristomenis , Lindqvist Per , Manna Daniel , Wieslander Björn , Kozor Rebecca , Strange Geoff , Playford David , Ugander Martin
Published: November 2023

Aims

Grading of diastolic function can be useful, but indeterminate classifications are common. We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP) and to compare its prognostic performance to diastolic dysfunction grading.

Methods and results

Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression in patients undergoing right heart catheterization (RHC). Prognostic associations were analysed in the National Echocardiography Database of Australia (NEDA). In patients who had undergone both RHC and echocardiography within 2 h (n = 90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n = 53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean ± standard deviation difference 0.5 ± 5.0 mmHg) and good diagnostic accuracy for estimating PAWP >15 mmHg [area under the curve (95% confidence interval) 0.94 (0.88–1.00)]. Among patients in NEDA [n = 38,856, median (interquartile range) follow-up 4.8 (2.3–8.0) years, 2756 cardiovascular deaths], ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading [hazard ratio (HR) 1.08 (1.07–1.09) per mmHg] and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, P < 0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function [HR normal, 1.07 (1.06–1.09); indeterminate, 1.08 (1.07–1.09); abnormal, 1.08 (1.07–1.09), P < 0.001 for all].

Conclusion

Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading.
Eccentric remodeling in patients undergoing mitral valve repair due to severe degenerative mitral regurgitation: impact of relative wall thickness on clinical outcomes
Authors: Kim M , Lee S A , Lee S M , Song J M , Kang D H , Song J K , Kim D H
Published: November 2023

Background

Left ventricular (LV) volume overload in mitral regurgitation (MR) leads to a progressive increase in LV mass. Eccentric hypertrophy is defined as the relative wall thickness (RWT) <0.43, and LV hypertrophy is a frequently observed LV remodeling phenotype in patients with severe MR. However, the prognostic impacts of RWT in these patient groups are not well known. We tested the relationship between RWT and clinical outcomes in severe MR patients undergoing MV repair (MVR).

Methods

A total of 979 consecutive adult patients with severe degenerative MR and eccentric hypertrophy (55 ± 13 years, 616 males) who underwent MVR were retrospectively analyzed. The study population was stratified by the median RWT value (RWT=0.34) on baseline echocardiography [the lesser RWT group (RWT< 0.34 (n=651)) and the greater RWT group (RWT ≥0.34 (n = 328)).

Results

The patients in the lesser RWT group were younger (54±13 vs. 57±13, p<0.001) and had a significantly higher prevalence of hypertension and diabetic mellitus than those in the greater RWT group. The greater RWT group had significantly lower indexed LV systolic dimension, thicker ventricular walls, and higher LV ejection fraction as compared with those in the lesser RWT group. In Kaplan-Meier analysis, the greater RWT group had a significantly higher incidence of all-cause death (6.4% vs. 2.3%; log-rank p<0.001) and cardiac death (3.0% vs. 0.9%; log-rank p = 0.01) at five years after MVR than in the low RWT group. RWT≥0.34 was independently associated with higher all-cause and cardiac mortality in the multivariate Cox regression analysis. In subgroup analysis, RWT≥0.34 was associated with worse outcomes in men (P <0.001) but not in women (P = 0.23). Moreover, hypertensive patients in the greater RWT group showed the worst outcomes as compared with the three other groups.

Conclusions

We concluded that excessive ventricular hypertrophy, manifested as an increased relative wall thickness, is associated with a significantly increased risk of postoperative mortalities after mitral valve repair in patients with severe degenerative MR and eccentric hypertrophy. We also found that eccentric remodeling patterns and clinical outcomes differ according to sex and the presence of hypertension.
Increasing left ventricular mass and mortality in 303,548 men and women investigated with echocardiography
Authors: Playford D , Strange G , Joseph M , Perry R , Chan Y K , Harris S , Stewart S , Selvanayagam J
Published: November 2023

Background and Aims

Left ventricular hypertrophy (LVH) categories are based on left ventricular mass index (LVMi). This study aimed to generate sex-stratified, statistically-derived thresholds of mortality according to LVMi within a large, real-world patient cohort.

Methods and Results

Echocardiographic and linked mortality data were extracted from the National Echocardiography Database of Australia. LVH categories were first defined according to American Society of Echocardiography (ASE) criteria in 303,548 adults comprising 155,668 men (aged 61.3±17.3 years) and 147,880 women (61.8±18.3 years). Sex-specific mild to severe thresholds of increasing 5-year mortality based on LVMi increments were generated. Overall, 36,198 men (23.3%) and 38,898 women (26.3%) had LVH. Actual 5-year mortality rose from 16.9%-38.3% and 11.9%-31.2% in men and women with no LVH versus LVH, respectively. The statistical threshold at which LVMi was associated with increased mortality was lower than traditional LVH criteria in both men (Figure A, ≥88g/m2 versus ≥115g/m2) and women (Figure B, ≥82g/m2 versus ≥95g/m2). For men versus lowest-risk LVMi, the fully adjusted risk of 5-year mortality was 14% (95%CI 1.03-1.25) and 68% higher (95%CI 1.49-1.90) when LVMi levels were mildly (88 to <116) to severely (≥140g/m2) increased, respectively. In women, the equivalent LVMi thresholds of 82 to <112 and ≥140g/m2 were associated with a 13% (95%CI 1.03-1.24), and 81% higher (95%CI 1.58-2.08) 5-year mortality risk.

Conclusion

A high proportion of men and women have LVMi levels associated with elevated mortality risk that are lower than those traditionally used to diagnose or manage LVH. Such individuals may benefit from more proactive recognition and clinical management.
Diastolic dysfunction and its association to renal outcomes in patients with chronic kidney disease
Authors: Zeuthen M , Landler N E , Olsen F R , Christensen J , Skaarup K G , Lassen M C H , Christoffersen C , Ballegaard E L F , Soerensen I M H , Bjergfelt S S , Bro S , Feldt-Rasmussen B , Hansen D , Biering-Soerensen T
Published: November 2023

Background

Left ventricular diastolic dysfunction is frequent in chronic kidney disease (CKD) and is suspected to be linked to a worse renal prognosis.

Purpose

To investigate the association between the ratio of early mitral inflow velocity to early diastolic tissue velocity (E/e') measured by Doppler echocardiography and development of end-stage kidney disease in patients with non-dialysis-dependent CKD.

Methods

This prospective cohort study included individuals with non-dialysis-dependent CKD with previous nephrology-related hospital contact. All participants underwent thorough, protocolized echocardiographic examination. Exclusion criteria were inadequate image quality for E/e'-assessment and prevalent heart failure at baseline. The primary endpoint was the composite outcome of time to dialysis treatment and/or kidney transplantation. The association between E/e' and the composite outcome was assessed with multivariable Cox proportional hazards regression models adjusted for age, sex, estimated glomerular filtration rate (eGFR), diabetes, Body Mass Index, albuminuria, systolic blood pressure, heart rate, coronary artery disease, and left ventricular ejection fraction.

Results

A total of 731 participants were included in the final study sample. Mean age was 57 ± 13 years and 61% were male. Median E/e' was 7.8 (IQR: 6.4; 9.5), median eGFR was 43 mL/min/1.73 m² (IQR: 28; 62), and 36% had a urine albumin/creatinine ratio >300.

During a median follow-up of 3.8 years (IQR: 3.3; 4.5), 102 individuals met the composite outcome. In univariable Cox regression both continuous E/e' and elevated E/e' (E/e' >14) were significantly associated with the outcome (P<0.001). Following multivariable adjustments, increasing E/e' remained significantly associated with the outcome (HR = 1.09, 95% CI [1.03; 1.15], P=0.004, per 1 unit increase) (Figure 1A). Elevated E/e' also remained significantly associated with the outcome following adjustments (HR = 2.95, 95% CI [1.33; 6.53], P=0.008), and more than 40% of patients with E/e' >14 were estimated to have reached the primary endpoint after 4 years (Figure 1B).

Conclusion

In patients with non-dialysis dependent CKD increasing E/e' and E/e' >14 were both associated with worse renal prognosis.
Left atrial coupling index and undiagnosed atrial fibrillation in elderly high-risk individuals
Authors: Ravnkilde K , Olsen F J , Skaarup K G , Landler N E , Graff C , Brandes A , Krieger D , Haugan K , Koeber L , Diederichsen S Z , Hoejberg S , Svendsen J H , Biering-Soerensen T
Published: November 2023

Background

Left atrial volumetric/mechanical coupling index (LACi) is a novel measure, which combines information on LA size and function in one variable and may therefore be capable of predicting atrial fibrillation (AF). Its association to undiagnosed AF has not yet been investigated.

Purpose

We aimed to investigate the association between LACi and undiagnosed AF in an elderly population.

Methods

This was a substudy based on a large, randomized, clinical trial of elderly population (≥ 70 years), no history with AF, with a CHA2DS2-VASc score≥2 (at least one of the risk factors: DM, hypertension, heart failure or previous stroke). Participants were randomized (1:3) to implantable loop recorder (ILR) screening for AF or usual care. This analysis presents findings for participants randomized to an ILR and with available echocardiographic left atrium (LA) measures (n=1020). LACi was calculated as the ratio of left atrial maximal volume index (LAVI) and mean peak tissue velocity at late diastole measured using tissue Doppler of the left ventricle. The outcome assessed was AF episodes lasting ≥6 minutes and ≥24 hours. Regression models were adjusted for CHARGE-AF, a risk score based on clinical parameters developed to predict risk of AF in the general population.

Results

A total of 955 individuals were included in the analysis. The mean age was 74 ± 4 years, 44% were female, and median LACi was 3.0 (IQR: 2.3, 3.9). During a median follow-up of 35 (20-40) months, a total of 277 participants were diagnosed with AF. In unadjusted analysis, LACi was significantly associated with both AF ≥6 minutes and ≥24 hours (Figure 1 and 2, respectively). Multivariable regression models adjusted for CHARGE-AF risk score revealed LACi to be independently associated with AF ≥6 minutes (HR 1.16, 95% CI [1.11-1.20], p<0.001, per 1 unit increase) and ≥24 hours (HR 1.14, 95% CI [1.08-1.20], p<0.001, per 1 unit increase). Participants with a LACi above 3.0 had a significantly increased risk of AF ≥6 minutes (HR 1.82 95% CI [1.42-2.33]) and ≥24 hours (HR 2.71 95% CI [1.29-5.26]).

Conclusion

In elderly high-risk individuals, increasing LACi was significantly associated with incident AF as detected by continuous long-term monitoring.
Standardized longitudinal strain curves stratified by age and sex in healthy individuals: The Copenhagen City Heart Study
Authors: Christensen J , Simonsen J O , Modin D , Skaarup K , Lassen M C H , Johansen N D , Sanchez-Martinez S , Claggett B L , Marott J L , Jensen G B , Schnohr P , Moegelvang R , Biering-Soerensen T
Published: November 2023

Introduction

Speckle-tracking echocardiography has gained widespread use, and strain parameters such as global longitudinal strain (GLS) and strain rates are strongly associated with risk of heart failure and cardiovascular death. Such strain measures, however, only represent limited features of the complete longitudinal strain (LS) curve. Thus, interpretation of entire curves might provide additional insight.

Purpose

To establish normal standardized LS curves over an entire heart cycle for healthy subjects stratified by age and sex. Furthermore, to assess how these curves vary with age and to compare this with conventional strain measures.

Methods

The study population consisted of 1790 healthy subjects free of cardiovascular disease and risk factors including diabetes mellitus and hypertension at baseline. Subjects were stratified by sex and further by age in groups as defined in the SCORE risk chart. Subjects underwent echocardiography, and LS curves from the apical four-chamber view were derived and standardized in length using linear interpolation. Terms to describe qualitative findings in the standardized strain curves were established (Figure 1). Early diastolic strain (EDS) was defined as the difference in strain from peak LS to maximal curvature after early diastolic filling, while late diastolic strain (LDS) was defined as the difference in strain from the plateau phase in late passive diastole to maximal curvature in active diastole. Conventional strain measures included GLS, systolic strain rate (SRS), early diastolic strain rate (SRE), and late diastolic strain rates (SRA). The association between these and age group were investigated using univariable linear regression for each sex.

Results

In the study population, 1101 (61.5%) subjects were female. The standardized strain curves (Figure 2) showed that aging primarily manifested in the diastolic part of the strain curve. Decreasing EDS was associated with increasing age group, while the opposite was true for LDS. In linear regression, both SRE (female: beta=-0.13; p<0.001, male: beta=-0.1; p<0.001) and SRA (female: beta=0.09; p<0.001, male: beta=0.09; p<0.001) were associated with age group for both sexes. Peak LS did not change notably with age, and in linear regression, GLS and SRS were only significantly associated with age for women (GLS: beta=0.12; p<0.001, SRS: beta=0.01; p<0.001).

Conclusion

We derived normal standardized LS curves for healthy individuals stratified by age and sex, which can serve as normal values in future studies. In addition, these showed that age was primarily associated with changes in the diastolic part of the strain curve in both sexes, which was consistent with conventional strain measures.Figure 1:Overview of termsFigure 2Standardized longitudinal strai
Preprocedural global myocardial work index independently predicts NT-proBNP in patients undergoing transcatheter aortic valve replacement: a prospective study
Authors: Ruppert M , Lakatos B K , Ladanyi Z , Fabian A , Turschl T , Balint T , Fejer C , Molnar L , Apor A , Molnar A A , Kovacs A , Merkely B
Published: November 2023

Global myocardial work index is a novel echocardiographic parameter of the left ventricular (LV) function, which may overcome the load-sensitvity of the traditional functional measures by measuring LV deformation in the context of simultaneous pressures. This approach may gain particular importance in pressure overload states, such as patients with severe aortic stenosis. However, the longitudinal changes of this recently introduced measure are scarcely investigated in this population, and data are also lacking about its association with functional improvement following transcatheter aortic valve replacement (TAVR).

Accordingly, our aim was to investigate the clinical determinants of preoperative and also postoperative GMWI in patients undergoing TAVR.

Eighty-four patients (54%% male, age: 79±6 years) were enrolled. Prior to the procedure, subjects underwent echocardiographic investigation and the detailed medical history was also recorded. Serum NT-proBNP levels were also measured. We calculated LV ejection fraction and LV end-diastolic volume (EDV), and speckle-tracking analysis was performed to measure global longitudinal strain (GLS). As an accepted method of its estimation, LV pressure curve was generated by adding the mean aortic valve gradient to the systolic blood pressure. Using these measures, global myocardial work index (GMWI) was quantified by commercially available software. 12 months after the procedure, the patients underwent a follow-up echocardiographic examination, and at that time point we determined the same measures.

At follow-up, GLS has significantly increased (-13.5±4.5 vs. -15.2±3.6%; p<0.001), while GMWI was significantly lower at the follow-up assessment (1913±786 vs. 1666±594 mmHg%, p<0.01). Compared to the preoperative values, LVEDV also showed a significant decrease at follow-up (115±46 vs. 105±41 mL, p<0.01). Using multivariable analysis, atrial fibrillation (β=0.36; p<0.001) ischemic heart disease (β=0.20; p<0.05) and also GMWI (β=-0.22; p<0.05) were found to be independent predictors of the postoperative NT-proBNP (R2=0.36; overall p<0.001). Importantly, by replacing GMWI to GLS, the latter did not enter the model as a predictor (β=0.17, p=0.11).

TAVR significantly alters LV functional and morphological measures. Regarding the functional outcome of the patients, different clinical factors influence NT-proBNP after the procedure. Possibly due to its significant load dependency, preoperative GLS failed to predict NT-proBNP at follow-up, while GMWI was an independent precictor of NT-proBNP at follow up along with atrial fibrillation and ischemic heart disease. GMWI may serve as a useful imaging marker of preprocedural patient assessment before TAVR.
Left atrial stiffness and sex differences in atrial fibrillation recurrence after catheter ablation
Authors: Cifci G , Wen S , Pislaru S V , Pellikka P A , Kane G C , Asirvatham S J , Pislaru C
Published: November 2023

Background

Atrial fibrillation (AF) occurs more frequently in men, but women suffer more AF recurrence; mechanisms are not completely understood.

Purpose

To explore whether sex related differences in LA stiffness (LAstiffn) in patients with AF ablation could potentially explain differences in AF recurrence.

Methods

We screened patients with catheter ablation for AF, in sinus rhythm at 3 months post-ablation, with no significant mitral valve disease (< moderate), and with prospectively measured LA volumes [maximum (LAVI) and minimum volume index] by echocardiography. LAStiffn index was estimated as (E/e’)/LA emptying fraction. Outcome endpoint was AF recurrence up to 14 years post ablation.

Results

A total of 591 patients with AF ablation were studied (mean age 60±10 years; 25% women; Table1). At 3 months post-ablation, LAVI was 36±10 mL/m2 and LAstiffn was 0.31±0.21 1/%. Compared to males, female patients were slightly older, had more frequently hypertension, congestive heart failure, prior stroke/TIA, higher CHA2DS2-VASc score; they less often had persistent AF, coronary artery disease, or dilated cardiomyopathy. Women also had higher LAstiffn (0.37±0.24 vs. 0.29±0.19, P <.0001, Figure 1), despite similar indexed LA volumes (Table1). Rates of AF recurrence at follow-up (median 7.5 years; 347 patients with events) were higher in women vs. men (Figure 2, left; log-rank P<.001) and persisted after adjustment for age, type and duration of AF, body mass index, cardiovascular risk factors and comorbidities, CHA2DS2-VASc score ≥2, LV ejection fraction, and LAVI (adjusted HR 1.58 [1.20-2.08], P=.001). Overall, LA volumes and LAstiffn were higher in patients with older age and more comorbidities (hypertension, congestive heart failure, coronary artery disease, persistent AF, CHA2DS2-VASc score ≥2, etc; P<.01 for all). At multivariable regression analysis, LAVI and LAstiffn correlated with E/e’, LV size and mass, degree of mitral/tricuspid regurgitation, and LV stroke volume index (only LAVI). In addition, LAstiffn was higher in patients with elevated right ventricular systolic pressure (RVSP) >35 mmHg and increase in RVSP more than 10 mmHg from pre-ablation (P<.0001) (correlation R=0.44, P<.0001). At follow-up, after adjusting for age and LAVI, higher LAstiffn remained associated with AF recurrence in women (P=.02, HR 2.82 per unit change, 95% CI, 1.08-6.72; Figure 2, right), but not in men (P=.30).

Conclusions

LAStiffn is higher in women vs. men and correlates with burden of comorbidities, aging, diastolic dysfunction and pulmonary hypertension, possibly reflecting more extensive LA myopathy, and potentially contributing to sex differences in AF recurrence.Figure 1Table 1
Echocardiographic probability of pulmonary hypertension: a real world audit comparing 2015 and 2022 ESC guidelines
Authors: Willis J , Henry F , Wild C , Slegg O , Rossdale J , Peacock O , Mackenzie Ross R , Suntharalingam J , Coghlan G , Augustine D X
Published: November 2023

Introduction

Transthoracic echocardiography (TTE) is an established screening tool used in the assessment of suspected Pulmonary Hypertension (PH). ESC guidelines released in 2015 recommend the use of specific echocardiographic parameters for the assessment of PH. Here, the tricuspid regurgitation velocity (TRV) together with echocardiographic markers of PH from three categories (the ventricles, the pulmonary artery, and the IVC/RA) are used to define the echocardiographic probability of PH being present (as either, low, intermediate or high).

In 2022, the ESC updated this algorithm to include a revised haemodynamic definition of PH and also additional parameters for estimating the echocardiographic probability of PH(1). New parameters include the TAPSE/sPAP ratio as well as the combined assessment of the pulmonary artery (PA) and aortic root diameter.

This retrospective audit evaluates the impact of the most recent 2022 ESC TTE PH algorithm in detecting PH in a real world cohort referred to a shared care PH centre.

Method

Between 2010 and 2020, a total of 306 patients referred for initial assessment of PH underwent TTE followed by RHC (mean interval 31±29 days). PH TTE probabilities were calculated using both 2015 and 2022 ESC guidance. The 2022 haemodynamic definition of PH was applied to both cohorts. The sensitivity and specificity of both 2015 and 2022 were calculated.

Results

The mean sample age is 67±14years (62% female). A summary of the TTE PH probability parameters is shown in Table 1. Using the 2015 ESC algorithm, the cohort comprised 24% (n=75), 23% (n=70) and 53% (161) for low, intermediate, and high TTE PH probability respectively. Within the low TTE probability group, 33% (n=25) had PH confirmed at RHC (see Figure 1). Sensitivity and specificity for the cohort is 88% and 65% respectively.

The same dataset analysed using the 2022 algorithm demonstrates that 23% (n=71) has a low TTE PH probability, 19% (n=58) intermediate and 58% (n=177) a high TTE PH probability. Within the low TTE group the percentage of patients with PH at RHC was 35% (n=25) (Figure 1). Sensitivity and specificity for the 2022 TTE PH probability algorithm was 89% and 62% respectively.

The introduction of the TAPSE/sPAP ratio (<0.55 mm/mmHg) contributed to 16 patients changing from intermediate to high TTE PH probability. Two patients with a low TTE probability demonstrated a ratio <0.55 mm/mmHg, of which one moved from low to intermediate probability. The PA/AR diameter led to 3 patients changing from low to intermediate TTE PH probability.

Conclusion

The sensitivity and specificity for the 2015 and new 2022 PH TTE probability algorithm are similar. Further developments in TTE algorithms are needed to improve the detection of PH in those thought to have a low TTE probability of PH.Table 1.0Figure 1.0
Significant disagreements between conventional functional metrics and 3D echocardiography-derived ejection fraction in the detection of right ventricular systolic dysfunction
Authors: Tolvaj M , Radu N , Cascella A , Muraru N , Lakatos B , Fabian A , Tokodi M , Tomaselli M , Gavazzoni M , Perelli F , Merkely B , Badano L P , Kovacs A , Surkova E
Published: November 2023

Background

The conventional echocardiographic parameters of the right ventricular (RV) systolic function (e.g., tricuspid annular plane systolic excursion - TAPSE, fractional area change – FAC, free wall longitudinal strain – FWLS) only partially portray the complex functional characteristics of the RV; therefore, they may fail to capture the full spectrum of RV dysfunction and associated adverse clinical outcomes. 3D echocardiography-derived RV ejection fraction (RVEF) is a well-validated and reproducible parameter that overcomes these limitations.

Purpose

We aimed to investigate the discordance between TAPSE, FAC, FWLS and RVEF in RV systolic function grading and associated outcomes.

Methods

Two retrospective databases from different centers including consecutive patients with various cardiac diseases who underwent clinically indicated 2D and 3D echocardiography (n=750) were analysed. Patients were followed up for the occurrence of all-cause mortality. RVEF was measured by a single, commercially available 3D software package. Guideline-recommended cut-off values were used to indicate RV systolic dysfunction (TAPSE<17 mm, FAC<35%, FWLS>-20%). RVEF <45% served as the "ground truth" of RV dysfunction.

Results

Among patients with normal RVEF (n=511), 109 (21%) had reduced TAPSE, 168 (33%) had reduced FAC, and 42 (8%) had reduced FWLS. Among patients with reduced RVEF (n=239), 109 (46%) had normal TAPSE, 61 (26%) had normal FAC, and 98 (41%) had normal FWLS. Correspondingly, sensitivity and specificity for discrimination of RV systolic dysfunction (RVEF<45%) were 66% and 70% for TAPSE, 71% and 76% for FAC, and 89% and 69% for FWLS on ROC analysis, respectively (Figure 1). During the median follow-up time of 3.5 years, 112 patients (15%) died. Using univariable Cox regression, TAPSE (HR [95% CI]: 0.911 [0.881 - 0.942]), FAC (0.940 [0.924 - 0.957]), FWLS (1.101 [1.071 - 1.133], and RVEF (0.928 [0.913 - 0.944]) were all significant predictors of mortality (p<0.001). Interestingly, combining the conventional functional measures based on how many of them indicate dysfunction shows that outcomes are the worst if at least two parameters are impaired and gradually better if only one or none of them (Kaplan-Meier curves, Figure 2, log-rank p<0.001).

Conclusion

Guideline-recommended cut-off values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. Impaired values of FWLS show the closest association with the RVEF cut-off. Our results emphasize a multiparametric approach in the assessment of RV function, especially, if 3D echocardiography is not available.Figure 1.Figure 2.