bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in the contemporary utilization and outcomes of left atrial appendage occlusion in the United States
Authors: Lopez J , Karpel D , Obaed N , Mark J , Ramos F , Jazaerly M , Wahood W , Chait R 
Published: October 2022

Abstract

Background
Racial and socioeconomic disparities in the utilization of percutaneous structural heart disease interventions have been described in previous years, reflecting significant gaps. However, it is unclear if increased awareness has created meaningful changes in the utilization of left atrial appendage occlusion (LAAO) in underrepresented populations.

Purpose
We aim to further clarify current practices in the United States and answer questions to help guide further efforts in attenuating health disparities.

Methods
The National Inpatient Sample (NIS) was queried from 2016–2019 to identify all patients &gt;65 years of age diagnosed with atrial fibrillation or atrial flutter who underwent left atrial appendage occlusion (LAAO) using the international classification of diseases, tenth revision clinical modification (ICD-10-CM) codes. We selected this age cutoff to minimize confounding bias from lack of insurance coverage as patients age 65 and older qualify for the Center of Medicare & Medicaid Services. We excluded patients with missing race information. In addition, we confined our analysis to patients of White, Black, and Hispanic ethnicity because the number of other races was insufficient for meaningful analysis. Multivariate linear and logistic regression analysis was performed to compare the odds of procedure utilization, in-hospital mortality, and significant periprocedural complications among study groups.

Results
We identified a total of 14,103,690 patients &gt;65 years of age diagnosed with either atrial fibrillation or atrial flutter. Of those, 53,350 (0.38%) underwent LAAO. The mean age of the sample was 79±7.6 years. Compared to White patients, Black patients had lesser odds of undergoing LAAO when controlling for multiple confounders (AOR = 0.49, 95% CI 0.44–0.55, p&lt;0.001). Among Hispanic patients, there was no statistically significant difference in the odds of undergoing LAAO compared to White patients. There was no statistically significant difference in mortality, vascular complications, non-home discharge, stroke, transient ischemic attack, pericardial tamponade, and length of stay in patients undergoing LAAO among different ethnicities.

Conclusions
Significant disparities, including procedure utilization and patient characteristics prior to the procedure, such as household income, still exist among Black patients compared to White patients undergoing the LAAO in the United States. Nevertheless, adjusted odds of in-hospital outcomes were similar among Black, Hispanic, and White patients. Further research is necessary to identify what mitigation strategies could be effective and what can be changed to close the remaining gap.

Funding Acknowledgement
Type of funding sources: None.
Counting the cost of progressive aortic valve stenosis: an international observational clinical cohort study
Authors: Stewart S , Afoakwah C , Playford D , Strom J B , Chan Y , Schuffham P , Strange G 
Published: October 2022

Abstract

Background
We sought, for the first time, to quantify the societal to healthcare burden associated with the entire spectrum of aortic stenosis (AS) - the most common cardiac valve disorder requiring clinical management.

Methods
In this observational clinical cohort study with individual data linkage to all-cause mortality, we examined the distribution of progressive stenosis in the native aortic valves of 98,565 men and 99,357 women aged ≥65 years within a multicentre cohort across 24 sites internationally. Individuals were grouped according to their peak aortic valve velocity on last electrocardiogram investigation: 1.0–1.99 m/s (no AS/reference groups) and then 0.5 m/s increments up to ≥4.0 m/s (severe AS). Sex-specific premature mortality and years of life-lost (YLL) during 5-year follow-up were calculated, along with willingness-to-pay (WTP) to regain quality-adjusted life-years (QALYs) and healthcare costs associated with concurrent heart failure (HF).

Results
Overall, 20,701 men (21.0%; 95% CI 20.8–21.3) and 18,576 women (18.7%; 95% CI 18.5–18.9) had AS at baseline. Five-year mortality in men and women with no AS was 38.6% and 36.8%, respectively. In both sexes, mortality rose from 46.8–49.0% to 59.5–65.7% in the least- to most-severe cases of AS. Premature mortality (53.5–59.1% in the no AS group) declined from 42.4–50.9% to 34.8–35.2% of all deaths. Per 1,000 individuals, AS in men and women was associated with 8 and 13 more premature deaths resulting in 36 and 62 more QALYs (societal cost of $AU1.54 and $AU2.68 million respectively) when compared to no AS. The additional 5-year cost of healthcare utilisation for the 25 and 35 more men and women with concurrent HF and AS was estimated to be $AU1.27 and $AU1.91 million, respectively.

Conclusions
The presence of any degree of aortic valve stenosis is associated with higher levels of premature mortality coupled with excess healthcare costs that impose a heavy societal burden. These findings indicate the need for proactive and cost-effective strategies to promptly detect this common condition.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Edwards LifeSciences: Investigator-initiated grant
Conflicts of interest among authors of the ESC guidelines for the management of atrial fibrillation between 2010 and 2020
Authors: Schneider B , Stoellberger C 
Published: October 2022

Abstract

Background
In 2011, the Institute of Medicine (IOM) published standards for developing trustworthy clinical practice guidelines. It is recommended that “Whenever possible guideline development group members should not have conflicts of interest (COIs)... Members with COIs should represent not more than a minority of the guideline development group members. The chair or cochairs should not be a person with COIs.”

Purpose
Aim of the present study was to assess if the ESC guidelines for the management of atrial fibrillation are in accordance with the standards proposed by the IOM.

Methods
The declaration of COIs from task force members (TFM) and reviewers of the ESC atrial fibrillation guidelines 2010, 2016 and 2020 were retrieved from the ESC homepage. The number and the type of COIs were assessed for each guideline and compared.

Results
Regarding the 2010 guidelines, 17 of 25 TFM (68%) declared COIs. Overall, 148 COIs were reported (8.7±10.2 per member, range 1–44). The chairperson declared 11 COIs. 15 of 25 TFM (60%) received direct personal payments (5.9±7.3 COIs per member, range 1–30). Research contacts were reported by 13 TFM (52%). Among the guideline reviewers, 14/26 (54%) indicated any COI (5.1±3.3 per reviewer, range 2–14).
Regarding the 2016 guidelines, 14 of 17 TFM (82%) declared COIs. Overall, 182 COIs were reported (13.0±10.4 per member, range 1–32). The chairperson of the task force had the second most COIs (n=30). 14 of 17 TFM (82%) received direct personal payments (7.7±7.4 COIs per member, range 1–22). Research funding of the department was reported by 10 TFM (59%). Among the guideline reviewers, 63/79 (80%) reported any COI (7.5±6.8 per reviewer, range 1–34).
In 2020, 21 of 24 TFM (87%) indicated any COI. Overall, 140 COIs were reported (6.7±4.5 per member, range 1–20). The chairperson of the task force declared 5 COIs. 18 of 24 TFM (75%) received direct personal payments (4.1±3.1 COIs per member, range 1–10). Research funding of the department was reported by 13 TFM (56%). Among the guideline reviewers, 87/105 (83%) reported COIs.
Comparing the guidelines between 2010 and 2020, there is an increasing proportion of TFM with COIs (from 68% in 2010 to 87% in 2020), and the proportion of TFM receiving personal payment remains high (75% in 2020). In addition, more guideline reviewers reported COIs (54% in 2010 vs 83% in 2020). Overall, the number of COIs per TFM was slightly decreasing in 2020. Companies marketing direct oral anticoagulants were most frequently mentioned in the COI declarations of the TFM in 2016 and 2020.

Conclusion
The high and increasing rate of TFM and reviewers with COIs is not in accordance with the recommendations of the IOM. Since COIs can influence healthcare decision makers and may consciously or unconsciously influence choices made throughout the guideline development process, the ESC should follow the standards of the IOM.

Funding Acknowledgement
Type of funding sources: None.
Novel complex-valued deep learning applied to automatic classification of heart sounds
Authors: Jojoa M , Percybrooks W , Rodrigo D , Garcia-Zapirain B 
Published: October 2022

Abstract

Introduction
Cardiovascular disease (CVD) is a problem facing governments around the world. Early detection saves the healthcare system thousands of dollars by allowing prevention and avoiding costly treatments when the disease has progressed to advanced stages. According to the World Health Organization (WHO), cardiovascular diseases represent the leading cause of mortality worldwide (WHO, 2019). That is why, we have decided to develop novel artificial intelligence models for the detection of heart disease, with accuracies that allow us to put the obtained algorithms into production. The revolution of artificial intelligence allows the application Deep Learning techniques of two-dimensional images in the domain of both real numbers and complex value numbers, as classifiers of heart sounds, for the detection of normality or abnormality in the functioning of the heart.

Purpose
In the present work, we propose the comparison of a novel 2D convolutional neural network (CNN) algorithm in the domain of complex value numbers with its counterpart in the domain of real numbers for the automatic classification of heart sounds into normal or abnormal.

Material
The database we decided to use for our research is Pascal, which has audio files of cardiac activity, distributed in 351 normal sounds and 129 pathological sounds.

Methods
The following steps were applied to get the objectives of our work: 1) automatic segmentation of a single heartbeat, 2) conversion of the segmented sound into its associated image scalogram using the Hilbert transform, 3) classification of the sounds into normal and abnormal using the proposed algorithms, and 4) measurement and comparison of the results obtained by performing a two-tailed t-student hypothesis test and cross-validation.

Results
We present a comparative table between the two proposed models, finding that Accuracy, F1 Score, Precision and Recall metrics obtained using complex-valued convolution networks present significant improvements compared with the real valued one. The following table show us the obtained numbers.
For all cases, the t-student test shows us p-values less than 0.05%, giving statistical evidence that the means are significantly different between the two proposed models. Besides, in all cases, the performance of the Complex-valued model is better compared with the Real-valued one.

Conclusion
Complex-valued neural networks propose a significant advance around Deep learning, since they present a better performance than the traditional counterparts based on real numbers. This proposes an experimental basis for the construction of a new Deep learning paradigm, where information in another numerical domain, is better exploited with the help of mathematical transforms. The latter is a significant advance in health sciences, where the demand is higher, in terms of performance of the proposed models.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): eVIDA research Group
Ascertainment of aortic valve disease using administrative claims
Authors: Strom J , Xu J , Sun T , Song Y , Sevilla-Cazes J , Wadhera R , Yeh R 
Published: October 2022

Abstract

Background
Administrative claims may be useful for characterizing patients with aortic stenosis (AS) and aortic regurgitation (AR) and estimating disease prevalence. However, the accuracy of diagnostic codes for aortic valve disease has not been well studied.

Purpose
To evaluate the validity of International Classification of Diseases, 10th Revision (ICD-10) codes for identification of AS and AR.

Methods
Using a large, transthoracic echocardiographic (TTE) report dataset linked to Medicare Fee-for-service (FFS) claims, 2017–2018, the performance of candidate claims to ascertain AS/AR status using standard TTE definitions was evaluated. Recursive partitioning with 10-fold cross validation was used to build the optimal prediction tree for AS/AR status using all ICD-10 codes as candidate predictors. The optimal performing claims algorithm was tested against patient outcomes in a separate 100% sample of Medicare FFS inpatient and outpatient claims, 2017–2019.

Results
Of those included in the derivation dataset (N=5497, mean age 74.4±11.0 years, 49.7% female), any AS or AR was present in 24% and 38.8%, respectively. The code I35.0 was optimal for identification of any AS with a sensitivity and specificity for any AS of 53.1% and 94.8%, respectively (Table 1). Amongst those with an I35.0 code, 40.3% had severe AS. Claims were unable to distinguish disease severity (i.e. severe vs. non-severe) or subtypes (e.g. bicuspid or rheumatic AS), and were insensitive and nonspecific for AR of any severity. Among all Medicare beneficiaries who received an TTE (N=3,783,249), those with an I35.0 code, compared to those without, had a higher risk of all-cause mortality (HR 1.65, 95% CI 1.63–1.67), heart failure hospitalization (HR 2.17, 95% CI 2.11–2.24), and aortic valve replacement (HR 32.35, 95% CI 31.46–33.27) (Table 2).

Conclusions
Amongst those receiving TTE, the ICD-10 code I35.0 in any position was optimal for identification of AS and identified a population at significant greater risk of all-cause mortality, heart failure hospitalization, and receipt of aortic valve replacement. Though 40.3% of those with I35.0 had severe AS, claims were unable to distinguish disease severity of subtype. Claims may be feasibly used to identify those with AS who may be at risk for adverse valve-related cardiovascular events and require future treatment.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): National, Heart, Lung, and Blood Institute
Development of a risk prediction score and equation for chronic kidney disease: a retrospective cohort study
Authors: Kawasoe S , Kubozono T , Ojima S , Kawabata T , Ikeda Y , Miyahara H , Tokushige K , Ohishi M 
Published: October 2022

Abstract

Background
Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future onset of CKD using large-scale health checkup data.

Methods
This retrospective cohort study included 58,423 participants without baseline CKD who were randomly assigned to Derivation (n=38,948) and Validation cohorts (n=19,475) at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In the Derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to determine the risk of developing CKD after 5 years and applied them to the Validation cohort to assess their reproducibility.

Results
The risk prediction scores ranged from 0 to 16, consisting of the seven indicators, including age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR). From the receiver operating characteristic (ROC) curve predicting CKD incidence, the area under the curve (AUC) was 0.78. A score of ≥8 showed the highest Youden index in the Derivation cohort, with a sensitivity of 0.90 and specificity of 0.52. The CKD incidence gradually and constantly increased as the score increased from ≤6 to ≥14 (Figure). The risk prediction equation consisted of aforementioned seven indicators: 1/(1 + exp[−(9.4876 + 0.0311×age + 0.2400×sex + 0.3470×hypertension + 0.0893×dyslipidemia + 0.3444×diabetes + 0.0832×hyperuricemia + (−0.1980)×eGFR]). The median probability obtained from the Derivation cohort was 0.018 (interquartile range 0.002–0.084), and the AUC value of the ROC curve for the development of CKD after 5 years was 0.88, with a sensitivity of 0.84 and a specificity of 0.78 at a cutoff value of 0.077. The Validation cohort analysis yielded similar results.

Conclusion
We developed a clinically useful risk score and equation to predict the CKD incidence after 5 years in the general Japanese population. These models have reasonably high predictability and reproducibility.

Funding Acknowledgement
Type of funding sources: None.
High resolution single cell analysis of the developing human heart
Authors: Bayraktar S , Colzani M T , Davaapil H , Knight-Schrijver V R , Rericha P H , Lee J C M , He X L , Gambardella L , Sinha S 
Published: October 2022

Abstract

The human heart is composed of various cell types with distinct embryonic origins and functions. Having an understanding of the components of the developing heart at a molecular level should provide better insights into its function in health and disease. Current single cell studies of human fetal hearts are limited by low cell numbers and poor cell type resolution. Here, we aimed to increase the number of cells studied while adding a spatial resolution. We analysed human hearts aged between post conception weeks of 8 and 11, where apex and base in each were processed, providing spatial resolution on cells constituting the myocardium and the great vessels. Our analysis suggests 6 main cell types in the developing hearts with a total of 28 subtypes and provides a differential expression signature for similar cell types with different origins and anatomical locations, including the smooth muscle cells and endothelial cells of the myocardium and the great vessels. Through immunohistochemistry, we validated our findings on these subtypes, as well as on the cells that were less clearly described before, such sinoatrial node cells or resident macrophages. Cell to cell interaction analysis inferred distinct molecular crosstalk across subtypes, including the cells of the great vessels or the vessels of the myocardium. Our findings suggest a list of transcription factors that might be involved in governing the identity of these cells. Collectively, our analysis provides a better understanding of human heart development, and will inform studies into disease modelling and disease progression.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation
Prognostic implication of unrecognized myocardial infarction in patients with non-ST-segment-elevation acute coronary syndrome
Authors: Sayama K , Hoshino M , Kanaji Y , Sugiyama T , Misawa T , Hada M , Nagamine T , Nogami K , Teng Y , Ueno H , Matsuda K , Yonetsu T , Kakuta T 
Published: October 2022

Abstract

Background
Prognostic value of unrecognized non-infarct-related territory (non-IR) myocardial infarction (UMI) in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) remains to be elucidated.

Purpose
This study sought to evaluate the prevalence of non-IR UMI and its prognostic value in patients with first NSTE-ACS presentation.

Methods
This retrospective single-center analysis was conducted in patients with NSTE-ACS without prior history of coronary artery disease, who underwent uncomplicated urgent percutaneous coronary intervention (PCI) within 48 hours of admission between August 2014 and January 2018. All patients underwent postprocedural cardiac magnetic resonance imaging (CMR) within 30 days after PCI. Non-IR UMI was defined as the presence of non-IR delayed gadolinium enhancement with an ischemic distribution pattern. We investigated the association of non-IR UMI, other CMR findings and baseline clinical characteristics with major adverse cardiac events (MACE), defined as all-cause death, non-fatal myocardial infarction, ischemic stroke, late revascularization and hospitalization for congestive heart failure.

Results
A total of 168 NSTE-ACS patients were included (124 males (73.8%); 66±11 years). Non-IR UMI was detected in 28 patients (16.7%). During a median follow-up of 32 months (15–58), MACE occurred in 10 (35.7%) patients with non-IR UMI, and 20 (14.3%) patients without (P=0.013). Patients with MACE showed higher frequency of non-IR UMI in RCA territory and multi vessel disease, higher level of NT-proBNP at admission, higher Genisini score, and greater extent of UMI. Cox's proportional hazards analysis showed that the presence of non-IR UMI was an independent predictor of MACE (HR 2.34, 95% CI 1.02–5.37, P=0.045), after adjusting confounding factors, such as multi vessel disease and serum levels of NT-proBNP at admission. The discriminant efficacy (IDI and NRI) of predicting MACE was significantly improved when the presence of non-IR UMI added to the reference clinical risk model. Kaplan-Meier analysis revealed that patients with non-IR UMI were significantly associated with poor prognosis. (Figure 1).

Conclusions
In patients with NSTE-ACS undergoing urgent PCI, the prevalence of non-IR UMI was 16.7%. Non-IR UMI provided prognostic information independent of conventional risk factors.

Funding Acknowledgement
Type of funding sources: None.
Cis-regulatory architecture and functions of a gene desert controlling pleiotropic expression and cardiac pacemaker development
Authors: Osterwalder M , Abassah-Oppong S , Mannion B , Rouco R , Zoia M , Roland V , Barozzi I , Lopez-Rios J , Andrey G , Visel A , Pennacchio L , Cobb J 
Published: October 2022

Abstract

Gene deserts are extensive genomic regions spanning more than 500 kilobases and enriched near developmental genes. Despite their proposed critical roles in development, the enhancer architecture, and biological functions of most gene deserts in mammalian genomes remain unknown. The Shox2 transcription factor is a key regulator of cardiac pacemaker differentiation and at the genomic level is flanked by a centromeric gene desert harboring a multitude of predicted cis-regulatory modules (CRMs). Using CRISPR-Cas9 we demonstrate a requirement of this gene desert for pleiotropic expression and embryonic survival through full control of Shox2 in the sinoatrial node (SAN). To decode the underlying chromatin architecture and CRM logic, we performed region-specific chromatin conformation capture, epigenomic analysis and transgenic in vivo reporter assays. While the Shox2 regulatory landscape was found partitioned into largely tissue-invariant chromatin loops, we identified a surprising cardiac-specific contact domain within the gene desert. Subsequent transgenic analysis revealed clustering of non-cardiac enhancers with activities in limb, craniofacial or neuronal populations in this domain, pointing to a potential tissue-specific 3D-mechanism for enhancer attenuation. In addition, SAN-chromatin assessment and H3K27ac profiling from human fetal cardiac compartments enabled the identification of a unique cardiac enhancer located outside of the contact domain and essential for robust Shox2 levels during cardiac pacemaker development. In summary, our results serve as a blueprint to investigate gene desert function in context to cardiac defects and identify the Shox2 gene desert as a robust cis-regulatory hub indispensable for pleiotropic patterning, cardiac pacemaker differentiation and embryonic survival.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF),National Institutes of Health (NIH)