bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically Predicted Immune Cell-Mediated Effect of Lipid Metabolism on Allergic Diseases: A Two-Step, Mediation Mendelian Randomization Study
Authors: Wang Yao , Mou Ya-Kui , Liu Wan-Chen , Wang Han-Rui , Song Xiao-Yu , Yang Ting , Ren Chao , Song Xi-Cheng
Published: November 2024

Introduction: An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear. Methods: We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757). Results: Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA− CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester’s metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33− HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38− B cells played the most mediating effect of phosphatidylethanolamine (O−18:2_20:4) in allergic asthma, phosphatidylinositol (16:0_18:1) in AR, and phosphatidylethanolamine (18:0_18:2) in allergic conjunctivitis. Conclusion: This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship.
Esteem® Active Middle Ear Implant versus Conventional Hearing Aids: Long-Term Performance
Authors: Barbara Maurizio , Filippi Chiara , Tarentini Silvia , Bandiera Giorgio , Monini Simonetta , Covelli Edoardo
Published: November 2024

Introduction: The totally implantable active middle ear implant Esteem® may be considered an effective alternative to conventional hearing aids (cHAs) to manage moderate-to-severe forms of sensorineural hearing loss. This study aimed to provide long-term comparative data of Esteem performances with those achieved by cHA. Methods: From a total of 46 subjects who received unilateral application of Esteem®, and were followed up over the years, ten underwent an audiological assessment that compared the outcomes with those achieved in the contralateral ear by a cHA, considering the initially symmetric auditory thresholds in both ears. Other than pure tone audiometry and speech audiometry in quiet, the assessment was performed by using the adaptive speech in noise, i.e., Matrix test. Results: The mean speech intelligibility in quiet shows in the unaided situation a recognition of 50.7% at 71 dBHL, 71% at 69 dBHL with only contralateral cHA, 92% at 66 dBHL with only Esteem device and 94% at 61 dBHL with Esteem® device and contralateral cHA. The mean speech intelligibility in noise shows in the unaided situation a recognition of 36% at 71 dBHL, 56% at 69 dBHL with only contralateral cHA, 79% at 66 dBHL with only Esteem® device and 84% at 61 dBHL with Esteem® device and contralateral cHA. At Matrix test in the unaided condition, 4 patients reached 50% of intelligibility and the 50% threshold was obtained with a mean sound/noise ratio of +10 dBHL. In the contralaterally aided condition, 10 patients reached a 50% threshold in a condition of mean S/N ratio of +10.6 dBHL. In the Esteem® only and Esteem® plus cHA condition, all patients reached the 50% threshold with a mean S/N ratio of +3.4 dBHL with the Esteem® device and +0.92 dBHL with Esteem® plus a contralateral cHA, with a statistically nonsignificant difference. The mean deviation from the reference value (7.1 dB in the normal hearing population) was 17.1 dBHL, in unaided situation; this condition did not change with only the contralateral cHA (17.6 dBHL), whilst a significant improvement could be identified with only Esteem® device, where the mean deviation was 10.5 dBHL, and mostly with Esteem® device associated with the contralateral cHA, with a value of 8.02 dBHL. Conclusions: The adaptive speech audiometry in noise (Matrix Test) showed that binaural stimulation provides greater benefits in the speech recognition in noise test in comparison to monaural stimulation, especially when this is carried out only by the cHA. However, the Esteem® device allowed to obtain audiological benefits that are significantly superior to those offered by cHAs, especially in cases where the hearing loss is severe and, in some cases, profound, achieving performances almost comparable to those of a cochlear implant.
Nota do Editor
Authors: Martins José Eduardo
Published: November 2024

Nota do Editor, vol. 11
Essência e Alcance das Manifestações Barrocas no Universo Luso-Brasileiro
Authors: Toledo Benedito Lima de
Published: November 2024

Ao estudar esse fenômeno artístico complexo e largamente difundido a que chamamos Barroco, todos parecem seduzidos por uma miragem. As teorias que buscam explicá-lo acabam por sofrer uma espécie de contaminação e se tornam, igualmente, prolixas e de difícil enquadramento. Se quisermos nos ater ao Barroco no Brasil, constatamos que, para sua correta compreensão, não se pode prescindir de uma certa familiaridade com o Barroco de Portugal, o que implica, por sua vez, uma avaliação das fontes que inspiraram seus artistas. Qual teoria poderia, então, ser invocada para compreensão desse quadro luso-brasileiro? O Absolutismo proposto pelo holandês Leo Ballet, a Contra-Reforma, invocada pelo alemão Werner Weisbach, ou nos contentaríamos com as categorias arroladas por Heinrich Wöllflin? Enquadrar o Barroco brasileiro em qualquer dessas teorias pode ser um exercício intrigante, mas pouco conclusivo. Abandonando a pretensão de transitar por complexas teorias formuladas em outros contextos, deveríamos, mais modestamente, considerar os pólos onde o barroco brasileiro começou a se desenvolver e as etapas de seu desenvolvimento.
A Trajetória da Missa de Réquiem de Henrique Oswald: Aspectos Estilísticos, Questões Musicológicas e Divulgação da Obra no Brasil e em Portugal
Authors: Igayara Susana Cecília
Published: November 2024

A Missa de Réquiem para coro misto e órgão de Henrique Oswald faz parte de um momento decisivo da produção sacra coral no Brasil e dá testemunho da nova orientação adotada pela Igreja Romana no início do século XX, após a promulgação do Motu Proprio do Papa Pio X, em 1903, cuja definitiva implantação no Brasil intensifica-se na década de 20. A obra insere-se, portanto, no movimento de reforma da música sacra iniciado ainda no século XIX.
A Organização de Acervos Musicais na ECA/ USP: As Experiências da Biblioteca e do Laboratório de Musicologia do Departamento de Música
Authors: Recine Analúcia dos Santos Viviani , Macambyra Marina
Published: November 2024

Histórico do processo de formação dos acervos musicais da Escola de Comunicações e Artes da USP, destacando a trajetória das coleções de partituras do século XIX provenientes de Minas Gerais e explicando o papel desempenhado pela Biblioteca da ECA e pelo Laboratório de Musicologia na organização desse material. Descreve a metodologia de catalogação de documentos musicais desenvolvida pela Biblioteca e as experiências de organização de coleções de partituras manuscritas empreendidas por pesquisadores ligados ao Departamento de Música.
Abstract 4138056: Publicly-Insured Patients Have Lower Rates of Cardiac Rehabilitation Enrollment: A Statewide Experience in Michigan__PRESENT
Authors: Pedamallu Havisha , Mantey Julia , Sukul Devraj , Keteyian Steven , Pagani Francis , Hawkins Robert , Likosky Donald , Thompson Mike
Published: November 2024

Introduction:
Cardiac rehabilitation (CR) is a clinically effective and underused service for patients with recent cardiac events, and insurance coverage is an important, yet understudied, mediator. The objective of this study was to evaluate the relationship between insurance type and CR participation.

Methods:
Data from the Michigan Value Collaborative multi-payer claims based registry were used to identify Michigan residents admitted for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) between 01/01/2018-12/31/2022. Payer categories included commercial insurance, Medicare Advantage (MA), Medicare fee-for-service (FFS), and Medicaid. CR participation was defined as having at least one approved CR claim within 365 days of discharge. Unadjusted comparisons of CR enrollment across payers were done using chi-square tests. Multivariable logistic regression adjusted for patient demographics and comorbidities evaluated the association between payer category and CR participation.

Results:
The final sample included 74,505 episodes of PCI (82%) or CABG (18%) with mean (SD) patient age 67.7 (11.4) yrs, 68% male, and a payer breakdown of 23% commercial insurance, 22% MA, 41% Medicare FFS, and 14% Medicaid. Overall, 29,829 (40%) patients participated in a single session of CR, with a higher participation in CABG vs. PCI (60% vs. 36%, p<0.001). There were significant differences in CR use across payers, with commercially insured individuals having highest rates (46%) followed by MA (43%), Medicare FFS (39%), and lowest for Medicaid (30%, p<0.001). Compared with commercially insured patients, individuals with Medicaid (adjusted odds ratio, aOR=0.55 [0.52-0.58], p<0.001) and Medicare FFS (aOR=0.87 [0.84-0.91], p<0.001) were significantly less likely to participate in CR (Figure). The relationship persisted when stratified by the method of revascularization.

Conclusion:
Individuals with Medicaid and Medicare FFS coverage had lower rates of CR participation than those with MA or commercial insurance following PCI or CABG. Understanding disparities in CR usage by payer may help target quality improvement efforts and increase equitable use of secondary disease prevention strategies.__PRESENT
Abstract 4138060: Comparison of Alcohol Septal Ablation with Mavacamten in Obstructive Hypertrophic Cardiomyopathy
Authors: Samhan Ashraf , Saleh Danish , Kim Ellis , Hu Mo , Mueller Kayla , Garza Abigail , Baldridge Abigail , Puthumana Jyothy , Flaherty James , Choudhury Lubna
Published: November 2024

Background:
Mavacamten is the first commercially available myosin inhibitor shown to improve cardiac hemodynamics and functional status in patients with obstructive hypertrophic cardiomyopathy (HCM). Mavacamten may be considered in patients who have not responded to first-line medical therapies and are being considered for septal-reduction therapy (SRT).

Research Question and Aims:
The efficacy of Mavacamten relative to SRT remains unknown. This study compares Mavacamten and SRT with alcohol-septal ablation (ASA) in modifying cardiac hemodynamics and functional status in patients with obstructive HCM.

Methods:
Patients of the Bluhm Cardiovascular Institute (BCVI) of Northwestern University in Chicago, IL, managed for HCM from January 2008 to May 2024 were sampled. Patients who had undergone ASA (N = 41) or initiated treatment with Mavacamten (N = 40) were identified. Clinical and echocardiographic data were collected and reported for individuals at baseline, at 16 weeks, and after 24 weeks following ASA or the initiation of Mavacamten, respectively.

Results:
Baseline demographics were similar for both groups except for age and tobacco use history (Table 1). Patients who underwent ASA were older compared to counterparts treated with Mavacamten (75 v 61, p < 0.001). Both ASA and Mavacamten were associated with a greater than 70% reduction in valsalva left-ventricular outflow tract (LVOT) gradient and mitral regurgitation. The maximal effect of ASA on LVOT gradient was observed at 16 weeks, whereas the maximal effect of Mavacamten was not appreciated until after 24 weeks. At baseline, the average left-ventricular ejection fraction (LVEF) was hyperdynamic in patients receiving Mavacamten relative to those treated with ASA. After 24 weeks, the average LVEF of patients treated with Mavacamten was reduced yet remained in the normal range. Patients who underwent ASA had a poorer NYHA functional class at baseline compared to those prescribed Mavacamten (~2.5 v 2.1, p < 0.001); however, each therapy significantly improved functional capacity, and average NYHA scores were comparable after 24 weeks (1.5 v 1.3, not significant).

Conclusion:
In patients with obstructive HCM, ASA and Mavacamten yield significant and comparable improvements in hemodynamics, mitral regurgitation, and functional status with lower, but normal, ejection fraction among patients on Mavacamten at the end of 24 weeks.
Abstract 4138075: Trends in the Prevalence of Co-morbid Cardiovascular Disease and Cancer Survivorship: a National Health and Nutrition Examination Survey Analysis
Authors: Truitte Ryan , Jacobs Joshua , Zheutlin Alexander , Ho Michael , Himbert Caroline , Florido Roberta , Bress Adam
Published: November 2024

Background:
Cancer and cardiovascular disease (CVD) share risk factors including smoking, obesity, hypertension, and sedentary lifestyle. Advancements in cancer therapies have increased survivorship thereby increasing the likelihood of developing CVD among cancer survivors. Quantifying national trends in co-morbid cancer and CVD can help improve the integration of CVD prevention strategies along the cancer care continuum.

Methods:
We conducted serial, cross-sectional analyses of National Health and Nutrition Examination Survey (NHANES) participants from 2009-2020. We analyzed trends in cancer history, prevalent CVD, and prevalent predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk (categorized as >20%, 7.5-<20%, and 5-7.5%). Cancer and CVD history were defined by self-reported cancer diagnosis, and self-reported history of coronary artery disease, heart attack, angina, heart failure, or stroke, respectively. Predicted 10-year ASCVD risk was estimated using the pooled cohort equations. National estimates with 95% confidence intervals (95% CI) were calculated using NHANES survey weighting.

Results:
Of the 24,196 NHANES participants aged 18-75, 1,392 reported a history of cancer, representing a weighted prevalence of 13.5 million people. Among participants with a history of cancer, 2.3 million (17.0%; 95% CI, 14.2-19.9) had CVD. In those without CVD, 18.3% (95% CI, 15.4-21.1) had a ≥20% predicted risk, 33.8% (95% CI, 30.4-37.3) had a 7.5-<20% risk, and 9.4% (95% CI, 7.4-11.4) had a 5-7.5% risk. Among the US population, the prevalence of co-morbid cancer and CVD, as well as a 10-year ASCVD risk ≥7.5%, increased from 0.93% (95% CI, 0.64-1.34) to 1.36% (95% CI, 0.99-1.87) and 2.02% (95% CI, 1.7-2.4) to 3.06% (95% CI, 2.4-3.8) respectively, between 2009 and 2020 (Figure).

Conclusion:
The rising prevalence of co-morbid CVD and cancer, coupled with the substantial proportion of cancer survivors at high risk for ASCVD, highlights the need to better integrate care strategies and preventive measures for CVD prevention and management among cancer survivors. Coordinated management and targeted interventions could significantly improve long-term health outcomes for this complex population.
Abstract 4138076: Clopidogrel plus aspirin vs. aspirin alone in patients with minor to moderate strokes within ≤ 72 hours onset. A meta-analysis of randomized controlled trials.
Authors: Mahmoud Abdelrahman , Elfil Mohamed , Abdelsayed Kerollos , Amin Ahmed Mazen , Ramadan Mohamed , Ahmed Ali Ashraf Salah , S.A Osman Ahmed , Banour Sandi , Abdelazeem Basel
Published: November 2024

Background&Objective:
Recurrent stroke is a common event following a previous transient ischemic attack (TIA) or minor to moderate ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin monotherapy. We aim to study the effects on using DAPT vs. aspirin alone in patients with TIAs or mild to moderate ischemic strokes within 72 hours of symptoms.

Methods:
We conducted a meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochran. We used mean difference (MD) to pool continuous outcomes presented and the risk ratio (RR) for the dichotomous outcomes, with the corresponding 95% confidence interval (CI).

Results:
We included seven RCTs with a total of 20,992 patients. DAPT was more effective in reducing combined ischemic and hemorrhagic strokes recurrence (RR = 0.77, 95% CI (0.70, 0.84), P < 0.00001)
Fig-A
, ischemic strokes (RR = 0.74, 95% CI (0.67, 0.82), P < 0.00001)
Fig-B
, early neurologic deterioration (RR= 0.46, 95% CI (0.24, 0.88), P = 0.04)
Fig-C
, poor functional outcome (RR = 0.89, 95% CI (0.81, 0.98), P = 0.02)
Fig-D
, and composite of ischemic stroke, myocardial infarction, death from ischemic vascular causes, and major hemorrhage [RR = 0.80, 95% CI (0.73, 0.88), P < 0.00001]
Fig-E
. However, DAPT led to more bleeding events occurrence (RR = 1.74, 95% CI (1.23, 2.48), P = 0.002)
Fig-F
.

Conclusion:
DAPT is a viable option for stroke recurrence prevention, leading to better functional outcomes, and less early neurologic deterioration; however, it increases the overall bleeding.
Abstract 4138176: Identifying Clinical Stability After Heart Failure Discharge: A machine learning-based decision aid based on continuous ECG and accelerometry
Authors: Martin Claire , Sideris Konstantinos , Cacho-Soblechero Miguel , Sekaric Jadranka , Hanff Thomas , SCHMALFUSS CARSTEN , Lewis Neil , SALLAM KARIM , Hanson Heather , Brinker Lina , Pipke Matt , Perez Alday Erick Andres , Alla Srilakshmi , Steinhubl Steven , Edelberg Jay , Koren Michael , Wegerich Stephan , Kurio Gregory , Serghiou Stylianos , Stehlik Josef
Published: November 2024

Introduction:
Heart failure (HF) is typified by disease exacerbations resulting in high readmission rate and mortality. Continuous electrocardiographic (ECG) and activity (ACT) data offer promise of a scalable noninvasive solution that may reduce 30-day readmissions. Using a data-driven approach, we developed a machine learning (ML) model including the FDA-cleared multivariate change index (MCI) to identify HF patients at low risk for near-term decompensation.

Methods:
The LINK-HF clinical trials used the Prolaio system to continuously record physiological parameters using a wearable device. We used ML to build predictive models of a composite outcome of near-term (7-day) risk of emergency room use, hospitalization or death. The model was derived using data from the previously published LINK-HF1 study (2015-2016), and externally validated using data from the control arm of the LINK-HF2 trial (2021-2024). Covariates were developed in LINK-HF1 and a selection procedure used the bootstrap to identify the 100 covariates most commonly chosen when training a ML model to classify patients into high vs. low near-term risk. All combinations of the top 3 covariates were then used to develop the final model. The best-performing model in the training set was evaluated in the validation set.

Results:
Patient data were segmented into 7-day windows, yielding 4,243 training windows (200 [4.7%] with events) and 3,551 validation windows (109 [3.1%] with events) (Fig. 1A). The chosen model utilized covariates related to changes in heart rate, atrial fibrillation burden, and MCI to achieve an area under the receiver operating characteristic curve (AUROC) of 73% (95% Confidence Interval [CI], 69-76%) in the validation set. The model stratified patients into high and low risk, with a Hazard Ratio (HR) for the outcome of 3.9 (95% CI, 2.7-5.6; P-value, 4 x 10-13) in the validation set (Fig. 1B).

Conclusions:
Using multivariable wearable sensor data and ML, we developed a model able to identify HF patients at low vs. high near-term risk for decompensation. Future work will determine how this knowledge may optimize and personalize HF care, improving outcomes and efficiency in care delivery.
Abstract 4138187: Right Atrial Pressure/Pulmonary Artery Wedge Pressure Ratio Correlates With Early Outcomes After Pulmonary Thromboendarterectomy
Authors: CHAN CZE CI , Bautista Marie , Yang Jenny , Alotaibi Mona , Fernandes Timothy , Papamatheakis Demosthenes , Poch David , Kerr Kim , Pretorius Victor , Madani Michael , Kim Hyong
Published: November 2024

Background:
Elevated right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio has been associated with poor outcomes in pulmonary arterial hypertension (PAH). However, the current risk assessment tools in PAH focus on absolute RAP values and cut-offs over the measured RAP in context of PAWP. This ratio has not been investigated in chronic thromboembolic pulmonary hypertension (CTEPH). The ratio of RAP to PAWP may help with risk assessment prior to pulmonary thromboendarterectomy (PTE).

Method:
We retrospectively reviewed patients with CTEPH who underwent PTE at the University of California San Diego between January 2021 and December 2023. Baseline characteristics including invasive pulmonary hemodynamics and post-operative outcomes were analyzed. Mean computer generated values were used for both RAP and PAWP. Post-operative outcomes of interest were reperfusion pulmonary edema (RPE), ventilator days, re-intubation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and 30-day mortality.

Results:
Of 532 CTEPH patients undergoing PTE during this time period, total of 496 patients with baseline hemodynamics meeting analysis criteria were categorized into 2 groups: RAP/PAWP ratio ≥1 (
inverse
group, n=133, 26.8%) and RAP/PAWP ratio <1 (control group, n=363, 73.2%). There were no differences in sex, age, body mass index and comorbidities. However, patients in the inverse group had a higher incidence of hemoptysis, worse baseline functional class, worse baseline hemodynamics including lower cardiac index, and higher median N-terminal pro-brain natriuretic peptide. Post PTE, rates of RPE and re-intubation were higher in the inverse group (14% vs. 6%,
p
=0.005 and 5% vs. 1%,
p
=0.036, respectively). Ventilator days (3.1±5.1 days vs. 1.9±2.7 days,
p
=0.009), ICU and hospital LOS (5.7±5.5 vs. 4.2±3.8 days,
p
= 0.005 and 15.0±7.2 vs. 12.4±7.0 days,
p
=0.001, respectively) were longer in the inverse group. Additionally, 30-day mortality was higher in the inverse group (4% vs. 1%,
p
=0.019). Overall 30-day post PTE mortality during this period was 1.6%.

Conclusion:
CTEPH patients with mean RAP equal or higher than the mean PAWP have higher rates of early complications following PTE surgery. Additional analysis is needed to evaluate if this ratio is an independent risk factor prior to CTEPH intervention.
Abstract 4138199: Examining the regulating mechanism of the HIF-FOXM1 axis in promoting adult pig cardiomyocyte proliferation
Authors: Nakada Yuji , NGUYEN THANH , Wu Yalin , Walcott Gregory , Garry Daniel , Sadek Hesham , Zhang Jianyi
Published: November 2024

Background:
Contractile tissue that is lost to myocardial infarction (MI) in adult mammalian hearts cannot be regenerated, because cardiomyocytes (CMs) undergo cell-cycle arrest within a few days after birth; however, when apical resection (AR) surgery was performed in neonatal pigs on postnatal day (P) 1 (AR
P1
), followed by MI induction on P28 (MI
P28
), the animals completely recovered, and the regenerative process was driven primarily by CM proliferation. Furthermore, analysis of single-nucleus RNA sequencing (snRNAseq) data collected from the hearts of animals studied in our pig AR
P1
MI
P28
model and in a mouse MI model indicated that FOXM1 expression was upregulated in clusters of CMs that were co-enriched for markers of proliferation, cytokinesis, mitosis, and DNA synthesis. FOXM1 also reactivated cell-cycle progression in CMs differentiated from human-induced pluripotent stem cells (hiPSC-CMs) after the cells had lost their intrinsic cell-cycle activity, and FOXM1 promotes proliferation in cancer cells, where its expression is regulated by HIF signaling. However, the mechanisms that regulate FOXM1-induced cell-cycle reactivation in CMs are not well studied.

Hypothesis:
The HIF signaling pathway regulates FOXM1 expression in the cycling CMs of AR
P1
MI
P28
pig hearts.

Approach:
The expression of FOXM1, four HIF proteins (HIF1A, ARNT, EPAS1, and ARNT2), and markers for reactive oxygen species (ROS) and DNA damage were compared in CMs from regenerating and nonregenerating hearts (i.e., pigs that underwent AR
P1
MI
P28
or MI
P28
alone, respectively) via snRNAseq analysis and immunohistochemistry.

Results:
Both FOXM1 and EPAS1 were upregulated in AR
P1
MI
P28
CMs, and these increases were accompanied by significant declines in ROS production and DNA damage, both of which are known downstream effects of HIF pathway activation. Furthermore, the results from Eukaryotic Promoter Database indicated that EPAS1 directly binds the FOXM1 promoter in CMs.

Conclusion:
Reactivation of the CM cell cycle in AR
P1
MI
P28
hearts was at least partially induced via the HIF-mediated upregulation of FOXM1 expression, which also protected CMs from ROS and DNA damage.
Abstract 4138210: In-hospital Mortality and Cardiovascular Complications in Acute Pericarditis among patients with Heart Failure with Preserved Ejection Fraction
Authors: Perry Jamal , Akinti Oluwasegun , poluyi Charles , Ukenenye Emmanuel , Aiwuyo Henry , Duodu Esther
Published: November 2024

Background:
Heart failure with preserved ejection fraction (HFpEF), often referred to as diastolic heart failure, presents significant treatment challenges. Acute pericarditis (AP) is a life-threatening illness, yet the literature on its epidemiology and outcomes in HFpEF patients is scarce.

Hypothesis:
Acute pericarditis in HFpEF patients is associated with increased risks of myocardial infarction, various types of heart block, cardiac tamponade, ventricular arrhythmia, cardiogenic shock, and in-hospital mortality.

Aim:
This study aims to outline the association of major cardiovascular outcomes with acute pericarditis in hospitalized HFpEF patients.

Methods:
A retrospective observational cohort study was conducted using the National Inpatient Sample from 2016 to 2020. We included patients with documented AP among those with HFpEF, identified using validated ICD-10 codes. Univariate and multivariate logistic regression analyses identified outcomes and adjusted for potential confounders using the Elixhauser comorbidity index.

Results:
Among 471,145 hospitalized HFpEF patients, approximately 424 (0.09%) had AP between 2016 and 2020. The mean age was 67, predominantly female (58%), with a mean length of stay (LOS) of 8 days. Among patients with HFpEF, increased cardiovascular complications were associated with AP, including heart block in 5% of patients (OR = 1.3, 95% CI 1.1 to 1.6, p = 0.002), cardiac arrest in 2.3% (OR = 1.6, 95% CI 1.2 to 2.1, p < 0.001), and myocardial infarction in 4.5% of patients (OR = 1.3, 95% CI 1.1 to 1.6, p = 0.015). Ventricular arrhythmias occurred in 2.4% (OR = 1.5, 95% CI 1.2 to 1.9, p < 0.001), cardiogenic shock in 0.39% (OR = 5.4, 95% CI 4.3 to 6.8, p < 0.001), cardiac tamponade in 16.5% (OR = 144, 95% CI 127.2 to 164, p < 0.001), and mortality was 4.25%. However, the association between AP and mortality was not statistically significant (OR = 2.4, p = 0.152) (see Figure 1).

Conclusion:
Acute pericarditis, while rare in HFpEF patients, is associated with increased major cardiovascular complications, including ventricular arrhythmias, tamponade, cardiogenic shock, and cardiac arrest, particularly with a significant odds ratio for cardiac tamponade.
Abstract 4138635: The Association of Perioperative Statins and Cardiac Surgery Associated Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Han Jiawei , Zhang Heng , Zeng Juntong , Su Xiaoting , Zhou Hongyan , Liu Sheng , Zheng Zhe
Published: November 2024

Backgrounds:
Cardiac surgery associated acute kidney injury (CSA-AKI) is a prevalent and detrimental complication following cardiac surgery, with significant effects on both in-hospital and long-term morbidity and mortality. The renal protective effect of statins for patients undergoing cardiac surgery remains unclear.

Purpose:
This study aims to evaluate the association between perioperative statin therapy and the risk of CSA-AKI following coronary artery bypass grafting (CABG).

Methods:
This retrospective cohort study included consecutive patients undergoing CABG between 2013 and 2022, with one year follow-up after hospital discharge. Any usage of statin initiated from admission to 72 hours after surgery was defined as perioperative statin therapy. The primary outcome was in-hospital postoperative AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes were composite measures including all-cause mortality and dialysis at 30 days and one year. Multivariate Cox proportional hazards regression models were constructed to assess the association between perioperative statin and pre-defined outcomes.

Results:
Among the included 36288 patients, 22272 (61.3%) patients received perioperative statin therapy, with a total of 19683 (54.2%) patients developing CSA-AKI. For the primary outcome, perioperative statin was associated with a significantly decreased risk of CSA-AKI (52.8% vs. 56.5%; adjusted Odds Ratio [OR], 0.865 [95% CI, 0.829-0.904]; p < 0.001). Additionally, the occurrence of a composite measure including all-cause mortality and dialysis was statistically lower in patients who underwent perioperative statin therapy at 30 days (0.7% vs. 1.6%; OR, 0.485 [95% CI, 0.394-0.597]; p < 0.001), as well as at one year (adjusted Hazard Ratio [HR], 0.632 [95% CI, 0.543-0.737], p < 0.001). For the subgroup analysis, the association between perioperative statin and reduced CSA-AKI risk was greater among patients with chronic heart failure and undergoing on-pump CABG.

Conclusions:
Perioperative statin therapy was associated with significantly lower risks of CSA-AKI following CABG, and a composite measure including all-cause mortality and dialysis at both 30 days and one year. The preventive effect of perioperative statin was more pronounced in patients with chronic heart failure and undergoing on-pump CABG.
Abstract 4138647: Opportunistic Screening for Cardiovascular Risk Using Chest X-Rays and Deep Learning: Associations with Coronary Artery Disease in the Project Baseline Health Study and Mass General Brigham Biobank
Authors: Chandra Jay , Raghu Vineet , Karady Julia , Sturniolo Audra , Klop-Packel Nory , Maron David , Rodriguez Fatima , Mahaffey Kenneth , Shah Svati , Lu Michael
Published: November 2024

Introduction/Background:
We previously demonstrated that an open-source deep learning model (CXR-CVD Risk) can predict 10-year major adverse cardiovascular events (myocardial infarction&stroke), based on a chest radiograph image (CXR). As deep learning models are black boxes, establishing the biological processes the model captures to predict risk may help build understanding and trust in the model.

Research Questions/Hypothesis:
To test associations between deep-learning derived CXR-CVD Risk and markers of cardiovascular disease including coronary artery calcium (CAC) and stenosis ≥50% on CT, systolic blood pressure (SBP), ankle brachial index (ABI), and prevalent myocardial infarction and stroke.

Methods/Approach:
We conducted external validation of CXR-CVD-Risk in two cohorts: 1) 2,097 volunteers in the Project Baseline Health Study (PBHS) and 2) 1,644 Mass General Brigham Biobank (MGBB) patients. The CXR-CVD-Risk model estimated 10-year cardiovascular event risk (probability between 0 and 1) from a CXR image. We calculated linear associations with SBP, ABI, and the logarithm of coronary artery calcium and odds ratios for prevalent hypertension, myocardial infarction, stroke, and, in the MGBB, coronary artery stenosis ≥50%. Analyses were adjusted for age, BMI, sex, smoking status, and enrolling site.

Results/Data:
CXR-CVD-Risk was associated with CAC in both populations (PBHS: 1.11-fold increase, 95% CI: [1.07-1.16]; MGBB: 1.03-fold increase [1.01-1.05] in CAC per 1% increase in CXR-CV-Risk). CXR-CVD-Risk was also associated with SBP (0.59 mmHg increase [0.24-0.93] in SBP per 1% increase in CXR-CV-Risk), history of hypertension, history of myocardial infarction, and stroke. There was an inverse association with ABI (0.010 decrease [0.005-0.014] in ABI) in the PBHS. In the MGBB, CXR-CVD-Risk was associated with coronary artery stenosis ≥50% (OR = 1.004 [1.002-1.007]). All estimates are after covariate adjustment.

Conclusion:
This deep learning CXR risk score was associated with coronary artery disease (calcium score and stenosis ≥50%), CVD risk factors, and prevalent CVD. Opportunistic screening using CXRs in the electronic record can identify patients at high risk of CVD who may benefit from prevention.
Abstract 4138715: Disparities in Aortic Dissection and Aortic Aneurysm-Related Mortality in The United States From 1999-2020
Authors: Shahzad Maryam , Irfan Mariyah Zainab , Danisha FNU , Jaiswal Vikash , Mattumpuram Jishanth
Published: November 2024

Background:
Aortic dissection (AD) and aneurysm (AA) have a low incidence but are severe health risks associated with high mortality rates, and based on location, can have a mortality rate of over 80%. We aim to highlight disparities in mortality based on gender, race, age and demographic background.

Methods:
This retrospective study analyzed death certificate data for AD and AA (ICD-10 code I71) from 1999 to 2020 using the CDC WONDER database. Age-adjusted mortality rates (AAMR) per 100,000 were assessed for adults aged 25 and older by gender, race, year, state, and place of death, while crude mortality rates (CMR) per 100,000 were used for age groups. Joinpoint regression calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals.

Results:
From 1999 to 2020, AD and AA resulted in 400,748 deaths in the US. During this period, AAMR for men (12.19) was approximately double that for women (5.77). Overall, the AAMR decreased from 12.40 to 6.71 (AAPC: -2.93; 95% CI: -3.06 to -2.79; p-value<0.000001). NH whites had the highest AAMR at 8.93, while Hispanic and Latino populations had the lowest at 4.20. Approximately 52.3% of the deaths occurred in inpatient medical facilities, whereas 18.4% occurred at home. Vermont, West Virginia, and Wyoming had the highest AAMRs, at 11.60, 11.47, and 11.30, respectively.

Among racial groups, both males and females experienced a decrease in AAMR except for NH black men. For this group, there was an increase in AAMR from 9.42 in 2012 to 10.43 in 2020 (APC:1.03; 95% CI: 0.15 to 2.22; p-value:0.028).

The CMR for young adults rose significantly from 0.62 in 2014 to 0.73 in 2020 (APC:2.55; 95% CI 1.11 to 6.74; p-value:0.02), and for middle-aged adults from 3.09 in 2010 to 3.61 in 2020 (APC: 1.57; 95% CI 1.04 to 2.25; p-value<0.000001). Conversely, a steep decline in CMR was observed for older adults from 27.93 in 2014 to 25.4 in 2020 (APC:-1.34; 95% CI -1.9 to -0.69; p-value:0.0004).

Conclusion:
Although AD and AA mortality rates have declined over time, significant disparities persist for NH Black men and young/middle-aged adults. This highlights the need for early screening programs and equitable healthcare provision for all populations.
Abstract 4138717: Infective Root Aortitis: Medical Therapy Alone or Medical Therapy and Surgery?
Authors: Henriquez Wilfredo , Pregenzer-Wenzler Arianna , Ratliff D Michelle , Raney Brannon , Blacklock Lisa , Petrechko Oksana , Kelly Breandan , Roldan Carlos
Published: November 2024

Clinical presentation:
A 75-year-old male with previous 3 vessel CABG and bioprosthetic aortic valve (BAV) surgical replacement in 2013 was admitted with severe sepsis from diabetic foot ulcer complicated with Group A Streptococcus bacteremia and infective root aortitis.

Imaging Findings:
Initial technically limited transthoracic echocardiogram was followed by a transesophageal echocardiogram (TEE) that demonstrated a well seated BAV with mildly thickened leaflets but no vegetations, mild intra-valvular regurgitation, and 9 mm end-diastolic soft tissue echoreflectant thickening of the posterior aortic root (AoR) extending up 3 cm from the aortic annulus to the ascending aorta (Fig 1A,B). There were no signs of perivalvular abscess formation. Initial FDG PET-CT demonstrated heterogenous hypermetabolic activity at the annulus of the BAV (Fig 1C) and AoR (Fig 1D) consistent with aortitis.

Decision-making:
In the absence of guidelines for the management of these patients, a multidisciplinary team including cardiology, cardiothoracic surgery, and infectious disease opted for a conservative medical therapy instead of high-risk surgery. Patient then underwent left foot first digit amputation to achieve infectious source control. Upon completion of 4 out of 6 weeks of intravenous ceftriaxone 2 grams daily, repeat TEE showed improved AoR thickening to 6 mm (Fig 1E,F), no AoR abscess, and unchanged BAV structure and function. Repeat FDG PET-CT at the same time of TEE demonstrated persistent but improved hypermetabolic activity of the BAV annulus and AoR. After 10 weeks of IV antibiotics, repeat FDG PET-CT showed further decrease in metabolic activity on both areas. However, an Indium-111 labeled leukocyte scan showed no activity at the BAV annulus and root (Fig 1G) and therefore indicated healed AoR aortitis, which was further supported by significant decrease of ESR and CRP initial values of 126 mm/hr and 122.7 mg/L to 11 mm/hr and 3 mg/L, respectively. Patient is currently clinically stable 8 months later.

Conclusion:
This case illustrates that a conservative management of infective AoR aortitis with an extended course of intravenous antibiotics is a reasonable alternative to high-risk re-do valve and root surgery.
Abstract 4138724: Artificial-Intelligence Based Tracking of Atrial Fibrillation Waves that Exit Pulmonary Veins Predicts Response to Ablation
Authors: Anbazhakan Suhaas , Abad Juan Ricardo Carlos , Ruiperez-Campillo Samuel , Rodrigo Miguel , Narayan Sanjiv
Published: November 2024

Background:
Pulmonary vein isolation (PVI) has been shown to reduce morbidity and mortality in patients with atrial fibrillation (AF). However, a major challenge is identify which patients will or will not respond.

Hypothesis:
We hypothesized that patients in whom AF activity
predominantly exits the pulmonary veins
(PV), identified using a novel artificial-intelligence (AI) wave tracking approach, will respond to ablation compared to patients in whom activity predominantly enters the PVs.

Methods:
We examined 26,640 electrograms in N=37 patients at AF ablation (age 66.3 ± 8.6 years, 13.5% females, 59.5% non-paroxysmal AF). Patients had AF recordings with multipolar catheters. We analyzed AF in 3X3 electrode grids, representing 1-3 cm
2
areas that approximate minimum tissue wavelength, near and remote from PVs. For each grid, we determined if AF waves exited PVs (i.e. active PVs) or entered PVs using AI-algorithms to assign electrode activations and grid vectors. We compared the numbers of waves that exited versus entered PVs relative to ablation success, defined using ambulatory ECGs over 1 year.

Results:
Spatial grids in Fig A show AF waves exiting the left superior PV in a 60 year old man with persistent AF whose PVI was successful. Fig B shows AF waves entering the PVs in a 70 year old woman whose subsequent PVI was unsuccessful. Examining 720 grids per patient (48 four second grids over 1 minute), AF waves varied considerably. Fig. C shows that more AF waves exited the PVs in patients with PVI success than in patients with PVI failure (p=0.03). Conversely, more AF waves headed towards the PVs in patients with PVI failure than with PVI success (p=0.04).

Conclusions:
In this study, AI-based wave identification enabled the identification of AF patients in whom PVI was more or less successful. The approach to determine active versus passive PVs could be extended to other metrics, including non-invasive tools.
Abstract 4138731: Clonal Hematopoiesis of Indeterminant Potential is Associated with Pulmonary Arterial Hypertension
Authors: Emon Isaac , Al-Qazazi Ruaa , Rauh Michael , Vlasschaert Caitlyn , Ott Benjamin , McNaughton Amy , Potus Francois , Pauciulo Michael , Bick Alexander , Nichols William , Chung Wendy , Archer Stephen
Published: November 2024

Background:
Pulmonary Arterial Hypertension (PAH) is a fatal cardiopulmonary disorder characterized by adverse vascular remodelling of small pulmonary arteries, which increases resistance and demand on the right ventricle (RV), ultimately leading to RV fibrosis and failure. Emerging evidence suggests that inflammation plays a crucial role in PAH pathogenesis. Here, we study Clonal Hematopoiesis of Indeterminate Potential (CHIP), a disorder characterized by somatic mutations in genes such as
DNMT3A
and
TET2
, that promotes an inflammatory phenotype, in the development of PAH.

Methods:
We performed deep, targeted panel sequencing on 1659 PAH patients from the PAH Biobank and 3644 controls (3401 Vanderbilt University Biorepository patients and 243 participants recruited by the Queen’s Genomics Centre at Ongwanada). Variants in known CHIP genes expressed at a variant allele frequency (VAF)
>
2% were classified as CHIP. Genes with a VAF
>
25% and <50% were considered CHIP if located in reported CHIP hotspot regions. The prevalence of CHIP mutations was compared between controls and PAH patients. Logistic regression was used for statistical analysis.

Results:
We identified 242 CHIP variants in the 1659 PAH patients.
DNMT3A
was the most mutated gene (116/242 = 48%), followed by
TET2
(46/242=19%). After adjusting for age and sex, we identified a significant association between all CHIP variants combined and PAH (OR: 23.35 [7.67, 71.03]; p<0.0001). Further,
DNMT3A
CHIP (OR: 25.44 [5.37, 120.40]; p<0.0001), non-
DNMT3A
CHIP (OR: 26.80 [5.56, 129.23]; p<0.0001) and
TET2
CHIP (OR: 13.69 [1.29, 145.30]; p=0.03) were all associated with PAH. A higher proportion of PAH patients under the age of 70 were found to have CHIP variants compared to controls and this was significant for individuals between 60-69 years of age (p=0.037). While there was a 3.8:1 female-to-male ratio of PAH patients, there was a 5.8:1 female-to-male preponderance of
DNMT3A
variants (p=0.039) (4.3:1 for all CHIP; p=ns), suggesting
DNMT3A
variants are more common in female patients. The presence of CHIP variants had no significant effect on PAH patient 10-year survival.

Conclusion:
This research reveals a significant association between CHIP variants, specifically in
DNMT3A
and
TET2,
and PAH. The prevalence of CHIP is higher in PAH patients aged 40 to 70 compared to controls and is more common in female patients. These findings suggest that CHIP is a significant risk factor for the development of PAH.
Abstract 4138782: A Meta-Analysis Comparing Same-Day Discharge to Later-Day Discharge in Transcatheter Aortic Valve Replacement
Authors: Jain Hritvik , Jain Jyoti , Goyal Aman , Wasir Amanpreet , Ahmed Mushood , Patel Nandan , Yadav Ashish , Shah Janhvi , Mehta Aryan , Passey Siddhant
Published: November 2024

Background:
One of the benefits of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) is the possibility of same-day discharge, allowing for early mobilization and reduced total hospital stay. However, there is limited evidence comparing same-day discharge to later-day post-TAVR discharge. This meta-analysis aimed to compare the outcomes of same-day and later-day discharge post-TAVR in patients with aortic stenosis.

Methods:
A systematic bibliographic search was conducted using electronic databases, including PubMed, Embase, and the Cochrane Library, from inception to May 23, 2024. We pooled the risk ratios (RR) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at p <0.05.

Results:
Six studies were included with 71,550 patients undergoing TAVR (2215: same-day discharge; 69335: later-day discharge). The mean age for the same-day and later-day discharge groups was 77.3 ± 8.3 and 78.3 ± 8.5, respectively. Same-day discharge for patients post-TAVR was associated with a higher risk of 30-day stroke [RR: 1.93; 95% CI: 1.14, 3.27] and 30-day major vascular complications [RR: 1.82; 95% CI: 1.02, 3.24] as compared to later-day discharge post-TAVR. However, no significant differences in the risks of 30-day mortality [RR: 0.30; 95% CI: 0.06, 1.57], 30-day readmission [RR: 0.93; 95% CI: 0.66, 1.32], 30-day major bleeding [RR: 0.86; 95% CI: 0.52, 1.42], 30-day new permanent pacemaker [RR: 1.00; 95% CI: 0.81, 1.22], 30-day acute kidney injury [RR: 1.04; 95% CI: 0.73, 1.49], and 30-day valve reintervention [RR: 5.77; 95% CI: 0.60, 55.39] were noted between the two groups.

Conclusion:
This meta-analysis concluded that same-day discharge post-TAVR is associated with a higher risk of 30-day stroke and 30-day major vascular complications than later-day discharge after TAVR. Same-day discharge was comparable to later-day discharge post-TAVR in terms of 30-day mortality, 30-day readmission, 30-day major bleeding, 30-day new permanent pacemaker, 30-day acute kidney injury, and 30-day valve reintervention. This study underscores the possibility of same-day discharge after uncomplicated TAVR in select patients. Further randomized studies are required to evaluate the safety and feasibility of the same-day discharge protocols.
Abstract 4138819: KLF2-dependent transcriptional regulation safeguards the heart against pathological hypertrophy
Authors: Huang Juan , Wu Yongqi , Song Yujuan , Xie Nan , Zhao Wanqing , Xiong Hui , Wang Li
Published: November 2024

BACKGROUND:
Our previous single-cell RNA sequencing study in the adult human heart revealed that cardiomyocytes from both the atrium and ventricle display high activities of Krüppel-like factor 2 (KLF2) regulons. However, the role of the transcription factor KLF2 in cardiomyocyte biology remains largely unexplored.

METHODS AND RESULTS:
We employed transverse aortic constriction surgery in male C57BL/6J mice to develop an in vivo model of cardiac hypertrophy, and generated different in vitro cardiac hypertrophy models in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes. Our results demonstrated a significant reduction in KLF2 expression during the progression of cardiac hypertrophy. In vitro, KLF2 deficiency exacerbates cardiac hypertrophy and enhances hypertrophic reprogramming, while KLF2 overexpression attenuates cardiac hypertrophy and reverses hypertrophic transcriptome reprogramming. Mechanistically, comprehensive RNA sequencing analysis revealed that KLF2 exerts its protective effects by activating the Hippo signaling pathway and inhibiting the MAPK signaling pathway. In vivo, overexpression of KLF2 specifically in cardiomyocytes effectively prevents TAC-induced cardiac hypertrophy in mice. Furthermore, we found that simvastatin elevates KLF2 expression in cardiomyocytes, which in turn mitigates cardiomyocyte hypertrophy.

CONCLUSIONS:
This study provides the first evidence that transcription factor KLF2 serves as a negative regulator of cardiac hypertrophy. Our findings highlight the therapeutic potential of enhancing KLF2 expression, particularly through simvastatin administration, as a promising strategy in the treatment of cardiac hypertrophy.