bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA005: Tumor cell-based liquid biopsy to characterize prostate cancer
Authors: Haber Daniel A , Maheswaran Shyamala , Guo Hongshan , Vuille Joanna , Huang Shih-Bo , Wittner Ben S , Sequist Lecia V , Lee Richard J , Brunker Patricia AR , Miyamoto David T , Mishra Avanish , Toner Mehmet
Published: November 2024

Circulating Tumor Cells (CTCs) hold the promise of comprehensive yet noninvasive molecular characterization of cancer cells during the course of tumor evolution and progression. To dissect the epigenetic profile of prostate CTCs, we undertook paired DNA methylation and RNA sequencing of single CTCs isolated from blood specimens of patients with prostate cancer. Across the genome, our study identified 40 core Partial Methylation Domains (PMDs) that arise early in tumorigenesis and are shared by all individual CTCs across multiple patients. Key among these is a single genomic locus harboring multiple interferon-inducible genes along with all the CD1 gene family members, implicated in innate immunity. Based on mouse models, we propose that early biallelic silencing of multiple genes residing within a single PMD may contribute to the escape from immune surveillance in prostate and potentially other cancers. Studies of CTC heterogeneity within individual patients are limited by the very small number of cells that can be isolated from standard 10ml blood volumes. To enable such analyses, we applied a new high throughput microfluidic platform, capable of processing an entire leukapheresis product, interrogating 2-3 L of blood volume equivalent. Applying this technology to patients with metastatic prostate cancer, we successfully enriched thousands of CTCs from individual cases, enabling the characterization of intra-patient heterogeneity at the level of cell morphology and marker expression, chromosome copy number variation and exome-wide genotyping, and transcriptionally-defined tumor cell subpopulations. Such high-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.

Citation Format: Daniel A Haber, Shyamala Maheswaran, Hongshan Guo, Joanna Vuille, Shih-Bo Huang, Ben S Wittner, Lecia V Sequist, Richard J Lee, Patricia AR Brunker, David T Miyamoto, Avanish Mishra, Mehmet Toner. Tumor cell-based liquid biopsy to characterize prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA005.
Abstract IA011: Heterogeneity of cancer-derived extracellular vesicles
Authors: Di Vizio Dolores
Published: November 2024

Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO). This study provides the first resource of label-free quantitative proteomics of LO and small EVs obtained from distinct cancer cell types (prostate, breast, and glioma). This dataset was integrated with a SWATH Proteomic assay on LO, rigorously isolated from the plasma of patients with metastatic prostate cancer (PC). Proteins enriched in LO, which were identified also at the RNA level, and found in plasma LO significantly correlated with PC progression. Single EV RNA-Seq of the PC cell-derived LO confirmed some of the main findings from the bulk RNA-Seq, providing first evidence that single cell technologies can be successfully applied to EVs. This multiomics resource of cancer EVs can be leveraged for developing a multi-analyte approach for liquid biopsy.

Citation Format: Dolores Di Vizio. Heterogeneity of cancer-derived extracellular vesicles [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA011.
Abstract IA017: ctDNA based detection of MRD in colon cancer: Towards clinical implementation
Authors: Tie Jeanne
Published: November 2024

Patient selection for adjuvant treatment remains a challenge with our current clinicopathologic criteria. While adjuvant chemotherapy has been shown to improve relapse risk and survival in stage III colon cancer and perhaps less so in stage II disease, the absolute benefit remains modest, risking the over-treatment of many patients and potential under-treatment of some. Additionally, beyond fluoropyrimidine and oxaliplatin, no new adjuvant therapy has been shown to improve survival over the past 2 decades, especially for MMR proficient tumors. The ability of ctDNA to detect minimal residual disease offers a paradigm shift to the conventional tissue- based risk assessment. Post-op ctDNA detection has been shown to be one of the strongest independent prognostic markers in curatively resected colorectal cancer. Alongside technological advancement, multiple randomized trials are investigating different applications of ctDNA MRD analysis in the clinic, from adjuvant treatment de-escalation in patients with ctDNA-negative result, treatment escalation in ctDNA-positive result to the role of ctDNA as a surveillance tool. Understanding the strengths and limitations of this test will help inform future trial design and optimize clinical implementation.

Citation Format: Jeanne Tie. ctDNA based detection of MRD in colon cancer: Towards clinical implementation [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA017.
Abstract IA025: A DNA methylation atlas of normal human cell types
Authors: Kaplan Tommy
Published: November 2024

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Citation Format: Tommy Kaplan. A DNA methylation atlas of normal human cell types [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA025.
Comparative study of the therapeutic effects of radiofrequency ablation of ganglionated plexi guided by high-frequency stimulation and anatomical localization methods in the treatment of vagal syncope in young people
Authors: Guo Yan , Li Yanzhuo , Li Si , Ma Jun , Liu Jun , Ruan Yunjun , Zhang Jinxia
Published: November 2024

Objective: To investigate the differences in safety and efficacy between high-frequency stimulation (HFS) and anatomically guided endocardial catheter ablation (AA) of the ganglionated plexi (GPs) for treating vasovagal syncope (VVS) in individuals engaged in high-intensity physical training.Methods: Forty-five patients (age 22.5 ± 4.4 years) undergoing high-intensity physical training were included from January 2020 to January 2023 at our hospital. Patients underwent GP ablation for recurrent syncope. Comprehensive evaluations, including head MRI, cardiac ultrasound, electrocardiogram (ECG), ambulatory ECG (Holter), ambulatory blood pressure monitoring, plate motion tests, and head-up tilt tests (HUT), were conducted to exclude other systemic disorders causing syncope. HFS and AA-guided GP ablation were performed on 10 and 35 patients, respectively, all of whom tested positive for HUT. Differences between the two groups were compared regarding ablation sites, ablation time, safety, and effectiveness.Results: The ablation time was significantly shorter in the AA group compared to the HFS group (P < 0.001). The number of GPs selected for ablation using the AA method was reduced (P < 0.001). All patients in the HFS group experienced palpitations and discomfort, whereas only 31.43% of patients in the AA group reported these symptoms (P = 0.001). Fentanyl analgesia was administered in both groups, and no significant complications arose from the ablation. The longest follow-up duration was 52 months, while the shortest was 15 months. One case of pre-syncope occurred in the HFS group 8 months post-ablation, and one case of pre-syncope and two cases of syncope occurred in the AA group at 1 and 3 months post-ablation, respectively. There were no statistically significant differences in heart rate variability (HRV) and cardiac deceleration capacity (DC) between the two groups after ablation (P > 0.05). Two cases in the AA group still exhibited type II second-degree atrioventricular block during sleep. Both groups of patients were able to complete high-intensity physical training and showed significant symptom improvement post-ablation.Conclusion: Young individuals with VVS engaged in high-intensity physical training can benefit from GP ablation using both HFS and AA methods. The AA method requires relatively simple equipment, shorter procedure time, and results in less discomfort during the ablation.
Da botica à genômica: 120 anos da Faculdade de Ciências Farmacêuticas da USP
Authors: Pereira Filho José Luiz dos Santos , Pereira Luiz Otávio dos Santos ,   Universidade de São Paulo. Faculdade de Educação
Published: November 2024

A Faculdade de Ciências Farmacêuticas da Universidade de São Paulo (FCF-USP), listada como uma das 50 melhores instituições mundiais da área farmacêutica nos mais diferentes rankings completa 120 anos. Para marcar essa data, a Comissão de Cultura e Extensão Universitária da Faculdade sugeriu a elaboração de um livro que contasse a sua história, do qual participei da idealização e da concepção. Este livro é fruto de mais de três anos de trabalho dos autores, José Luiz dos Santos Pereira Filho e Luiz Otávio dos Santos Pereira, que buscaram reconstituir o percurso da FCF-USP pesquisando em atas das Associações Farmacêuticas, da Câmara Municipal da então província de São Paulo, em jornais e revistas, além, obviamente, dos registros disponíveis sobre a Escola Livre de Pharmacia, a Escola de Pharmacia e Obstetrícia, a Faculdade de Farmácia e Odontologia e, finalmente, a Universidade de São Paulo e a Faculdade de Ciências Farmacêuticas. A presente obra resgata a sua trajetória, como sugere o subtítulo “Da botica à genômica”, desde os primórdios da fundação como uma Escola Livre de Pharmacia (instituição particular), sua consolidação como Faculdade e, em 1934, como Unidade de ensino da Universidade de São Paulo, até os dias atuais. O livro se constitui em um importante recurso, não só para a comunidade acadêmica como também para a sociedade em geral, ao analisar como o contexto geopolítico interferiu e definiu o processo de construção da faculdade pública e gratuita, que tantos serviços tem prestado na área de saúde, através do conhecimento produzido e das mulheres e homens que por ela passaram. A obra leva o leitor a conhecer como nossa sociedade foi moldada a partir de decisões que afetaram parte da nossa história; o papel do farmacêutico, seu campo de trabalho nesses anos e as perspectivas futuras; o resgate da memória de uma das maiores instituições de ensino no Brasil; o reconhecimento daqueles que formaram toda uma geração de homens e mulheres e que nos inseriu no contexto internacional.
Associação entre peptídeos natriuréticos e gravidade clínica em pacientes internados por insuficiência cardíaca descompensada
Authors: Brunetto Mariana , Jacomasso Jessica Moraes , Nascimento Eduardo Vieira , Julião Eduardo Campos , Haluch Edgar , Seleme Vinícius Bocchino
Published: November 2024

This study aims to associate the values of natriuretic peptides (NP), BNP, and NT-proBNP, with the severity of clinical presentation in patients hospitalized with decompensated heart failure (HF). METHODS: This is a historical cohort study where data was collected from the medical records of patients admitted to a private hospital with decompensated heart failure between 2016 and 2023. RESULTS: The most common comorbidities included systemic arterial hypertension in 79 out of 96 patients (82.2%), previous HF in 46 (47.9%), dyslipidemia in 41 (42.7%), and diabetes mellitus in 38 (39.5%). The data revealed that patients who died of cardiac causes during hospitalization had higher NP values compared to those who did not experience the same outcome. Among these deaths, 57.14% of patients exhibited hemodynamic instability on hospital admission (p=0.017). Additionally, two patients were readmitted within 6 months of discharge due to a new episode of decompensated HF, both presenting hemodynamic instability on admission (p=0.03), and eventually progressed to cardiac death. Cardiac and non-cardiac deaths were associated with higher NT-proBNP values (p=0.043). CONCLUSION: The findings indicate that higher NP levels in patients hospitalized with decompensated HF correlate with greater initial severity and long-term, including an increased likelihood of hemodynamic instability and a higher risk of readmission, respectively. Elevated NT-proBNP values are also linked to a higher mortality rate.
Uso de doxazosina off label para o alívio de pesadelos no contexto do Transtorno de Estresse Pós-Traumático: uma revisão sistemáticaresse Pós-Traumático: uma revisão sistemática
Authors: Ribas Gabriel de Oliveira , Cunha Sara Regina Corrêa , Calixto Amanda Vilela Nasser , Miranda Pedro Paulo Fagundes , Boze Ana Luísa , Koseki Fábio Yutani , Candido Carolina Pola
Published: November 2024

A CID-10 define o Transtorno de Estresse Pós-Traumático (TEPT) como uma resposta prolongada e desproporcional aos eventos traumáticos, caracterizada por reexperimentação do evento traumático, esquiva persistente e hiperexcitabilidade. Neste contexto, estudos sobre pesadelos de eventos traumáticos têm ganhado notoriedade e, a doxazosina, um antagonista seletivo de receptor alfa-1 adrenérgico, surge como um fármaco potencial para o tratamento neste contexto. O objetivo desta revisão sistemática é elucidar os mecanismos de ação, eficácia, potenciais efeitos colaterais, preditores de resposta ao tratamento, considerações de segurança associados ao uso da doxazosina no contexto do TEPT, identificando lacunas na literatura. Materiais e Métodos: Essa revisão sistemática seguiu critérios das Diretrizes de Itens e Preferenciais para Revisões Sistemáticas e Meta-análises (PRISMA) e utilizou a estratégia PICO na formulação da pergunta norteadora.  Utilizou-se para esta revisão as bases de dados Google Acadêmico, LILACS, PubMed e Science Direct. A análise foi conduzida com os descritores conforme a plataforma DECS/MESH (descritores em saúde): “Doxazosina”, “Transtorno de Estresse Pós-Traumático” e “Pesadelos”. Resultados: Dos artigos revisados, todos apresentaram resultados positivos para o uso da doxazosina no tratamento de pesadelos relacionados ao TEPT, embora muitos não tenham sido realizados em comparação com placebo. Relatos de casos demonstram uma melhora dos pesadelos, mesmo em casos graves com comorbidades. Alguns estudos observaram reduções significativas dos pesadelos após o tratamento. Apesar disto, o uso da doxazosina, com este intuito, ainda não se encontra como recomendação pela Academia Americana de Medicina do Sono, mesmo sendo uma alternativa à prazosina. Efeitos colaterais mais relatados foram sonolência e cefaleia, mas foram bem tolerados. Conclusão: Apesar de existirem controvérsias, conclui-se que o uso da doxazosina pode ser uma alternativa no tratamento dos pesadelos, no contexto do TEPT. Por fim, destaca-se a necessidade de mais pesquisas sobre esta temática.
Indicators of sarcopenia and purpose in life levels in older adults: the influence of sociodemographic factors
Authors: Silva Larissa Karla , Tavares Bruno Fernando , Silva Talita , Marques Izabela Vitória , Santos Aliny , Garcia Lucas , Nascimento Júnior José Roberto , Oliveira Daniel
Published: November 2024

This study aimed to compare the indicators of sarcopenia and the level of purpose in life among older adults, considering sociodemographic factors. It is a quantitative, analytical, observational, and cross-sectional study conducted with 128 older adults (≥60 years old) of both sexes residing in Brazil's Midwest and South regions. The study employed a unique methodology, including a sociodemographic questionnaire, the Purpose in Life Scale, and the SARC-f, which were administered to the participants. Data collection took place online from January 2024 to April 2024. The study's data analysis included the Kolmogorov-Smirnov test, measures of skewness and kurtosis, bootstrapping procedures, independent t-test, one-way ANOVA, and Tukey's post-hoc test, with a significance level of p < 0.05. The older adults showed a low risk of sarcopenia (1.23±1.97) and a moderate level of purpose in life (3.77± 0.63). Younger older adults (p = 0.005), those with completed higher education (p = 0.018), and those with higher income (p = 0.007) had a lower risk of sarcopenia. Younger older adults (p = 0.035) and those with higher incomes (p = 0.007) also had higher levels of purpose in life. Purpose in life showed a significant negative weak correlation with age (r = -0.24) and sarcopenia risk (r = -0.33) (p < 0.05). In conclusion, younger older adults and those with higher monthly incomes demonstrated a lower risk of sarcopenia and a higher level of purpose in life.
Current approaches and future perspectives on hypertrophic cardiomyopathy
Authors: El Husseini Hanin El Husseini , Vale Eise Souza do , Zschoerper Erika Resner , Ferraz Maria Luiza Vaz , Ferreiro Mariana Romiti , Falkowski Rafaela Santana , Bettini Luiz Antonio Fruet
Published: November 2024

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by significant myocardial hypertrophy and varying degrees of fibrosis, affecting approximately 0.2% of the general population, with a higher prevalence in those with cardiac conditions. Despite its frequency, HCM remains underdiagnosed due to its broad clinical spectrum. The disease is equally prevalent in men and women, presenting in forms ranging from mild to severe, and it is the leading cause of sudden cardiac death in adolescents and young adults, particularly athletes. Recent advances in genetic engineering and biotechnology have significantly improved the understanding, diagnosis, and treatment of HCM, emphasizing the importance of early diagnosis in preventing severe complications. This review synthesizes findings from a narrative literature review, highlighting advances in risk stratification, gene therapy, biomarker utilization, and the need for further research to make these innovations more widely available in clinical practice. The study also examines the disease's pathophysiology, genetics, diagnostic methods, and treatment strategies, underlining the importance of personalized approaches to managing HCM.
Abstract 4112716: The Trend In Racial Differences In Mortality Attributed To Congenital Heart Diseases In Infants In The United States From 2005 To 2019
Authors: Danso Kwadwo , Owusu Yaw , Aghasili Chukwuemeka , Karikari Yaa , Ansong Annette
Published: November 2024

Background:
Deaths from congenital heart disease (CHD) in children have been decreasing in the United States. We examined the differences in mortality trends between Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) infants.

Methods:
We retrospectively analyzed publicly available data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). The data was obtained from the linked birth/infant deaths from 2005 to 2019. We evaluated all infant deaths up to 1 year of age with the cause of death listed as CHD (International classification of diseases, 10
th
revision (ICD-10) codes Q20-Q26 (except atrial septal defect, Q21.1 and patent ductus arteriosus, Q25. CHD infant mortality rate (IMR) was calculated per 100,000 live births. Race was ascertained based on death certificate reporting. Joinpoint regression was used to examine CHD-IMR by year, including stratification by NHB vs NHW, and neonatal vs postneonatal. The difference between NHB and NHW CHD-IMR was ascertained via the Mann-Whitney U test. P<0.05 was considered statistically significant.

Results:
Out of 60,243,988 live births, there were 19,004 CHD-related infant deaths. The characteristics of the study population are displayed in Table 1. The overall CHD-IMR declined from 36.1 to 27.0 per 100,000 live births (25.2%) with an average annual percentage change (AAPC) of -2.1 [95% CI -2.6, -1.572] (Figure 1). The CHD-IMR was significantly higher in NHB than in NHW (40 vs 29.3; P<0.0001) and this difference remained when the mortality rate was stratified by neonatal and post-neonatal periods. The CHD-IMR decreased significantly in NHW [AAPC: -2%; 95% CI: -2.5, -1.5%], but not in NHB [AAPC of -1.4%, 95% CI, -3.0, 0.3%]. The NHB-to-NHW CHD-IMR ratio, a measure of CHD-IMR disparity averaged 1.4 over the study period [AAPC: 0.8%; 95% CI: -0.2, 1.8%] (Figure 2).

Conclusions:
The CHD-IMR declined significantly for NHW, but not in NHB in the US from 2005 to 2019. The CHD-IMR was higher in NHB than in NHW. There was no significant change in the NHB-to-NHW CHD-IMR ratio, signifying no change in the disparity that exists between NHB and NHW IMR. These findings may have implications for patient care and public health policymaking. They lay the groundwork for additional studies to determine and understand the drivers behind these findings such as in prenatal diagnosis.
Abstract 4112845: Trends in Cardiovascular Risk Factors Among Children and Adolescents by Race and Ethnicity and Socioeconomic Status, 1999-2020
Authors: Junwen Wang , YE Yuyang , CHEN Xuefeng , HU Xinru , PENG Yong
Published: November 2024

Background:
Recent findings from large-scale cohort studies indicate that risk factors such as body mass index (BMI), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), and smoking during youth, starting in early childhood and adolescence, are associated with cardiovascular events and cardiovascular-related mortality in adulthood. The secular trends of cardiovascular risk factors among US children and adolescents remain unclear.

Objectives:
To examine 20-year trends in cardiovascular risk factors in the children and adolescents population by race and ethnicity and by socioeconomic status.

Methods:
The primary objective of the NHANES is to evaluate the overall health and nutritional status of the U.S. population. In this analysis, data from ten NHANES survey cycles, conducted from 1999-2000 through 2019-2020, were utilized. We calculated the mean and proportion changes in cardiovascular risk factors, and used linear and quadratic tests to assess the linear and nonlinear trends in their changes.

Results:
A total of 27891 participants aged 6 to 19-year-olds were included. Mean BMI increased significantly from 20.61kg/m
2
in 1999 to 21.71kg/m
2
in 2020 (P for trend < 0.001). COT means decreased from 11.47 ng/ml to 6.17 ng/ml (P for trend < 0.001). The prevalence of high COT decreased from 14.64% to 8.68% (P for trend < 0.001). TC decreased from 4.22mmol/L to 4.02 mmol/L (P for trend < 0.001). In the study population, TG levels decreased from 0.9mmol/L to 0.79 mmol/L (P for trend < 0.001). Mean LDL levels decreased from 2.45 mmol/L to 2.27 mmol/L (P for trend < 0.001).

Conclusion:
Positive trends were observed in the levels of TG, TC, LDL, and COT in US children and adolescents. Mean BMI and the prevalence of obesity exhibited a gradually increasing unfavorable trend.
Abstract 4113301: A Rare Cause of Recurrent Heart Failure Exacerbations After Transcatheter Aortic Valve Replacement: Ventricular Septal Defect and Significant Paravalvular Leak
Authors: Medina Jesse , Vincent Louis , Rodriguez Esteban , Spence-Miller Shanice , Fernandez Joel , Colombo Rosario , Calfa Marian
Published: November 2024

Introduction:
Ventricular septal defects (VSD) have been reported in <1% of cases following transcatheter aortic valve replacement (TAVR). A retrospective record review of VSD cases occurring after all TAVRs performed between January 2012 and September 2020 at one urban US tertiary hospital showed 0.37% incidence of these complications, mostly with small and restrictive VSD.

Case Description:
An 80-year-old woman with history of hypertension, HFpEF, and TAVR 8 months prior for severe aortic stenosis (AS) at an outside hospital presented with worsening dyspnea and peripheral edema over the past month. Blood pressure was 148/53mmHg, heartrate 83bpm, oxygen saturation 98% and auscultation revealed a harsh holosystolic murmur 4/6 loudest at left sternal border and bibasilar rales. Chest X-ray showed pulmonary edema and bilateral pleural effusions. NT-proBNP was 17,000pg/ml and troponin-I was negative. Echocardiogram showed EF55-60%, a membranous VSD, severe pulmonary hypertension, and moderate paravalvular leak (PVL). Coronary angiogram showed non-obstructive disease. Right heart catheterization confirmed significant left to right shunting.

Treatment/Outcomes:
Cardiothoracic surgery was consulted for multidisciplinary evaluation, and joint recommendation was for surgical aortic valve replacement and VSD closure which was successfully performed. One month follow-up echocardiogram showed normal aortic valve gradient without PVL and normal right ventricular pressure.

Discussion/Conclusion:
Numerous potential risks such as severe and uneven calcification of the native valve, an elliptic aortic annulus, excessive valve sizing, or elevated valve placement can lead to VSD. A recurrent element in many of these instances involves direct trauma to the septum caused by the implanted valve, exacerbated by subsequent annulus dilation. The presence of PVL is common post-TAVR and is an established independent prognostic factor, while VSD post-TAVR is uncommon, but may be associated with low implantation position relative to the aortic annulus or post-implantation balloon dilatation. Rarely, worsening VSD may require operative management. In this case, the improvement of heart failure symptoms and echocardiogram parameters after transthoracic surgery confirmed successful repair.
Abstract 4114220: Majority of Patients with New Ventricular Dysfunction After Acute COVID-19 Infection Did Not Have Cardiac Recovery
Authors: Yan Crystal , Rivera Rodriguez Beatriz , Andrade-Bucknor Sharon
Published: November 2024

Background:
It is still not well understood whether cardiac injury observed during acute COVID-19 infection extends after recovery from the initial viral infection. The purpose of this study was to determine the incidence of left and right ventricular dysfunction in patients hospitalized with acute COVID-19 and evaluate for cardiac recovery.

Methods:
A multicenter, retrospective cohort study was conducted. Adult patients were identified by hospitalizations using ICD-10 code U07.1 from March 2020 to October 2021. Patients were included if they had: 1) acute COVID-19 infection confirmed by RT-PCR and 2) a transthoracic echocardiogram (TTE) performed during their hospitalization. Clinical and echocardiographic data were collected and analyzed. Longitudinal TTE parameters were obtained from follow-up studies performed after discharge.

Results:
A total of 750 patients (mean age 64.3 ± 15.3 years, 60.0% male) were included. The average time to follow-up TTE was 8.7± 7.4 months. 133 patients (17.7%) had new LV dysfunction seen on TTE (
Figure 1
). LV recovery (defined as normalization of LVEF or improvement of LVEF by
>
10% from baseline) was observed in 28 of 74 (37.8%) survivors. 9 of 26 patients (34.6%) who had a follow-up TTE <6 months post-discharge recovered their LV function, while 19 of 48 patients (39.6%) who had a follow-up TTE ≥6 months had LV recovery. 94 of 725 patients (13.0%) with reported RV parameters had new RV dysfunction seen on TTE. RV recovery (defined as normalization of RV function) was observed in 11 of 38 (28.9%) survivors. 6 of 18 patients (33.3%) who had a follow-up TTE <6 months post-discharge recovered their RV function, while 5 of 20 patients (25%) who had a follow-up TTE ≥6 months had RV recovery.

Conclusions:
Most surviving patients who developed new LV or RV dysfunction did not recover their ventricular function at follow-up, but recovery extended beyond 6 months follow-up.
Abstract 4114436: Feto-maternal outcomes of subsequent pregnancy among women with Peripartum Cardiomyopathy in Tanzania.
Authors: Pallangyo Pedro , Mkojera Zabella , Komba Makrina , Kisenge Peter Richard
Published: November 2024

Background:
Besides survival and recovery, women afflicted with peripartum cardiomyopathy (PPCM) harbor significant apprehension regarding the safety of future pregnancies. Current knowledge regarding the maternal and fetal outcomes in subsequent pregnancies among women with a history of PPCM is sparse. Likewise, there is insufficient medical evidence to provide guidance for women who opt to become pregnant again after experiencing PPCM.

Research Questions:
What is the feto-maternal prognosis of subsequent pregnancies following a history of PPCM?

Aims:
To describe the fetal and maternal outcomes of subsequent pregnancies following a history of PPCM.

Methods:
We included women from the Tanzania PPCM registry who had subsequent pregnancies after PPCM and assessed PPCM recurrence, maternal prognosis, and fetal outcomes.

Results:
Among the 870 survivors (286 of whom left ventricular function had returned to normal [group 1] and 584 with persistent left ventricular dysfunction [group 2]), subsequent pregnancies were observed in 121 (13.9%) women (78 in group 1 and 43 in group 2). Forty (51.3%) women in group 1 had PPCM relapse, and during a mean follow-up of 896 days, 34 (85.0%) had complete recovery, 3 (7.5%) had persistent heart failure, and 3 (7.5%) died. In group 2, four (9.3%) women had complete recovery, 32 (74.4%) had persistent heart failure, and 7 (16.3%) died. The infant mortality rate was 23.4%.

Conclusions:
After the initial pregnancy complicated by peripartum cardiomyopathy, subsequent pregnancies could lead to PPCM relapse and deleterious feto-maternal outcomes, including death.
Abstract 4114625: Upregulation of Palmitoylating Enzymes, DHHC2 and DHHC5, in Failing Human Hearts Protects Impulse Propagation but Endangers Myocyte Survival after Ischemia/Reperfusion (I/R) Injury
Authors: Lyu Yankun , Kanshin Evgeny , Ponce Jackeline , Ueberheide Beatrix , Bernas Tytus , Tseng Gea-Ny
Published: November 2024

Background:
Palmitoylation 'Palm* catalyzed by DHHC enzymes promotes protein binding to membranes, impacting protein translocation and function. Palm* dysregulation has been linked to cancers and neurogenerative disorders; its impact on cardiac function is unclear. We have used global purification of palmitoylated proteins from human and animal hearts followed by proteomic analysis to build 'cardiac palmitoylome', whose 454 constituents are involved in organizing/stabilizing cardiomyocyte microdomains (intercalated discs 'ICD', dyads, and costameres) critical for myocyte functions/homeostasis. We confirmed 11 of the 23 DHHC genes are expressed in human&animal hearts. In particular, DHHC2 and DHHC5 were upregulated in human failing hearts. DHHC enzymes are membrane-embedded, limiting their substrates to enzymes' 'territories' in cells.

Objective:
To identify DHHC2 and DHHC5 distribution patterns and substrates in myocytes, and to understand how upregulation of DHHC2 or DHHC5 affects myocyte function.

Methods:
Track adenovirus-expressed mCherry-DHHC2 and -DHHC5 (mChr-DHHCx, x=2 or 5, Adv-mChr as control) in ventricular myocytes from adult Sprague-Dawley rats. Globally purify palmitoylated proteins for proteomic analysis/quantification. Use high-resolution quantitative imaging to analyze how mChr-DHHCx affects myocyte response to ischemia/reperfusion (I/R) injury and the expression/organization of palmitoylated proteins at ICD and lateral surface.

Results:
mChr-DHHC2 is mainly present in cytoplasmic vesicles bearing markers of recycling or autophagy, with a minor presence along lateral surface, dyads, and ICD. mChr-DHHC5 is mainly present along the lateral surface, dyads and ICD, with a minor presence in small endosomal vesicles. Palmitoylome normalized by proteome identifies DHHC2 and DHHC5 substrates that overlap with cardiac palmitoylome, and match the enzymes' distribution patterns. I/R injury increases endocytosis in myocytes, quantified by uptake of plasma-membrane marker, wheat germ agglutinin. I/R-induced endocytosis is exacerbated by mChr-DHHC2 but, surprising, alleviated by mChr-DHHC5. mChr-DHHC2 and -DHHC5 increase internalization of ICD and lateral membrane proteins, n-cadherin and NCX1 respectively.

Conclusions:
DHHC2 and DHHC5 have non-overlapping distribution patterns, consistent with varying substrate groups. DHHC2, but not DHHC5, appears involved in the previously reported palm*-dependent massive endocytosis in I/R-stressed cardiomyocytes.
Abstract 4115015: Hyperpolarized Carbon-13 Metabolic Imaging Detects Changes in Cardiac Mitochondrial Metabolism in Patients Before and After Coronary Artery Bypass Graft Surgery
Authors: Sharma Gaurav , McNeil Sarah , Lin Sung-Han , Harrison Crystal , Park Jae Mo , Peltz Matthias , Malloy Craig , Jessen Michael
Published: November 2024

Background:
Coronary Artery Disease (CAD) is a significant global health issue, necessitating improved diagnostic tools for visualizing cardiac energetics. Traditional imaging methods such as PET and dobutamine stress echocardiography do not directly assess mitochondrial metabolism. Hyperpolarized Carbon-13 metabolic magnetic resonance imaging (HP-
13
C MRI) offers a promising non-invasive method for investigating mitochondrial function in CAD. This study utilizes HP-
13
C MRI to detect changes in mitochondrial metabolism in patients undergoing Coronary Artery Bypass Graft (CABG) surgery (Fig.1).

Methods:
We conducted HP-
13
C MRI examinations on two patients with advanced CAD before and (~4-6 months after CABG surgery and one healthy subject (Fig. 2 A,B). Participating subjects provided informed consent according to a protocol approved by the Institutional Review Board and Protocol Review Committee. Baseline blood samples were analyzed for pyruvate, triglycerides, free fatty acids, and insulin levels. Post-glucose load, patients received an intravenous injection of an IND-approved metabolic probe, [1-
13
C] pyruvic acid, prepared under Good Manufacturing Practice regulations. The HP solution was administered after polarization in a clinical polarizer (SPINlab™, GE Healthcare). Imaging was performed using a GE MR750 MR system with a Helmholtz loop-pair
13
C coil (PulseTeq Limited, UK). Data were reconstructed and analyzed with MATLAB scripts.

Results and Discussion:
Baseline blood measurements were normal for the healthy subject, but those with advanced CAD showed variable and abnormal values (Fig. 2C). HP-
13
C MRI safely assessed cardiac metabolism in patients with advanced CAD. Patients with advanced CAD exhibited reduced pyruvate metabolism compared to healthy controls, shown by lower myocardial bicarbonate/(bicarbonate+lactate) ratios (Bic/(Bic+Lac)). Following CABG, only Patient 2 showed improved Bic/(Bic+Lac), while Patient 1 did not (Fig. 3A-B). This variability may be influenced by differences in nutrition, hormonal status, medication regimens, or other factors. Changes in % Bic/(Bic+Lac) across different coronary artery segments were observed post-CABG in CAD patients (Fig. 3C).

Conclusion:
HP-
13
C MRI non-invasively assesses cardiac metabolism in CAD patients, demonstrating the potential to evaluate post-CABG metabolic changes. Our efforts continue to recruit large cohort to understand individual variability.
Abstract 4115399: Comparative Outcomes of Local-Regional Versus General Anesthesia in Endovascular Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis
Authors: Queiroz Ivo , Mesquita Cynthia , Barbosa Lucas , Fernandez Miguel , Diaz Braiana , Pimentel Junior Dilson , Monteiro Mastra Fontoura Milena , Bertolino Enrico , Tavares Arthur , Mulatti Grace
Published: November 2024

Background:
Endovascular Aortic Aneurysm Repair (EVAR) has emerged as a less invasive approach to aneurysm repair. However, the optimal anesthesia modality for elective cases—general or local-regional—remains uncertain. This meta-analysis compares the outcomes of local-regional versus general anesthesia (GA) for abdominal EVAR.

Methods:
We searched MEDLINE, Embase, and Cochrane databases for studies comparing local-regional and general anesthesia for EVAR up to May 2024. Following the PRISMA protocol, 1,796 articles were screened. Endpoints included 30-day mortality, type I endoleaks, length of hospital stay (LHS), and Intensive Care Unit (ICU) admissions. A random-effects model with odds ratios (OR) and 95% confidence intervals (CI) was used for binary endpoints and mean difference (MD) for continuous endpoints. Heterogeneity was assessed using Q and I2 statistics. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach evaluated the quality of evidence.

Results:
Sixteen cohort studies, encompassing 70,654 patients treated with EVAR after excluding overlapping populations, were included. All groups had similar demographics, American Society of Anesthesiologists physical status, and aneurysm type. The mean age was 73.6 years, and 88.1% were male. Local-regional anesthesia was associated with significantly lower 30-day all-cause mortality (OR 0.74; 95% CI 0.55 to 0.99; p=0.049; I2=0, Figure A), shorter LHS (MD -0.72 days; 95% CI -1.29 to -0.15; p=0.01; I2=87%), and less ICU admissions (OR 0.53; 95% CI 0.31 to 0.93; p=0.027; I2=98%). There was no increase in endoleaks in the local-regional group (OR 0.78; 95% CI 0.55 to 1.09; p=0.143; I2=29%, Figure B). The GRADE rated this evidence as moderate certainty and high importance.

Conclusion:
Local-regional anesthesia may be preferable to general anesthesia for EVAR, as it reduces 30-day mortality, ICU admissions, and hospital stay length without increasing the risk of type I endoleaks.
Abstract 4115541: Association of Glucagon-like Peptide 1 Receptor Agonist Use with Incident Atrial Fibrillation
Authors: Khalil Suzan , Hicks William , BURKE FLOYD , mansi ishak
Published: November 2024

Background:
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown efficacy for reducing cardiovascular morbidity and mortality in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies suggested a possible association between GLP-1RA use and arrhythmogenesis, other studies suggested decreased association with atrial fibrillation (AF). Overall, large-scale real-world data evaluating risk of AF in association with GLP-1RAs are lacking.

Objective:
To compare risk of incident AF after initiation of GLP1-RA vs Dipeptidyl peptidase-4 inhibitors (DPP4i), as active comparators, in patients with DM.

Methods:
This retrospective propensity score-matched cohort study was conducted within the Veterans Health Administration from fiscal years 2006 to 2021. The study included U.S. veterans aged 35 years or older who initiated either GLP1-RA or DPP4i prescriptions. The primary outcome assessed was a composite outcome of atrial fibrillation (AF), defined as a diagnosis of AF/flutter based on administrative codes or undergoing an AF procedure.

Results:
Out of 116,235 GLP1-RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics, including demographics, comorbidities, vital signs, cardiovascular risk score, healthcare utilization, DM control, laboratory investigation, and medications. Composite outcome of AF was similar in GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (P>0.05). Notably, individuals achieving weight loss of 2%, 5%, or 10% of baseline body weight had significantly lower AF incidence, whereas no significant differences were observed in those with no weight loss or weight gain (OR 0.99, 95% CI 0.91-1.07).

Conclusions:
Use of GLP1-RA in patients with DM was not associated with a decreased risk of AF when compared with the use of DPP4i. In the subgroup analysis, significantly lower AF risk was seen in the GLP-1 RA group who achieved weight loss vs. DPP4i and this highlights weight loss as a potential modifier of cardiovascular outcomes in DM.
Abstract 4115642: Resonance Sonomanometry in an Early Prototype Device Effectively Measures Continuous, Noninvasive Blood Pressure
Authors: Rajagopal Alaina , Jimenez Raymond , Fu Matt , Yurk Dominic , Yanuck Justin , Dempsey William , Rajagopal Aditya
Published: November 2024

Background:
Nearly half of American adults have hypertension; however, reliable, continuous, noninvasive blood pressure (BP) measurement (cNIBP) for inpatient and outpatient use is not currently available. This study evaluated a new method for cNIBP measurement called resonance sonomanometry (RSM). RSM derives blood pressure using first-principles physics, is applicable to any artery, and requires no calibration, blood vessel deformation, or dependence on demographic inputs.

Methods:
A prospective, observational feasibility study was undertaken to compare carotid artery BP measurements with a prototype ultrasound-based cNIBP device incorporating RSM, to arterial catheter BP measurements in the radial arteries of 60 test subjects. Catheter measurements were obtained from a distal peripheral artery (radial), oscillometric cuff from the brachial artery, and RSM was obtained from a central artery (carotid). This study was the first-in-human study for the RSM method in comparison to arterial catheters.

Results:
RSM-induced arterial resonance was observed in all tested subjects. For each of the subjects, the arterial resonant frequency increased with increasing BP during systole, and decreased with diastole (consistent with the cardiac cycle), as predicted by the physical model. RSM-derived BP traces were qualitatively similar to catheter data, exhibiting features such as the dicrotic notch. The RSM method yielded similar diastolic BP (DBP), but lower systolic BP (SBP) compared to the arterial catheter, likely due to expected peripheral pulse amplification. RSM DBP was not significantly different from the catheter (+1.5mmHg, p = 0.187), while BP cuff DBP was significantly different from the catheter (−4.3mmHg, p=0.002). There were significant differences in the catheter to RSM SBP (34.1 mmHg, p < 0.01), consistent with the aforementioned expectations from a central-versus-peripheral continuous pressure measurement.

Conclusions:
RSM is a novel BP measurement technique that could enable cNIBP measurements with accuracy required in hospitals. While the data are promising, significant future work remains. The study was meant to test the RSM method, not the device or form factor. Consequently, the form factor will need to be improved prior to clinical use. The prototype was designed for manual operation; thus, future work will also be needed to enhance the ability of the device to autonomously locate and track the artery for ease of use.
Abstract 4116093: High Intensity Statin Use Improved ASCVD Outcomes in Patients with Severe Hyperlipidemia in a Primary Prevention Cohort
Authors: Hallihan Cameron , Zhu Jianhui , Thoma Floyd , Nambi Vijay , Mehta Anurag , Agarwala Anandita , Marroquin Oscar , Mulukutla Suresh , Saeed Anum
Published: November 2024

Background:
High intensity statin therapy is currently recommended for primary prevention of ASCVD in patients with severe hyperlipidemia (HLD), defined as low-density lipoprotein cholesterol (LDL-C) of ≥190 mg/dL. We examined statin use for patients with severe HLD and associated ASCVD outcomes in a large contemporary healthcare network.

Methods:
Using EMR data, patients between the ages of 20 and 79 with a lipid bloodwork result between 2013 and 2017 without ASCVD by
ICD9
and
ICD10
codes were identified. Patients with LDL-C ≥ 190 mg/dL were identified. Statin use was stratified by no statin, guideline directed statin intensity (GDSI), and less than guideline directed statin intensity (<GDSI). Cox proportional hazards (HR) models were used to assess the relationship between statin use, future ASCVD events, and all-cause mortality. Time to initiation of GDSI was calculated using Kaplan-Meier (KM) methods.

Results:
Out of 282,298 primary prevention patients, a total of 5,205 (1.8%) had LDL-C ≥ 190 mg/dL. These patients were 55.6% female and had an average age of 52.5 ± 12.2. At first encounter, 3.7% were on GDSI. Over a 5-year follow up, KM probabilities revealed 42% of high-risk patients with severe HLD not initially on GDSI would achieve new GDSI use. Compared to patients on GDSI, those on no statin therapy were at significantly higher risk of MI (HR = 2.36, 95% CI [1.38 – 4.04]) and stroke/TIA (HR= 2.70, 95% CI [1.43 – 5.09]); both p < 0.05. There was no significant difference in risk of all-cause mortality (HR = 1.41, 95% CI [0.90 – 2.21]). Patients on <GDSI were found to have significantly higher risk of MI (HR = 1.72, 95% CI [1.05 – 2.81]) compared to patients on GDSI. There was no significant difference between the GDSI and <GDSI groups in risk of stroke (HR = 1.28, 95% CI [0.69-2.37] and all-cause mortality (HR = 0.98, 95% CI [0.65-1.47]).

Conclusion:
Among primary prevention patients with severe HLD, high intensity statins are underutilized. Prevalence of this suboptimal use of statins is linked to greater risk of ASCVD events. Healthcare system-wide interventions can identify measures to assess burden of high-risk patients with severe HLD and implement lipid-lowering therapies optimally.