tbuckley/cabot-search huggingface dataset:
Abstract 4141398: Relationship between Gut Microbial Butyrate and Hypertension
Authors: Pritha Das, Sebastian Reczek, Taylor Hogue, Marc Cook, Jarrad Hampton-Marcell
Journal: Circulation (2024)

Background: Hypertension is the most common cardiovascular disease risk factor of which African Americans have a greater burden. Gut microbial production of short chain fatty acids (SCFA) has been associated with blood pressure status in animals, with limited evidence in humans. The complex and diverse gut microbial ecosystem contributes to synthesizing the SCFA butyrate. Aim: The goal of the study is to determine if butyrate production in the gut is associated with hypertension and how the microbial composition differs in normal and hypertensive participants. Methods: Fecal samples from 20 participants diagnosed with normal (n = 10) or high (n = 10) blood pressure were sequenced via the 16S rRNA gene. Inference-based modeling generated functional (PICRUSt2) and metabolic (MICOM) models of microbial communities focusing on carbohydrate fermentation pathways. Supervised learning was conducted to identify significant (p &lt; 0.05) differences in predicted functional genes and microbial communities. Results: Microbial dominance was inversely correlated with increasing systolic blood pressure (Pearson, p &lt; 0.05, R = -0.44); however, no significant correlation was measured for beta diversity between the two groups. More importantly, inference modeling showed differences in microbial function and metabolism between groups. Functional pathways associated with carbohydrate fermentation were significantly (ANOVA, p &lt; 0.05) lower for hypertensive compared to normal participants. Carbohydrate fermentation accounted for only 8.05% of the predicted functions of the identified pathways. Within this subset, pyruvate fermentation to isobutanol was the most abundant pathway (12.6%), followed by starch degradation (9.6%) and glycolysis III (9.34%). Additionally, metabolic flux models revealed Catenibacterium, Subdoligranulum , and Roseburia were predicted as butyrate producers. Catenibacterium and Subdoligranulum produced 51% and 44% butyrate, respectively, in the normal group. In contrast, a different distribution was observed in the hypertensive group, with Catenibacterium accounting for 97% and Roseburia contributing 3% of the butyrate production. Conclusion: Our preliminary investigation elucidates the potential relationship between SCFA producers (as well as butyrate producers) and blood pressure status among minority participants, providing insights into how gut microbiota may influence or be influenced by blood pressure.
Abstract 4141686: Chromatin Remodeling Drives Immune-Fibroblast Cell Communication in Heart Failure
Authors: Michael Alexanian, Arun Padmanabhan, Tomohiro Nishino, Joshua Travers, Lin Ye, Pelonero Angelo, Clara Lee, Nandhini Sadagopan, Yu Huang, Kirsten Auclair, Ada Zhu, Yuqian An, Christina Ekstrand, Cassandra Martinez, Barbara Gonzalez Teran, Will Flanigan, Charis Kee-Seon Kim, Devon Conradson, Zachary Gardner, Li Li, Mauro Costa, Rajan Jain, Israel Charo, Alexis Combes, Saptarsi Haldar, Katherine Pollard, Ronald Vagnozzi, Timothy McKinsey, Pawel Przytycki, Deepak Srivastava
Journal: Circulation (2024)

Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet the molecular mechanisms governing their crosstalk are poorly understood. In diseased organs, stress-induced changes in gene expression fuel maladaptive cell state transitions and pathological interaction between diverse cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lung, liver, kidney, and heart, and exacerbates many cancers, the stress-sensing mechanisms initiating the transcriptional activation of fibroblasts are not well understood. Here, we show that conditional deletion of the transcription co-activator Brd4 in infiltrating Cx3cr1 -positive myeloid cells ameliorates heart failure and is associated with a dramatic reduction in fibroblast activation. Analysis of single-cell chromatin accessibility and BRD4 occupancy in vivo in Cx3cr1 -positive cells identified a large enhancer proximal to Interleukin-1 beta ( Il1b) , and a series of CRISPR deletions revealed the precise stress-dependent regulatory element that controls expression of Il1b in disease. Secreted IL1B functioned non-cell autonomously to activate a p65/RELA-dependent enhancer near the transcription factor MEOX1 , resulting in a profibrotic response in human cardiac fibroblasts. In vivo , antibody-mediated IL1B neutralization improved cardiac function and tissue fibrosis in heart failure. Mechanistically, systemic IL1B inhibition or targeted Il1b deletion in Cx3cr1 -positive cells prevented stress-induced expression of MEOX1 and inhibited fibroblast activation. The elucidation of BRD4-dependent crosstalk between a specific immune cell subset and fibroblasts through IL1B provides mechanistic insights into how inflammation drives profibrotic cell states and presents new therapeutic strategies for heart disease and other chronic inflammatory disorders featuring maladaptive tissue remodeling.
Abstract 4141106: AIR-TELTEC-HF Medical Expert System: a new rule-based tool of Intelligent Telemedicine for Chronic Heart Failure
Authors: Annamaria Vianello, Martina Olivelli, Massimiliano Donati, Luca Fanucci, Alessio Bechini, Ilaria Petrucci, STEFANO MASI
Journal: Circulation (2024)

Background: Medical expert systems (MES) proceed on a “knowledge base” of clinical variables linked together by a set of rules written by medical experts. The main goal of our multidisciplinary team of medical experts and knowledge, information engineers was to create an “intelligent telemedicine” able to improve outcomes through early detection of clinical instability in patients with chronic heart failure (CHF) and multimorbidity. Methods: General Practitioners (GP) and Internal Medicine Specialists designed the "knowledge base" including 30 variables and 283 IF/THEN rules. Variables were: vital signs and symptoms, antropometric, age, sex, pharmacological, clinical and instrumental values of heart and renal failure, indices of cardiovascular comorbidities and other comorbidities determining cardiac and/or renal deterioration. A set of hierarchically organized rules identify: 1) the risk class at the time of enrollment, 2) the global risk, continuously updated from self-measurement data and clinical surveys, 3) the most appropriate monitoring plan (Fig.1). Medical experts provided 8 plans (Fig.2a) for CHF patients, according to their global risk of worsening heart failure (WHF). The higher intensity of monitoring was assigned to all cases the MES was not able to handle. Results: AIR-TELTEC-HF MES underwent a first validation on 66 clinical cases, comparing its output vs the expected monitoring defined by medical experts. All cases with clinical instability and WHF (n° 18) were correctly assigned by the MES to the highest intensive monitoring plan. Overall, in 56 cases there was agreement between human expert and MES, leading to an F1-Score of 84% (Fig.2b). Conclusions: Our AIR-TELTEC-HF MES prototype for “intelligent telemedicine” reproduces the work of an expert medical team in telemonitoring settings. This prototype can be further improved involving other leading HF experts to enhance the clinical rules for many other cases of CHF and multimorbidity. It is easy-of-use and explainable enough to assist GP in clinical practice, and to facilitate multidisciplinary clinical discussion on complex patient with CHF and multimorbidity. Using MES for student training would increase the future accuracy in following CHF patients. Thanks to an appropriate monitoring of the initial phase of WHF, we would have a sensible decrease in hospitalizations. Moreover AIR-TELTEC-HF MES could be integrated with other MES, clinical records, and information systems to exchange data.
Abstract 4141082: Effects of lactate production caused by acetylcholine provocation tests on ketone bodies concentration in coronary artery spasm.
Authors: Sou Ikebe, Masanobu Ishii, Yasuhiro Otsuka, Yuichiro Arima, Yasushi Matsuzawa, Eiichiro Yamamoto, Kenichi Tsujita
Journal: Circulation (2024)

Background: Lactate measurement during acetylcholine (ACh) provocation tests can indicate the presence or absence of myocardial ischemia. Despite ACh-provoked spasm, including epicardial coronary artery spasm (CSA) and microvascular spasm (MVS), lactate production from coronary circulation is not observed in some cases. This may be attributable to the severity of myocardial ischemia. The relationship between lactate production due to coronary spasms and myocardial metabolism is not fully understood. Hypothesis: We hypothesized that there was a significant difference of ketone bodies concentration between patients with and without lactate production in ACh-provoked spasm patients. Method: This retrospective analysis included 81 CSA or MVS patients (excluding myocardial infarction) diagnosed by ACh provocation test from May 2018 to February 2024. During the test, blood sample was collected from aortic root (Ao) and coronary sinus (CS) before and after ACh provocation, in order to measure lactate and ketone bodies, such as acetoacetic acid (AcAc) and 3-hydroxybutyric acid (3-OHBA). The patients were categorized into two groups based on lactate production during ACh provocation test. Lactate extraction ratio was calculated as follows: lactate extraction (%) = {([lactate concentration at Ao] – [lactate concentration at CS]) / [lactate concentration at Ao]} x 100. Ketone bodies concentration from Ao was used before ACh provocation. Results: During ACh provocation test, 63 patients had lactate production, and 18 did not. The patients with lactate production had significantly higher concentration of ketone bodies (235.0 [IQR: 120.7-426.4] vs 90.5 [IQR: 62.2-286.7] mmol/L, p value = 0.007), AcAc (87.5 [IQR: 48.9-124.7] vs 44.9 [IQR: 29.8-88.8] mmol/L, p value = 0.006), and 3-OHBA (147.4 [IQR: 70.0-290.9] vs 51.0 [IQR: 35.1-197.4] mmol/L, p value = 0.006). Multiple logistic regression analysis adjusted for brain natriuretic peptide showed that ketone bodies (p = 0.048) and AcAc (p = 0.035) were associated with lactate production, but 3-OHBA (p value = 0.053) was not. Conclusion: This study showed that CSA or MVS patients with lactate production during ACh provocation tests have higher levels of ketone bodies concentration. These results implied that there was the differential severity of myocardial ischemia caused by ACh provocation, and that severity might affect the ketone metabolism in myocardium.
Abstract 4140791: Two-Year Clinical Outcomes of Patients with Critical Limb Ischemia versus Claudication in Femoropopliteal Artery Disease following Endovascular Therapy : An Analysis from K-VIS ELLA Registry
Authors: Seung-Woon Rha, Soohyung Park, Woo Jin Ahn, Jinah Cha, sujin hyun, Se Yeon Choi, Byoung Geol Choi, Markz Sinurat, Cheol Ung Choi, Chang Gyu Park, Dong Oh
Journal: Circulation (2024)

Background: Endovascular therapy (EVT) is a prevalent treatment option for femoropopliteal artery (FPA) disease, manifesting as critical limb ischemia (CLI) or intermittent claudication (IC). However, there is a lack of evidence regarding comparative outcomes between patients with CLI and IC following EVT in real-world settings. Research Questions: This study aimed to investigate the clinical outcomes of patients with native FPA disease, specifically comparing those with CLI and IC at 2 years following the EVT procedure from a real-world multicenter cohort. Methods: From K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) multicenter registry cohort, a total of 1924 patients with FPA disease (CLI, n=812; IC, n=1112) between 2006 and 2021 were analyzed. The primary endpoint was target limb amputation or clinically driven (CD)-target extremity revascularization (TER) at 2 years post-procedure. Results: After Inverse Probability of Treatment Weighting (IPTTW), the incidence of the primary endpoint was significantly higher in the CLI group (HR 1.314; 95% CI [1.105-1.561]; p=0.002) compared to the IC group. The incidence of loss of clinical patency, major adverse limb events (MALEs), and all-cause death was also higher in CLI group (HR 1.312; 95% CI [1.157-1.488]; p&lt;0.001). No significant differences were observed in the risk of repeated percutaneous transluminal angioplasty (PTA) (HR 1.014; 95% CI [0.833-1.234]; p=0.920). Treatment with drug-coated balloon (DCB) showed favorable outcomes for the primary endpoint in both groups compared to other treatment modalities, particularly in patients with IC [HR of 0.429 (CI: 0.25-0.734, p=0.002)]. Conclusions: EVT for FPA disease in patients with CLI is associated with worse clinical outcomes compared to those with IC. Nevertheless, the risk of repeated PTA did not differ in both groups. The use of DCB shows promising results in both groups.
Abstract 4141076: Shared Genetic Characteristics and Molecular Mechanisms between Atrial Fibrillation and Aortic Valve Calcification: Insights from Transcriptome Data
Authors: Yichao Xiao, Mali Qin, Zhenyu Li, Qiming Liu, Shenghua Zhou
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is often linked to aortic valve calcification (AVC), leading to compromised valve elasticity and increased morbidity. Although clinically overlapping, the molecular interplay between AF and AVC has not been well elucidated. This study aimed to dissect the genetic and regulatory landscape of AF and AVC to identify potential therapeutic targets. Methods: We systematically retrieved genes related to AF and AVC from databases and clinical datasets. Intersection analysis identified common genes, followed by differential expression analysis, Gene Ontology (GO) enrichment, protein-protein interaction (PPI) network construction, and transcription factor (TF) regulatory network analysis. Results: Enrichment analyses revealed ten genes common to both AF and AVC, revealing their involvement in multiple pathways. PPI analysis highlighted six hub proteins: FCGR3A, S100A12, MNDA, S100A8, NCF2, and CASP1. The key transcription factors ETS1 and SPI1 were found to regulate these common genes, underpinning distinct TF-gene and TF-miRNA networks. Conclusion: This study identified key genes and transcription factors, including FCGR3A, MNDA, S100A8, S100A12, ETS1, and SPI1, that are central to both AF and AVC. Our findings offer insights into their molecular connections and propose avenues for further research and therapeutic intervention.
Abstract 4141368: Increasing handgrip strength in patients with cardiovascular diseases is associated with improving ejection fraction in the longitudinal study
Authors: Satoko Ojima, Takuro Kubozono, Satoshi Yamaguchi, Shin Kawasoe, Mitsuru Ohishi
Journal: Circulation (2024)

Background: Weakness of muscle strength is one of the indicators of frailty. Moreover, frailty is associated with the prognosis of cardiovascular disease (CVD). However, no reports examine the association between improving ejection fraction (EF) and handgrip strength (HGS) in the longitudinal study. Purpose: To investigate the factors related to handgrip muscle strength in patients with CVD Methods: We recruited 133 patients with CVD who all performed HGS and echocardiography twice on the first and second visit. Furthermore, we measured blood samples such as brain natriuretic peptide (BNP) and haemoglobin (Hb) twice on the first and second visit as well. We applied to investigate factors such as the newly presented anaemia, ΔBNP(second visit-first visit), ΔHGS (second visit-first visit), Δleft ventricular end-diastolic diameter (Dd) (second visit-first visit). Two types of assessment were used for EF improvement. One is improving ΔEF, defined as an increase from the baseline. The other is improving ΔEF &gt; 10%, defined as a 10% increase from the baseline. Results: The average follow-up period was 1.5±1.1 years. EF, BNP, and HGS baseline data were 50±19 %, 128±178 pg/mL, and 28.6±10.2 kg, respectively. In multivariate logistic regression analysis adjusted for age and sex, increasing HGS and decreasing Dd were independent risk factors for improving ΔEF &gt; 10% (increasing HGS: OR 3.69 CI 1.32-10.3, p=0.013; decreasing Dd: OR 3.76 CI 1.41-10.0, p=0.008). Moreover, in multivariate logistic regression analysis adjusted for age and sex, increasing HGS was only an independent factor for improvingΔEF (OR 2.31 CI 1.05-5.07, p=0.038). Conclusions: In patients with CVD, improving ΔEF &gt; 10% was associated with decreased Dd and increasing HGS. Furthermore, improving ΔEF was associated with increasing HGS. Increased handgrip strength was a significant factor in EF improvement.
Abstract 4141004: Efficacy of calf neuromuscular electrical stimulation program on maximal walking distance in peripheral artery disease patients: results of the ELECTROPAD randomized controlled trial.
Authors: Guillaume Mahe, Adrien Chanteau, Pierre Jehannin, Mary Lynn Mimassi, Alan Donnelly, Marjolaine Talbot, Clement Hoffmann, Samir Henni, Estelle Le Pabic, Alessandra Bura, Adrien Kaladji, Damien Laneelle, Alexis Le faucheur
Journal: Circulation (2024)

Introduction: Lower extremity peripheral artery disease (PAD) can lead to walking impairment. To date, no clear clinical indication can be drawn regarding the efficacy of neuromuscular electrical stimulation (NMES) for the management of impaired walking function in patients with PAD. The ELECTROPAD study aimed to investigate the efficacy of NMES program on maximal walking distance (MWD) in patients with PAD. Methods: In this multicenter trial (NCT03795103), PAD patients with a maximal treadmill walking distance ≤300 m were randomized in the NMES or control group. The NMES program consisted of a 12-week program of NEMS sessions at the calf-muscle level, 2-3 h/day, 5 days/week. The primary outcome of the study was the change in treadmill MWD at 12 weeks. Main secondary outcomes included changes in the treadmill pain-free walking distance (PFWD) and 6 min total walking distance (6MWD). Results are reported in median [IQR]. Mann-Whitney Wilcoxon or Student t tests were used for comparisons. Results: Between 2019 and 2022, 73 patients were randomized and 63 with a mean age of 63 ± 9 years old were analyzed. Baseline treadmill MWD was 131[108;166]m and 130[98;213]m (p=0.85) in the control and NMES groups, respectively. The change of treadmill MWD was greater in the NMES group compared to the control group (58[18;139]m vs 19[3;55]m; p=0.026). The change of PFWD was not different between the NMES and control groups (23[2;48]m vs 10[-2;30]m; p=0.209). The change of 6MWD was greater in the NMES group compared to the control group (29[3;54]m vs 2[-14;30]m; p=0.019). Conclusion: A 12-week NMES program significantly improves treadmill and 6-minute walking performance in PAD patients. NMES could be considered as a complementary therapeutic option for PAD patients.
Abstract 4141103: Impact of Atrial Fibrillation and Atrial Fibrillation Therapies on Sports Performance in Female vs Male Athletes
Authors: Ali Khan, Hyon Jae Lee, Mellanie Hills, Melissa Moss, Brenna Lara, RAYMOND BAUMANN, cynthia brandt, Rachel Lampert
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) decreases sports performance in athletes, and ablation is associated with a greater improvement in performance compared to medication. Endurance sports predispose males to AF more than females. However, once AF develops, it is unknown whether its impact in female athletes differs from that of males. Aims: To investigate the impact of AF and AF treatments in female versus male athletes. Methods: An internet-based survey, initiated via StopAfib.org, queried the impact of AF and treatment modalities on sports performance, training, and symptoms. Responses were categorized by reported sex. Reported performance (rated in comparison to personal best), frequency of training, and competition engagement were compared before the onset of AF symptoms versus when symptoms were at their worst, between males and females. These outcomes were similarly compared in relation to participants’ AF treatments. Results: Between 5/13/2019 and 2/29/2020, 219 female and 772 male athletes, 40% of whom were less than 60s years old, answered the survey. Development of AF was associated with declining reported sports performance, competition, and training frequency, with no significant difference between genders. Ablation in both males and females was associated with greater reported improvement in sports performance than the use of medications. Among 141 female athletes and 509 male athletes who have taken medication currently and/or in the past, 52% and 40% reported side effects, respectively. The most prevalent side effects for both males and females were fatigue/low energy and decreased athletic performance. Conclusion: Once AF develops, the impact on decreasing sports performance is similar in females and males. Both genders similarly reported more improvement with ablation than medications, which were frequently and similarly associated with side effects for females and males.
Abstract 4140781: Impact of Tricuspid Regurgitation on In-hospital Mortality in Patients with Heart Failure – United States Population-Based Survey Analysis
Authors: Muhammad Yousuf, Noor Fatima, Muhammad Usman Almani
Journal: Circulation (2024)

Background: Tricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. While TR can worsen the clinical outcomes in HF patients, its impact on gender, racial and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever. Methods: Data was extracted from the National Inpatient Sample 2016 - 2020 Database. We used ICD-10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into two groups based on presence or absence of TR using the ICD-10 codes I36.1 and I07.1. We performed multivariable Logistic regression analysis to determine odds of in-hospital mortality in HF patients with and without TR. Subgroup analyses were performed based on (1) gender, (2) age, (3) race, (4) insurance status, (5) location and teaching status of admitting hospital, and (6) patients’ household neighborhood income quartile. All the analyses were adjusted for age, gender, insurance status, Charlson co-morbidity index (CCI) and hospital characteristics. STATA 16 software was used for analysis. Results: Mean age of HF patients with TR was 71.3 years, mean CCI was 3.4 and 55.8% were women. In-contrast, mean age of HF patients without TR was 70.7 years, mean CCI was 3.5 and 47.5% were women. Among 1,365,529 HF patients, 41177 (3.15%) patients without TR and 1965 (3.37%) patients with TR died during the hospitalization. There was no difference in overall in-hospital mortality of HF patients with and without TR (OR: 1.04, 95% CI 0.94 – 1.16, p = 0.442). However, in subgroup analysis African Americans (OR: 1.70, 95% CI 1.31 – 2.19, p &lt; 0.001), patients with Medicaid insurance (OR: 1.96, 95% CI 1.43 – 2.68, p &lt; 0.001) and patients belonging to the lowest neighborhood income quartile (OR: 1.29, 95% CI 1.07 – 1.55, p = 0.008) had higher risk of in-hospital mortality as shown in Figure 1. Conclusion: In our population-based survey analysis, we observed significant racial and socioeconomic disparities in clinical outcomes of HF patients with TR compared to those without TR. Among HF patients with TR, African Americans, patients with Medicaid insurance and patients belonging to lowest neighborhood income quartile had higher risk of in-hospital mortality compared to those without TR.