tbuckley/cabot-search huggingface dataset:
Abstract 4140884: <i>Cardiovascular Stroke Nursing Best Abstract Award:</i> Digital Health-Based Interventions Improve Healthy Behaviors, Weight Loss, and Psychological Well-Being in Older Adults at Risk for Cardiovascular Diseas
Authors: Dion Candelaria, Andrew Thomas Reyes, Reimund Serafica, Janett Hildebrand, Marysol Cacciata, Axel Sta. Maria, Jung-Ah Lee, Anna Stromberg, Lorraine Evangelista
Journal: Circulation (2024)

Background: Evidence on the use of digital health technologies by older adults is growing. However, the impact of these technologies in health promotion and disease prevention among older adults at risk for cardiovascular disease is not fully explored. Aims: This study aimed to compare the effect of two digital health technology-based interventions on engagement in healthy behaviors, weight loss, and psychological well-being over time (baseline [pre-intervention] to three months [post-intervention] to six months [long-term]) and explore outcome predictors. Methods: This randomized, longitudinal study examined the intermediate (three months) and long-term (six months) effects of two digital health technologies, Get FIT vs. Get FIT+ . Over 12 weeks, Get FIT participants (n = 24) received one face-to-face counseling session on healthy food and exercise, an activity tracker (Fitbit Charge), and access to a nutrition app (MyFitnessPal app). The Get FIt+ group (n = 30) received all the same components as Get FIT , plus weekly personalized text messages to motivate and encourage them to meet their goals. General Linear Models were used for analysis. Results: Fifty-four older adults (mean age 65.6 ± 5.8 years, 60% women, 65.5% Hispanic) were randomly assigned into the two groups. Table 1 shows the group comparisons between Get FIT vs. Get FIT+ in terms of healthy behaviors, weight loss, and psychological well-being outcomes at the three time-points. At six months, the group assignment was associated with greater weight loss, higher physical activity levels, reduced calorie intake, and lower depression scores. Being Hispanic was associated with higher weight, whereas being non-Hispanic and higher education with higher levels of depression. Conclusion: Digital health technologies increased the adoption of healthy behaviors, weight loss, and better psychological well-being over time, with greater improvements observed in the Get FIT+ group. Likewise, Get FIT+ participants sustained these improvements in the long term. A large randomized clinical trial is needed to evaluate the efficacy of both interventions in older adults at risk for cardiovascular disease.
Abstract 4141522: VTRNA 2-1 Promoter Methylation and HDL as Predictors of Excess Weight Loss After Bariatric Surgery: The Influence of Maternal Nutrition
Authors: Yi-Chun Huang, Chao-Yung Wang, Ming-lung Tsai
Journal: Circulation (2024)

Background: Maternal nutritional status and periconceptional environmental conditions have been previously linked to the methylation of the vtRNA 2-1 promoter. Bariatric surgery is an effective treatment for morbid obesity, with most patients achieving significant weight control within 1-2 years post-surgery. However, some patients do not experience the desired weight loss. The clinical correlation between the methylation of the vtRNA 2-1 promoter and postoperative outcomes in obese patients remains unclear. This study aims to elucidate the relationship between the methylation of the vtRNA 2-1 promoter and the effectiveness of bariatric surgery. Hypothesis: The degree of methylation of the vtRNA 2-1 promoter is related to excess weight loss (EWL) after bariatric surgery. Methods: The OCEAN registry (Obesity and Clock for Elegant AgiNg) is a prospective cohort study collecting data from 2011 to 2017, including 381 obese patients, 179 of whom underwent bariatric surgery. Quantitative pyrosequencing was performed on all patients. Postoperative weight and EWL were tracked and recorded at 3, 6, 12, and 24 months. Statistical analyses were conducted using SPSS.26. Results: The degree of methylation of the vtRNA 2-1 promoter shows a bimodal distribution. Compared to the normal group from the Taiwan Biobank, the methylation distribution between the two groups differs significantly. Patients were categorized into hypomethylation (≤10%), intermediate-methylation (10-40%), and hypermethylation (≥40%) groups. Statistics indicate that hypermethylation is associated with higher EWL at one year (p=0 .047) and two years (p=0.04) post-surgery compared to the hypomethylation group. In the linear regression model, after controlling for variables including age, creatinine, cholesterol, TG, LDL, AC sugar and HbA1c, our analysis revealed a positive correlation between HDL and one year EWL. Conclusion: Obese patients who have hypermethylation of the vtRNA 2-1 promoter demonstrate improved EWL one and two years following bariatric surgery. Given the previous links between the methylation of the vtRNA 2-1 promoter and maternal nutritional status, these findings suggest that early life nutritional factors may influence the effectiveness of bariatric surgery outcomes. Further comprehensive and long-term studies are needed to confirm the methylation of the vtRNA 2-1 promoter as a viable indicator for predicting bariatric surgery outcomes and improving cardiovascular health.
Abstract 4141574: LOSS OF ROR2 IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PAH VIA INAPPROPRIATE INTEGRIN B1 ACTIVATION
Authors: Ankita Mitra, Ananya Chakraborty, Brian Zhong, Ramesh Nair, Lyong Heo, Stuti Agarwal, Alexander Dunn, Prakash Chelladurai, Vinicio Dejesus
Journal: Circulation (2024)

Rationale: Endothelial dysfunction is a major hallmark of PAH whose underlying mechanism remains unexplored. We recently showed the vital role of the Wnt7a ligand, promotes pulmonary angiogenesis via ROR2, a tyrosine kinase receptor. We sought to elucidate how ROR2 activation orchestrates angiogenic responses in endothelial barrier establishment in pulmonary microvascular endothelial cells (PMVEC), and its potential contribution to endothelial dysfunction in PAH. Hypothesis: ROR2 regulates lung angiogenesis, and its loss is associated with PAH. Methods: Healthy and PAH PMVECs and lung tissues were obtained from transplants and commercial sources. PMVECs were transfected with ROR2 siRNA/constructs for functional and molecular studies. Bulk RNA-seq of control and siROR2 PMVECs was followed by bioinformatic analysis. Focal adhesion (FA) activation and force generation were measured using FRET-based total internal reflection microscopy (TIRF). Endothelial-specific conditional ROR2 KO (ROR2 ECKO) mice exposed to normoxia and hypoxia were phenotyped using echocardiography, hemodynamics, and lung morphometry. Results: ROR2 expression was significantly reduced in PAH lesions versus healthy. ROR2 knockdown (siROR2) reduced vascular sprouting and VEGF response comparable to control PMVECs. siROR2 and ROR2-deficient PAH PMVECs shows increased adhesion to fibronectin and barrier permeability. Confocal and TIRF microscopy of siROR2 and ROR2-deficient PAH PMVECs showed increased FA number and force generated by individual FAs that inversely correlated with reduced VE-cadherin at cell-cell junctions. ROR2 overexpression in PAH PMVECs normalized ROR2 protein expression, FAs activity, and junctional integrity and promoted recovery. Proteomic studies showed, ROR2 interacts with Integrin b1 in focal adhesions, and its loss results in Integrin b1 activation, FA clustering, and high mechanical forces. RNA-seq of siROR2 PMVECs showed dysregulation of vesicular trafficking and adhesion genes and enriched vesicular trafficking and angiogenic pathways. In animal studies, ROR2 ECKO developed severe PH, right ventricular remodeling, microvascular reduction, and muscularization in hypoxia, correlating with increased integrin-b1 activation and decreased VE-cadherin expression. Conclusions: ROR2 promotes vessel sprouting and barrier formation, and its loss is associated with dysfunctional angiogenesis in PAH. Restoring ROR2 signaling activity could be a novel therapeutic strategy in PAH.
Abstract 4141166: Identification of Clinical Phenotypes and Heterogeneous Treatment Effects of Surgical Revascularization in Ischemic Cardiomyopathy: A Machine Learning Consensus Clustering Analysis
Authors: Tongxin Chu, Zhuoming Zhou, Mengya Liang, Zhong-kai Wu
Journal: Circulation (2024)

Introduction: The Surgical Treatment for Ischemic Heart Failure (STICH) trial confirmed the survival benefits of surgical revascularization compared to medical therapy alone in patients with ischemic cardiomyopathy (ICM). However, the complexities of clinical characteristics in this population may lead to distinct clinical phenotypes with heterogeneity in risk stratification and therapeutic responses to medical therapy or surgical revascularization. Aims: To identify ICM patients with different clinical phenotypes for evaluating their outcomes and heterogeneous treatment effects (HTEs) of coronary artery bypass grafting (CABG). Methods: We applied a machine learning-based consensus, K-Medoids clustering analysis to the STICH trial dataset. A total of 20 clinically available variables were utilized to distinguish the phenotypes. We compared the risk of all-cause mortality and cardiovascular mortality among different phenotypes. Then, the survival benefits of CABG compared with medical therapy alone were assessed in the identified phenotypes for evaluating HTEs. Results: From July 2002 to May 2007, 1212 patients with ICM were enrolled in the STICH trial, with a median follow-up time of 9.7 years. Consensus clustering analysis identified four distinct clinical phenotypes. Specifically, phenotype 1 (n=415) was characterized by higher hemoglobin (14.4 ± 1.4 g/dL) and hyperlipidemia rate (75.2%). Phenotype 2 (n=263) was younger (56.9 ± 8.5 years) and tended to be male (92.4%), with lower LVESVI (69.2 ± 25.2 mL/m 2 ). Phenotype 3 (n=280) was older (62.3 ± 9.5 years), with higher creatinine (1.3 ± 0.7 mg/dL) and lower LVEF (24.0 ± 7.8 %). Phenotype 4 (n=254) had higher LVEF (31.4 ± 8.7 %), and higher rates of diabetes mellitus (62.2%) and hypertension (72.8%). Compared with other phenotypes, phenotype 3 had the highest risk of all-cause mortality (HR 1.69, 95% CI 1.41-2.02; P &lt;0.001) and cardiovascular mortality (HR 1.80, 95% CI 1.45-2.22; P &lt;0.001). Among phenotype 2, CABG was associated with a significantly lower risk of all-cause mortality (HR 0.70, 95% CI 0.50–0.98; P =0.033) and cardiovascular mortality (HR 0.63, 95% CI 0.43–0.92; P =0.015) compared with medical therapy alone. Conclusions: We identified four clinical phenotypes with distinct outcomes and HTEs among ICM patients. Phenotype 3 (older, higher creatinine, lower LVEF) had the poorest clinical outcomes. Phenotype 2 (younger, male, lower LVESVI) was more likely to derive greater survival benefits from CABG.
Abstract 4141001: Pulsed field ablation of recurrent atrial tachyarrhythmias after prior thermal ablations
Authors: Rong Bai, Caijie Shen, Tsai-Lin Chou, Mischa Eng, Yi Dai, Jake Martinez, Praneeth Katrapati, Michael Zawaneh, Peter Weiss, Roderick Tung, Wilber Su
Journal: Circulation (2024)

Background: Pulsed field ablation (PFA) has emerged as a safe and effective alternative to thermal ablation modalities for treatment of paroxysmal and persistent AF in a de novo procedure. Research Questions: Since the FaraPulse system (Boston Scientific) was approved by FDA, no data was reported on whether PFA can be used in redo procedures. Aims: We reported our initial experience with PFA in patients with recurrent atrial tachyarrhythmias (ATs) who failed at least one thermal ablation of AF. Methods: Consecutive patients receiving redo ablation using PFA (FaraPulse) for recurrent ATs were enrolled. ICE and fluoroscopy were used to guide the placement of FaraWave catheter. Voltage and activation mapping of LA were performed in all patients before ablation using Orion high density mapping catheter and Rhythmia system. Ablation strategy included PV re-isolation as needed, LA posterior wall (PW) isolation if low voltage zone was identified, and ablation of any organized ATs. Procedural endpoints were PVs and LAPW isolation, non-inducibility for ATs and bidirectional block for linear ablation. Results: 15 patients (12 male; age 66.3±10.3 years) were included. The median number of prior RF ablations was 2; 2 patients also received one cryoballoon ablation. Patients presented with persistent (80%) AF or paroxysmal (20%) AF with/without documented organized ATs. By using PFA, LAPW isolation was performed and achieved in all patients, while 11 (73.3%) patients required reisolation of at least one PV ( Figure ). Organized ATs were present/induced in 7 (46.7%) patients including 3 peri-mitral AFL, 3 LA roof-dependent AFL, 3 CTI AFL and 3 atrial tachycardias from LA roof, LA septum and RA roof respectively. RF ablation was required in 2 patients (2/7, 28.5%) to eliminate CTI AFL. Per case total PFA applications number were 48.7±24.4 (46, 22-90); total fluoroscopy time was 6.8±5.6 mins. No major peri-procedural complication was observed except for one case (90 PFA applications) of hemolysis and acute renal failure that completely recovered. Conclusion: PFA of recurrent ATs after failed thermal ablation is feasible and safe acutely if limited the applications. The long-term outcome of this strategy warrants further investigation.
Abstract 4141426: Electronic Health Record-Integrated Platform for Patients with Severe Hypercholesterolemia and Familial Hypercholesterolemia Reveals Opportunities for Quality Improvement in a Large Healthcare System
Authors: Tanvi Ingle, Jessica Moon, Spencer Carter, Ruth Schneider, Zahid Ahmad, Mujeeb Basit, Amit Khera
Journal: Circulation (2024)

Background: Familial Hypercholesterolemia (FH) is a genetic predisposition to high LDL-C levels and premature atherosclerotic cardiovascular disease (ASCVD) that remains underdiagnosed and undertreated. We developed a patient registry within the EPIC (Epic Systems Corp., Verona, WI) electronic health record (EHR) system to identify patients who have severe hypercholesterolemia or FH. We illustrate how our platform reveals gaps in treatment and outcomes for these patients across a large academic medical center. Methods: We extracted health information for all living, adult patients from UT Southwestern Medical Center who have ever had an LDL-C &gt;= 190 mg/dL or an FH diagnosis (ICD-10 E78.01) from our FH patient registry. Patients with only laboratory data and no other meaningful encounter or treatment data were omitted from the cohort. We characterized LDL-C levels across the patient cohort and determined the proportion who had seen cardiology or endocrinology, had an FH diagnosis, and received LDL-C lowering therapy. We further analyzed how many patients achieved LDL-C levels at goal (defined as LDL-C &lt; 70 mg/dL for patients with ASCVD or LDL-C &lt; 100 mg/dL for all others in the cohort). Data were extracted from EPIC’s Clarity reporting database. Results: Of the 7026 patients included in our study, the median age was 62 years, 64.5% were female, 56.7% were white, 16.3% had an unknown/declined race, 9.7% were Hispanic, and 14.2% had an unknown/declined ethnicity. The highest LDL-C among the cohort averaged 216.4 (±43) mg/dL. The most recent LDL-C values recorded averaged 158.5 (± 63.7) mg/dL. We found 6.7% of the cohort had an FH diagnosis, 38.1% were seen by cardiology or endocrinology, and 66.6% were prescribed an LDL-C lowering therapy (63.1% any statin, 53% high intensity statin, and 11.8% a non-statin therapy). Additionally, only 19.1% of those receiving treatment achieved LDL-C levels at goal. Conclusion: We showcased how an EHR-integrated patient registry can provide rapid insights into the status of FH and severe hypercholesterolemia care at an institution while also elucidating opportunities for targeted intervention. Since EPIC is the most prevalent EHR system in the United States, our methodology can be readily adopted to improve care of patients with severe hypercholesterolemia and FH on a national scale.
Abstract 4141139: Decreased CD34 <sup>+</sup> Peripheral Cell Count is Associated with Worse Left Ventricular Function in Patients with Takotsubo Cardiomyopathy
Authors: Gregor Poglajen, Mark Jovanovic, Sabina Frljak, Neza Zorz, Bojan Vrtovec
Journal: Circulation (2024)

Background: The underlying mechanisms of microvascular dysfunction in Takotsubo cardiomyopathy (TCM) remain incompletely understood. Aim: As CD34 + cells are central to coronary microvascular homeostasis we investigated the potential association between CD34 + cell count and changes in left ventricular function in patients with TCM. Methods: In a single-center prospective pilot cohort study we included 19 consecutive patients with TCM treated at our center between January 1 st , 2022, and December 31 st ,2023. Patients with a history of malignancy were not considered for this analysis. TCM diagnosis was established per InterTac Registry criteria. Patients were enrolled within 24h of admission and underwent comprehensive clinical examination, blood biochemical and hematological analysis, and echocardiography at baseline and 6-month follow-up. CD34 + cell count was measured using Beckman-Coulter Navios EX flow cytometry with standard antibodies according to ISAGE protocol. Results: Patient average age was 66±7 years, all patients were female, and hypertension and diabetes were present in 11 (57%) and 16 (84%) patients, respectively. The initial clinical presentation of TCM was acute chest pain in 15 (79%) patients and 16 (84%) patients displayed symptoms and signs of acute heart failure. Physical or psychological stress was identified in 17 (89%) of patients. Mean baseline left ventricular ejection fraction (LVEF) was 53±11% with apical dyskinesia being present in all patients. A peak mean troponin and NT-proBNP serum levels were 2353±2917 pg/mL and 3273±3196 pg/mL, respectively. The average baseline CD34+ cell count was 1.26±1.0x10 6 /L. We established a significant positive correlation between baseline LVEF (r=0.54; P=0.03) and LVOT VTI (r=0.61; P=0.01) and CD34+ cell count. When stratifying patients on LVEF, patients with LVEF≥50% displayed significantly higher CD34+ cell count than patients with LVEF&lt;50% (1.7±0.9x10 6 /L vs. 0.7±0.0.8x10 6 /L; P=0.04). In the latter group, we also established a positive correlation between CD 34+ cell count and improvement in LVEF at 6-month follow-up (r=0.6; P=0.02). Conclusion: In patients with Takotsubo cardiomyopathy CD34+ peripheral cell count appears to correlate with the magnitude of left ventricular functional impairment and with the dynamics of left ventricular recovery. Further studies are needed to confirm our preliminary data and to explore CD34+ cells as a potential therapeutic target in this patient cohort.
Abstract 4141657: Lipoprotein Apheresis improves HDL Proteomics and reduces the risk of Aortic Stenosis in patients with elevated Lipoprotein(a) levels and Familial Hypercholesterolemia
Authors: Patrick Moriarty, Maya Safarova
Journal: Circulation (2024)

Background: The prevalence of calcific valve stenosis (CAVS) in familial hypercholesterolemia (FH) is 30-40%. Eleveated Lp(a) levels independently promotes faster progression of CAVS. Low HDL particles (HDL-P), increase apoC3 and serum amyloid A (SAA)-bound HDL are associated with long-term incidence and progression of CAVS. Aim: Dextran-sulfate-adsorption lipoprotein-apheresis (LA), the only LA device available in the United States, reduces LDL-C and Lp(a) by an average of 60%-80% via binding positive-charged apolipoprotein B to a negative-changed environment. Despite the negative charge of HDL-C, it is acutely reduced by 10%-20%. However, the total HDL-P number, as measured by nuclear magnetic resonance testing, is increased by an average of 16% following LA therapy. We hypothesized that regular LA may improve cardiovascular outcomes and slow the progression of CAVS via its effects on HDL functionality and Lp(a) levels. Methods: This case series describes 39 Caucasian patients (mean age 61 years, 70% female, 80% statin intolerant) with FH and/or elevated Lp(a) (Liposorber LA-15, Kaneka) over a mean treatment period of 4.8 years, as compared to an average of 5.3 years pre-treatment. Pre-treatment LDL-C and Lp(a) levels were 144 mg/dL (range, 35-314) and 167 nmol/L (range 2-530). HDL proteomic analysis was performed to identify numerous proteins and lipids segregated into distinct subclasses. Major adverse cardiovascular events were defined as: MI=myocardial event, PCI=percutaneous cornary intervention, CABG=coronary artery bypass surgery, TIA=transient ischemic attack, CAVS=calcific artic stenosis. Results: LA therapy reduced mean LDL-C to an average of 40 mg/dL and Lp(a) to 24nmol/L, while total HDL-C was lowered by 14%. Extra small and small-sized HDL-P was reduced by 42% and 20%, respectively (P&lt;0.001). Medium-sized HDL-P increased by 12% (P&lt;0.001). We observed significant modifications in the HDL-bound proteins (Table 1). There was an 88% reduction in major adverse cardiovascular events, with no patient developing CAVS (Table 2). Conclusions: In patients with FH and/or elevated Lp(a) with established ASCVD, LA effectively lowered the incidence rate of cardiovascular events. LA selectively reduced pro-inflammatory apoC3- and SAA-bound HDL and increased HDL-P, potentially explaining the lack of development and progression of CAVS in patients with elevated Lp(a). This observation merits further investigation with a dedicated controlled clinical study.
Abstract 4141421: Soluble adenylyl cyclase prevents cardiac rupture and adverse ventricular remodeling after myocardial infarction.
Authors: M. Ahsan Siraj, Robert Lao, Abdul Momen, Dorrin Zarrin Khat, Mansoor Husain
Journal: Circulation (2024)

Background: The ubiquitous second messenger cyclic adenosine monophosphate (cAMP) plays a key role in post-myocardial infarction [MI] remodeling, influencing apoptosis, inflammation, fibrosis and metabolism. Unlike transmembrane activators of cAMP, soluble adenylyl cyclase (sAC) represents a unique source of intracellular and mitochondrial cAMP, and metabolic sensor due to its ability to regulate oxidative metabolism and cell survival. However, a role for sAC in post-MI remodeling was not known. Methods and Results: Permanent LAD ligation was used to induce experimental MI in 10-12 wk old sAC knockout ( sAC -/- ) mice and wild-type littermates ( sAC +/+ ) [ n =26-31/group]. Compared to wild-type, sAC -/- mice had more cardiac rupture events (17/26 vs. 13/31) and reduced survival at 28-d post-MI (35 vs. 58%, P&lt;0.05). Echocardiography showed more cardiac dysfunction in sAC -/- mice (LVEF: 20±4 vs. 28±4%, P&lt;0.05). Heart to body weight ratio was higher in sAC -/- mice (9.1±1.5 vs. 7.7±0.3 mg/g, P&lt;0.05 ) with no differences in lung to body weight [n=15/group]. Importantly, no structural or functional cardiac differences were found between sham-operated sAC -/- and sAC +/+ mice [n=6 each]. To elucidate underlying mechanisms, we assayed infarct size, hemodynamics, inflammation and fibrosis at 3-d post-MI, a time point that precedes cardiac rupture ( n =10 each). Sections stained with 2,3,5-triphenyltetrazolium chloride reveal larger infarcts in sAC -/- mice (43±2 vs. 37±2%, P&lt;0.05). Pressure-volume loops show lower LVEF (31±1% vs. 34±1%, P&lt;0.05), cardiac output (21,634±825 vs. 25,515±612 µl/min, P&lt;0.01), and stroke volume (39±1 vs. 46±1 µl, P&lt;0.001) in sAC -/- mice. Luminex® multiplex assay for cytokines and chemokines revealed higher serum TNFα (14±1.6 vs. 8.4±1 pg/ml), CCL5/RANTES (66.6±7.2 vs. 36.3±5 pg/ml) and MCP-1 (81.8±15 vs. 50±11.4 pg/ml) levels in sAC -/- vs. sAC +/+ mice (P&lt;0.05 for all comparisons), with no differences in IL-6, IL-1β, INF-γ, GM-CSF, G-CSF, IL-10, IL-12 and TGF-β. Finally, Masson’s trichrome staining demonstrated no differences in interstitial or perivascular fibrosis in sAC -/- vs. sAC +/+ hearts. Conclusion: In an experimental mouse model of MI, sAC prevents cardiac rupture and adverse cardiac remodeling by reducing infarct size, improving cardiac function and limiting specific inflammatory cytokines. Further studies are needed to define which cell-types expressing sAC mediate these findings.