tbuckley/cabot-search huggingface dataset:
Abstract 4131838: Heart’s Deception: A Venous Villain Hiding in the Heart
Authors: Justin Haloot, Umair Khalid, Jing Liu
Journal: Circulation (2024)

A 66-year-old male presented with 5 months of worsening left flank and lower back pain. Three weeks prior to this presentation, he was seen at an outside facility where he was found to have a left renal mass that was not further worked up. CT Abdomen and Pelvis showed an enhancing heterogenous lesion at the left superior renal pole, left adrenal gland lesion, and a pulmonary artery filling defect. This defect, along with concern for metastasis, led to a CT chest angiogram that reported small left upper and lower lobe pulmonary emboli. A transthoracic echocardiogram (TTE) was ordered and showed a linear highly mobile mass in the right atrium that was intermittently protruding into the right ventricle and into the main pulmonary artery through the pulmonic valve. There was no visible evidence of tumor extension of the renal mass into the inferior vena cava. Based on this, the highest differential was a clot-in-transit. After collaboration with the pulmonary embolism response team and echo team, the patient underwent aspiration thrombectomy via AngioVac system with transesophageal echocardiography (TEE) guidance. Most of the mass was removed, but there was a residual small portion adherent to the superior vena cava that was not amenable to aspiration. Grossly, the removed mass did not have the classic appearance of thrombus. The specimen was sent to pathology and returned as poorly differentiated carcinoma with spindle cell pattern positive for PAX8, CK7, CD10, pancytokeratin, and vimentin concerning for renal cell carcinoma. Post procedural transthoracic echo found to have new basal septal globular mass with vascularity seen on echo contrast imaging concerning for vascular involvement consistent with myocardial metastatic invasion. Cardiac magnetic resonance imaging could have aided in more precise tissue characterization to differentiate between clot or tumor prior to aspiration thrombectomy. This case demonstrates the significance of a detailed history and physical exam, use of multimodality imaging, and multidisciplinary collaboration to manage a rare cardiac condition.
Abstract 4128919: A Study Using Team Based Hypertension Care Focused on Black Patients to Inform a Future Randomized Trial
Authors: Srista Manandhar, Sunit Chhetri, Danielle Sutton, Animita Saha, Suneet Kaur, Josh Brown, Justin Moore, Kate Callahan, Jeff Williamson, Yhenneko Taylor, Hayden Bosworth, Yashashwi Pokharel
Journal: Circulation (2024)

Background: Current telemedicine programs to manage hypertension are less effective in Black patients perhaps due to insufficient support for self-care skills and social needs. We describe a tailored program for Black patients emphasizing self-management support and social needs to inform future studies. Method: We piloted a 12-week telemedicine intervention comprising home blood pressure (BP) guided pharmacotherapy, frequent self-management support and social support using pharmacist, nurses, community health workers (CHW) and social workers (SW) among 20 patients in 2 clinics. At enrollment, we trained patients to use a BP monitor and a telemonitoring app that transmits BP real-time via a smartphone and provided a pill box to facilitate medication adherence. We asked patients to measure BP at least once daily and used 6 weeks average to guide pharmacotherapy. Trained nurses helped patients achieve self-care goals and provided 8-12 self-management support calls discussing hypertension, medication adherence, diet, physical activity, weight management, sleep, and BP measurement techniques. SWs and CHWs provided social support to address social needs such as food, transportation, and housing, and also offered home visits. Result: Eighteen patients completed the study of which 15 were Black, 2 White, and 1 Korean (9 were women). Mean age was 61.7 ± 11.8 years. Patients measured BP 10 ± 8.6 times/week and completed 8.3 ± 2.5 self-management calls. Over 12 weeks, SBP/DBP decreased by 16.5 ± 26.2/10.2 ± 18.5 mmHg without safety events (Table). There were 1.1 ± 0.8 (range 0-3) medication adjustments (dose or medication changes) per patient. Patients had 8 minor technical difficulties that were promptly resolved. 17 patients used pill boxes to improve medication adherence. Conclusion: Our tailored telemedicine program to manage hypertension is feasible among Black patients and offer valuable insights for future research.
Abstract 4127792: Age-stratified Monogenic and Polygenic Contributions for Atrial Fibrillation in the <i>All of Us</i> Research Program
Authors: Zhanlin Chen, Adam Gordon, Gregory Webster
Journal: Circulation (2024)

Background: Rare and common genetic variation both contribute to atrial fibrillation (AF), but the effects may not be uniform across ages. The All of Us Research Program contains whole-genome sequencing of 100,574 adult participants with electronic health records. Hypothesis: Rare genetic variants are associated with early-onset AF; common genetic variants are associated with late-onset AF. Aims: To quantify the diagnostic yield provided by rare and common genetic variation in AF across age. Methods: The clinical, monogenic, and polygenic contributions to AF were assessed in a cross-sectional group of participants in the NIH-funded All of Us Research Program, stratified by three age groups: &lt;45 years (n=22,290), 45-60 years (n= 26,805), &gt;60 years (n=51,659). Variant discovery was performed for pathogenic or likely pathogenic (P/LP) variants among 145 candidate cardiac genes with dominant inheritance for cardiomyopathy and arrhythmia. A previously established polygenic risk score (PRS) was calculated. After adjusting for known clinical factors, multivariable analysis quantified the associations between monogenic and polygenic factors versus AF status in each age group. Results: There were 100,574 participants: 7,811 with AF and 92,763 without AF. The presence of ≥1 P/LP variant(s) were associated with AF across all age groups, with stronger associations in the age &lt;45 group (OR 2.3 [95% CI 1.4-4.1]) compared older groups (OR 1.5 [95% CI 1.1-2.1] in age 45-60, and OR 1.4 [95% CI 1.2-1.7] in age &gt;60). In contrast, PRS was not associated with AF in participants &lt;45 years (OR 1.02 [95% CI 0.88-1.17]) but was associated with AF in the older groups: OR 1.54 [95% CI 1.31-1.80] in age 45-60 and OR 1.49 [95% CI 1.40-1.59] for age &gt;60. Overall, clinical risk factors are highly associated with AF (AUC 0.84 [0.83-0.85]); adding polygenic and monogenic factors contribute only marginal improvement (AUC 0.86 [0.85-0.87]). Conclusion: In this cross-sectional dataset, monogenic and polygenic factors have opposite associations with AF. Monogenic variants are associated with early-onset AF, whereas PRS has no association with AF at younger ages. Clinical risk factors continue to explain the majority of the variation in AF status.
Abstract 4129965: Efficacy of Sodium Glucose Cotransporter 2 Inhibitors In Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials
Authors: Mushood Ahmed, Hritvik Jain, Hira Javaid, Areeba Ahsan, Kamleshun Ramphul, Adeel Ahmad, Farhan Shahid, Jawad Basit, Raheel Ahmed
Journal: Circulation (2024)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with or without type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a systematic review and meta-analysis to synthesize the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. Methods: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library, and Embase databases to identify randomized controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4, and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results: Five RCTs reporting data for 11,211 patients were included in our study. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalizations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001; high certainty). In terms of absolute effects, this translated to 12 fewer HHF per 1,000 patients who received SGLT2 inhibitors compared with the placebo (absolute risk difference 12 (95% CI 17 to 5) fewer per 1000 patients) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76; high certainty), cardiovascular (CV) mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73; high certainty), and all-cause hospitalizations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25; high certainty) remained comparable across the two groups. Conclusion: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality, and all-cause hospitalizations. However, further evidence is required to reach a definitive conclusion.
Abstract 4131128: Cardiomyocyte-specific Deletion of <i>Creg1</i> Impairs Autophagy and Leads to Age-dependent Dilated Cardiomyopathy
Authors: Yanmei Qi, Yechaan Joo, Russell Pepe, Glenn Tejeda, Kevin Hayes, NaYoung Yang, Joshua Chao, Saum Rahimi, Leonard Lee, Shaohua Li
Journal: Circulation (2024)

CREG1 is a small glycoprotein predominantly localized in the endolysosomal system. In mouse heart, CREG1 expression increases with age. We previously observed cardiac hypertrophy and ventricular non-compaction in a small percentage of constitutive Creg1 knockout mice during the neonatal stage. To elucidate the physiological function of CREG1 in the heart, we generated cardiomyocyte-specific Creg1 knockout (cm Creg1 KO) and knock-in (cm CREG1 KI) mice by crossing Creg1 fl/fl and Rosa hCREG1/hCREG1 with Myh6-Cre mice, respectively. By 6 months of age, the cm Creg1 KO mice developed severe myocardial interstitial fibrosis. Echocardiography at 10 months revealed markedly dilated left ventricles and significantly reduced ejection fractions. All the cm Creg1 KO mice succumbed to heart failure between 10-12 months, while Creg1 fl/fl control littermates exhibited no obvious cardiac abnormalities. Necropsy of deceased cm Creg1 KO mice showed increased heart-to-body weight ratios, enlarged cardiac chambers, and left atrial thromboses. Electron microscopy revealed sparse and elongated myofibers, scant and bizarre-shaped mitochondria, empty cytoplasm, and increased interstitial collagen accumulation. The cm CREG1 KI mice exhibited better endurance to nutritional deprivation than Rosa hCREG1/hCREG1 littermate controls. In sharp contrast to cm Creg1 KO hearts, cm CREG1 KI and Rosa hCREG1/hCREG1 control hearts displayed very mild fibrosis at 8 months, suggesting that CREG1 overexpression may confer cardioprotective effects. In cultured cardiomyocytes, CREG1 colocalizes with the autophagosome marker LC3B following serum deprivation. Immunofluorescence microscopy demonstrated a marked reduction of LC3B puncta in cm Creg1 KO hearts. Analysis of autophagic flux using CAG-RFP-EGFP-LC3 transgenic mice and immunoblotting indicated that the absence of CREG1 impairs both autophagosome formation and degradation, whereas knock-in of CREG1 enhances these autophagic processes. These findings suggest that CREG1 promotes autophagy and protects the heart from age-dependent dilated cardiomyopathy.
Abstract 4131100: Effect of metabolic surgery on cardiovascular outcomes in people with obesity and pre-existing cardiovascular disease: A systematic review and meta-analysis
Authors: Shurjeel Qazi, Hassan Ali, Huzaifa Ansari, Sana Qazii, Muhammad Hamza Dawood, Ruqiat Batool, Muhammad Ahmed Shaikh, Syed Zaeem Ahmed, Eliza Aisha, Tariq Jamal Siddiqi, Michael Hall
Journal: Circulation (2024)

Background: Previous literature shows that metabolic surgery effectively decreases the risk of cardiovascular disease (CVD) events in patients with obesity. The use of metabolic surgery has, however, been limited in people with obesity and pre-existing CVD due to concerns of poor post-operative cardiovascular outcomes. This study aims to determine the effectiveness and safety of metabolic surgery in patients with pre-existing CVD. Methods: A search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from their inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Outcomes of interest were risk of all-cause mortality, major adverse cardiovascular events (MACE), risk of myocardial infarction (MI), and cerebrovascular events in patients with and without prior CVD undergoing bariatric surgery. Data was pooled as generic inverse variance using a random effects model, and presented as hazard ratios (HR) with their 95% confidence intervals (CI). Results: We included four studies in our analysis (n = 5,244). Our pooled analysis shows that metabolic surgery leads to significant reduction in risk of all-cause mortality (HR = 0.51, 95% CI: [0.42, 0.61]; p&lt;0.01). We also observed a significant risk reduction of 43% in MACE with metabolic surgery (HR = 0.57, 95% CI: [0.5, 0.64]; p&lt;0.01). Metabolic surgery was not associated with a significant reduction in the risk of MI (HR = 0.53, 95% CI: [0.24, 1.18]; p = 0.12, I 2 = 83%). Similarly, a non-significant decrease in risk of cerebrovascular events was observed with metabolic surgery (HR = 0.89, 95% CI: [0.65, 1.22]; p = 0.48) Conclusion: Metabolic surgery is associated with decreased risk of all-cause mortality and MACE in patients with obesity and established CVD. These results are thought to be mediated through reduction in risk factors such as obesity, but also by reducing inflammatory mediators and having other beneficial effects on cardiac structure and left ventricular workload.
Abstract 4130641: The Role of Oxidized Phospholipids in Triggering Trained Immunity and Accelerating Atherosclerotic Plaque Inflammation during Cholesterol Cycling
Authors: Zhixing Li, Maxwell La Forest, Ada Weinstock, Bianca Scolaro, Konstantinos Fortounas, Franziska Krautter, Maria Laskou, Amaia Obieta, Maria Nacher Espuig, Chenxi Xu, Joseph Witztum, Edward Fisher
Journal: Circulation (2024)

Introduction: Oxidized phospholipids (OxPL) derived from LDL play a crucial role in the development and progression of atherosclerosis by promoting chronic inflammation and formation of foam cells. The natural antibody E06, binding to OxPL, diminishes macrophage uptake of OxLDL in vitro and decreases atherosclerosis progression in vivo. In our prior work using a model of plasma cholesterol cycling (high-low-high), resulting in atherosclerotic plaque Progression (P)-Regression (PR)-re-Progression (PRP), respectively, we observed accelerated plaque inflammation in the PRP group relative to mice with non-cycling high cholesterol. Hypothesis: OxPL promotes plaque inflammation in the cholesterol cycling model via trained immunity and that the E06 antibody will mitigate this process. Methods: We utilized transgenic "E06 mice" that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter on the Ldlr−/− background. Both E06 mice and Ldlr-/- mice were subjected to high cholesterol diets (HCD) and categorized into three groups in the cholesterol cycling model: Baseline Progression (P), PR and PRP. Plaque regression was induced by ApoB-ASO injection, which significantly lowered cholesterol levels by inhibiting LDL production. Results: As before, Ldlr-/- mice in the PRP group exhibited accelerated plaque inflammation post-regression shown by CD68 staining on aortic roots. Notably, this acceleration was significantly inhibited in the E06 mice, highlighting the protective effects of E06 against plaque re-progression. Additionally, flow cytometry of peripheral blood exhibited reduced total monocytes and Ly6Chi-monocytes (thought to become inflammatory macrophages in plaques), alongside increased Ly6Clo-monocytes (thought to become inflammation resolving macrophages in plaques) among E06 mice in the PRP group compared to Ldlr-/- mice. Ex-vivo stimulation of bone marrow cells with the inflammatory stimulus LPS demonstrated higher IL-6 levels in supernatant in Ldlr-/- mice versus E06 mice in the PRP group, suggesting OXPL-induced trained immunity in bone marrow precursors of monocytes and macrophages is involved. Conclusion: The acceleration of plaque inflammation in cholesterol cycling model was significantly inhibited in the E06 mice. These results provide insight into the increased risk of cardiovascular disease in individuals with intermittent adherence to statins who undergo cholesterol cycling.
Abstract 4129195: Mechanisms of Healthy Aging in the Prevention of Atrial Fibrillation
Authors: Andrew ROSE, Rim Younes, Jiening Xiao, Harika Dasari, Yasemin Altuntas, Feng Xiong, Patrice Naud, Martin Sirois, Jean-Francois Tanguay, Jean-Claude Tardif, Jose Morais, Guylaine Ferland, Pierrette Gaudreau, Roddy Hiram
Journal: Circulation (2024)

Introduction: Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia. AF can lead to severe complications such as myocardial infarction, strokes, and sudden death. With 70% of AF patients aged 65 and older, aging stands as the major risk factor for AF. Our group have recently contributed to reveal that old Wistar rats (20 months) are more susceptible to AF than younger rats (5 months). Interestingly, Lou/c/jall (LOU) rats, a model of healthy aging derived from Wistar rats, can live up to ~35 months old (equivalent to 100 human years). LOU rats have been identified as resistant to age-related diseases such as obesity, hypertension, and neurodegenerative disorders, which are major risk factors for AF. However, the susceptibility of LOU rats to AF have never been reported. Hypothesis: LOU rats may carry specific molecular adaptations conferring resistance to age-related cardiac remodeling and low AF vulnerability. Objectives: Characterize the vulnerability of very old LOU rats (32 months) to AF compared to old Wistar rats (22 months). Determine the atrial inflammatory profile of LOU rats and identify the molecular adaptations that may explain their resistance to AF Methods: Male and Female rats were divided into five groups: LOU and Wistar rats of 5 months (young), 20 months (old), and 32 months (very old: LOU/c rats only). AF inducibility was assessed in vivo using transesophageal electrophysiological study and cardiac structure and function were analyzed by in vivo echocardiography. Atrial electrical conduction was examined using ex vivo optical mapping. Histological analyses were performed to assess atrial fibrosis. Additionally, immunoblot analysis, qPCR, and RNA sequencing were employed to investigate the levels of biomarkers involved in atrial inflammation and fibrosis. Result: Old Wistar rats were more vulnerable to AF than young rats. Old and very old LOU were significantly more resistant to AF than old Wistar animals. LOU rats’ low susceptibility to AF was accompanied with absence of cardiac structural and functional remodeling and low levels of atrial fibrosis compared to old Wistar. Additionally, advanced age did not affect LOU rats’ atrial electrical conduction properties as compared to old Wistar rats. Conclusion: Promotion of healthy aging conditions mimicking LOU rats’ resistance to cardiac remodeling and reduction of atrial fibrosis may contribute to prevent AF in subjects with pathological aging.
Abstract 4129453: Comparing Cardiovascular Outcomes in Patients with Lyme Disease and Babesiosis: A Retrospective Cohort Study
Authors: Riya George, Shruti Varadarajan, Joshua Chang, Aditya Sood, Matthew Pierce
Journal: Circulation (2024)

Intro: In the U.S, Lyme disease and Babesiosis are among the four most common tick-borne illnesses, with an annual average of 36,000 and 2200 cases respectively from 2016-2019. Both have cardiac involvement; 1% of lyme disease cases result in lyme carditis, while babesiosis is associated with arrhythmias and heart failure. Little research has explored the comparative risk of developing cardiac complications between the two. This study investigates cardiovascular complications in cases of Lyme and Babesiosis. Methods: We conducted a retrospective cohort study utilizing data from the TriNetX database and the US Collaborative Network, which together cover 60 healthcare organizations providing real-world electronic health records. We included all individuals diagnosed with either Lyme disease (Cohort A, pre-match n = 317368/post-match n = 4115 ) or babesiosis (Cohort B, pre-match n=4173/post-match n = 4115), identified using ICD-10-CM codes. Patients under 18 years of age, diagnosed with both diseases, or with incomplete follow-up data were excluded. We employed propensity score matching to adjust for age, race, sex, and other clinical parameters to compare the two cohorts equitably. We focused on 4 key outcomes over a 5-year period: arrhythmias, the need for PPM implantation, ACS and HF, utilizing both risk analysis and Kaplan-Meier survival analysis. Results: Interestingly, patients with babesia exhibited a greater likelihood of developing HF (OR: 1.279, 95% CI (1.073,1.524)). The development of arrhythmias between the two groups was not statistically significant with an OR of 1.013 (95% CI (0.837, 1.227)). The need for PPM implantation was not statistically significant between the two groups with an OR of 1.269 (95% CI (0.785, 2.052)). The risk of developing ACS was not statistically significant with an OR of 1.103 (95% CI (0.838, 1.451)) . Conclusion/Discussion: Our findings indicate that patients with babesiosis have a higher likelihood of developing HF compared to those with lyme disease. Surprisingly, there were no significant differences in the rates of arrhythmias or pacemaker implantations between the two cohorts. These results suggest that while overall cardiovascular risks are comparable between the groups, the increased risk of HF in babesiosis needs to be further explored.