tbuckley/cabot-search huggingface dataset:
Abstract 12723: Smooth Muscle-Derived CD34 <sup>+</sup> Cells After Vascular Injury Contribute to Vascular Remodeling
Authors: Yao Xie, Yunrui Lu, Hui Ni, Meixiang Xiang
Journal: Circulation (2023)

Introduction: Vascular remodeling after injury participates in several atherosclerotic cardiovascular diseases. Vascular progenitors are thought to play vital roles in vascular remodeling, while the specific contribution of newly-generated progenitors from non-progenitors after injury is neglected. Methods: We generated a Cd34 lineage tracing system and marked newly-generated CD34 + cells in vascular injury models. Single-cell transcriptomes revealed cellular changes of CD34 + cells during vascular remodeling. To explore the cell origin of these CD34 + cells, we applied bone marrow (BM) transplantation, pseudo-time analysis of femoral artery cells, and further generated a smooth muscle (SM) lineage tracing system. To examine the role of Doublecortin Like Kinase 1 (DCLK1) in SM-derived CD34 + cell generation, overexpression of DCLK1 in primary VSMCs and genetic knockout of DCLK1 in SM lineage tracing system was performed. Results: A cluster of CD34 + cells was identified in femoral artery wire injury, which were CD34 negative before injury but CD34 positive after injury. These newly-generated CD34 + cells co-expressed VSMC or immune cell markers in neointima. BM transplantation clarified that vascular resident newly-generated CD34 + cells expressed VSMC makers or CD68, while BM CD34 + cells turned to immune cells but not VSMCs in neointima. These non-BM newly-generated CD34 + cells partly derived from VSMCs after injury. DCLK1 expression increased along the VSMCs-to-CD34 + cells transition. DCLK1 overexpression in VSMCs increased progenitor cell marker expression and decreased contractile VSMC marker expression. Genetic depletion of DCLK1 in VSMCs impaired SM-derived CD34 + cell generation during vascular remodeling. Conclusions: A novel cluster ‘SM-derived CD34 + cells’ was defined after vascular injury. These findings enriched our knowledge in pathological process of vascular remodeling and provided an avenue for future clinical interventions.
Abstract 13425: Outcomes of Delayed vs Early Cardioversion in Patients With Paroxysmal Atrial Fibrillation: A Population-Based Study (2015-2020)
Authors: Mohamed Salah Mohamed, Anas Hashem, Amani Khalouf, Muhammad Osama, Venkata Satish Pendela, Devesh Rai, Wilbert S Aronow, Mallory Balmer-Swain
Journal: Circulation (2023)

Introduction: Data on clinical outcomes of Delayed Cardioversion (DCV) compared to Early Cardioversion (ECV) in patients with paroxysmal atrial fibrillation (PAF) remains limited. Hypothesis: Is there a difference in clinical outcomes between both procedures? Methods: We used the National Inpatient Sample database by utilizing ICD-10 codes to identify all hospitalizations with a diagnosis of PAF and cardioversion (CV) (2015-2020). The associations between the time of CV and outcomes were examined using multivariable logistic or generalized linear model regression. Propensity-score matched (PSM) analysis was utilized to determine adjusted odds ratio (aOR) of major clinical outcomes. Results: A total of 17,879 patients with PAF were included: 9,725 (54.4%) and 8,154 (45.6%) underwent ECV and DCV, respectively. Regarding inpatient mortality, there was no significant difference between both groups (aOR 0.81 [0.52-1.25], p=0.76). Considering cardiovascular outcomes, DCV was more associated with acute heart failure (AHF) (aOR 1.79 [1.67-1.92], p&lt;0.01) with no significant difference in cardiac arrest (aOR 1.16 [0.73-1.84], p=0.38), cardiogenic shock (aOR 0.83 [0.59-1.17], p=0.97), need for permeant pacemaker (aOR 1.18 [0.91-1.54], p= 0.13), and arrhythmias (supraventricular and ventricular tachycardia) (aOR 0.97 [0.86-1.10], p=0.98) compared to ECV. As to neurological outcomes, there was no difference between both groups including transient ischemic attack (aOR 1.58 [0.82-3.04], p=0.12), ischemic stroke (aOR 1.06 (0.59-1.90), p=0.77), and hemorrhagic stroke (aOR 1.35 [0.36-5.07], p=0.45). Compared to ECV, DCV was associated with a higher median length of stay (4 days vs. 2 days, p&lt;0.01) and cost of hospitalization ($33,410 vs. $21,738, p&lt;0.01). Conclusions: Compared to ECV, DCV was associated with more AHF and resource utilization without significant differences in inpatient mortality and other major cardiovascular and neurological outcomes.
Abstract 16558: Revascularization in Patients With Ischemic Cardiomyopathy and Viability: A Meta-Analysis of Randomized Controlled Trials
Authors: Vien T Truong, Tam Ngo, Hoang N Duong, Vivek Patel, Phan Q Dai, Mansoor Ahmad, Krunalkumar Patel, Abhishek Dutta, Amna Khan, Jay Jaiswal, Syed Muhammad Usama, Minh A Vo, Devendra Tripathi, Sonela Skenderi, Thomas Metkus, Sunil Dhar
Journal: Circulation (2023)

Introduction: Observational studies have suggested that revascularization improves survival in patients with ischemic cardiomyopathy (ICM) with left ventricular ejection fraction less than less than or equal to 35% and demonstrable myocardial viability compared to medical therapy alone. However, the recent Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial revealed that among patients with severe ischemic left ventricular systolic dysfunction receiving optimal medical therapy, percutaneous coronary intervention did not reduce the incidence of major adverse cardiac events. Hypothesis: This meta-analysis aims to evaluate the impact of revascularization on patients with ICM and demonstrable myocardial viability, specifically focusing on randomized controlled trials (RCTs). Methods: We conducted a systematic search of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from inception to February 8th, 2023. The primary outcome assessed in this study was mortality. A random-effects models were applied to pool effect sizes. Results: Four RCTs involving 1365 patients with ICM and viability met the inclusion criteria. Among them, 684 patients were included in the revascularization group, while 681 patients received optimal medical therapy. In the revascularization group, 232 patients (34%) died, compared to 266 patients (39%) in the medical therapy group. The meta-analysis revealed that revascularization in this patient population was not associated with a significant improvement in survival (pooled odds ratio [OR]: 0.82; 95% CI: 0.59-1.14; p = 0.24). Furthermore, revascularization did not show a significant reduction in major adverse cardiac events (pooled odds ratio [OR]: 0.56; 95% CI: 0.27-1.16; p = 0.12). Conclusions: This meta-analysis of randomized controlled trials does not provide evidence supporting the effectiveness of revascularization in patients with ICM and demonstrable myocardial viability
Abstract 11548: An Examination of Differences in Ideal Cardiovascular Health Between Sexual Minority and Heterosexual Adults in the All of Us Research Program
Authors: Danny Doan, Rohith Ravindranath, Joseph Belloir, Vince Nguyen, Ipek Ensari, Yashika Sharma, Stephanie Cook, Billy A Caceres
Journal: Circulation (2023)

Introduction: Although cardiovascular health (CVH) disparities have been documented among sexual minority (e.g., gay/lesbian, bisexual) adults, research has been limited by a focus on sexual identity differences in individual, rather than composite, measures of CVH. Composite measures of CVH provide more comprehensive assessments of future cardiovascular disease risk. Methods: We analyzed data from the All of Us Research Program to examine sexual identity differences in CVH using the American Heart Association’s Life's Essential 8 measure of ideal CVH. Participants received a score from 0-100 for each CVH metric. We calculated an unweighted average to determine cumulative ideal CVH (range 0-100). Higher scores indicated a more favorable CVH profile. We used sex-stratified multiple linear regression models to estimate differences in individual CVH metrics and cumulative ideal CVH between sexual minority and heterosexual adults. All models were adjusted for age, race, ethnicity, household income, education, and insurance status Results: The sample included 6,597 participants with a mean age of 63.3 years (±13.89) of which 57% were female and 79% were Non-Hispanic White. Lesbian women (B = -7.43, 95% CI = -13.20, -1.65), gay men (B = -6.39, 95% CI = -10.17, -2.61), and bisexual men (B = -7.41, 95% CI = -14.71, -0.10) had less favorable nicotine exposure scores than their heterosexual counterparts of the same sex. Gay (B = -9.65, 95% CI = -16.60, -2.71) and bisexual men (B = -14.12, 95% CI = -27.53, -0.72) had less favorable physical activity scores than heterosexual men. Bisexual men also had lower cumulative ideal CVH scores than heterosexual men (B = -5.22, 95% CI = -9.16, -1.29). In contrast, gay men had more favorable body mass index scores (B = 6.23, 95% CI = 2.24, 10.22) than heterosexual men. Conclusions: This is the first study to examine ideal CVH in sexual minority adults in the All of Us Research Program. Findings have important implications for the development of interventions to promote optimal CVH among middle-aged and older sexual minority adults. Interventions to reduce nicotine exposure are needed for lesbian women and sexual minority men. Efforts to improve the CVH of sexual minority men should also focus on increasing physical activity.
Abstract 14140: Management and Outcomes of Bacteremia After Transvenous Lead Extraction Complicated by Retained Lead Fragments
Authors: William M DeVries, Emmanuel Danso, Emma Francis, Tanner Robl, Nicholas Kettelkamp, Jacob Cushing, Loren D Berenbom, Raghuveer Dendi, Amit Noheria, Rhea C Pimentel, Rigoberto Ramirez, Madhu Reddy, john anderson, Seth H Sheldon
Journal: Circulation (2023)

Introduction: Complete hardware removal is indicated for cardiovascular implanted electronic devices (CIED) infection. While transvenous lead extraction (TLE) is often successful in removing the entire device, some patients are left with residual hardware due to lead breakdown or unsuccessful attempts at removal. We sought to assess the outcomes and management in patients with retained CIED components that can be a nidus for ongoing infection. Methods: Single center retrospective case series among patients with lead extraction between 2010 and 2022. Results: There were 9 of 930 TLE patients (1%) who met study criteria (age 68 ± 23 yrs, 78% men, 67% ICD, 44% CRT, oldest lead 10.1 yrs IQR 6.1-22.2, combined lead age 21.2 yrs IQR 14.7-54.9). Two patients (22%) had epicardial leads as well. The majority of patients (n=8/9, 89%) had systemic infection, including lead vegetations in 22% (n=2). The most common infection organism was Staphylococcus aureus (n=5, 56%). Residual CIED components included lead tips (n=4, 44%), epicardial leads (n=2, 22%), entire intravascular lead portion (n=2, 22%), and a remnant ICD coil remaining in the SVC (n=1, 11%). TLE attempt was halted in 1 patient with a right atrial perforation during extraction (only removed 4/6 leads) and another patient with unsuccessful removal via laser, mechanical, and snaring attempts. Device reimplantation was performed in 4 patients (44%). The patient with the RA perforation underwent reimplantation of an epicardial system at the time of repair. Median follow-up was 0.9 years (IQR 0.4-7.2). Three patients (33%) were managed with indefinite antibiotic suppression, while the median antibiotic duration for the remainder was 35 days (IQR 14-43). Two patients (22%) had recurrent infections, both of which occurred despite the use of indefinite antibiotic suppression. None of the patients with residual lead tip alone had subsequent infections or were managed with suppressive antibiotics. Conclusion: Recurrent infection can be problematic when retained lead components are present after TLE and occurred despite the use of indefinite suppressive antibiotics in some patients. Further investigation is necessary to determine if the risk of recurrent infection varies by the type of residual CIED components.
Abstract 15928: D-dimer as a New Biomarker of Aortic Stenosis Progression and Outcomes: Results From the PROGRESSA Study
Authors: Kathia Abdoun, Lionel Tastet, Hecht Sebastien, Yassine Abdeldjebbar, Marie-Ange Fleury, Simon Jacob, Romain Capoulade, Mylene Shen, Marie Arsenault, Élisabeth Bédard, Nancy Cote, Marie-Annick A Clavel, Philippe Pibarot
Journal: Circulation (2023)

Background: Aortic stenosis (AS) induces left ventricular (LV) remodeling and hypertrophy, which are key markers of the transition to heart failure. The present study aimed to evaluate the association between D-dimer plasma levels, LV hypertrophy and mortality with AS. Method: One-hundred and forty-six asymptomatic patients (mean age 65±13, men 76%) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography annually to measure AS severity, LV mass indexed to body surface area (LVMi) and myocardial contraction fraction (MCF). The annualized changes in LVMi and MCF were calculated between baseline and last follow up. Results: Higher plasma levels of D-dimers at baseline were significantly associated with faster progression rate of LVMi and MCF (r 2 =0.18 and -0.22, respectively; all p&lt;0.01). On multivariable analysis adjusted for age, sex, comorbidities, creatinine level, peak aortic jet velocity at baseline, D-dimers remained significantly associated with faster change in LVMi and MCF (all, p&lt;0.01). Moreover, in multivariate analysis adjusted for age, sex, AS severity at baseline, higher levels of D-dimer were significantly associated with the progression to a higher grade of AS severity (HR [95% CI] 1.67 [1.14-2.46], p=0.009). During a median follow-up of 8.1 (5.6-9.9) years, 38 (26%) patients died. On multivariable Cox regression analysis, higher levels of D-dimer were associated with an increased risk of all-cause mortality (HR [95% CI]: 1.97 [0.98-1.97], p=0.05). Conclusion: Higher levels of D-dimer are associated with faster progression of AS severity, LV hypertrophy and dysfunction, and increased risk of mortality in patients with AS. This new blood biomarker may improve risk stratification and management of asymptomatic patients with AS. Further studies are needed to determine the mechanisms underlying this association between D-dimer and outcomes in AS.
Abstract 13588: A Generalizable Deep Learning System for Cardiac MRI
Authors: Rohan Shad, Cyril R Zakka, Dhamanpreet Kaur, JOHN MONGAN, Kimberly G Kallianos, Ross Filice, Nishith Khandwala, David Eng, Curtis Langlotz, William Hiesinger
Journal: Circulation (2023)

Introduction: Our goal was to create a generalizable Cardiac MRI (CMR) deep learning system capable of understanding the breadth of human disease and health. With traditional supervised approaches, parameters learned for one clinical problem rarely generalize to others. Models must be re-trained from scratch for each new clinical task of interest, requiring thousands of training examples every time. Unlike human clinicians, deep learning models lack a baseline fund of clinical knowledge over which learning specific tasks can be accelerated. Methods: We use self-supervised contrastive learning to train a video transformer system that learns complex pathophysiological visual representations guided by natural language supervision from text reports accompanying each CMRI study. Two parallel deep learning systems - one processing text, and the other processing CMR cine sequences learn from each other, allowing the vision system to learn from radiologist reports as training progresses. Training was performed on a multicenter clinical dataset of 17000 patients. We subsequently freeze the vision network, and apply it to the task of calculating left ventricular ejection fraction (LVEF%) from the UK BioBank (45,6323 participants) Results: On a hold-out test subset of UK BioBank participants, we report a mean absolute error (mae) of 3.344 (sd 3.615), with Bland Altman limits of agreement -9.91% to +9.61%. Using this network to screen for HFrEF (Heart Failure with reduced ejection fraction &lt; 40%), the AUC is 0.880 (95%CI: 0.835-0.925; n=4259). This is significantly more performant compared to our baseline, where we finetune the exact same network architecture using traditional supervised approaches (AUC 0.751 (95% CI: 0.692-0.811; p &lt; 0.001)). Finally, our network achieves superior results with 1/100 th the data. Conclusions: We show that contrastive text-video pre-training can be used to train powerful and generalizable deep learning systems for CMR.
Abstract 16398: Impact of Low-Dose Rivaroxaban Plus Aspirin on Total Vascular Events in Fragile Patients With Peripheral Artery Disease: Insights From VOYAGER PAD
Authors: Mario Enrico Canonico, Cecilia C Low Wang, Sebastian Debus, Mark Nehler, Manesh R Patel, Sonia S Anand, Warren Capell, Eva Muehlhofer, Lloyd P Haskell, Scott D Berkowitz, Rupert Bauersachs, Marc P Bonaca
Journal: Circulation (2023)

Background: Rivaroxaban 2.5 mg BID reduced major adverse limb events (MALE) and total vascular events in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization (LER) in VOYAGER PAD. The safety and efficacy of rivaroxaban on MALE and total vascular events in fragile patients with PAD has not been described. Hypothesis and Methods: Patients were categorized as fragile based on prespecified criteria (age &gt; 75 years or weight ≤ 50 kg or baseline eGFR &lt; 50 mL/min). MALE was defined as composite of acute limb ischemia (ALI) and major amputation. Total vascular events include cardiovascular, MALE, peripheral revascularizations and venous thromboembolism events. Same-day vascular events are consolidated into a single event. The main safety outcome was TIMI major bleeding. Results: A total of 1,669 (25%) subjects of 6,564 randomized were categorized as fragile at baseline. Rivaroxaban reduced the risk of MALE particularly in fragile (HR 0.56; 95% CI 0.38 - 0.81) vs non-fragile patients (HR 0.82; 95% CI 0.67 - 1.00, p-interaction 0.07, figure upper panel) with the benefits in fragile patients driven by reduced ALI (HR 0.47; 95% CI 0.30 - 0.75). Rivaroxaban reduced the occurrence of total vascular events at 3 years in fragile patients with absolute rates of 82.1 events/100 patients on rivaroxaban vs 99.3 events/100 patients on placebo (HR 0.81; 95% CI 0.68 - 0.98). Similar benefit was seen in non-fragile patients 70.4 events/100 patients on rivaroxaban vs 81.6 events/100 patients on placebo, HR 0.90; 95% CI 0.81-1.00 (figure, lower panel). Rivaroxaban increased TIMI major bleeding similarly in fragile (HR 1.66; 95% CI 0.87 - 3.19) and non-fragile (HR 1.37; 95% CI 0.83 - 2.24, p-interaction 0.65). Conclusions: In a high-risk PAD population rivaroxaban reduces MALE and total vascular events and increases bleeding regardless of fragile status. These data may assist in personalization of antithrombotic therapy in this high-risk population.
Abstract 14156: Promotion of Human Pluripotent Stem Cell-Engineered Cardiac Tissue Maturation by Non-Physiological Intermittent Hydrostatic Pressure
Authors: Maihemuti Wusiman, Kozue Murata, Jun Iida, Keisuke Hakamada, Akane Sakaguchi, Abulaiti Mosha, Yuichi Saito, Kenji Minatoya, Wataru Kimura, Hidetoshi Masumoto
Journal: Circulation (2023)

Background: The immaturity of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and hPSC-engineered cardiac tissues (ECTs) hinder their potential for cardiac regenerative therapy. Multiple studies have demonstrated the crucial role of ventricular loading pressure in cardiac repair and regeneration. Hypothesis: We postulated that hydrostatic pressure could enhance the maturation and functionality of the ECTs. Methods: To create ECTs, a mixture of hPSC-derived cardiovascular cells was co-cultured with Collagen I and Matrigel, then subjected to hydrostatic pressure. The functionality of the ECTs was assessed using a video-based system to measure contractile capacity, a flux analyzer to evaluate metabolic function, and a calcium indicator. Histological assessments were conducted to examine the structural maturation. CM maturation were evaluated through scRNA-seq. The trained ECTs were transplanted onto a rat myocardial infarction (MI) model followed by echocardiogram (N=3). Results: The optimized protocol consisting of intermittent pressure (1 hour/day) at 50 kPa (equivalent to 375 mmHg), for a duration of 3 days, preceded by a 2-week pre-culture period, remarkably enhanced the CM component and collagen alignment of the ECTs. This training led to increased expression of various genes associated with CM maturation. The trained ECTs exhibited a positive force-frequency relationship in terms of contractility, along with an elevation in peak calcium flux, indicating functional maturation. The training resulted in increased mitochondrial content and maximum respiration capacity, indicating metabolic maturation. Combination of the hydrostatic training and dynamic culture promoted vascular network formation of the ECTs. The maturation was dependent on the presence of endothelial cells (ECs), as ECTs without ECs failed to exhibit the maturation. The ECTs demonstrated a significant increase in ejection fraction of a rat MI model at 4 weeks post-transplantation (control vs training: 42.8±13.0 vs 80.7±8.5 %, P= 0.0045). Conclusion: The application of non-physiological and intermittent hydrostatic pressure training has led to significant maturation of ECTs, showcasing their therapeutic potential.
Abstract 14907: Trends in Management Practices of Cardiovascular Implantable Electronic Device Infections in Patients With End-Stage Kidney Disease
Authors: Sania Jiwani, Wan-Chi Chan, Suveenkrishna Pothuru, Madhu Reddy, Rhea C Pimentel, Kamal gupta
Journal: Circulation (2023)

Introduction: End-stage kidney disease (ESKD) patients with cardiovascular implantable electronic devices (CIEDs) are at higher risk of bloodstream infection. While prior studies have shown high procedural success rates of lead extraction and improved outcomes, the rates of lead extraction in these patients at the national level are not known. Aim: To evaluate trends in management practices of CIED infections in ESKD patients. Methods: Utilizing the United States Renal Data System and ICD 9 codes, we identified patients aged &gt;18 years with ESKD on hemodialysis who underwent first CIED implant from January 2006-September 2014. For study purposes we studied management strategy in those who developed CIED infection within 1 year of device implant. We excluded patients with a prosthetic valve as the ICD 9 code for CIED infection also includes prosthetic valve infection. We restricted the study population to those with CIED implanted until September 2014 as ICD 10 codes were implemented in September 2015 and the ICD 10 code is not specific code for CIED infection (it also includes vascular device infections). After identifying patients diagnosed with CIED infection, we utilized procedure codes for lead extraction within 60 days of the infection diagnosis to determine the mode of management. In the absence of procedure codes for extraction, patients were presumed to have been managed medically. Results: A total of 380 ESKD patients undergoing CIED implant from 2006-2014 were diagnosed with CIED infections within 1 year of device implant. Of these, 183 (48.16%) patients underwent lead extraction within 60 days. When analyzed by year, the rates of utilization of lead extraction in these patients have not changed significantly from 2006 to 2015 (Table). Conclusions: The utilization of lead extraction for management of CIED infections in ESKD patients remains low (~50%). This data calls for a reassessment of management strategy for device infections in ESKD patients.