tbuckley/cabot-search huggingface dataset:
Abstract 4123674: The role of CD34+ PI16+ fibroblast progenitor cells in transplant arteriosclerosis
Authors: Xiaodong Xu
Journal: Circulation (2024)

Background: Transplantation arteriosclerosis is one of the major complications for the mid- and long-term survival of recipients with organ transplantation. Although previous studies suggest that CD34 stem/progenitor cells are involved in this process, the heterogeneity and potential adverse effects of CD34 + SPCs have not been fully determined. Methods and Results: A mouse model of transplant arteriosclerosis was established by using Balb/c, C57BL/6J, CD34-CreERT2, R26-tdTomato, Rosa26-iDTR, CD34-Dre, PI16-CreERT2, CAG-LSL-RSR-tdTomato-2A-DTR mice. Using single-cell RNA-seq and the innovative application of genetic lineage tracing with dual recombinases, we identified a subpopulation of fibroblast progenitor cells marked by high CD34 and PI16 expression. Interestingly, this progenitor cell group gave rise to a distinct chemotactic fibroblast subset. Based on chemokine antibody microarray assay and transcriptome analysis, the subgroup with increased CD34 expression and decreased PI16 expression promoted intimal hyperplasia, acting through the paracrine release of a specific chemokine CCL11 (eotaxin-1). Moreover, the binding of CCL11 to its receptor CCR3 triggered the PI3K-AKT signaling pathway in smooth muscle cells, promoting their proliferation and migration to form neointimal lesions. Overexpression of CCL11 by adeno-associated virus can promote neointimal hyperplasia in vivo, while neutralization of CCL11 or inhibition of receptor CCR3 can alleviate neointimal lesions. Conclusion: Our findings identified CD34 + /PI16 + fibroblast progenitors able to differentiate into specific chemotactic fibroblasts that release chemokines pivotal for neointima formation, implicating a therapeutic potential targeting the chemotactic behavior of these cells.
Abstract 4141481: Outcomes of the upfront two stent strategies for bifurcation percutaneous coronary interventions: Insights from PROGRESS-BIFURCATION registry
Authors: Deniz Mutlu, Athanasios Rempakos, Dimitrios Strepkos, Michaella Alexandrou, Pedro Carvalho, Ahmed Al-Ogaili, Barkin Kultursay, ali karagoz, Oleg Krestyaninov, Dmitrii Khelimskii, Mahmut Uluganyan, korhan soylu, Ufuk Yildirim, Olga Mastrodemos, Bavana Rangan, Sandeep Jalli, Konstantinos Voudris, Yader Sandoval, M Nicholas Burke, Emmanouil Brilakis
Journal: Circulation (2024)

Background: Upfront two-stent techniques are often used in bifurcation percutaneous coronary interventions (PCI), but there is controversy about optimal strategy selection. Methods: We examined the clinical, angiographic characteristics, and long-term outcomes of 206 bifurcation PCIs using the double kissing (DK) crush or the culotte techniques in 192 patients between 2014-2023 from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (NCT05100992). For the long-term outcomes adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using the mixed effects Cox proportional hazards model. Results: DK crush was more commonly used (70.4%). Patients in the culotte group had similar baseline characteristics with the DK crush group. Lesions treated with culotte were more likely to be in the left anterior descending (54.1% vs. 35.9%, p&lt;0.001) and circumflex arteries (21.3% vs. 9.0%, p&lt;0.001), had smaller proximal (3.50 [3.00, 3.75] vs. 3.50 [3.30, 4.00] mm, p=0.032) and distal (3.00 [2.75, 3.00] vs. 3.00 [3.00, 3.50] mm, p=0.047) main vessel diameters, and were less likely to have severe calcification (6.6% vs. 32.4%, p&lt;0.001). Technical success (96.7% vs. 98.6%, p=0.583), procedural success (93.1% vs. 93.9%, p=0.758), and in-hospital major adverse cardiovascular events (MACE) (3.4% vs. 6.1%, p=0.726) were similar in both groups. During a mean follow-up of 38-month, 32 (28.3%) patients experienced MACE. On multivariable analysis, culotte was associated with similar MACE (aHR 1.19; 95%CI 0.78-1.80; p=0.680), mortality (aHR 1.11; 95%CI 0.68-1.79; p=0.810), and target vessel PCI revascularization (aHR 0.58; 95%CI 0.30-1.13; p=0.460) compared with DK crush (Figure). Conclusions: Bifurcation PCI with DK crush and culotte had similarly high technical and procedural success, low in-hospital MACE, and long-term outcomes.
Abstract 4140120: Artificial intelligence-driven morbidity prediction in acute kidney injury after acute type A aortic dissection surgery
Authors: Zhihui Zhu, Zheyuan Chen, Nan Liu, Yongqiang Lai
Journal: Circulation (2024)

Background: Acute kidney injury (AKI) often complicates acute type A aortic dissection (ATAAD), with elevated comorbidity rates and a significant tie to in-hospital mortality. Identifying risk factors early can mitigate AKI severity. Research Questions: This research endeavors to develop and corroborate predictive models leveraging Machine Learning (ML) techniques from Artificial Intelligence to forecast AKI occurrences in ATAAD-afflicted individuals. Methods: The study employed various machine learning (ML) algorithms including Gradient Boosting Machine (GBM), LightGBM, Random Forest (RF), K-Nearest Neighbors (KNN), Multi-Layer Perceptron Neural Network (MLP-NN), Naive Bayes (NB), Logistic Regression (LR), and ensemble methods (combining LR&amp;LightGBM), employing tenfold cross-validation. Model performance was evaluated using SHapley Additive exPlanations (SHAP). A web-based tool for predicting AKI incidence was developed using Streamlit, based on the most effective model. The analysis involved 1350 ATAAD patients, among whom 586 (43.4%) developed post-operative AKI. Patients were divided into two cohorts: 85% for training and 15% for testing, with 126 features included in the predictive model. Results: Incorporating top 10 features, LightGBM (AUROC=0.886, 95% CI 0.841-0.930) excelled in predictive accuracy, calibration, and clinical utility, identifying key factors such as ventilation time in ICU, hourly urine output post-surgery, diuretic use, Scr, heart rate, urea, administration of recombinant human brain natriuretic peptide and ebrantil, MCHC, and blood glucose as associated with ATAAD-AKI. Conclusion(s): These ML models are robust tools for predicting AKI in ATAAD patients, with LightGBM's superior predictive ability standing out. They offer valuable support for clinical decision-making in ATAAD management, helping optimize postoperative strategies to minimize AKI occurrence after surgery.
Abstract 4147625: Cardiometabolic Syndrome and Incident Alzheimer’s Disease: The Predicative Value of Age and CMS Using Cox and Machine Learning Models
Authors: Longjian Liu
Journal: Circulation (2024)

Background: Cardiometabolic syndrome (CMS) poses a significant public health concern. The study aimed to investigate the predictive value of age and CMS for incident Alzheimer’s disease (AD) in women aged≥50. Methods: A cohort of women aged 50-79 ( n = 63,117) who participated in the Women’s Health Initiative Observational Study (WHIOS) in 1993-1998, without baseline AD and followed through to March 1, 2019, were analyzed. CMS was defined as having ≥3 of five CMS components: large waist circumference, HBP, elevated triglycerides, elevated glucose, and low HDL-cholesterol. AD was classified by physician-diagnoses of incident AD. Hazards ratios (HR) of AD risk associated with CMS by age were analyzed using Cox’s proportional hazards regression analysis. Machine learning (ML)-XGBoost and Lasso Cox models clustered individuals with low, mild, moderate, and severe risk of incident AD. Results: During a median follow-up of 20 years (range: 3.36 to 23.36 years), 8340 developed incident AD. The incident rate (95%CI) of AD was 8.6 (8.1-9.1) per 1000 person-years (PY) in women with CMS, and 7.0 (6.9-7.2) per 1000 PY in those without CMS (p&lt;0.001). Multivariate Cox’s regression analysis indicated that women with CMS versus non-CMS had significantly higher risks of AD in those aged 50-59 [HR (95%CI): 1.37(1.12-1.68)], followed by in those aged 60-69 [1.26 (1.14-1.40)], but nonsignificant in those aged≥70 [1.00 (0.87-1.14)]. Elevated glucose concentration ranked as the top predictor for AD, followed by triglyceride and HBP. Four levels (low to severe) of AD risk were significantly clustered using ML-XGBoost and Lasso Cox models. Conclusions: Women aged 50-69 with CMS vs those without CMS had significantly higher relative risks of AD, but the risk was not significant in those aged≥70. The application of ML prediction models holds potential promise in the early identification of AD risk among U.S. adults.
Abstract 4122348: APOL1 Risk Variants and Risk of Incident Atrial Fibrillation in Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Muhammad Ahmad, Richard Kazibwe, Mohamed Mostafa, Rimsha Naeem, Sanjay Singh, Nisha Bansal, Elsayed Soliman
Journal: Circulation (2024)

Background: Apolipoprotein L1 gene (APOL1) G1 and G2 risk variants (RVs) have been associated with the progression of chronic kidney disease in individuals of recent African descent. However, the association of APOL1 RVs with atrial fibrillation (AF) is unknown and may help identify individuals at risk. Aim: To examine the association of APOL1 RVs with incident AF in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: This post-hoc analysis included SPRINT participants free of AF at baseline who had baseline APOL1 and follow-up AF data. Cox proportional hazard regression models were used to examine the risk of AF for Black individuals with high-risk APOL1 (2 RVs) compared with low-risk (0-1 RVs) (reference). Additionally, three analyses were performed: a comparison of the risk of AF between all Black and White participants, Black participants with low-risk APOL1 RVs and White participants, and Black participants with high-risk APOL1 RVs and White participants. Results: 2,254 Black and 4694 White participants were included in the analysis. During a median follow-up of 2 years, there were 16 and 134 cases of incident AF among Blacks and Whites, respectively. In a multivariable-adjusted model, compared with Black individuals with low-risk APOL1 RVs, high-risk APOL1 RVs were associated with approximately 3.5 times greater risk of AF. This association was stronger among participants without chronic kidney disease (CKD) compared to those with CKD (hazard ratio (HR) (95% confidence interval (CI)), 6.01 (1.44-25.0) vs. 2.98 (0.21-41.7), respectively, interaction p -value=0.11). Compared to White participants, all Black and Black participants with low-risk APOL1 RVs had a significantly lower risk of AF. In contrast, Black individuals with high-risk APOL1 RVs had a similar risk of AF compared to White participants ( Table ). Conclusions: In hypertensive, non-diabetic Black participants, high-risk APOL1 RVs are associated with a higher risk of AF, and these individuals had an AF risk comparable to White participants. These hypothesis-generating findings underlie the need for future investigation to confirm this association and whether APOL1 status can explain racial differences in the risk of AF.
Abstract 4148096: Discrimination Abilities of Euroscore and SYNTAX score for Prognostic Outcomes in patients with Stable Coronary Artery Disease: A Systematic Review and Meta-analysis
Authors: Prakash Upreti, Jawad Basit, Muhammad Hammad Khan, Mushood Ahmed, Mohammad Hamza, Muhammad Ans Sharif, Ankit Hanmandlu
Journal: Circulation (2024)

Introduction: There is a lack of good risk prediction models in patients with stable coronary artery disease (SCAD). We conducted a meta-analysis of validation studies to compare and determine the discrimination abilities of Euroscore (ES) and Syntax score (SS) for prognostic outcomes in patients with SCAD. Methods: A comprehensive literature search was conducted across MEDLINE, Cochrane and Embase from inception till May 2024. All studies that reported C-statistic/AUC for predicting all cause mortality, cardiac death or Major adverse cardiovascular events (MACE) for patients with stable coronary artery disease (SCAD) were included in the analysis. Studies lacking confidence intervals (CI) for C-statistic or those which reported C-statistics in patients with acute coronary syndromes or mixed SCAD and ACS patients were excluded. A generic inverse variance method was used to pool C-statistics and their corresponding standard errors (SEs). The SEs were calculated from CI wherever needed. A pooled C statistic of &gt;0.8 was considered to be a good discrimination ability. Results: A total of 5 studies with a patient population of 5903 were included in the meta-analysis. For ES, the pooled C-statistic for all cause mortality (n=2666) was 0.69[0.51-0.87] while for cardiac death (n=2666) it was 0.77[0.60-0.71]. The discrimination ability of ES for MACE as reported by one study (n=305) was 0.54[0.49-0.60]. For SS, the summary AUC for all cause mortality (n=2936) was 0.77[0.69-0.85] while for cardiac death (n=305) it was 0.52[0.46-0.57]. The pooled AUC of SS for occurrence of MACE(n=2666) was 0.56[0.45-0.66]. Conclusion: None of the two scores have a a good discrimination ability for risk stratification in SCAD patients. The predictive accuracy of SS is comparatively better than ES for all cause mortality. However, ES performs better for predicting cardiac death. Better risk prediction models with large scale external validations are needed.
Abstract 4136911: Daily Dyadic Symptom Appraisal Dynamics During Care Transitions in Persons with Heart Failure and Their Care Partners
Authors: Julie Bidwell, Emilio Ferrer, Christopher Lee, Martin Cadeiras, Monica Godden, Marnie Livingston, Ladson Hinton
Journal: Circulation (2024)

Background: Symptom monitoring after heart failure (HF) hospitalization is a central aspect of patient education. However, appraising symptoms can be difficult for persons with HF (PWHFs), and studies suggest family care partners (CPs) play a key supportive role. The purpose of this study is to examine dyadic HF symptom appraisal dynamics in PWHF-CP dyads during hospital-to-home transitions. Methods: We conducted a daily diary study of dyadic symptom appraisal in which PWHFs and CPs were enrolled during a HF hospitalization. Over 5 weeks, both completed daily assessments of the PWHF’s symptoms (HF Somatic Perception Scale, PROMIS Fatigue 4a). Each dyad’s appraisal dynamics were quantified using a set of N of 1 dyadic autoregressive time series models examining total symptoms, hallmark symptoms (dyspnea, edema) and nonspecific symptoms (early/subtle cluster, fatigue). Models were examined for within-dyad dynamics (within-dyad associations on the same day or on a 1-day lag). Patterns in significant dynamics across dyads were narratively described. Results: This analysis includes n=14 cohabitating dyads, all partnered. On average, PWHFs and CPs were 69.6±5.4 and 67.4±8.0 years of age. The sample was relatively gender balanced (43% of PWHFs and 64% of CPs identified as female), and primarily identified as non-Hispanic (86% of PWHFs, 93% of CPs) and White (93% of PWHFs, 86% of CPs). Most PWHFs had non-ischemic cardiomyopathy (64%) and were NYHA Class III/IV (86%), with 57% HFrEF (mean EF 37%±17%). Symptom appraisals were highly variable within and across dyads (Fig 1). Most (n=11, 79%) had significant dyadic dynamics, but dynamics across dyads varied by symptom type and time structure (Fig 2). Conclusions: The types of symptoms that HF care dyads are able to appraise together and the time structure of appraisals are variable during care transitions. Precision approaches tailored to individual dyads are needed to optimize inclusion of CPs in symptom monitoring interventions.
Abstract 4112952: Developing culturally informed materials to enhance Native Hawaiians' and Pacific Islanders’ participation in clinical trials
Authors: Claire Ing, Anna Fan, Kiilaweau Aweau, sheryl yoshimura, Meghan Kenney, Joseph Kaholokula
Journal: Circulation (2024)

Background: Native Hawaiians and Pacific Islanders (NHPI) suffer disproportionately from cardiometabolic disorders and are underrepresented in related clinical trials, limiting our ability to control these disorders for this population. We identified recruitment and retention barriers (complicated clinical language) and facilitators (relationship-building opportunities). Addressing recruitment and retention barriers and facilitators can increase NHPI representation in clinical trials. Goal: To develop culturally informed, educational videos and infographics to improve NHPI trust and attitudes toward research and recruitment and retention in clinical trials. Methods: The videos and infographics are based on focus group data with NHPI past clinical trial participants or staff. The videos focus on recruitment. The infographics focus on recruitment and retention. The videos address the complicated clinical language and hesitancy in disclosing information while leveraging trial outcomes relevant to NHPI health concerns and cultural inclusiveness. The infographics build on the video content. Facilitators include relationship-building opportunities, seeking healthier outcomes for future generations, relationship-building opportunities, and sharing and learning opportunities provided in clinical trials. Results: The Co-Principal Investigators, NHPI clinical trial participants, and NHPI researchers and clinicians contributed to the videos. We created a 5-minute and a 10-minute video. The videos provide 1) an overview of clinical research, 2) considerations for participating in clinical trials, and 3) reasons to participate. Researchers present the first 2 topics, while past participants provide testimonials for the third topic. The 8 infographics include 1) an overview of clinical research, 2) the importance of randomization, 3) research benefits from NHPI participation, 4) the importance of a control group, 5) clinical trial outcomes, 6) individual benefits from research participation, 7) community benefits from research participation, and 8) trust in research. Discussion: We will test the impact of these materials on trust and attitudes towards research and recruitment and retention among NHPI in a randomized clinical trial (RCT). Half of the participants (n=104) will be recruited using traditional strategies and half (n=104) using our novel strategy. Rigorous qualitative (interviews with participants) and quantitative (retention rates) analysis will be conducted.
Abstract 4147632: Unusually Expeditious Expansion of an Atrial Myxoma
Authors: Raul del Toro Mijares, Hedaia Algheriani, Marco Alan Cazares Parson, Joseph Chang, Sunil Srinivas
Journal: Circulation (2024)

Description of the Case Report: A 44-year-old female with a past medical history of unspecified skin cancer presented with exertional dyspnea for 1 day before admission and syncope 7 months before admission. Physical exam was noted for soft low low-pitched diastolic murmur at the cardiac apex, not appreciated on prior exam. Echocardiography revealed a 3.3x4.7 cm pedunculated, homogenous mass in the left atrium obstructing the mitral valve. Serum BNP was measured as 326. An echocardiogram from less than 29 months prior was reviewed and showed no mass in the left atrium. The patient underwent successful surgical resection of the mass. The mass measured approximately 7x6x2 cm. Histologic analysis reported a proliferation of myxoid stroma with cytologically bland spindle cells positive for calretinin, compatible with cardiac myxoma. Following the surgery, the patient experienced resolution of symptoms. Discussion: Atrial myxomas are the most common primary cardiac tumors. They present as mitral valve obstruction, mitral valve regurgitation, arrhythmias, or systemic thromboembolism. They are exceedingly rare with an incidence of 0.5 to 1 case per million individuals annually and typically resected immediately. Therefore, instances with well-documented growth rates are uncommon. In this case, we present an unusually fast-growing myxoma in a woman with shortness of breath and syncope. The reported growth rate of atrial myxomas ranges from 1.3 to 6.9 mm a month. Our patient had a negative echocardiogram less than 2.5 years before her presentation, followed by the development of a 7 x 6 x 2 cm mass. Since the onset is unknown, the precise growth rate of our patient's tumor is unknown but was at least 24 mm/month. It is important to consider myxoma in the differential diagnosis of a woman with new onset murmur and syncopal episode. Furthermore, recognizing the potential for rapid expansion is crucial to assessing the risks versus benefits of myxoma section.
Abstract 4140148: Genetic Influence in Patients Transplanted for Myocarditis in the TOPMed-TOPCHeF Cohort of Explanted Hearts
Authors: Max Jason, Raffaella Lombardi, Sharon Graw, Kristen Medo, Sarah Newman, Michael Bristow, Amrut Ambardekar, Joseph Cleveland, Peter Buttrick, Luisa Mestroni, Matthew Taylor
Journal: Circulation (2024)

Background: Myocarditis is a leading cause of secondary cardiomyopathy and stems from infection, medications, or immune etiologies. Recent reports identify an overlap between myocarditis and pathogenic / likely pathogenic (P/LP) genetic variants of dilated and arrhythmogenic cardiomyopathies (DCM/ACM). Hypothesis: We hypothesized that myocarditis leading to heart failure and transplantation could be influenced by P/LP mutations for DCM/ACM. Aims: To evaluate the impact of genetics in myocarditis, we investigated a series of patients presenting with symptoms consistent with myocarditis who were found to have P/LP genetic signatures for dilated and arrhythmogenic cardiomyopathies DCM/ACM. Methods: Patients with myocarditis, defined by retrospective clinical diagnosis, were selected from the NHLBI Trans-Omics for Precision Medicine (TOPMed) - Trans-Omics for Precision Medicine for Congestive Heart Failure (TOPCHeF) cohort. After informed consent, patients’ explanted hearts were collected in the University of Colorado Heart Tissue Bank. A total of 837 hearts (697 failing and 140 control hearts) underwent whole genome DNA sequencing (WGS). Results: 11 patients had a diagnosis of myocarditis based on clinical history. None had acute myocarditis at time of transplantation. P/LP variants in DCM/ACM genes were found in 6 patients. The average age at transplantation was 42.8 years for patients with genetic variants and 38.9 without. Demographics are included in table 1. The most common genetic variants were Titin truncations. Full genetic data are included in table 2. Conclusion: 50% of patients undergoing transplantation with a clinical diagnosis of myocarditis in the TOPMed-TOPCHeF population had P/LP variants in DCM/ACM genes. This underscores the importance of genetic testing in patients with a clinical presentation of myocarditis for future management implications.