tbuckley/cabot-search huggingface dataset:
Abstract 4140605: Challenges in Coronary Angiography Through Radial Artery Access due to Anatomic Variations: A Single-Center Experience
Authors: Wissam Harmouch, Alan Villarreal Rizzo, Ravi Thakker, Selma Abdurrahman, Vishal Patel, Neha Kumar, Salman Farooqi, Danielle El Haddad, Syed Gilani, Wissam Khalife
Journal: Circulation (2024)

Background: Radial artery (RA) access has become common in cardiac catheterization due to fewer vascular complications and MACE compared to transfemoral approach (TFA). However, anatomic variations are more profound in the upper-extremity. Research Question: What are common anatomic variations encountered during transradial approach (TRA) coronary angiography and what association do they have with adverse outcomes and procedural challenges? Methods: We performed a single-center retrospective analysis of 926 patients who underwent coronary angiography through TRA via the right upper-extremity where RA angiogram was performed from 01/2010 to 01/2023. Multivariate logistic regression was utilized to estimate the odds ratio (OR) of the association between anatomic variations and adverse outcomes and procedural challenges. Results: A total of 926 patients with a mean age of 59.9 years were studied with 30.4% being female. Common comorbidities were HTN (82.2%), HLD (51.8%), and DM (45%). About 32% of patients had an anatomic variation. Prevalences were 14.4% radial tortuosity, 12% high RA bifurcation, 11.9% M-sign, and 1% RA loops. These patients were older (P&lt;0.001) and more likely to have HLD (P=0.049). They had high odds of high contrast dose (OR 1.73; 95% CI 1.28-2.34, P&lt;0.001), long fluoroscopy time (OR 2.02; 95% CI 1.50-2.73, P&lt;0.001), high radiation exposure (OR 2.47; 95% CI 1.79-3.42, P&lt;0.001), difficulty engaging coronary arteries (OR 2.70; 95% CI 1.94-3.74, P&lt;0.001), and transfer to TFA (OR 4.89; 95% CI 2.36-10.12, P&lt;0.001). Females (OR 2.89; 95% CI 2.01-4.15, P&lt;0.001), small RA size (OR 2.61; 95% CI 1.76-3.86, P&lt;0.001), high RA bifurcation (OR 1.68; 95% CI 1.02-2.75, P=0.04), and M-sign (OR 2.04; 95% CI 1.24-3.35, P=0.005) were associated with RA spasm. Major complications were not significant. Conclusion: We found a high prevalence of anatomic variations. They were associated with high odds of adverse outcomes and procedural challenges during TRA coronary angiography.
Abstract 4140078: Association of Extreme Heat with Cardiovascular and All-cause Emergency Department Visits in the United States
Authors: Jonathan Szeto, Kaitlyn Shultz, Esha Bansal, Jagadeesh Puvvula, Sean Hennessy, Aimin Chen, Sameed Ahmed Khatana
Journal: Circulation (2024)

Background: Extreme heat events have increased in frequency and intensity and are projected to continue increasing due to climate change. Extreme heat is associated with an increase in both all-cause and cardiovascular (CV) mortality. However, how extreme heat impacts CV disease related emergency department (ED) visits is not well studied. Methods: Data on all ED visits among adults 20 years and older from 16 US states in summer months (May through September) for 2010 to 2018 were obtained from State ED all-payer claims databases. After determining the monthly number of ED visits in each county, the county-level monthly number of extreme heat days was determined. Extreme heat days were defined as any day with a maximum heat index ≥90°F (32.2°C) and in the 97.5 th percentile based on a county-specific historical period (1979-2007). CV ED visits were identified using ICD-10 diagnostic codes (I00-I99). A Poisson fixed effects regression model with county, year, and month fixed effects was estimated with monthly ED visits as the outcome and the monthly number of extreme heat days as the primary predictor of interest. Environmental, economic, and demographic variables were also included in the model. Excess ED visits were estimated as the difference between the number of visits, in each county, with the observed number of extreme heat days and the estimated number of visits if no extreme heat days had occurred. Results: There were approximately 91 million all-cause and 1.5 million CV ED visits across 985 counties during summer months in 2010 to 2018. The population-weighted, total median number of extreme heat days over the study period was 79 (IQR 63-98). From 2010-2018, each additional extreme heat day per month was associated with a 0.21% (95% CI 0.02-0.41, p =0.03) increase in monthly CV ED visits and a 0.20% (95% CI 0.06-0.35, p =0.006) increase in monthly all-cause ED visits. The estimated number of extreme heat associated excess CV ED visits over the study period was 5658.4 (95% CI 525.0-10791.9). The estimated number of excess all-cause ED visits was 329055.4 (95% CI 95625.4-562485.4) Conclusion: Extreme heat was associated with an increase in CV and all-cause ED visits in 16 states in the US between 2010 and 2018. As extreme heat events continue to increase, understanding how this will impact emergency departments and health systems across the country is important to be able to devise strategies to address the associated increase in utilization.
Abstract 4140451: Loss of Stem Cell Antigen-1 Worsens Aortic Remodeling in Angiotensin II-Induced Hypertension
Authors: Tao Wang, Abdul Momen, Mansoor Husain
Journal: Circulation (2024)

Background: Stem cell antigen-1 (Sca-1) marks progenitor cells that contribute to vessel remodeling by differentiating into vascular smooth muscle cells and related myofibroblasts. We previously demonstrated that Sca-1 is required for pro-fibrotic differentiation following arterial injury. Here, in a mouse model of experimental hypertension (HTN), we assessed the requirement for Sca-1 in aortic dysfunction and remodeling. Methods&amp;Results: Male and female mice homozygous for GFP knock-in/Sca-1 knockout (Sca1KI -/- ), heterozygous littermates (Sca1KI +/- ), and control GFP-labeled Sca-1 reporter mice (Sca1GFP), age 12-14-wk, were subjected to angiotensin II-induced HTN (Ang-II 1000 ng/kg/min) by osmotic mini-pump for 28d, or vehicle (0.9% saline). GFP + CD31 - CD45 - cells from Sca1KI -/- , Sca1KI +/-, and Sca1GFP represent progenitor cells with no-, partial-, or normal Sca-1 expression, respectively. Partial- or total loss of Sca-1 expression exacerbated aortic GFP + CD31 - CD45 - cell expansion, compared to Sca1GFP [Sca1KI -/- 32±7-fold change of vehicle vs. Sca1KI +/- 39±9 vs. Sca1GFP 5±1; n=11-13/group; p&lt;0.0001], suggesting disinhibited progenitor responses. Interestingly, Sca1KI -/- mice manifest blunted HTN in response to Ang-II [Sca1KI -/- 130±9 mmHg vs. Sca1KI +/- 159±8 vs. Sca1GFP 160±10; n=6-7/group; p&lt;0.01]. Partial- or total loss of Sca-1 worsened aortic dilation [Sca1KI -/- 1.25±0.06 mm vs. Sca1KI +/- 1.21±0.06 vs. Sca1GFP 1.04±0.05; n=6-7/group; p&lt;0.05], aortic wall thickness [Sca1KI -/- 105±9 μm vs. Sca1KI +/- 136±16 vs. Sca1GFP 82±5; n=6-7/group; p&lt;0.01], adventitial area [Sca1KI -/- 79±13 mm 2 vs. Sca1KI +/- 178±46 vs. Sca1GFP 51±6; n=6-7/group; p&lt;0.01], and aortic aneurysm formation [Sca1KI -/- 6/17 vs. Sca1KI +/- 6/20 vs. Sca1GFP 2/18]. Underlying these differences, in cultured progenitor cells subjected to TGFβ, pro-fibrotic CD44 expression increased 3.4-fold in Sca-1 deficient progenitors vs . wild-type [54±9% vs. 16±2; n=2-3/group]. Concomitantly, stem cell marker PDGFRα expression on these cultured progenitors was reduced [0.4±0.1% vs. 11±1; n=2-3/group], suggesting depletion of progenitors skewed towards a pro-fibrotic lineage. Conclusion: Partial or complete loss of Sca-1 worsens aortic remodeling in Ang-II HTN by increasing progenitor expansion and pro-fibrotic contributions. These data highlight a critical role for vascular Sca-1 expression, which may inform a novel approach to preventing and treating HTN and associated vascular remodeling.
Abstract 4140612: Non-canonical CDC20 signaling promotes smooth muscle and adventitial fibroblasts hyper-proliferation and remodeling in pulmonary arterial hypertension
Authors: Tapan Dey, Dmitry Goncharov, Iryna Zhyvylo, Derek Lin, Maanvi Shah, Aisha Saiyed, Sanjana Neeli, Tatiana Kudryashova, John Greenland, Paul Wolters, Lifeng Jiang, Elena Goncharova
Journal: Circulation (2024)

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs) due to hyper-proliferation and apoptosis resistance of resident PA cells, the mechanisms of which are not completely understood. Specifically, the role of cell division cycle protein 20 (CDC20), a key regulator of cell cycle, canonically acting as an APC/C E3 ubiquitin ligase activator and substrate recruiter, is not known. Goals: To determine the role of CDC20 in PA remodeling in PAH. Methods: RNAseq, immunoblot, immunohistochemistry, proliferation, apoptosis assays; SU5416/Hypoxia (SuHx) mouse model of PH. Results: CDC20 was over-expressed in lungs, small PAs, isolated PA smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs), but not endothelial cells from PAH patients compared to non-diseased controls. siRNA CDC20 significantly reduced proliferation and induced apoptosis in PAH PASMCs and PAAFs. This effect was re-capitulated by CDC20 inhibitor apcin (blocks binding of CDC20 with substrates); however, pan-APC inhibitor proTAME had no effect. Over-expression of CDC20 in PAH PASMCs and PAAFs was correlated with over-accumulation of its substrate, pro-proliferative protein securin, and deficiency of pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM). Depletion of CDC20 with specific siRNA, but not treatment with proTAME, dramatically reduced securin and restored BIM protein levels in PAH PASMCs and PAAFs. Apcin restored BIM protein content in human PAH PASMCs, and siRNA BIM protected PAH PASMCs from apcin-induced apoptosis. Pharmacological targeting of CDC20 with specific PROTAC degrader CP5V down-regulated CDC20 and securin, restored BIM, inhibited hyper-proliferation, and induced apoptosis in PAH, but not in control PASMCs, and reversed SuHx-induced pulmonary vascular remodeling, PH, and right ventricular hypertrophy in male and female mice. Conclusions: Collectively, our data demonstrate that CDC20 is overexpressed and supports proliferative, apoptosis resistant PASMC/PAAF phenotype in PAH via non-canonical APC/C independent upregulation of pro-proliferative securin and downregulation of pro-apoptotic BIM. Our data also suggest that targeting CDC20 could represent a novel potentially attractive strategy to suppress PA resident cells proliferation and reverse established PAH.
Abstract 4140400: Risk of Atherosclerotic Cardiovascular Disease after Cancer Diagnosis: Findings from Three Prospective Cohort Studies
Authors: Qiang Liu, Qiaoli Wang, Molin Wang, Jing Wang, Mingyang Song, Edward Giovannucci
Journal: Circulation (2024)

Background: Evidence linking cancer diagnosis to risk of incident atherosclerotic cardiovascular disease (ASCVD) remains inconclusive. Research Questions: Do cancer patients experience a higher risk of ASCVD independent of shared risk factors? How does the risk of ASCVD evolve over time following a cancer diagnosis? Aims: To determine the association between cancer diagnosis and subsequent risk of ASCVD (coronary heart disease and stroke), and its trajectory over time after cancer diagnosis. Methods: We prospectively followed 108,689 women in the Nurses’ Health Study (NHS) (1984-2020), 113,608 women in the NHSII (1991-2019) and 45,327 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) who were free of ASCVD and cancer at baseline. We conducted multivariable-adjusted time-varying Cox proportional hazards models to assess ASCVD risk following individual cancer diagnosis. We conducted restricted cubic spline analyses to assess the varied ASCVD risk over time after cancer diagnosis. Results: During up to 36 years of follow-up, 48,069 incident cancer cases and 32,592 ASCVD cases were documented. After adjusting for shared risk factors, ASCVD risk was significantly elevated after diagnosis of cervical cancer (HR: 1.63; 95%CI: 1.10-2.42) and Hodgkin lymphoma (HR: 2.17; 95%CI: 1.42-3.30) compared with non-cancer participants. Prostate cancer diagnosis was associated with a lower ASCVD risk (HR: 0.91; 95% CI: 0.85-0.97). Breast cancer diagnosis was associated with decreased ASCVD risk during the first 15 years after diagnosis, but this risk gradually increased afterward (P =0.02). Bladder cancer was associated with increased ASCVD risk during the first 10 years and attenuated afterward (P=0.03). The risk of ASCVD increased over time after cancer diagnosis among patients with cancers of colorectum (P=0.003), lung (P=0.007), and endometrium (P=0.05). No significant association with ASCVD risk was observed for cancers of oral cavity and pharynx, sarcoma, melanoma, kidney, thyroid, leukemia, or ovary. Results were consistent across sensitivity analyses. Conclusions: Increased ASCVD risk was observed for patients diagnosed with cervical cancer or Hodgkin lymphoma, independent of shared risk factors. ASCVD risk trajectories varied over time after diagnosis according to different cancer types. These findings support a need for tailored ASCVD screening among cancer survivors based on specific cancer types and post-diagnosis durations.
Abstract 4140516: Systemic Inflammation Increases 30-Day Mortality of Patients with ST-Segment Elevation Myocardial Infarction
Authors: Jorge Cuéllar Vargas, Perla Lizeth Torres Ramirez, Eduardo Malchan, Diego Araiza, Jorge Daniel Sierra Lara Martinez, Jose Luis Briseño, Rodrigo Gopar-Nieto, Alexandra Arias, Héctor González Pacheco
Journal: Circulation (2024)

Background: The inflammatory response plays a crucial role in various aspects of acute coronary syndrome. However, there is limited data associating a validated inflammation risk score and overall mortality prediction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Hypothesis: We hypothesize that patients with STEMI exhibiting a severe inflammatory profile undergoing primary PCI have a higher incidence of all-cause mortality within 30 days. Methods: This retrospective cohort study obtained from the Coronary Care Unit of a tertiary center in Mexico, included 2,473 patients with acute STEMI who underwent pPCI between October 2005 and December 2023. We employed an inflammation score which comprises: high-sensitivity C-reactive protein (≥ 13.0 mg/L), white blood cell count (≥ 9.3 x10 3 /µL), and serum albumin level (≤ 3.6 g/dL) upon admission. We categorized systemic inflammation into four distinct levels. Mortality risk across these cohorts was compared using the Kaplan-Meier method. Results: The cohort included 248, 1035, 851, and 339 patients with no, mild, moderate, and severe inflammation, respectively. A significant proportion of the sample (76.3%) displayed mild to moderate inflammation, underscoring its prevalence in the studied population. Notably, 13.7% exhibited severe inflammation, potentially indicating high-risk groups. At the 30-day follow-up, patients with severe inflammation exhibited the highest mortality rates ( Image 1 ; 1.2% vs. 2.5% vs. 5.4% vs. 13%, respectively; Log-rank p&lt;0.001). The hazard ratio for mild inflammation is 2.07 (95% CI, 0.605-7.08; p=0.2), for moderate inflammation it is 4.47 (95% CI, 1.36,-14.69; p&lt;0.05), and for severe inflammation it is 10.73 (95% CI, 3.65-31.27; p&lt;0.0001) compared to the no inflammation group. Conclusions: The observed prevalence of inflammation across the studied population suggests a prevailing inflammatory trend influenced by underlying medical conditions, social factors and the STEMI process itself. We suggest a noteworthy association between heightened systemic inflammation during the acute phase of STEMI and increased overall 30-day mortality risk in patients undergoing pPCI.
Abstract 4139767: Automated IVUS Image Analysis for Cardiac Allograft Vasculopathy Surveillance in Heart Transplant Recipients
Authors: Antoinette Birs, Wenzhou Lyu, Lawrence Ang, Eric Adler, Ehtisham Mahmud, Francisco Contijoch
Journal: Circulation (2024)

Background: Cardiac allograft vasculopathy (CAV) is a heterogenous and poorly understood process of immune and non-immune factors occurring within the coronary artery and a leading cause of graft failure in heart transplant recipients. Intravascular ultrasound (IVUS) is used as an adjunct to angiography to significantly increase the sensitivity for detection disease, however by current standards &lt; 1% of IVUS images are graded for maximal intimal thickness (MIT) or scored for severity of CAV. The majority of IVUS frames remain unanalyzed. Aims: Demonstrate the application of pre-trained DeepIVUS machine learning model to annotate IVUS images obtained from transplant patients, establishing the accuracy of this tool in a new patient population. Methods: We reviewed 963 clinically annotated IVUS frames from heart transplant recipients, 706 were selected after screening for completeness. DeepIVUS was used to segment the frames and create predictions of the vessel lumen, plaque area and intimal thickness (IT) measurements around the entire vessel lumen. To compare with expert annotations, typically a single caliper measurement, the 90th percentile value of DeepIVUS-predicted IT was used. A confusion matrix was used to assess the model's ability to accurately classify predicted and true IT values, utilizing a threshold of 0.5 mm. Results: In 163/706 frames (23.1%), DeepIVUS labeling resulted in segments with jagged or non-physiologic shapes. These were automatically discarded using a quantitative ovalness criteria, Figure 1. Agreement between DeepIVUS predicted MIT and expert measured MIT in the remaining 543 frames yielded a strong Pearson correlation coefficient of 0.81 with an R2 of 0.65, Figure 2A. The linear fit was used to determine the DeepIVUS IT cutoff (0.554mm) which corresponded to clinical cutoff of 0.5mm. Using this value, DeepIVUS correctly classified 86.6% of frames (sensitivity 85.1%, specificity 87.9%, aF1 0.86), Figure 2B. Conclusion: We present a first use applcation of a pre-trained Deep IVUS image analysis in a transplant population demonstrating good agreement with expert clinical annotation. In current practice, a small fraction of images from each IVUS study are annotated. With an ovalness criteria providing quality control, DeepIVUS may be applied to non-annotated frames, allowing significantly more frames per IVUS study to be analyzed. Future studies are warranted to understand the prognostic capabilities of these automated annotations.
Abstract 4140600: Safety and Efficacy of Left Atrial Appendage Occlusion Procedure for Patients with Nonvalvular Atrial Fibrillation and Prior Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Veda Chanda, Vinicius Bittar, Pedro Carvalho, Philippe Garot
Journal: Circulation (2024)

Background: Patients with nonvalvular atrial fibrillation (AF) and a history of intracranial bleeding while on anticoagulant therapy commonly undergo left atrial appendage occlusion (LAAO) to prevent thromboembolic events. Despite being suitable candidates for LAAO, treatment for this patient population is underrepresented in clinical trials. Methods: PubMed, Cochrane, and Embase databases were systematically searched for studies reporting clinical outcomes after LAAO in patients with prior intracranial bleeding. Pooled incidence data were presented as mean percentages with 95% confidence intervals (CI) using a random-effects model. Results: A total of 20 observational studies were included comprising 1,945 patients with nonvalvular AF and prior intracranial bleeding receiving LAAO. The mean age was 73.2 years, 35.2% were women, 49.8% received Watchman device. The mean CHA 2 DS 2 -VASc was 4.48 and the mean HAS-BLED was 3.74. In patients with prior intracranial bleeding, the LAAO procedure was associated with an all-cause mortality pooled incidence rate of 4.42% (95% CI 2.40-8.02; I 2 =81%, Figure 1A), major bleeding rate of 3.93% (95% CI 2.43-6.30; I 2 =54%, Figure 1B), device-related thrombosis rate of 1.46% (95% CI 0.83-2.66; I 2 =0%), peri device leak rate of 4.70% (95% CI 1.61-12.97; I 2 =86%), and stroke rate of 3.48% (95% CI 2.14-5.63; I 2 =47%). Conclusion: This meta-analysis of 20 studies found that, in patients with history of intracranial bleeding receiving LAAO, the incidence of clinical outcomes is comparable to the overall population undergoing LAAO.
Abstract 4140468: Tet Methylcytosine Dioxygenase 2 mutation drives a global hypermethylation signature in patients with pulmonary arterial hypertension resulting in a common T cell phenotype.
Authors: Charles Hindmarch, Francois Potus, Ruaa Al-Qazazi, William Nichols, Michael Pauciulo, Michael Rauh, Stephen Archer
Journal: Circulation (2024)

Background: Epigenetic changes in gene expression due to DNA methylation regulate pulmonary vascular structure and function. Genetic or acquired alterations in DNA methylation or demethylation promote development of pulmonary arterial hypertension (PAH). However, the DNA methylome signature of human PAH and its transcriptomic consequences are unknown. Methods: Reduced Representation Bisulfite Sequencing was used for epigenome-wide mapping of DNA methylation in whole peripheral blood of 10 healthy people and 20 age/sex matched PAH patients from the PAH Biobank. We used whole-exome sequencing to identify two PAH cohorts, one free of mutations of know PAH-associated gene variants, and a second with mutations of TET2 , a newly identified PAH gene that encodes TET2, which mediates DNA demethylation. Results: Patients carrying TET2 mutations had greater DNA CpG methylation compared to mutation-free PAH patients, who themselves had increased methylation compared to controls. Differentially Methylated Regions (DMR) were more common in patients with PAH with TET2 mutations (1,135 DMR) than without mutations (260 DMR). In a public, blood-derived, PAH transcriptomic dataset, we assayed for transcript downregulation of genes that were hypermethylated in our cohort. 161 TET2 DMRs (38 of which were common to PAH without TET2 mutation) corresponded to downregulated transcripts. Functional analysis of the hypermethylated genes in TET2 patients revealed similar conserved functions, related to T cell differentiation and metabolism. Functional comparison of the 38 hypermethylated genes found in both PAH cohorts and the 161 hypermethylated genes unique to TET2 mutation also revealed regulation of T cell pathways. The most hypermethylated and downregulated genes was transcription factor 7 (TCF7), a regulator of T cell differentiation, which would be predicted to promote inflammation. Conclusion: Pan-chromosomal hypermethylation in PAH is greatest in patients with TET2 mutations. Gene hypermethylation may contribute to hallmarks of PAH, including alterations in immune function, T cell differentiation, and metabolism.