tbuckley/cabot-search huggingface dataset:
Abstract 4143742: A Tale of Two Surgeries: Single Stage Versus Two Staged Approach to Creating an Ovine Model of Fontan Palliation
Authors: Jennifer Kievert, Joshua Spiess, Cameron DeShetler, Satoshi Yuhara, Tatsuya Watanabe, Michael Jimenez, Aymen Naguib, Christopher McKee, Andrew Yates, Adrienne Morrison, Kirsten Nelson, Eric Heuer, Toshiharu Shinoka, christopher breuer, Sergio Alejandro Carrillo, John Kelly
Journal: Circulation (2024)

Introduction: Children born with single ventricle heart disease must undergo Fontan palliation. The lack of chronic preclinical animal models has limited the study of the significant end-organ complications that reduce the quality and duration of life. Here, we explore surgical strategies to improve animal survival in a chronic model of Fontan palliation. Methods: Sheep were divided based on the surgical approach: single stage Fontan (SS) versus staged Fontan. Controls were age/sex matched to the surgical cohort. The SS surgery consists of the Glenn, direct anastomosis of the SVC to the main pulmonary artery (MPA), and the Fontan, IVC connection to the MPA using a Gore-Tex conduit. Stage palliation consists of two stages. During stage 1 (S1), the IVC is connected to the MPA. A year later, stage 2 (S2) Glenn surgery is completed. Early post-op hemodynamics were monitored for 2 weeks through daily blood gases, an implanted telemetry device, and chest tube output. Results: SS had 5/6 sheep survive. S1 had 8/9 sheep survive (7/9 sheep continued to S2). S2 had 3/7 sheep survive. The trend in heart rate was not significantly different across the groups. However, we note a trend of an increase in heart rate in all groups on post-operation day (POD) 3 (144.90±20.72 BPM), which normalized POD10 (118.63±23.84 BPM) (p=0.006). Similarly, lactate peaked on POD0 (3.37±2.53mmol/L) and normalized POD2 (0.59±0.20 mmol/L) (p=0.0003) with no significant difference across groups. Creatine increased (SS) 1.7-fold (p=0.016) and (S2) 1.4-fold (p=0.032) from PO to POD1 and normalized by POD14. There was no significant elevation in creatine in S1. The chest tube output was not significantly (p=0.270) different across SS (4827.83±435.71 mL (11.6 days)), S1 (3305.33±1086.18 mL (10.5 days)), and S2 (4056±1890.26 mL (7 days)). Conclusions: We have demonstrated a similar clinical course for both surgical approaches of our ovine model with animals alive 1 to 3-year(s) post-operation. Future studies will follow the single stage approach given the improved animal survival and reduced surgical complexity. The ovine surgical model will allow the study of Fontan associated end-organ complications and be a testbed for potential curative solutions.
Abstract 4143791: Second Chances: Outcomes of Left Atrioventricular Valve Re-intervention Following Initial Repair of Atrioventricular Septal Defect
Authors: Mario O'Connor, Catherine Stauber, Neil Venardos, Charles Fraser, Carlos Mery, Andrew Well
Journal: Circulation (2024)

Background: Outcomes after initial atrioventricular septal defect(iAVSD) repair are excellent in the current era. The need for left atrioventricular valve(LAVV) intervention and further reinterventions after iAVSD repair are common and poses significant clinical and surgical challenges. Data on the outcomes after initial LAVV repair remain limited. Research Question / Hypothesis: What is the incidence and outcomes of LAVV reintervention after initial LAAV repair following iAVSD repair? Methods: Retrospective review of the Pediatric Health Information System from 1/2004-12/2023. All patients who underwent AVSD repair were included. LAVV reintervention was defined as LAVV repair or replacement after iAVSD repair. ICD 9/10 codes were used to identify diagnoses and procedures. Results: A total of 7,745 patients underwent AVSD repair. Following iAVSD repair, 503(7%) required LAVV reintervention. Of those, 292(58%) were White Non-Hispanic, 310(62%) female, 255(51%) government insured, and 267(53%) had Down syndrome. Median age was 4.3[2.9-6.7] months at iAVSD repair[cm1] . 405(81%) underwent LAVV repair and 98(20%) replacement. 127(31%) had LAVV repair and 26(27%) had LAVV replacement during the same admission as iAVSD repair. Of the 503, 73(15%) had a second reintervention; 19(26%) had a repeat LAVV repair and 54(74%) LAVV replacement. Freedom from a second reintervention at 15 years was 77%(95%CI:72.1-82.2). Of the 98 patients that underwent initial replacement, older age at initial valve replacement was associated with a decreased risk for second replacement (HR:0.78;95%CI:0.65-0.93,p=0.007). Freedom from re-replacement at 15 years was 44.1%(29.3-67.6) and differed by age at initial replacement.(Figure 1.) Conclusion: LAVV reintervention after iAVSD repair is common and frequently followed by a need for additional LAVV reintervention. Need for early LAVV repair is associated with increased risk of further interventions. These data reinforce the chronic nature of LAVV pathology in AVSD and helps inform counseling for families and patients.
Abstract 4143704: Systemic Arterial Aneurysms in Kawasaki Disease: An Important Evidence Gap
Authors: William Orr, Geetha Raghuveer, Michael Portman, Audrey Dionne, Marianna Fabi, Nilanjana Misra, Balasubramanian Sundaram, Mona El Ganzoury, Seda Tierney, Deepa Prasad, Simon Lee, Matthew Elias, Tyler Harris, Ana Caro, Kambiz Norozi, Daniel Mauriello, Kimberly McHugh, Sean Lang, Cedric Manlhiot, Brian McCrindle
Journal: Circulation (2024)

Introduction: Non-coronary artery systemic arterial aneurysms (SAA) are a rare and under-reported sequelae of Kawasaki disease (KD), for which data and guidance are limited. Methods: A survey was sent to members of the International KD Registry (IKDR) regarding their experiences and practices with SAA in KD patients. For comparison, a systematic review was conducted following PRISMA methodology; after evaluation, a total of 21 studies with 75 patients total were included. Results were compared qualitatively. Results: Surveys were completed by 48 (56%) of 86 IKDR investigators; 35 (73%) respondents had &gt;10 years of experience caring for KD patients. Experience with SAA was limited, with 33% not having cared for a patient with SAA. Reported screening practices included 81% screening only patients with coronary artery (CA) involvement, 8% reporting screening all patients with KD, and with 11% using other criteria. The degree of CA involvement influenced screening, with 56% screening only those with giant CA aneurysms, 20% also small/medium aneurysms, 6% included dilation and 18% not using any specific CA criteria. Additional factors reported included multiple or rapidly expanding CA aneurysms, clinical features such as prolonged/persistent fever, progressing/persistent elevation of inflammatory markers, and resistance to standard treatment. These screening practices were somewhat concordant with the characteristics of patients with SAA reported in the literature ( FIGURE ). Initial preferred assessment method was CT angiography for 48%, ultrasound 28% and MRI for 24% of respondents. In contrast, SAA reported in the review were most commonly assessed with conventional coronary artery angiography. From the review, SAA were associated with a high rate of regression (62-93%). Longer-term complications reported included SAA thrombosis, calcification, stenosis, occlusion and collateral formation. Clinical and management factors associated with SAA outcomes were not defined. Conclusion: While the development of SAA is a known but rare complication of acute KD, there remains a gap in evidence as to which patients are at risk, best practices for screening and management, and outcomes. Protocol driven cohort studies are needed.
Abstract 4143675: The epigenetically regulated transcription factor ZBTB16 protects against cardiac aging
Authors: Julian Wagner, Kathrin Stilz, Lukas Tombor, David Rodriguez Morales, Simone-franziska Glaser, Ariane Fischer, Katja Schmitz, Michail Yekelchyk, Thomas Braun, Andreas Zeiher, Stefanie Dimmeler
Journal: Circulation (2024)

Aging is a major risk factor for cardiovascular diseases contributing to the progressive deterioration of heart function. Since the vascular niche was shown to maintain cardiac homeostasis, we explored the epigenomic and transcriptional circuits driving endothelial cell (EC) impairment with aging. Analysis of chromatin accessibility by snATAC-seq and gene expression by RNA-seq of hearts from 18- to 20-month-old mice revealed a significant reduction in chromatin accessibility and expression of the zinc finger transcription factor ZBTB16, which was also confirmed in aged human hearts. Haploinsufficiency of Zbtb16 reduced diastolic function at 3 months of age and was associated with typical hallmarks of cardiac aging, such as hypertrophy, fibrosis, decreased innervation, elevated perivascular senescence, and lower capillary density. In vitro studies confirmed the crucial role of ZBTB16 in endothelial cells. Silencing of ZBTB16 impaired EC proliferation, migration, and network formation while inducing senescence. RNA-seq from ZBTB16-silenced EC and snRNA-seq of hearts from Zbtb16+/- mice further showed an induction of secreted senescence-associated secreted proteins and several growth factors. To assess a potential effect of ZBTB16 on the paracrine communication, we performed co-culture experiments with fibroblasts, cardiomyocytes and nerves. Indeed, supernatants of ZBTB16 -silenced ECs induced activation of cardiac fibroblasts, while ZBTB16 overexpression in long-term cultured ECs prevented paracrine fibroblast activation. Supernatants of ZBTB16 silenced ECs additionally induced cardiomyocyte hypertrophy and reduced neuronal sprouting. In silico ligand-receptor analysis additionally confirmed the augmented interaction of EC and fibroblasts in vivo and showed and increased PDGFB signaling between the two cell types. Neutralizing antibodies against PDGFB attenuated the effects of conditioned ZBTB16 -repressed EC medium on fibroblasts. Using chromatin-immunoprecipitation-sequencing, we further identified ZBTB16 targets, which include the nuclear receptor-interacting protein 1, which mediates PDGFB expression and paracrine fibroblast activation. In conclusion, ZBTB16 is a master regulator of cardiac aging. Its reduction induces a pro-inflammatory and pro-fibrotic endothelial cell secretome, which affects fibroblast, cardiomyocytes and nerves in vitro. These findings highlight the role of ZBTB16 in maintaining vascular niche functions during aging.
Abstract 4143515: Microbubble Cavitation Under Ultrasound Causes Microvessel Deformation at Mega-Hertz Frequency: Insights into Microvascular Mechanics
Authors: Sae Jang, Cheng Chen, Xucai Chen, Brandon Helfield, Flordeliza Villanueva
Journal: Circulation (2024)

Background: There is growing interest in understanding microbubble ( MB ) behavior under ultrasound ( US ) in complex in vivo environments, to optimize safety and efficacy for various clinical applications, e.g. , large molecule drug delivery, temporary blood-brain-barrier opening, and thrombus disintegration. However, there have been few mechanistic in vivo studies due to the challenges of visualizing vibrating MBs in the circulation at high temporal resolutions. Our study elucidates MB interactions with surrounding microvessels using ultra-fast intravital imaging of the rat cremaster muscle. Hypothesis: MB vibration-induced stress deforms surrounding microvessels in vivo. Deformations are influenced by not only the US parameters, but also the biomechanical properties of the vessel wall. Methods: Definity® was injected via the femoral artery of anesthetized rats and imaged in externalized cremaster muscle using an ultrafast microscope (up to 12 Mfps). Concurrently, a single US pulse of 6-10 cycles [1 MHz, peak negative pressures ( PNP ) 0.5-2.0 MPa] was delivered. Images were analyzed to calculate MB and vessel dimensions and to perform Fourier analyses. Stress-strain curves were generated using normal stress exerted by the MB (derived from the linearized Euler’s equation) and measured circumferential vessel strain (Diameter/initial Diameter-1). Results: MBs expanded in both circular and elliptical shapes (Fig 1A), and vibrated nonlinearly under US. Vessels vibrated in-phase with the MBs at higher PNP (Fig 1B). Fourier analyses revealed nonlinear vessel vibration (Fig 1C) at fundamental and harmonic US frequencies. Calculated normal stress exerted by the MB of three MB-vessel pairs displayed linear relationships with measured circumferential vessel strain (Fig 1D), with slopes (representing Young’s modulus, or stiffness) between 0.6-1.7 MPa. Conclusions: We demonstrate, for the first time, microvascular harmonic behavior in response to MB vibration under US; the associated bioeffects warrant further investigation. Finally, we introduce a novel method for measuring in vivo microvessel stiffness using MBs as mechanical probes, where vessel stiffness is represented by the slope of the presented stress-strain curve.
Abstract 4143583: Impact of Heart Failure Readmission in HeartMate 3 LVAD Recipients
Authors: Flavia Tejada Frisancho, Zhi Li, Liza Shaban, Ajay Kadakkal, Michael Hockstein, Richa Gupta, Shawn Glocker, Miguel Pinilla-Vera, Maria Rodrigo, Keki Balsara, Farooq Sheikh, Phillip Lam
Journal: Circulation (2024)

Background: Despite the survival benefit of durable left ventricular assist device (LVAD) therapy in patients with advanced heart failure, hospital readmissions due to heart failure (HF) remain a significant morbidity and determinant of quality of life. Objective: This study aimed to characterize patients with and without a HF readmission and determine its clinical impact following HeartMate 3 (HM3) LVAD implantation. Methods/Approach: A single-center retrospective analysis was performed of patients who underwent HM3 LVAD implantation from January 1, 2015 to December 31, 2021. Patients with and without a HF readmission were compared based on 53 variables. Cox proportional hazard model was performed to investigate the association between HF readmission and survival. Results: A total of 273 patients underwent HM3 implantation. The average implant age was 58 years, 75% were men, and 78% were Black patients. Of the 273 patients, 78 (29%) had a HF readmission and 58 (74%) occurred within the first year following implant. Predictors of a HF readmission include pre-implant diabetes mellitus (HR 1.96; 95% CI, 1.2-3.2; p=0.007), pre-implant body mass index (HR 1.05; 95% CI, 1.02-1.09; p&lt;0.001) and post implant BUN (HR 1.02; 95% CI, 1-1.04; p=0.018). There was no significant difference in survival in patients with and without a HF readmission (multivariate-adjusted HR 1.44; 95% CI, 0.87-2.37; p=0.153; Figure) at long-term follow up (6 years). Conclusion: Readmissions for HF remain an opportunity for improvement in the care of HM3 LVAD patients. However, a HF readmission was not associated with an increased risk of death. Addressing comorbid conditions and identifying strategies to optimize LVAD and HF management in this high-risk cohort warrant further exploration to improve clinical outcomes.
Abstract 4143621: Efficacy and Safety of Rivaroxaban and Lower Molecular Weight Heparin in Preventing Venous Thromboembolism in Cancer Patients; A Systematic Review and Meta-analysis.
Authors: Abhigan Shrestha, Ashok Adhikari, Anirudra Devkota, Aayush Shrestha, Syed Muhammad Muneeb Akhtar, Aman Goyal, Sajina Shrestha, Vikash Jaiswal
Journal: Circulation (2024)

Introduction: As per current guidelines, low molecular weight heparin (LMWH) has been commonly used as prophylaxis for venous thromboembolism in cancer patients. Directly acting anticoagulants (DOACs) having ease of administration, oral availability despite renal dysfunction, and possibly higher adherence, are also being used as an alternative to prevent venous thromboembolism Events (VTE) recently. In addition, rivaroxaban is among the first DOACs used in the prophylaxis for VTE. Hypothesis: This study intends to compare the efficacy and safety of rivaroxaban and LMWH (enoxaparin, dalteparin, and nadroparin) in preventing VTE in cancer patients. Methods: A comprehensive literature search was performed on PubMed, Embase, Scopus, and Cochrane libraries from inception until March 2024, with suitable Mesh terms. The random effects model was used to calculate the pooled Odds Ratio (OR) with their corresponding 95% confidence intervals (CI). A p-value of &lt;0.005 was considered statistically significant. Results: Four studies including two cohort studies and two Randomized Controlled trials (RCTs) with 1515 patients (rivaroxaban: 753 and LMWH: 762) with mean ages of 58.15 and 58.6 years respectively were included in the analysis. Up to 30 days after follow-up, the rates of VTE (OR, 0.38, 95% CI: 0.10 – 1.40, p=0.42), DVT (OR, 0.74, 95% CI: 0.48 – 1.16, p= 0.76) and major bleed (OR, 0.88, 95% CI: 0.36 – 2.14, p=0.26) were lower with rivaroxaban compared to LMWH. But, the minor bleeds (OR, 3.82, 95% CI: 1.76 – 8.29, p=0.38), clinically relevant non-major bleeding (CRNMB) (OR, 1.09, 95% CI: 0.11 – 10.79, p=0.16), bleeding (major + CRNMB) (OR, 1.47, 95% CI: 0.82 – 2.61, p=0.27), all-cause mortality (OR, 1.17, 95% CI: 0.70 – 1.96, p=0.54) were higher with rivaroxaban compared to LMWH. Conclusion: In cancer patients for the prevention of venous thromboembolism, rivaroxaban shows non-inferior efficacy and questionable safety profile as compared to LMWH. Further research needs to be done to confirm the above findings.
Abstract 4143528: HeartMap: An Integrated Cell Atlas of 2.6 million cells across 260 individuals
Authors: Yesh Datar, Mark Chaffin, Bridget Simonson, Patrick Ellinor
Journal: Circulation (2024)

Background: Single-nucleus RNA sequencing (snRNA-seq) is a powerful tool to define the cell-type specific transcriptional signature in health and disease. Although it has been applied to study many forms of cardiovascular disease, few resources exist to compare results across studies and disease states. Methods: We identified 9 studies from the literature with &gt; 10k nuclei, individuals &gt; 18 years, and non-diseased controls. Existing data was downloaded, similarly re-processed, aligned to the GRCh38 reference transcriptome, and aggregated for quality control. Sixteen versions of data integration methods were benchmarked with the single-cell integration benchmarking (scIB) package. Clustering analysis was conducted in SCANPY using established methods to identify global cell types and distinct cell states within cell types. Cell type and cell state labels were assigned to clusters based on differential expression testing using limma-voom. Compositional analysis was conducted using scCODA. Results: HeartMap contains 2,600,078 cells across 36,601 genes from 9 studies, 260 individuals, 7 disease states and normal controls, and 8 anatomical regions. The median age was 54 years (IQR: 17) and 40% were female. Benchmarking selected single cell annotated variational inference as the optimal integration method. Global clustering of all nuclei revealed 14 major cell types. At the sample level, after controlling for differences between studies, the strongest sources of variation in transcription included disease status, patient sex, and anatomical region of sample. To demonstrate the utility of this resource, we identified 10 distinct fibroblast sub-populations among ~580,000 fibroblast cells. Two sub-populations of activated fibroblasts show POSTN+COL22A1+ and POSTN+TNC+ enrichment in primary (DCM/HCM) and ischemic (ICM/AMI/CAD) cardiomyopathies, respectively. Validation using RNA-scope and immunofluorescence staining revealed peri-vascular patterns of TNC+ fibroblasts and interstitial patterns of COL22A1+ fibroblasts in diseased tissues. Conclusions: HeartMap provides a unique resource to the cardiovascular research community and provides additional insights into the transcriptional diversity in health and disease.
Abstract 4143475: Early Dementia Prediction Using Electrocardiogram: Insights from Variational Autoencoder-Derived Features
Authors: Yujeong Kim, Yu Rang Park, Woo Jung Kim, Dukyong Yoon
Journal: Circulation (2024)

Introduction: Dementia, characterized by cognitive decline and impaired judgment, imposes a significant economic burden due to its rising prevalence and high diagnostic costs. Recent research has linked dementia to various biomarkers, including cardiac biomarkers like heart rate variability. This study investigates the use of Variational Autoencoder (VAE)-derived features from electrocardiogram (ECG) data for predicting dementia, offering a cost-effective alternative to traditional diagnostics. Hypothesis: Features derived from VAE applied to ECG data can be utilized to predict dementia. Methods: ECG data from Sinchon and Yongin Severance Hospital, South Korea, were used to develop a VAE-based predictive model. Patients diagnosed with dementia and matched controls without dementia were included, using propensity score matching for age and gender. For the dementia-develop group, data from the 5 years preceding the first diagnosis were used; for the dementia-free group, the ECG date at the median age served as the index date. Each median ECG was processed through the VAE to derive 32 features. A Deep Neural Network (DNN) was used to predict dementia 5 years before the index date, with Sinchon data for training and Yongin data for testing. Trajectory analysis of VAE features revealed distinct trends between the groups. Results: The model achieved AUROCs of 0.749 (training) and 0.701 (testing), and AUPRCs of 0.490 (training) and 0.358 (testing). Further analysis of VAE-derived feature trajectories showed significant temporal patterns. ECG markers that increased markedly in the dementia-develop group as the index date approached were associated with QT interval differences and T-wave morphology variations. Conversely, markers that increased in the dementia-free group but decreased in the dementia-develop group were linked to ST wave differences and amplitude disparities (Figure1). These findings underscore the potential of VAE-derived ECG features to distinguish between dementia-develop and dementia-free individuals over time. Conclusion: The model using VAE-derived ECG features highlighted the potential of combining ECG data with advanced machine learning techniques for early dementia screening.