tbuckley/cabot-search huggingface dataset:
Abstract 12002: Predictors of ICD Implantation in Patients With Normal or Low-Normal Systolic Function and Coronary Heart Disease at Baseline
Authors: Natasha Cuk, Min Wu, Vinayaga Moorthy, Julie Pester, Susan Cheng, Sumeet S Chugh, Nancy R Cook, Christine M Albert
Journal: Circulation (2021)

Introduction: Few post-MI or CHD patients fulfill guideline-based criteria for ICD implantation; however, limited data exist regarding the proportion and predictors of patients who subsequently undergo ICD implantation during long term follow-up. Methods: PREDETERMINE [NCT01114269] is an ongoing, prospective, multicenter cohort of adults with CHD and mild-moderate left ventricular dysfunction (LVEF=35-50%) and/or history of MI not meeting guideline criteria for primary prevention ICD at inclusion based on LVEF and NYHA. ICD implantation events/indications were captured. Multivariable Cox regression was used to estimate the hazard ratios for the outcome of ICD implantation using demographic, clinical, ECG, and biomarker parameters as prespecified covariates. Results: In 5738 patients (mean age=64.4, 76.2% male, mean LVEF=52.1%), 293 ICD implantations (5.1%) occurred over a median follow-up of 7.3 years. Of these, 217 were for primary prevention, 65 for secondary prevention, and 11 for unclear indications. In age-adjusted models, patients who received an ICD differed according to several clinical, ECG, and biomarker parameters [Table]. After multivariable adjustment, male sex, HTN, prior CABG, contiguous Q waves on ECG, QRS duration &gt; 110 ms, and NT-proBNP levels were directly associated with ICD implantation, while age, LVEF and CRP were negatively associated [Table]. In multivariable models, ICD implantation was associated with a trend towards reduced mortality (HR=0.80; 95% HR, 0.62-1.03, P=0.08). Conclusion: In this long-term prospective cohort of CHD patients without ICD indications at baseline, 5% of the population underwent ICD implantation, which was associated with a trend toward reduced mortality. Several clinical factors were independently associated with ICD implant and may assist in the identification of subgroups of CHD patients at risk for worsening LV dysfunction and/or sustained ventricular arrhythmias.
Abstract 12890: Prognostic Value of Relative Flow Reserve by Hybrid <sup>13</sup> N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease
Authors: Keiichiro Endo, Takatoyo Kiko, Takeshi Shimizu, Yamaki Takayoshi, Hiroyuki Kunii, Kazuhiko Nakazato, Yasuchika Takeishi
Journal: Circulation (2021)

Background: 13 N-ammonia PET has been used to evaluate myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitatively. Relative flow reserve (RFR) was defined as the ratio of hyperemic MBF in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to examine the prognostic value of RFR in patients with coronary artery disease (CAD). Methods: We enrolled consecutive 66 patients with suspected CAD who underwent hybrid 13 N-ammonia PET/MRI. Under vasodilator stress with intravenous injection of adenosine, MBF and CFR were calculated from dynamic acquisition of 13 N-ammonia PET. RFR was calculated as the ratio of hyperemic MBF of a stenotic myocardial area to hyperemic MBF of a non-stenotic reference vascular territory. MRI images were simultaneously acquired with PET. Left ventricular ejection fraction (LVEF) was calculated from cine mode MRI. The end points were defined as composite of all-cause death, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure and coronary artery revascularization. Results: Over the median follow-up of 3.6 ± 1.3 years, there were 22 (33.3%) adverse cardiac events. Kaplan-Meier analysis demonstrated lower event free rates in patients with CFR &lt; 2.0 (P &lt; 0.01, Figure A) and RFR &lt; 0.81 (P = 0.022, Figure B), but not in those with stress MBF &lt; 1.34 (P = 0.295) and stress LVEF &lt; 55% (P = 0.187). Univariate Cox regression analysis showed that abnormal RFR (&lt; 0.81) was significantly associated with adverse events (HR 3.72, 95% CI 1.21-18.01, P = 0.02). Conclusion: RFR is a useful marker to predict cardiac adverse events in patients with CAD. It would be an alternative approach to perform only stress scan without rest scan to reduce radiation exposure and scan time.
Abstract P340: Histone Methyltransferase Smyd1a Protects Heart From Ischemic Injury By Regulating Mitochondrial Respiration
Authors: Marta Szulik, Steven Valdez, Maureen Walsh, Ryan Bia, Kathryn Davis, Emilee Horiuchi, Sean O'Very, Anil Laxman, Mickey R Miller, Li Wang, Garcia-Llano June, Christopher Tracy, Stavros G Drakos, Katsuhiko Funai, Dipayan Chaudhuri, Sihem Boudina, Sarah Franklin
Journal: Circulation Research (2021)

SMYD1a, a myosin-specific histone lysine methyltransferase, plays a major role in regulating disease-induced remodeling in the adult heart. Previously, we demonstrated that the inducible loss of this chromatin-bound enzyme is sufficient to induce cardiac hypertrophy and failure in vivo , which is preceded by downregulation of mitochondrial proteins involved in oxidative phosphorylation (OXPHOS), and reduction of mitochondrial respiration capacity. However, our most recent data in transgenic mice (TG) displaying inducible, cardiomyocyte-specific overexpression of SMYD1a show that these mice are protected from ischemic injury after permanent occlusion (PO) of the LAD manifested by reduced infarct size and cardiac dysfunction compared to littermate controls (WT), suggesting that SMYD1 plays a protective role in the heart and mitigates disease-induced remodeling. Additionally, global proteomic evaluation of cardiac tissue from TG mice showed unique expression of metabolic enzymes, including proteins from the electron transport chain, and our high-resolution mitochondrial respirometry analysis showed that overexpression of SMYD1a leads to increased oxygen consumption rates through Complex I and II. To further asses OXPHOS efficiency in TG mice we subjected them to permanent occlusion of the LAD and evaluated ATP production rates in isolated mitochondria from TG and WT mice, by measuring the molar amount of ATP produced per mole of atomic oxygen consumed (known as ATP:O ratio). Interestingly, we observed a significant increase in ATP:O ratio in TG mice 24h after PO suggesting that they are much more efficient at producing ATP. Finally, we show that the global regulation of mitochondrial respiration in TG mice occurs through transcriptional control of Ppargc1α . Our results confirm that cardiac expression of Ppargc1α was significantly reduced in WT mice (48h after PO) but maintained at basal levels in TG mice, which also corroborated with our ChIP-qPCR data showing SMYD1a binding to the Ppargc1α promoter and regulating its expression. Overall, these results show that SMYD1a can mitigate ischemic injury and adverse remodeling in the adult myocardium, which occurs through Ppargc1α expression and regulation of cardiac energetics and metabolism.
Abstract 11500: General Evaluation of the Aorta by Computed Tomography in a Latin Population
Authors: Mickael Henriques, Ryan Gouveia e Melo, André Peixoto, Ruy Fernandes e Fernandes, Augusto A Ministro, João Leitão, Daniel Caldeira, Luis Mendes Pedro
Journal: Circulation (2021)

Introduction: The normal diameter values of the aorta are controversial, dictate when aneurysmal disease develops and when it should be treated. They differ between populations implicating that the indications for treatment are not universal. The need arises for regional registries so that treatment may be personalized. However, there are no previous registries in a latin population. Therefore, we performed a population based study on aortic diameters based on CTs measures. Methods: Cross-sectional study based on retrospective analysis of random CTs performed during 2018 in the largest Portuguese hospital. Patients with aneurysms were excluded. Diameter was presented in millimeters using outer to outer wall measurements, in an anterior-posterior or transverse plane, perpendicular to the lumen center line. Diameter was adjusted for age and sex, and measured in the locations specified in table 1. Age was categorized in 3 groups: &gt;=50; 50-75; &gt;75. This project was submitted and approved by the Ethics Committee of our institution (ref336/20). Results: The mean age of the population analyzed was 64 years old (SD 17; min-max 18-98) and 53.3% were male. A total of 396 CTs were analyzed, and of these 45% had thorax, 97% had abdominal and 83% had pelvic imaging. Mean aortic and iliac diameter are presented in table 1 and were adjusted for age and sex. In all locations of the aorta, the diameter was significantly higher in men than in women, except for the ascending aorta in women under 50 (p&lt;0.001). Diameters increased with age and were significant for all age groups and measured locations (p&lt;0.001). We found intra and interobserver measures to be fairly agreeable (Cohen k : 0.21 and 0.24, respectively). Conclusions: We defined a set of normal values at key aortic locations. Age and sex significantly influenced these measures, while the dimensions follow a similar pattern through the vessel regardless of these factors. Table 1. Mean aortic diameter by location, age and sex.
Myocardial Infarction, Stroke, and Pulmonary Embolism After BNT162b2 mRNA COVID-19 Vaccine in People Aged 75 Years or Older
Authors: Marie Joelle Jabagi, Jérémie Botton, Marion Bertrand, Alain Weill, Paddy Farrington, Mahmoud Zureik, Rosemary Dray-Spira
Journal: JAMA (2021)

Nicola P. Klein, MD, PhD; Ned Lewis, MPH; Kristin Goddard, MPH; Bruce Fireman, MA; Ousseny Zerbo, PhD; Kayla E. Hanson, MPH; James G. Donahue, DVM, PhD; Elyse O. Kharbanda, MD, MPH; Allison Naleway, PhD; Jennifer Clark Nelson, PhD; Stan Xu, PhD; W. Katherine Yih, PhD, MPH; Jason M. Glanz, PhD; Joshua T. B. Williams, MD; Simon J. Hambidge, MD, PhD; Bruno J. Lewin, MD; Tom T. Shimabukuro, MD, MPH, MBA; Frank DeStefano, MD, MPH; Eric S. Weintraub, MPH
CD24/Siglec-10 "Don't Eat Me" Signal Blockade Is a Potential Immunotherapeutic Target in Mantle-Cell Lymphoma
Authors: Andrea Aroldi, Mario Mauri, Matteo Parma, Elisabetta Terruzzi, Marilena Fedele, Paola Perfetti, Federica Cocito, Luca Mologni, Roberto Chiarle, Rocco Piazza, Carlo Gambacorti-Passerini
Journal: Blood (2021)
TMOD-28. MYC GENERATES AGGRESSIVE MEDULLOBLASTOMA BY HSP90 PATHWAY ACTIVATION AND ARF SILENCING
Authors: Oliver Mainwaring, Holger Weishaupt, Sonja Hutter, Miao Zhao, Anna Borgenvik, Gabriela Rosén, Laura Breinschmid, Annemieke D Verbaan, Anders Sundström, Karl Annusver, Maria Kasper, Fredrik Swartling
Journal: Neuro-Oncology (2021)

Abstract Medulloblastoma, the most common malignant pediatric brain tumor, often shows amplification or overexpression of the MYC transcription factor and arises in the presence of a functional p53 tumor suppressor protein. To elucidate the mechanism behind this inexplicable tumor development we generated an inducible, immunocompetent transgenic mouse model of MYC-expressing medulloblastoma. Aggressive tumors developed clonally in the presence of an unaltered p53 gene that molecularly resembled Group 3 medulloblastoma. Compared to MYCN-expressing medulloblastoma driven from the same promoter, we instead discovered pronounced and MIZ1-independent silencing of the ARF suppressor, which was also suppressed in MYC-amplified as compared to MYCN-amplified human medulloblastoma. While MYCN-driven tumor malignancy was more sensitive to ARF depletion, it dramatically increased metastatic spread of MYC-driven tumors. DNMT inhibition could restore ARF levels in MYC-expressing tumors but did not show any therapeutic advantage in tumors in vivo. Bioinformatics analysis further showed a strong correlation of the HSP90 pathway with MYC in human Group 3 MB and in the MYC-driven mouse model. The HSP90 inhibitor Onalespib showed significant selectivity for targeting MYC-driven as compared to MYCN-driven tumors. The drug promoted ARF restoration and increased the survival in our animal model which suggests that it could be potentially used in the treatment of MYC-driven ARF-silenced brain cancer patients.
Abstract 10811: Hemodynamic Optimization of Left Ventricular Assist Devices During Right Heart Catheterization Ramp Studies
Authors: Alexander Hajduczok, Katherine Julian, Carly Maucione, Brinnae Bent, Laura DiChiacchio, Omaima Ali, John Boehmer
Journal: Circulation (2021)

Background: Studies have shown that hemodynamic LVAD ramp studies can be used to optimize speeds and improve clinical outcomes, yet these studies lack external validation. Methods: 470 LVAD patients, including 3 LVAD subtypes, were retrospectively analyzed and 53 ramp studies were identified. Measurements (RA, mean PA, PCWP, and CI) were taken at speeds +/- 20% of the manufacturer recommended set speed for HM2, HM3, and HVAD devices. Primary outcomes were all-cause and heart failure (HF) hospitalizations in the 6-month period pre- and post-ramp study. Secondary outcomes included final LVAD speed and hemodynamic measurements following ramp study. Time to first hospitalization and cumulative incidence rate of all-cause and HF hospitalization were reported. Results: Baseline characteristics of 53 studies included: mean age of 60.1 (+/- 10.9), 84.9% male, 56.6% ischemic etiology, 71.7% destination therapy, and average NYHA class and INTERMACS of 2.5 (+/- 0.7) and 5.9 (+/- 1), respectively. 38 of 53 studies (71.7%) showed PCWP decompression &gt;20%, with average PCWP decompression of 51.2% (+/- 21.0%), and CI increase of 22.5% (+/- 18.7%). Optimal LVAD speeds were chosen to maintain CI &gt; 2.2, PCWP &lt; 15 and minimize RAP, in the absence of suction events. 31 (58.5%) of studies resulted in an LVAD speed change and 16 (30.2%) of studies resulted in diuretic change. All-cause and HF hospitalizations were significantly decreased in the 6-months following ramp studies compared the 6-months pre-ramp (total days hospitalized for all causes: 12.0 vs 26.6, p=0.0002; total days hospitalized for HF, 4.8 vs 22.1, p=0.00003). Speed changes were associated with a nonsignificant improvement in time to first hospitalization. Conclusion: This externally validates previous data suggesting that LVAD hemodynamic ramp studies decrease hospitalizations. Larger, prospective studies may elucidate specific hemodynamic targets to improve mortality and reduce rehospitalizations.
Abstract 11985: Association of GlycA and Progression of Coronary Artery Calcification: The Multi-Ethnic Study of Atherosclerosis
Authors: Venkat Sanjay Manubolu, Daniel A Duprez, David R Jacobs, James D Otvos, Moyses Szklo, Matthew Budoff
Journal: Circulation (2021)

Background: GlycA, a composite biomarker of systemic inflammation, predicts cardiovascular morbidity and mortality. Despite growing evidence regarding the association of GlycA and CVD, there are no data about the association of GlycA with coronary artery calcium (CAC), a marker of subclinical atherosclerosis. Objective: To investigate the relationship between GlycA levels and progression of CAC. Methods: MESA is a multiethnic cohort study of 6814 men and women aged 45-84 years, free of clinical CVD at baseline. Serum level of GlycA was measured by nuclear magnetic resonance (NMR) spectroscopy at baseline. CAC score was assessed by CT at baseline and follow up using either a cardiac gated electron beam CT scanner or 4-16 detector CT systems. Progression of CAC from baseline was defined as average yearly change in Agatston score &gt;= 3 for CAC 0 to 100 and &gt;=10% for CAC &gt;100. Mean follow up period was 9.6±0.6 years. Multivariate regression analysis was performed adjusting for atherosclerotic risk factors. Results: Cross-sectional mean GlycA level, stratified by race/ethnicity, was higher in those with CAC &gt; 0 compared to no CAC across all race/ethnicity groups and in both men and women (Fig1A). In regression analysis, the progression of annualized CAC was associated with higher baseline GlycA levels (Fig1B). Analysis was stratified due to interaction between GlycA and BMI (Fig2). In multivariable adjusted models, a one unit increase in GlycA was related to 0.23% higher average annual CAC change in normal BMI (p=0.002). In those who were excess weight (BMI &gt;25) one unit increase in GlycA was associated with a 0.04% yearly average CAC change, after adjusting for covariates(p=0.07). Conclusion: Participants with higher baseline GlycA levels have CAC &gt;0 as compared to lower baseline GlycA levels. The annualized progression of CAC is also higher in participants with baseline elevated GlycA levels. This association was statistically significant in participants with normal BMI.
Susceptibility-Weighted Imaging of Intravascular Lymphoma of the Central Nervous System
Authors: Megan B. Richie, Elan L. Guterman, Maulik P. Shah, Soonmee Cha
Journal: JAMA Neurology (2021)

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Abstract 12449: Clinical Impact of Reducing Bedrest After Pulmonary Vein Isolation
Authors: Benjamin L Freedman, Shu Yang, David Shim, Jonathan W Waks, Patricia Tung
Journal: Circulation (2021)

Background: Following pulmonary vein isolation (PVI), patients are typically prescribed 6 hours of bedrest to minimize bleeding. To streamline post-procedural care, our institution recently switched to a reduced bedrest period of 3 hours. Objective: To determine if reduced bedrest after PVI results in increased bleeding. Methods: We prospectively examined rates of bleeding, length of hospital stay, and urinary catheterization among patients undergoing PVI at our institution from April-May 2021. We compared these metrics to patients who underwent PVI with 6-hour bedrest in April-May 2019, predating our institutional protocol change. Figure-of-8 (FO8) sutures were used to achieve hemostasis in all patients. Continuous and categorical variables were compared using Student’s t-test and Fisher’s exact test, respectively. Results: Bilateral access was more common and procedure times were slightly longer in the 6-hour cohort; other baseline characteristics were similar between groups (Table 1). There was 1 major vascular access site complication (a retroperitoneal bleed) in the 6-hour and none in the 3-hour cohort. Minor bleeding occurred in 11% of each group. Same-day discharge was achieved in 42/45 (93%) of the 3-hour and 4/55 (7%) of the 6-hour group (p&lt;0.001). Nine of 45 patients (20%) in the 3-hour group required urinary catheterization compared with 33/55 (60%) in the 6-hour group (p&lt;0.001). Catheter-associated urinary tract infections (2% vs. 4%) and opioid analgesia use (22% vs. 36%) were lower in the 3- vs. 6-hour cohort, but these differences were not statistically significant. Conclusion: These data suggest that reducing post-PVI bedrest from 6 to 3 hours decreases length of hospital stay and urinary catheterization rates without increasing the risk of bleeding or vascular access site complications. Use of FO8 sutures, enhanced procedural efficiency and a shift toward unilateral femoral access may have contributed to the safety of this protocol change.
PATH-34. MOLECULAR AND CLINICAL HETEROGENEITY WITHIN SPINAL EPENDYMOMAS
Authors: Sina Al-Kershi, Catena Kresbach, Lara Pohl, Mario M Dorostkar, Abigail K Suwala, Annika K Wefers, Leonille Schweizer, Lara Engertsberger, Theresa Mohme, Martin Mynarek, Katrin Lamszus, Lan Kluwe, Andreas von Deimling, Martin Benesch, Christian Hagel, Viktor Mautner, Stefan Rutkowski, Ulrich Schüller
Journal: Neuro-Oncology (2021)

Abstract Ependymomas encompass multiple clinically relevant tumor types based on localization, genetic alterations, as well as epigenetic and transcriptomic profiles. Distinct global DNA methylation signatures serve as the most powerful diagnostic tool to distinguish these types. The methylation class of spinal ependymomas (SP-EPN) comprises mostly WHO°II tumors with slow progression and incomplete surgical resection rate. Molecular data of SP-EPN are scarce and clear treatment recommendations are lacking although these neoplasms represent the most common intramedullary tumors in children and adults. The only known recurrent genetic events in SP-EPN are the loss of chromosome 22q and mutations of the NF2 gene. However, data on the frequency of NF2 mutations range from 16 % to 71 % and originate from small series that lack epigenetic or transcriptomic characterization. Furthermore, it remains unclear whether SP-EPN with germline or sporadic NF2 mutation or with NF2 wild type status display clinical and other molecular differences. Finally, the underlying genomic and transcriptomic changes of SP-EPN without NF2 mutations are fully unclear. To provide a comprehensive molecular profile of SP-EPN, we integrated genomic and epigenetic analyses and clinical data of 170 cases. Unsupervised hierarchical clustering and t-SNE analyses of methylation data revealed three distinct molecular SP-EPN subtypes. Of the three subtypes, only subtype 1 and subtype 2 contained tumors with NF2 mutations, either as previously known germline mutations or as sporadic mutations without evidence for a syndromic disease (p&amp;lt; 0.0001). Besides the lack of NF2 mutations, subtype 3 tumors showed a higher frequency of MGMT promoter methylation (p= 0.0015) and occurred in significantly older patients compared to tumors of subtypes 1 and 2 (p= 0.0038). Further investigations such as whole-exome sequencing, copy number variation profiling, gene expression analysis, and histological evaluation are ongoing and will add to the picture of molecular and clinical heterogeneity within SP-EPN.
Abstract 13984: The Feasibility and Safety of Left Bundle Branch Pacing in Patients With Tricuspid Valve Disease
Authors: Xueying Chen, Jiahui Chen, YANGANG SU
Journal: Circulation (2021)

Background: Although left bundle branch pacing (LBBP) has emerged as a novel physiological pacing strategy, it is still challenging in cases with tricuspid valve disease. Meanwhile, the influence of LBBP lead on tricuspid regurgitation has not been well established in these patients. In the present study, we evaluate the feasibility and safety of LBBP in patients with tricuspid valve disease. Methods: We enrolled 24 patients with tricuspid valve disease who received LBBP procedure in Zhongshan Hospital, Fudan University, between January 2018 and July 2020. Regular follow-ups were conducted (at 1 and 12 months), and the echocardiography data of the patients were collected and analyzed. Results: One postoperative lead dislodgements (1/24, 4.2%) occurred during the follow-up. Mean fluoroscopy time of placing LBBP lead was 19.75±08.23 minutes. Mean follow-up period was 9.64±4.17 months. Pacing parameters were stable during follow-up in all cases. The severity of tricuspid regurgitation(TR) (no 0, slight 1. mild 2, medium 3 and severe 4) under echocardiography were measured and compared at baseline and 1-year follow-up post-procedure. No significant aggravation occurred (2.88±1.57 vs 3.00±1.44, P=0.13). Left ventricular ejection fraction remain stable from baseline to 1-year follow-up(56.27±11.73% vs 59.30±8.17%, P=0.09). Conclusion: LBBP was feasible and safety in patients with tricuspid valve disease though these cases were always challenging such as longer fluoroscopy time, more technocratic requirements, higher rates of failure and procedure-related complications than HBP. Lead parameters were stable during follow-up. No significant aggravation of TR was found.