tbuckley/cabot-search huggingface dataset:
Abstract 15005: Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank
Authors: Jennifer L Halford, Lu Chen Weng, Seung Hoan Choi, Sean J Jurgens, Valerie Morrill, Shaan Khurshid, Ludovic Trinquart, Emelia J Benjamin, Patrick T Ellinor, Steven A Lubitz
Journal: Circulation (2020)

Introduction: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We sought to characterize the association between alcohol intake and incident AF and determine whether the effect of alcohol is modified by inherited predisposition to AF. Methods: We analyzed UK Biobank participants without prevalent AF and with complete alcohol consumption, genomic, and clinical data collected between 2006-2010. Exposures included alcohol consumption (stratified by an acceptable range of ≤98 grams/week for women or ≤196 grams/week for men and analyzed as a continuous variable) and an AF polygenic risk score (PRS). Cox proportional hazard models were adjusted for established AF risk factors. The cumulative incidence of AF was assessed at 5 years. Results: Among 376,776 participants (47.5% male, mean age 56.9 years), 6,293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio [HR] 1.10; 95% CI 1.05-1.16 for intake above an acceptable range; HR 1.04 per 100 grams/week; 95% CI 1.02-1.06). An AF PRS was associated with AF (HR 1.38 per standard deviation [SD]; 95% CI 1.35-1.41). In models including both alcohol intake and the AF PRS, each remained associated with AF. The 5-year cumulative incidence of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI 2.07-2.59), compared to 0.69% (95% CI 0.58-0.80) for those with alcohol intake within acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with risk of incident AF across a range of polygenic predisposition to AF. Preventive counseling regarding alcohol intake may reduce the risk of AF regardless of the degree of risk conferred by inherited predisposition.
Abstract 14468: Right Heart: Renal Venous Stasis Determinant in Acute Heart Failure
Authors: Alessandro Vella, Gianmarco Carenini, Francesco Bandera, Marco Guazzi
Journal: Circulation (2020)

Introduction: The heart-kidney interaction in heart failure (HF) is a matter of special interest, especially due to its strong prognostic significance. The search for a reliable, non-invasive parameter with high pathophysiological and prognostic impact to evaluate HF-related renal congestion remains attractive. Doppler evaluation of intra-renal venous flow (IRVF) has been recently employed in HF patients, with a spectrum of findings ranging from a normal continuous flow to a monophasic discontinuous one, indicative of low and high degrees of renal congestion, respectively. Hypothesis: We postulated a role for right atrial dynamics in the renal congestion pathophysiology. The impairment in atrial deformation and pump function may play a primary role increasing the pulsatile backward load in the venous system, especially in acute heart failure (AHF) patients. Methods: 119 consecutive AHF patients were prospectively investigated within 48 hours from admission. Doppler-derived descriptors of renal hemodynamics included the renal arterial resistive index, IRVF pattern, venous impedance index and renal venous stasis index (RVSI). Results: Right atrial peak longitudinal strain (RAPLS) showed a strong correlation with IRVF pattern (Fig A) and various indices of RV function (TAPSE, S’, FAC) and RV coupling as represented by the TAPSE/PASP ratio (Fig B). At multivariate regression analysis, TAPSE/PASP ratio emerged as the main determinant of RVSI. On the other hand, considering only patients with a clearly impaired RV coupling (TAPSE/PASP &lt;0.30), RAPLS emerged as the best determinant of RVSI (Fig C-D). Conclusions: Our data confirms the main role of the right heart in determining renal stasis in HF patients. When RV to pulmonary circulation uncoupling is severe, the right atrium becomes the key balancing factor in the venous renal flow response. Studies on the mechanistic contribution of the RA dysfunction and the recovery potential of interventions are warranted.
Variations in Anticoagulation Practice Following Bioprosthetic Aortic and Mitral Valve Replacement and Repair
Authors: Makoto Mori, Geliang Gan, Syed Usman Bin Mahmood, Yanhong Deng, Clancy W. Mullan, Roland Assi, Prashanth Vallabhajosyula, Vinay Badhwar, Arnar Geirsson
Journal: Journal of the American College of Cardiology (2020)
Comment on Pantalone et al. The Probability of A1C Goal Attainment in Patients With Uncontrolled Type 2 Diabetes in a Large Integrated Delivery System: A Prediction Model. Diabetes Care 2020;43:1910–1919
Authors: Alice Larroumet, Ninon Foussard, Marie Monlun, Laurence Blanco, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2020)

We were interested in the recent article from Pantalone et al. (1), who reported that 23.7% of 6,973 subjects with poorly controlled type 2 diabetes (HbA1c >9%) attained HbA1c below 8% within 1 year, based on the electronic health record at Cleveland Clinic. Although the 6,973 participants represented only 6.7% of the 103,969 encountered patients in the database, their fate is a matter of concern, as high rates of vascular and infectious complications have been related to HbA1c above 9%. The follow-up of HbA1c trajectories has shown that high HbA1c usually remains stable or ascending for years, and long-term frank reductions are uncommon, only occurring for 3–4% of the patients (2). Real improvement of …
Abstract 335: The Impact of Early Coronary Angiography on Outcomes in Out-of-hospital Cardiac Arrest: The Singapore Experience
Authors: Shir Lynn Lim, Yee How Lau, Mark Chan, Terrance Chua, Huay Cheem Tan, David Foo, Patrick Lim, Boon Wah Liew, Khung Keong Yeo, Marcus Ong
Journal: Circulation (2020)

Background and Aim: The benefit of early coronary angiography (CAG) and revascularization in resuscitated out-of-hospital cardiac arrest (OHCA) is unclear. We evaluated the association between early CAG and clinical outcomes in these patients. Methods: Data on all resuscitated adult OHCA cases of cardiac etiology between 2011-2015 were extracted from the prospective Singapore Pan-Asian Resuscitation Outcomes Study and linked with data from the national database of cardiac procedures. The 30-day survival and neurological outcomes (good outcome defined as Cerebral Performance Category [CPC] 1 or 2) were compared between patients undergoing early CAG (within 1-calender day) and patients not undergoing early CAG. Inverse probability weighted estimator was used to adjust for propensity to perform early CAG and PCI. Results: Of 976 consecutive patients who survived to admission (mean age 64±13, 73.7% males), 401 (41.1%) patients underwent CAG and obstructive coronary artery disease (CAD) was present in 352 (87.8%), of whom 284 (70.8%) underwent revascularization. Patients who underwent early CAG (n=337[34.5%]) were significantly different compared to those who underwent delayed or no CAG (n=639[65.5%]) (Table 1). Early CAG and PCI patients had improved survival and better neurological outcomes (adjusted odds ratio [AOR] 3.806 [95% CI 1.675 - 8.648] and AOR 3.075 [95% CI 1.119 - 8.451]), compared to those without. The odds of survival decreased with epinephrine administration (AOR 0.357 [95% CI 0.199 - 0.640]), but increased with an initial shockable rhythm (AOR 6.587 [95% CI 3.659 - 11.861]). The rates of bleeding (2% vs 0%, p=0.300) and stroke (1.6% vs 1.9%, p=0.880) were not increased with early intervention. Conclusion: Early CAG and PCI after OHCA were associated with improved clinical outcomes after OHCA without increasing complications. Further studies are required to identify the characteristics of patients who would benefit most from this invasive strategy.
Abstract 16348: Comparison of Heart Rate Variability, Physical Activity, and Fitness Parameters Between Healthy Women and Breast Cancer Survivors
Authors: Elena Martínez-Rosales, Alba Hernández-Martínez, Manuel Alcaraz-Ibáñez, Laura López-Sánchez, David Manuel Díez-Fernández, Alberto Soriano-Maldonado, Enrique G Artero
Journal: Circulation (2020)

Introduction: Breast cancer remains the most commonly type of cancer. Heart rate variability (HRV), a clinical indicator of autonomic dysfunction and premature mortality, has been found to be impaired in breast cancer survivors immediately after treatment and in the last stages of metastasis. Physical activity and fitness represent relevant health markers that might prevent some of the side effects following breast cancer treatment, so it would be of clinical interest assessing potential differences with healthy controls. Hypothesis: Compared to healthy women, breast cancer survivors are expected to show impaired HRV-derived parameters, as well as lower physical activity and fitness. Methods: This cross-sectional study included 20 women that survived breast cancer (post-operative period &gt;2 years) and 20 healthy women controls, matched by age and BMI. Fitness evaluations included the modified Ruffier-Dixon test and handgrip strength. Moderate-to-vigorous physical activity (MVPA) was assessed through a self-reported questionnaire. Short-term HRV was measured using 5-minutes recording and were analyzed with Kubios Premium. Sample size was determined for two-tailed tests, statistical power of 0.8, effect size &gt;0.7, and significance level of p&lt;0.05. Between-groups differences were examined using Mann–Whitney U test and Student’s t-test, for normally and not-normally distributed variables, respectively. Results: Concerning HRV parameters, breast cancer survivors presented lower Very Low Frequency and Low Frequency, and higher Low Frequency/High Frequency ratio (all p &lt;0.001), compared to controls. No statistically significant differences were observed in MVPA time ( p =0.48) or estimated VO 2max ( p =0.24), although handgrip strength was decreased in cancer survivors ( p =0.02). Conclusions: A cardiovascular imbalance in breast cancer survivors may be suggested in comparison to healthy age- and BMI-matched controls, as evidenced by reduced HRV after &gt;2 years of post-operative treatment. In contrast, there were no differences in weekly MVPA or VO 2max between groups, although muscular strength could still be affected. These results need to be contrasted by future long-term prospective research.
Abstract 14458: Repeated Social Defeat Exaggerates Fibrin-rich Clot Formation in Fecl3 Induced Arterial Thrombosis Mice Model by Enhancing Nets Formation
Authors: Takeshi Sugimoto, Hiroyuki Yamada, Hiroshi Kubota, Daisuke Miyawaki, Noriyuki Wakana, Satoaki MATOBA
Journal: Circulation (2020)

Background and Objective: Depression is an independent risk factor of cardiovascular disease (CVD). We have recently shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular traps (NETs) formation. Here, we investigated the impact of RSD on arterial thrombosis. Methods and Results: Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same gage without physical contact. After social interaction test to confirm depressive-like behaviors, defeated mice (19 of 31) and control mice (12 of 14) were underwent arterial injury at 10 wks of age. A filter paper saturated with 10% FeCl3 was applied on the adventitial surface of left carotid artery for 3 min and analyzed 3 hrs later. The volume of thrombi was comparable between the two groups. However, fibrinogen/fibrin-positive areas in immunofluorescent images significantly increased in defeated mice (48.8% vs. 27.8%, p &lt; 0.01). The number of Ly-6G-positive cells in thrombi was markedly higher in defeated mice (878/mm2 vs. 144/mm2, p &lt; 0.05). Further, Ly-6G-positive cells were co-localized with neutrophil elastase, Cit-H3, and CD42b-positive staining. Percentage of CD42b-positive area in thrombi and in vitro platelets aggregations induced by ADP or collagen were comparable between the two groups. Treatment with DNase I completely diminished the exaggerated fibrin-rich clot formation in defeated mice to an extent similar to that in control mice (22.3% vs. 25.7%, p = ns), although the number of Ly-6G-positive cells in thrombi was not affected. We therefore examined the vulnerability to NETs formation induced by thrombin-activated platelets. Flow cytometric analysis showed that in vitro NETs formation assessed by Cit-H3/MPO double-positive cells was significantly higher in defeated mice (20.7% vs 12.5%, p &lt; 0.01). Conclusions: Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NETs formation via platelet-neutrophil interactions, suggesting that NETosis could be a new therapeutic target in depression-related CVD development.
Abstract 15839: Patients With Abdominal Aortic Aneurysms Have Reduced Levels of MicroRNA 122-5p in Circulating Exosomes
Authors: Jose L Lopez, Joel L Ramirez, Tuan Anh Phu, Phat Duong, Laura Bouchareychas, Christina R Kuhrau, Pei Yu Lin, Michael S Conte, Shant M Vartanian, Robert L Raffai, Adam Z Oskowitz
Journal: Circulation (2020)

Introduction: There are currently no specific biomarkers to screen and monitor disease progression in abdominal aortic aneurysms (AAA), which are the 15 th leading cause of death in the United States. Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAA in order to identify novel markers of disease. Methods: A total of 109 patients scheduled to undergo a duplex ultrasound (US) for screening or surveillance of AAA were screened to participate in the study. Eleven patients with AAA (max aortic diameter &gt;3cm) and 15 non-aneurysmal controls (max aortic diameter &lt;3cm on screening US) were enrolled. Circulating plasma exosomes were isolated using Cushioned-Density Gradient Ultracentrifugation and total RNA was extracted. Next Generation Sequencing was performed on the Illumina HiSeq4000 SE50 after NEBNext Multiplex Small RNA Library Prep. Differential miRNA expression analysis was performed using DESeq2 software with a Benjamini-Hochberg correction. MicroRNA expression profiles were validated by Quantitative Real-Time PCR. Results: Aortic diameter, as measured by US, was significantly larger in the AAA group (mean maximum diameter 5.2 vs 2.3 cm, p =2.84x10 -6 ). Aneurysm patients were more likely to suffer from CAD (5/11 vs 1/15, p = 0.05) but had similar levels of PAD (4/11 vs 2/15, p =0.35) and COPD (4/11 vs 4/15, p =0.68) compared to controls. A total of 40 miRNAs were differentially expressed ( p &lt;0.05). Of these, 18 miRNAs were up-regulated and 22 were down-regulated in controls compared to AAA. After false discovery rate (FDR) adjustment, only miR-122-5p was expressed at significantly different levels in AAA compared to controls (fold change = 5.03 controls vs AAA; raw p = 1.8x10 -5 ; FDR p =0.02). Conclusions: Plasma exosomes from AAA patients have significantly reduced levels of miRNA-122-5p compared to controls.
Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism
Authors: Yi Fu, Yu Sun, Mei Wang, Yunfeng Hou, Wei Huang, Di Zhou, Ziying Wang, Shuting Yang, Wei Tang, Junhui Zhen, Yujia Li, Xiaojie Wang, Min Liu, Yan Zhang, Baobao Wang, Guangyi Liu, Xiao Yu, Jinpeng Sun, Chun Zhang, Fan Yi
Journal: Cell Metabolism (2020)
Abstract 15024: Efficacy of Bretylium in Termination of Treatment Resistant Ventricular Tachycardia and Ventricular Fibrillation
Authors: Janos Molnar, John C Somberg
Journal: Circulation (2020)

Bretylium is the only drug approved by the FDA specifically to terminate ventricular fibrillation (VF). It has also been approved to treat life threatening ventricular tachycardia (VT) as a second line agent. Due to shortage of drug substance, bretylium became unavailable for clinical use and has been dropped from ACLS guidelines in 2000. Recently, intravenous (IV) bretylium became available again in the U.S. This study evaluated the efficacy of bretylium IV in the termination of treatment resistant VT and VF. In 4 studies, a total of 85 patients with sustained VT and/or VF were administered IV bretylium 5 mg/kg: 23 patients had VT and 62 had VF. Resistant VT/VF was defined as VT or VF that could not be terminated by shock or other anti-arrhythmics or recurred before bretylium was administered. All patients received IV lidocaine; 71 received between 1 to 5 additional antiarrhythmics, and all patients with VF received DC shocks and failed all pharmacologic therapies prior to bretylium administration. Overall, 61 patients (72%) were successfully treated with IV bretylium and 31 survived to discharge from the hospital (36%). A meta-analysis of these studies indicates that the weighted conversion rate across the studies was 70% (see figure). The only study that compared IV bretylium and amiodarone did not find superiority of amiodarone in the suppression of hemodynamically destabilizing VT or VF. In patients with resistant VT or VF bretylium is reported to be effective in acute termination of the VT or VF that otherwise was not responsive to shock or other anti-arrhythmic drugs. These results suggest that bretylium should be employed in the pharmacotherapy of VT and VF when DC shock or other anti-arrhythmic drugs fail. The studies this report is based on are small studies and thus there is a need for a large controlled clinical trial to provide a better understanding of bretyliums effectiveness and if a higher than 30 mg/kg dose of bretylium would be more effective.
Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment
Authors: Zhenghang Wang, Xiaochen Zhao, Chan Gao, Jifang Gong, Xicheng Wang, Jing Gao, Zhongwu Li, Jie Wang, Bo Yang, Lei Wang, Bei Zhang, Yifan Zhou, Dalei Wang, Xiaofang Li, Yuezong Bai, Jian Li, Lin Shen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Microsatellite instability (MSI) represents the first pan-cancer biomarker approved to guide immune checkpoint blockade (ICB) treatment. However its widespread testing, especially outside of gastrointestinal cancer, is hampered by tissue availability. Methods An algorithm for detecting MSI from peripheral blood was established and validated using clinical plasma samples. Its value for predicting ICB efficacy was evaluated among 60 patients with advanced gastrointestinal cancer. The landscape of MSI in blood was also explored among 5138 advanced solid tumors. Results The algorithm included 100 microsatellite markers with high capture efficiency, sensitivity, and specificity. In comparison with orthogonal tissue PCR results, the method displayed a sensitivity of 82.5% (33/40) and a specificity of 96.2% (201/209), for an overall accuracy of 94.0% (234/249). When the clinical validation cohort was dichotomized by pretreatment blood MSI (bMSI), bMSI-high (bMSI-H) predicted both improved progression-free survival and overall survival than the blood microsatellite stable (bMSS) patients (HRs: 0.431 and 0.489, p=0.005 and 0.034, respectively). Four patients with bMSS were identified to have high blood tumor mutational burden (bTMB-H) and trended towards a better survival than the bMSS-bTMB-low (bTMB-L) subset (HR 0.026, 95% CI 0 to 2.635, p=0.011). These four patients with bMSS-bTMB-H plus the bMSI-H group collectively displayed significantly improved survival over the bMSS-bTMB-L patients (HR 0.317, 95% CI 0.157 to 0.640, p&lt;0.001). Pan-cancer prevalence of bMSI-H was largely consistent with that shown for tissue except for much lower rates in endometrial and gastrointestinal cancers, and a remarkably higher prevalence in prostate cancer relative to other cancer types. Conclusions We have developed a reliable and robust next generation sequencing-based bMSI detection strategy which, in combination with a panel enabling concurrent profiling of bTMB from a single blood draw, may better inform ICB treatment.
Abstract 17103: Elevated NT-proBNP Level is Not a Prognostic Marker for Patients Hospitalized With SARS-CoV-2 Infection
Authors: Farukh G Ikram, Priyanka Acharya, Nicholas Nguyen, Manavjot S Sidhu
Journal: Circulation (2020)

Introduction: NT-proBNP is a widely available and frequently utilized laboratory marker in patients with congestive heart failure. Its availability and use as a surrogate marker for elevated ventricular filling pressures and ventricular strain that frequently manifests as shortness of breath makes it an attractive laboratory marker to triage patients with SARS-CoV-2 infection. Hypothesis: Elevated NT-proBNP is correlated with higher mortality and/or rate of major adverse cardiovascular events (MACE) in patients admitted with SARS-CoV-2 infection. Methods: A retrospective analysis was performed on 225 patients admitted for SARS-CoV-2 infection at a major metropolitan hospital located in the Southwestern United States from the period of March 2020 to May 2020. NT-proBNP levels were recorded in 117 patients (52.7%) on admission. Elevated NT-proBNP was defined as: above 450 pg/ml in patients less than 50 years old, above 900 pg/ml if 50 to 75 years old, and above 1,800 pg/ml if above 75 years old. The primary endpoint was a composite of MACE and mortality during hospitalization. MACE was defined as stroke, myocardial infarction, DVT or PE and shock requiring vasopressor support. Two-sample Wilcoxon rank-sum (Mann-Whitney) test, Pearson’s chi square test and Fisher’s exact test were utilized for data analysis. Results: Of the 117 SARS-CoV-2 positive patients that had admission NT-proBNP levels available for analysis, 23 (19.66%) met age-adjusted criteria for elevated NT-proBNP. There was no significant correlation between elevated NT-proBNP levels and MACE (p = 0.482) or mortality (p = 0.737) in patients with SARS-CoV-2 infections. There was no statistical difference in total length of stay (p-value = 0.6384) or ICU admission (p-value = 0.354) between those with elevated admission NT-proBNP and those without. Conclusions: An elevated NT-proBNP at time of admission does not significantly correlate with higher rates of MACE, hospital length of stay, ICU admission, and mortality in patients admitted with SARS-CoV-2 infection.
Abstract 13333: Prolonged Targeted Temperature Management Improves Memory Retrieval Six Months Post Cardiac Arrest: A Randomised Controlled Trial
Authors: Lars Evald, Kolbjørn Selvåg Brønnick, Christophe Henri Valdemar Duez, Anni Nørgaard Jeppesen, Anders Grejs, Eldar Søreide, Hans Kirkegaard, Jørgen Feldbæk Nielsen
Journal: Circulation (2018)

Introduction: Cognitive sequelae are frequently reported among out-of-hospital cardiac arrest (OHCA) survivors with memory problems being the most commonly impaired cognitive domain followed by att...
West Nile virus keeps on moving up in Europe
Authors: Tamás Bakonyi, Joana M Haussig
Journal: Eurosurveillance (2020)

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