tbuckley/cabot-search huggingface dataset:
Abstract 271: Care Patterns for Out Of Hospital Cardiac Arrest Differ From Other Emergency Care Sensitive Conditions
Authors: David G Buckler, Douglas Wiebe, Sarah Sims, Ronan Doorley, Alexis Zebrowski, Brendan Carr
Journal: Circulation (2020)

Background: Understanding utilization patterns for out of hospital cardiac arrest (OHCA) is critical to organizing regional systems of care as recommended by the American Heart Association. We examined the agreement between regional utilization patterns for out-of-hospital cardiac arrest (OHCA) and other emergency care sensitive conditions (ECSCs). Methods: We used Medicare fee-for-service outpatient and inpatient claims from 2013-2014 to describe geographic utilization patterns for 5 emergency care conditions as has been done previously. We compared these regional clusters developed for OHCA to similarly created clusters for other emergency cardiovascular (ECV) conditions (by adding STEMI and stroke). Regional ZIP code attributions were compared using a modified Jaccard index, measuring the agreement between region membership. We also calculated patient-level risk-adjusted survival probabilities (controlling for patient age, sex, race and presenting condition) and summarized for each region as an observed-to-expected (O:E) ratio. O:E ratios higher than 1 indicate better than expected survival. Each region was ranked based on its O:E ratio and ranks between the two sets of conditions were compared. Results: The analysis included 3,279,013 ECSC claims containing 246,342 OHCA and 1,037,472 ECV claims grouped into 234 OHCA regions and 343 ECV regions. When comparing OHCA only to all ECV utilization (clusters), agreement was 64%. O:E survival to hospital discharge for OHCA regions showed greater variability compared to ECV regions (OHCA: 0.53-2.2 vs. ECV: 0.90 - 1.10). In comparing ranked O:E outcomes between OHCA and ECV regions, we found 72% discordance in quartile rankings (κ = 0.28). Conclusion: Care utilization pattern and risk-adjusted survival for OHCA in older adults vary greatly when compared to other emergency cardiovascular conditions and should be benchmarked separately. Further research is needed to understand the role strong regionalization of care policies could play in improving outcomes and streamlining care processes.
Abstract 15067: Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes Mellitus - Findings From the Look Ahead Trial
Authors: Kershaw V Patel, Judy Bahnson, Sarah Gaussoin, Karen C Johnson, Xavier Pi-Sunyer, Ursula White, KayLoni L Olson, Alain G Bertoni, Dalane W Kitzman, Jarett D Berry, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes mellitus (T2DM). However, the contribution of changes in body composition measures [lean mass (LM), fat mass (FM), waist circumference (WC)] to the risk of HF and myocardial infarction (MI) is not well-known. Methods: Adults with T2DM who had overweight or obesity enrolled in the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. LM and FM were predicted using validated equations and compared with DXA measurements. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in LM, FM, and WC over 1- (Y0 to Y1) and 4-year (Y0 to Y4) follow-up with risk of overall HF, HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) and MI. Results: Among 5,103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured LM and FM were highly correlated (R 2 =0.87-0.92). LM and FM decreased with greater declines in the intensive lifestyle intervention arm (Figure 1A). In adjusted analyses, baseline measures of body composition were not significantly associated with risk of HF. Decline in FM, but not LM, over 1- and 4-year follow-up was significantly associated with lower risk of HF (Figure 1B). A significant association was observed between decline in WC and risk of overall HF and HFpEF but not HFrEF. Among adults without a history of CVD, changes in body composition were not associated with risk of MI. Conclusions: In adults with T2DM who had overweight or obesity, a lifestyle intervention is associated with significant loss of FM and LM. Decline in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HFpEF but not HFrEF.
Use of Deep Learning to Examine the Association of the Built Environment With Prevalence of Neighborhood Adult Obesity
Authors: Adyasha Maharana, Elaine Okanyene Nsoesie
Journal: JAMA Network Open (2018)

More than one-third of the adult population in the United States is obese. Obesity has been linked to factors such as, genetics, diet, physical activity and the environment. However, evidence indicating associations between the built environment and obesity has varied across studies and geographical contexts. Here, we used deep learning and approximately 150,000 high resolution satellite images to extract features of the built environment. We then developed linear regression models to consistently quantify the association between the extracted features and obesity prevalence at the census tract level for six cities in the United States. The extracted features of the built environment explained 72% to 90% of the variation in obesity prevalence across cities. Outof-sample predictions were considerably high with correlations greater than 80% between predicted and true obesity prevalence across all census tracts. This study supports a strong association between the built environment and obesity prevalence. Additionally, it also illustrates that features of the built environment extracted from satellite images can be useful for studying health indicators, such as obesity. Understanding the association between specific features of the built environment and obesity prevalence can lead to structural changes that could encourage physical activity and decreases in obesity prevalence.
Abstract 16774: Adverse Childhood Experiences Reported by Adults With Congenital Heart Disease
Authors: Marshall A Taunton, Sheldon Levy, Adrienne H Kovacs, Abigail M Khan
Journal: Circulation (2020)

Introduction: Adverse childhood experiences (ACEs), such as witnessing domestic abuse or experiencing physical/sexual abuse, are associated with poorer long-term health outcomes, including acquired cardiovascular disease. This study offers the first investigation of ACEs in adults with congenital heart disease (CHD). Methods: In this cross-sectional study, adult CHD outpatients completed the ACE Questionnaire, the Relationship Scales Questionnaire, the Perceived Stress Scale, and a 0 - 100 linear analogue scale of quality of life. Total scores on the ACE Questionnaire range from 0 - 10 (a point for each ACE reported) and scores ≥ 4 are associated with poorest health outcomes. We performed correlations, t-tests, and analyses of variance to explore relationships between ACE Questionnaire scores and demographics, medical variables, and other survey scores. Results: A total of 100 patients were enrolled in the study (40 ± 13 years; 60% female). Ninety percent had defects of moderate or great complexity and 79% were categorized as American Heart Association anatomy + physiology stage B, C or D (i.e., some degree of symptoms and/or functional impairment). Total scores on the ACE Questionnaire ranged from 0 - 9, with a mean of 2.6 ± 2.5; 30% reported ≥ 4 ACEs. The most frequently reported ACEs were parental divorce (46%), emotional abuse (42%), and parental substance abuse problem (32%). ACE Questionnaire scores did not differ as a function of age, sex, defect complexity, or anatomy + physiology stage. However, total ACE score was significantly correlated with all 4 relationship styles (secure, preoccupied, dismissive and fearful; p-values &lt; 0.05). Quality of life scores were lower among those with elevated ACEs, although this did not reach statistical significance (69 vs. 76, p = 0.07). Conclusion: It is well accepted that adults with CHD face many health-related challenges throughout their lives. This study serves as an important reminder to providers that many patients will also experience other significant (and potentially traumatic) stressors in childhood. Further research is needed to determine whether the impact of ACEs on adults with CHD extends beyond relationship and stress outcomes and also includes cardiac morbidity and mortality.
Abstract 15893: Rf vs Cryo: Effect of Ablation Energy Source on Outcomes of Pediatric AVNRT Ablation - Insight From the NCDR® Impact Registry
Authors: Shankar Baskar, Maully Shah, David Spar, Shashank P Behere, kevin kennedy, Christopher Janson, Richard J Czosek
Journal: Circulation (2020)

Introduction: AV nodal reentrant tachycardia (AVNRT) is a common form of SVT in pediatrics. Ablation can be curative; however, the choice between radiofrequency ablation (RF) and cryoablation (Cryo) remains controversial due to a lack of contemporary large comparison studies in the pediatric population. Methods: AVNRT ablation outcomes were retrospectively analyzed utilizing the NCDR ® IMPACT Registry from 4/1/16 to 3/31/19. Data from subjects aged 1-21 years undergoing elective first-time slow pathway (SP) modification for AVNRT were included. Exclusion criteria were age&lt;1-year, structural heart disease, &gt;1 targeted arrhythmia mechanism, and &gt;1 ablation catheter/energy source. The primary outcome was acute ablation success, defined as elimination of SP conduction or SP conduction with ≤ 1 AV nodal echo without SVT. Secondary outcomes included major adverse effects (MAE) of AV block, temporary or permanent pacing, death, cardiac arrest, tamponade, or embolic stroke. Results: Among 2235 patients (mean age: 13.6 ± 3.4 years, 59% female), there was comparable use of Cryo (53%, n=1183) and RF (47%, n=1052). Cryo was more commonly used in patients &lt; 8years of age (p &lt; 0.01). Amongst 60 participating centers, 24 sites (40%) used Cryo predominantly (&gt;90%), while 24 sites (40%) used RF predominantly. Acute success was 98.6% for Cryo and 99% for RF (P = 0.27). AV block was reported in 6 (0.005%) patients with Cyro and 3 (0.003%) with RF (p=0.34), without the need for temporary or permanent pacemaker in either group during the hospital admission. No other MAE occurred in either group. Conclusion: In this largest pediatric study of AVNRT ablation, RF and Cryo demonstrated comparable high acute success and rare documentation of AV block that did not result in temporary or permanent pacing. Longitudinal data are important for further comparison of these two modalities with regard to AVNRT recurrence risk and the need for pacemaker implantation outside of the hospitalization period.
Abstract 14219: Oxidation of PKA-RIα Protects Against Ischemia-reperfusion Injury by Inhibiting Lysosomal-triggered Calcium Release
Authors: Jillian N Simon, BESARTE VRELLAKU, Stefania Monterisi, Sandy Chu, Nadiia Rawlings, Oliver Lomas, Gerard A Marchal, Dominic Waithe, Parag R Gajendragadkar, Raja Jayaram, Rana Sayeed, Keith M Channon, Pawel Swietach, Manuela Zaccolo, Phil Eaton, Barbara Casadei
Journal: Circulation (2020)

Introduction: Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, the regulatory Iα subunit of Protein Kinase A (PKARIα) can be reversibly oxidised, forming interprotein disulfide bonds within the holoenzyme complex. However, the impact of disulfide formation on kinase function, and its influence on PKA signaling in the context of heart disease remains unknown. Methods &amp; Results: Myocardial ischemia-reperfusion (I/R) was found to be a potent inducer of PKARIα disulfide formation in vivo , both in mice and in humans. Using imaging modalities with high spatial and temporal resolution, we found that this conformation did not increase intrinsic PKA catalytic activity, but rather facilitated enhanced AKAP-dependent compartmentation of PKARIα in the adult mouse left ventricular (LV) myocyte, with preferential localization to the lysosome under oxidized conditions (n=38-41 myocytes, N=3 animals, p&lt;0.01). Investigations in isolated LV myocytes revealed disulfide-modified PKARIα to be a significant regulator of lysosomal two pore channel (TPC)-dependent calcium-induced calcium release, with myocytes from ‘redox dead’ PKARIα mice (Cys17Ser) displaying spontaneous sarcoplasmic reticulum calcium release events and pronounced intracellular calcium oscillations. These events were prevented by ryanodine receptor blockade (1 mM tetracaine; n=14, p&lt;0.01), acute depletion of lysosomal calcium stores (100 nM bafilomycin; n=7; p&lt;0.01), or TPC inhibition (5 μM Ned-19; n=9; p&lt;0.05). Absence of I/R-induced disulfide formation in “redox dead” PKARIα mouse hearts resulted in larger infarcts (2-fold increase, p&lt;0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, p&lt;0.001), which could be fully prevented by administering the TPC inhibitor, Ned-19, at the time of reperfusion. Conclusions: Oxidised PKARIα acts as a potent inhibitor of intracellular calcium release in the heart through its redox-dependent interaction with the lysosome. In the setting of I/R, where PKA oxidation is induced, this regulatory mechanism is critical for protecting the heart from injury and offers a novel target for the design of cardioprotective therapeutics.
Abstract 15452: Low Dp/dt <sub>Max</sub> , When Indexed to Central Venous Pressure, is Associated With Severe Right Ventricular Failure Following Left Ventricular Assist Device Implantation
Authors: Leila Y Beach, William Hiesinger, Matthew T Wheeler
Journal: Circulation (2020)

Introduction: Right ventricular failure (RVF) is a common complication following LVAD implantation and a significant driver of post-LVAD mortality. dP/dt max , the maximum rate of rise in ventricular pressure, is a validated hemodynamic parameter of ventricular contractility that, when indexed to CVP, accounts for loading conditions. This parameter has not, however, been studied in the context of post-LVAD RVF. We therefore evaluated the relationship between dP/dt max /CVP and post-LVAD RVF in a cohort of LVAD recipients at Stanford. Methods: We conducted a retrospective, single-center analysis of patients who underwent continuous-flow LVAD implant at Stanford between January 2010 and June 2019. Preoperative RV dP/dt max /CVP values were extracted from right heart catheterization (RHC) reports. For cases in which dP/dt max /CVP was not reported, preoperative RA and RV pressure tracings were utilized to manually calculate the index. We then performed unpaired t-tests to evaluate for the presence of associations between dP/dt max /CVP and early post-LVAD RVF, defined as the prolonged (&gt;7 days) requirement for inotropic or pulmonary vasodilator therapy or the need for RVAD support, and between dP/dt max /CVP and severe post-LVAD RVF, defined only by the requirement for RVAD support. Results: This cohort included 202 LVAD recipients who had available preoperative RHC data. Of these, 14.4% (n = 29) required an RVAD and 50.5% (n = 102) experienced early post-LVAD RVF. Mean values of dP/dt max /CVP amongst patients with and without early post-LVAD RV failure were 94.9 ± 128.5 s -1 and 105.6 ± 125.5 s -1 (p = 0.56), respectively, while mean values of dP/dt max /CVP amongst those who did and did not require an RVAD were 53.2± 42.0 s -1 and 108.2 ± 129.5 s -1 (p = 4.2 х 10 -5 ), respectively. Conclusion: In continuous-flow LVAD recipients, low preoperative RV dP/dt max /CVP is strongly associated with severe post-LVAD RVF requiring RVAD support but not early post-LVAD RVF more generally.
Cardiac Risk Assessment in Liver Transplant Candidates: Current Controversies and Future Directions
Authors: Pranab M. Barman, Lisa B. VanWagner
Journal: Hepatology (2020)

In the changing landscape of liver transplantation (LT), we are now evaluating older and sicker patients with more cardiovascular comorbidities, and the spectrum of cardiovascular disease is uniquely physiologically impacted by end‐stage liver disease. Cardiac complications are now the leading cause of morbidity and mortality in LT recipients, and the pretransplant risk is exacerbated immediately during the transplant operation and continues long term under the umbrella of immunosuppression. Accurate risk estimation of cardiac complications before LT is paramount to guide allocation of limited health care resources and to improve both short‐term and long‐term clinical outcomes for patients. Current screening and diagnostic testing are limited in their capacity to accurately identify early coronary disease and myocardial dysfunction in persons with end‐stage liver disease physiology. Furthermore, a number of testing modalities have not been evaluated in patients with end‐stage liver disease. As a result, there is wide variation in cardiac risk assessment practices across transplant centers. In this review, we propose a definition for defining cardiac events in LT, evaluate the current evidence for surgery‐related, short‐term and long‐term cardiac risk assessment in LT candidates, propose an evidence‐based testing algorithm, and highlight specific gaps in knowledge and current controversies, identifying areas for future research.
Abstract 15448: Association of Kidney Dysfunction and Damage to Incident Heart Failure With Reduced and Preserved Ejection Fraction in Older, Community-dwelling Adults: The Atherosclerosis Risk in Communities Study
Authors: Leo F Buckley, Brian Claggett, Kunihiro Matsushita, Hicham Skali, Josef Coresh, Suma H Konety, Lynne E Wagenknecht, Thomas Mosley, Amil M Shah
Journal: Circulation (2020)

Introduction: Older adults are at heightened risk for both kidney disease and heart failure, but there is limited data regarding the associations of kidney damage and dysfunction with incident heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction in late life. Hypothesis: Kidney dysfunction, as assessed by lower estimated glomerular filtration rate (eGFR), and kidney damage, as assessed by higher urine albumin-to-creatinine ratio (UACR), are each independently associated with incident HFrEF and HFpEF in late life. Methods: We studied 4,563 elderly participants in the community-based, prospective ARIC study who were free of HF at study Visit 5 (2011-2013) at which time they had UACR measured and Cystatin-C-based eGFR estimated using the CKD-EPI formula. We estimated the association of Visit 5 eGFR and UACR with post-Visit 5 incident HF overall, HFrEF, and HFpEF using multivariable Cox proportional hazards regression models adjusted for demographics, diabetes, hypertension, coronary artery disease, atrial fibrillation, body mass index, pulse pressure, and either eGFR or UACR. Results: The mean age at Visit 5 was 75±5 years, 57% were female, 21% were black. Mean Visit 5 eGFR was 67±18 mL/min per 1.73 m 2 and median UACR was 10.2 [6.2 to 21.4] mg-g. Lower eGFR and higher UACR each associated with older age, wider pulse pressure and higher prevalence of diabetes, hypertension, coronary disease and atrial fibrillation (all p&lt;0.02). At a median follow-up of 5.2 years, 289 participants developed HF (127 HFpEF, 123 HFrEF, 42 with unknown LVEF). In fully adjusted models, lower Visit 5 eGFR and higher Visit 5 UACR were each associated with higher risk of incident HF overall, incident HFrEF, and incident HFpEF ( Figure ). Conclusions: Lower eGFR and higher UACR are independently and additively associated with both incident HFrEF and incident HFpEF in late life.
Multifunctional tumor-targeted PLGA nanoparticles delivering Pt(IV)/siBIRC5 for US/MRI imaging and overcoming ovarian cancer resistance
Authors: Yanhua Zhang, Yang Dong, Hao Fu, Hui Huang, Zhihua Wu, Meng Zhao, Xupeng Yang, Qianqian Guo, Yourong Duan, Ying Sun
Journal: Biomaterials (2020)
Abstract 13920: Improved Outcome Prediction Modelling in Neonatal Congenital Heart Disease With Metabolomic Feature Clustering
Authors: Jessica J Heibel, Eric M Graham, Aurelie Roux, David Graham, Cedric Manlhiot, Allen D Everett
Journal: Circulation (2020)

Introduction: Neonatal heart surgery requiring cardiopulmonary bypass (CPB) is associated with significant morbidity and mortality. Methods to improve outcome prediction are lacking. Hypothesis: Targeted metabolic profiling can identify critical metabolites associated with important post-operative clinical outcomes. These in turn could be integrated into clinical prediction models. Methods: Secondary analysis of serum samples from the neonatal congenital cardiac surgery with CPB methylprednisolone trial, which evaluated effects of steroids on outcomes. Samples were from pre-op, immediate post-CPB, and 12 hrs post op. Outcomes were a cardiac dysfunction composite (death, ECMO, cardiac arrest and lactate) and low cardiac output syndrome (LCOS). Metabolite levels were determined with targeted mass spectrometry (LC/MS/MS). Principal component (PC) analysis and multivariable regression analysis with bootstrapping were used to assess the association between metabolic profiles and outcomes. Results: Total cohort had 149 patients. PC analysis identified 6 PCs (PC1-PC6) that explained 51% of variance. When PCs and metabolites were added to a base clinical model, model fit for the cardiac dysfunction composite outcome was significantly improved (c-stat 0.819 vs 0.902, p&lt;0.001) as well as LCOS (c-stat 0.576 vs. 0.803, p=0.76 vs. p=0.01). Using adjusted regression models, metabolites (some of which are included in PCs) significantly associated with cardiac dysfunction composite outcome were proline (p=0.004) and leucine (p=0.01). Metabolites associated with LCOS were n-acetyltryptophan (p=0.01), glycocholic acid (p=0.001), cortisol (p=0.02), nicotinamide (p=0.04), methyladenosine (p=0.01) and methionine (p=0.01). For cardiac composite outcome, cumulative and post op values were significant, whereas all time points were for LCOS. Conclusions: Combining metabolic profiles with patient characteristics revealed significant pre-op metabolites associated with important clinical outcomes. Given that the association held true for all time points, these observations could be used to design molecular signature for post-operative cardiac complications or, to create prediction models based on pre-operative metabolic profiles.