tbuckley/cabot-search huggingface dataset:
Abstract 16704: Treating Children Like Little Adults: Pediatrician Communication About High Blood Pressure Includes Diminution and Targeting Children With High Systolic Blood Pressures Exceeding Adult Thresholds
Authors: Nora Bismar, Tammy M Brady, Christy B Turer
Journal: Circulation (2018)

Introduction: High blood pressure (BP) in children is under recognized by pediatric providers. Our aim was to describe and determine factors associated with provider communication of high BP during visits with a child with an elevated BP. Hypothesis: Few providers will communicate that BP is high. Methods: Cross-sectional analysis of video/audio-recorded well-child visits of 6–12-year-olds with overweight/obesity recruited from academic and private clinics (2014–15). Elevated BP and hypertension (HTN) were identified by applying contemporary pediatric HTN thresholds to EHR-stored BP data. Systolic BP (SBP) exceeding the adult threshold of ≥120 mmHg also was determined. Recorded visits were transcribed/analyzed. Two independent reviewers used transcript data to identify BP communication and establish communication themes. Chi-square was used to test if SBP elevation ≥120 mmHg is associated with communication of high BP in children. Results: A child had an elevated BP at 34 of 100 visits; 30 were valid recordings with 23 providers. Of these encounters, mean age was 8.7 years (y); 37% were overweight, 63%, obese; 37%, Black, and 47%, Latino. At the visit, 53% had elevated BPs (of which, 38% met diagnostic criteria for elevated BP and 0% for HTN); 47% had HTN-level BPs (29% met criteria for elevated BP and 43% for HTN); 37% had SBP ≥120 mmHg. Major themes for how pediatricians communicate about BP included: direct, unclear, minimize and absent. Communication of high BP was direct in 17% of visits, unclear, 17%, minimize, 13%, and absent, 67%. Exemplifying direct communication, a pediatrician said, ‘ Your BP’s a little bit high [avg. SBP 134] . 120 is the highest we want for her age [11 y].’ An example of ’unclear’ was, ‘ The biggest reason I worry about this [obesity] is you can start having adult problems like high BP ,’ (8 y, BP 115/76, 93%). A quote illustrating ’minimize’ was, ‘ BP is a bit high. He’s just nervous ,’ (8 y, BP 114/75, 91%). Exceeding the adult elevated-BP threshold was associated with direct communication, which occurred in 80% of visits with SBP ≥120, vs. 20% with &lt;120 ( P =.047). Conclusions: During well-child visits, most overweight children with high BP receive no communication that BP is high. Of those who do, communication commonly is unclear or dismissive, and more likely when SBP exceeds the adult high-BP threshold.
Abstract 16789: Pulmonary-Systemic Effective Arterial Elastance Ratio is Associated With Increased Adverse Outcomes in Advanced Heart Failure
Authors: Araba Bruce-Mensah, Kenneth Bilchick, Khadijah Breathett, Alex Parker, Hunter Mwansa, Jose Tallaj, Edward McMillan, Sula Mazimba
Journal: Circulation (2018)

Introduction: Advanced heart failure (HF) is characterized by ventricular arterial (VA) uncoupling and inefficient myocardial contractile mechanics. Effective arterial elastance (Ea) is a marker of total arterial load on the ventricle. There is paucity of data on the interaction between pulmonary-systemic effective arterial elastance (PSEa) [(Pulmonary systolic pressure/Stroke volume)/ (systolic blood pressure x 0.9)/Stroke volume)] with clinical outcomes in HF. Hypothesis: We hypothesized that increasing PSEa would be associated with higher adverse outcomes in patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Methods: Cox proportional hazards analysis and Kaplan Meier survival curves were used to assess associations between PSEa at end of pulmonary artery catheter (PAC) monitored therapy with clinical outcomes of time to death, transplant or LVAD (DTxLVAD) and time to death, transplant, LVAD or heart failure re-hospitalization (DTxLVADHF) over 6 months. Results: Among 165 patients (age 56.6 +/- 13.7 years, 29.1% female), the median PSEa ratio at the last PAC measurement was 0.48 (IQR 0.38 to 0.62). During 6 months of follow-up, PSEa ratio was significantly associated with the outcome of DTxLVAD in a Cox proportional hazards model (HR 2.18 per 0.25 increase in PSEa; 95% CI 1.41-3.37; P=0.0004), as well as the outcome of DTxLVADHF (HR 1.39 per 0.25 increase in PSEa; 95% CI 1.04-1.86; P=0.026); Kaplan-Meier curves demonstrated an increased rate of DTxLVAD in PSEa among patient in the highest quartile of PSEa (≥0.62) during follow- up period (Figure). Conclusion: PSEa is a novel marker of interventricular arterial coupling, that is associated with increased adverse events in advanced HF. These findings support further investigation of PSEa to guide risk stratification and prognosis in HF.
Abstract 16781: The Association Between Electronic Cigarette Use and Cardiovascular Disease According to Smoking Status: Brfss 2016
Authors: Hassan Mirbolouk, Sina Kianoush, Paniz Charkhchi, Olusola A. Orimoloye, S M Iftekhar Uddin, Andrew P. DeFilippis, Aruni Bhatnagar, Khurram Nasir, Michael J Blaha
Journal: Circulation (2018)

Background: E-cigarettes are a consumer product designed to deliver nicotine by heating a liquid produced from tobacco. Usage in the US is growing rapidly and is common among combustible cigarette users (dual use). The impact of E-cigarettes on cardiovascular disease is unknown. Aim: A cross-sectional examination of e-cigarette use with self-reported cardiovascular disease, according to smoking status, using the nationally representative health survey - the Behavioral Risk Factor Surveillance System (BRFSS) 2016 Methods: We included 404,332 BRFSS 2016 participants with information on the history of CVD and e-cigarette use. E-cigarette use was categorized as never (reference), occasional, and daily with daily +occasional e-cigarette users considered current e-cigarette users. The association of e-cigarette use and CVD (defined as self-reported coronary heart disease, myocardial infarction, or stroke) was assessed using multivariable logistic regression models stratified by smoking status (never, former, current [occasional or daily]), adjusted for age, sex and race. Results: Of the total population, there were 15,240 e-cigarette users and 85,402 with CVD. Compared to those who never used e-cigarettes, current e-cigarette users had significantly higher odds of having CVD among current smoker groups (occasional smoker: Odds Ratio (OR)= 1.36 (95% CI= 1.06 - 1.76); daily smoker: OR=1.34 (1.12 - 1.62)). Daily use of e-cigarettes among occasional smokers was significantly associated with higher odds of having CVD (OR=1.64 (1.05 - 2.57)). (Table) There was no association between e-cigarette use and CVD among never and former smokers. Strengths and Limitations: Because of large sample size, we were powered to stratify e-cigarette use by smoking status. However, BRFSSS does contain directly measured risk factors or pack-years of smoking. Conclusions: Dual use of e-cigarette and combustible cigarettes is a new pattern of tobacco product use that may be associated with more CVD.
Abstract 13909: Multi-Marker Risk Assessment in Patients Hospitalized With Coronavirus Disease-2019: <i>Results From the American Heart Association COVID-19 Cardiovascular Disease Registry</i>
Authors: Ankeet Bhatt, Erin Bohula, Lori Daniels, James A De Lemos, Erica Goodrich, David A Morrow
Journal: Circulation (2021)

Introduction: The pathobiology of inflammation, thrombosis, and myocardial injury associated with SARS-CoV2 may be assessed by circulating biomarkers. However, their relative prognostic importance has been incompletely described. Methods: We analyzed data from pts hospitalized with COVID-19 in Jan to Nov, 2020 at 107 US hospitals in the AHA COVID-19 Cardiovascular (CV) Disease Registry who had biomarker data for D-Dimer, CRP, ferritin, natriuretic peptides [NP], or cTn at admission. We assessed the association between each biomarker by quintile [Q] and odds of in-hospital death and a composite of CV death, myocarditis, AMI, HF, or ischemic stroke. cTn quintiles were indexed to the assay-specific 99 th %ile ref limits. Multivariable logistic regression determined the relative prognostic performance of each biomarker. Results: 17,829 (83% of total) had admission values reported for at least 1 of the 5 key biomarkers (n= 2422 with values for all). Each biomarker revealed a gradient of mortality risk from Q1 to Q5: D-dimer 17-35%, CRP 11-30%, ferritin 11-29%, cTn 13-42%, and NPs 7-35% (p trend for each &lt;0.001; Panel A ). After adjustment for all biomarkers, the highest values (Q5) of NP, CRP, and cTn independently identified pts at greater odds of death ( Panel B ) and the highest values of NP, CRP, cTn and D-dimer identified greater odds of the CV composite. After further adjustment for clinical variables, Q5 values for NPs (OR:4.07, 95% CI: 2.40 to 6.92) and CRP (OR: 2.43, 95% CI:1.62 to 3.66) retained the strongest prognostic value for death; NP (OR:6.79, 95% CI: 3.56 to 12.94) and cTn (OR:4.44, 95% CI:2.75 to 7.18) were associated with the greatest odds of the CV composite. Conclusions: Among pts hospitalized with COVID-19, high levels of NPs, CRP and hsTn at the time of admission were associated with the greatest risk of death, independent of other biomarkers and clinical variables, whereas D-dimer and ferritin did not offer independent prognostic information for mortality.
Abstract 16677: Protein Kinase G I Alpha Attenuates Inducible Ventricular Tachycardia and QRS/T Wave Alternans in the Type II Diabetic Heart
Authors: Robert M Blanton, Hongwei Jin, Chris Madias, Yali Zhang, Bo Wang, Mark J Aronovitz, Daniel A Richards, Jonas B Galper
Journal: Circulation (2018)

Introduction: Diabetes increases ventricular tachycardia (VT) and sudden cardiac death risk in humans. We previously found the type I diabetic (DMI) heart displays: reduced responsiveness to parasympathetic stimulation; increased QRS/T Wave alternans (marker of proarrhythmic calcium dyshomeostasis); and hyperactive GSK3beta. Cardiac parasympathetic stimulation promotes production of intracellular cyclic GMP (cGMP). The effects of cGMP and its downstream effector PKG, on these indices of VT in type II diabetes (DMII) remain poorly understood. Hypothesis: PKGIa modulates inducibility of VT and QRS/TWA in the DMII heart and mediates the cGMP effect on VT through inhibition of myocardial GSK3beta. Methods: Using an established protocol of programmed ventricular stimulation we measured: VT incidence, duration, and QRS/T Wave alternans. We studied the following mice: wild type; Db/Db model of DMII; high fat high sucrose (HFHS) model of insulin resistance; and the PKGIa leucine zipper mutant (LZM) mouse, which has no DM but has PKGIa disrupting mutations. Mice were treated with or without the cGMP-augmenting phosphodiesterase inhibitor sildenafil 10 mg/kg, or the GSK3b inhibitor TWS119 20 mg/kg. Results: LVs of HFHS mice displayed 30 ± 8% reduction of cGMP compared with control (p&lt;0.05, n=3 per group), while myocardial cGMP in LZM mice did not differ from control. In failing LVs from humans, there was also a 46% reduction in myocardial cGMP in DM compared with nondiabetic (p= .058, n=3 per group). Db/Db and HFHS mice had increased inducible VT (0.25 +/- 0.1 s in Db/Db, 2.2 +/- 1 s HFHS, vs 0 s in WT control, p &lt;0.05), as well as TWA. Treatment with sildenafil reduced VT incidence, duration, and TWA in Db/Db and HFHS mice. LZM mice also had increased VT duration and TWA incidence (0 of 4 in WT vs 5 of 6 in LZM, p&lt;0.05). Inhibition of GSK3β rescued inducibility of VT in Db/Db, HFHS, and in LZM mice. Conclusions: These findings support that in the DMII heart reduced cGMP promotes VT, whereas pharmacological augmentation of cGMP inhibits VT. Inducible VT and TWA in the PKG LZM mouse provides direct support that PKGIa opposes VT in the DMII heart. These support that cGMP activation of PKG inhibits GSK3beta, leading to reduced incidence of inducible VT.
Abstract 13980: The Association of Education and Household Income With the Lifetime Risk of Incident Atrial Fibrillation: The Framingham Heart Study
Authors: Feven Ataklte, Qiuxi Huang, Jelena Kornej, Favel L Mondesir, Emelia J Benjamin, Ludovic Trinquart
Journal: Circulation (2021)

Introduction: Social determinants of health, in particular education and income, influence the incidence, management, and outcomes of cardiovascular diseases including atrial fibrillation (AF). However, data are limited on the effect of socioeconomic status on the lifetime risk of incident AF. We assessed the association of income and education with lifetime risk of AF in the Framingham Heart Study (FHS). Methods: We selected 2172 FHS participants (51% women) who were free of AF at the index age of 55 years. We assessed educational attainment (some college or more) at the last exam prior to index age and household income ($40k/50k/55k or more depending on the FHS cohort). We estimated the lifetime risk of AF as the cumulative incidence of AF, accounting for the competing risk of death, at age 95 years. We analyzed strata defined by education and household income separately, and by combining education and household income. We adjusted analyses on sex, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, history of myocardial infarction, and history of heart failure. Results: Over a mean follow-up of 13 years, 265 participants developed incident AF. The lifetime risk of developing AF was 32.5% (95%CI, 26.5% to 38.5%) and 32.5% (95%CI, 28.7% to 38.3%) among participants with lower and higher education attainment (p=0.98). The lifetime risk of developing AF was 32.1% (95%CI, 26.7% to 37.5%) and 31.8% (95%CI, 26.6% to 36.9%) among participants with lower and higher household income (p=0.79). There was no evidence of an interaction between education and income on lifetime risk of AF (p = 0.84). Results were similar in subgroups of women and men. Conclusions: In our community-based sample, there was no evidence of association between education or household income and lifetime risk of AF
Abstract 13675: Temporal Trends and Prognostic Significance of Coronary Artery Disease in Patients With Critical Limb Ischemia: Insights From the National Inpatient Sample
Authors: Zainali Chunawala, Christopher Chew, Michael Hendrickson, Sameer Arora, Gregory Mishkel, Alfonso J Tafur, Justin p Levisay, Mark Ricciardi, Cheong Jun Lee, Arman Qamar
Journal: Circulation (2021)

Background: It is uncertain whether presence of CAD has a prognostic implication in patients (pts) with CLI. We sought to compare the trends and outcomes of pts with CLI based on presence of history of CAD. Methods: Temporal trends in hospitalization for CLI based on history of CAD were determined using the 2000-2018 NIS database. A multivariable regression analyses of outcomes was performed based on the CAD status and revascularization type. Propensity score matching was used to compare outcomes based on type of revascularization. Primary outcome of interest was in-hospital mortality. Results: Among 13,570,000 pts with CLI (41% female, 69% whites, mean age 69 years), 23% had concomitant CAD and 9.6% underwent revascularization (42.6% endovascular &amp; 57.4% surgical). In pts with CLI, there was an increasing trend in the prevalence of CAD (Figure; Panel A). Furthermore, in pts with CLI + CAD, the frequency of endovascular revascularization increased from 15% to 48% while there was a decreasing trend of surgical revascularization (85% to 52%). After multivariate adjustments, CLI + CAD was associated with increased risk of in-hospital mortality (OR: 1.40; CI: 1.32-1.47) &amp; bleeding requiring transfusion (OR: 1.10; CI: 1.06-1.12) than those with CLI without CAD (Figure; Panel B). Among both patients with CLI + CAD &amp; CLI without CAD, endovascular revascularization was associated with lower likelihood of in-hospital mortality (OR: 0.69; CI: 0.63- 0.76 &amp; OR: 0.71; CI: 0.67-0.76) &amp; bleeding requiring transfusion (OR: 0.40; CI: 0.38- 0.43 &amp; OR: 0.44; CI: 0.43- 0.46) than surgical revascularization. Conclusions: Increasing prevalence and poor prognosis of CAD among patients with CLI warrants immediate attention to optimize preventive and treatment strategies.
Abstract 16713: Defining the Tbx5-Dependent miRNA Regulatory Networks of Atrial Fibrillation
Authors: Sonja Lazarevic, Rangarajan D Nadadur, Margaret Gadek, Kaitlyn M Shen, Carlos Perez-Cervantes, Brigitte Laforest, Xinan H Yang, Christopher R Weber, Ivan P Moskowitz
Journal: Circulation (2018)

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmic disorder, characterized by random electrical activity in the heart. Complications of AF include stroke and heart failure, which makes understanding the molecular mechanism underlying this conduction defect imperative. The Tbx5 locus has been implicated by genome wide association studies (GWAS) to have an increased risk for AF. Our lab has previously demonstrated the absence of this transcription factor leads to spontaneous and sustained AF, which corroborates the importance of Tbx5 in the maintenance of cardiac rhythm. While Tbx5 is known to drive the network for cardiac rhythm, the downstream regulatory components need to be further characterized, including the downstream miRNAs. The components involved in cardiac rhythm are dose sensitive, therefore small perturbations in gene expression can lead to arrhythmias. Maintaining stable levels of gene expression can be regulated with miRNAs, which provide a negative feedback in dose sensitive pathways. Tbx5 -deficient mice developed spontaneous, sustained AF; in order to further interrogate the TBX5-dependent pathway that led to AF, we transcriptionally profiled small RNAs from the left atrium of Tbx5 -deficient mice. The most downregulated TBX5-dependent miRNA was miR10b. In concordance with previous publications, our miR10b mimic and inhibitor experiments in HL-1 cardiomyocytes demonstrate that miR10b negatively regulates Tbx5 expression. Therefore, we hypothesized that miR10b was crucial in the maintenance of atrial rhythm. Cellular electrophysiology studies with the overexpression of miR10b in HL-1 cardiomyocytes led to the elongation of atrial action potentials, similar to the phenotype we saw in the Tbx5 -deficient atrial tissue. Using whole mouse electrophysiology, we found that the mir10b removal in the hearts leads to increased AF susceptibility. Thus, providing evidence that mirR10b is crucial for the maintenance of normal cardiac conduction. In order to identify other miRNAs essential for cardiac conduction, we examined the other TBX5-dependent miRNAs in a high-throughput calcium screen. Further defining the miRNAs can provide a better understanding of the regulatory mechanisms crucial for cardiac conduction.
Abstract 16708: Inhibition of Alpha-Ketoglutarate Dehydrogenase Activates Autophagy
Authors: Anja Karlstaedt, Heidi Vitrac, Koen Raedschelders, Weston Spivia, Walter Schiffer, Daniel McNavish, Jennifer VanEyk, Heinrich Taegtmeyer
Journal: Circulation (2018)

Introduction: Metabolic reprogramming is a hallmark of cancer and heart failure. In isocitrate dehydrogenase 1 and 2 mutant tumors, increased plasma levels of the oncometabolite D-2-hydroxyglutarate (D2-HG) inhibit α-ketoglutarate dehydrogenase (α-KGDH) in the heart. This inhibition is associated with muscle atrophy and reduced ATP and NADH provision. The connection between metabolic changes and proteome remodeling are still poorly understood. Hypothesis: Inhibition of α-KGDH promotes autophagy activation through the sirtuin family of NAD + -dependent deacetylases. Methods: We treated both male and female wild-type C57BL/J6 mice (n=12) with D2-HG in vivo, and cultured L6 myocytes (L6Ms) and adult mouse ventricular cardiomyocytes (AMVMs) with D2-HG. We constructed LC3 mutants with a lysine-to-arginine (GFP-LC3K49R-K51R) and lysine-to-glutamine (GFP-LC3K49Q-K51Q) replacement at Lys49 and Lys51 mimicking deacetylated and acetylated LC3, respectively. Results: Inhibition of α-KGDH by D2-HG is accompanied by heart and skeletal muscle atrophy, as well as increased LC3 and p62 expression in mice treated over 30-days. In vivo and in vitro treatment with D2-HG for 24h, increases phosphorylation and activation of AMPK, while phosphorylation of mTOR and p70S6K decreases. Thus, acute α-KGDH inhibition impacts protein turnover. Autophagy activation is highly dependent on D2-HG concentration and duration. ATP levels significantly decrease in differentiated L6Ms and AMVMs when treated with D2-HG levels above 0.13 mM over 24 to 96 h. GFP-tagged LC3 co-localizes with lysosomes labeled with LysoTracker Blue dye and mitochondria labeled with MitoTracker Red CMXRos dye upon α-KGDH inhibition, which indicates the presence of autophagosomes and mitophagosomes. We show that upon α-KGDH inhibition and subsequent NAD + increase, Sirt1 forms a molecular complex with LC3 and activates autophagy through deacetylation of LC3. In these conditions, LC3K49R-K51R mutants show puncta formation in the cytoplasm indicating that in addition to NAD + increase other factors are driving autophagy activation. Mass spectrometry-based proteomics and metabolomics revealed that α-KGDH inhibition induces upregulation of tropomyosin, NADH dehydrogenase and proteins involved in glycolysis and pentose phosphate pathway. Conclusions: Inhibition of α-KGDH promotes autophagy activation through deacetylation of LC3 by Sirt1 and culminates in proteome remodeling.
Abstract 16628: Improvement of LV-Strain in HFrEF-Patients at 12 Months Follow-Up Using the Revivent <sup>TM</sup> System (Bioventrix) Compared to Patients Treated by OMT- Results From a CMR-Multi-Center-Trial
Authors: Tomas Lapinskas, Christoph Klein, Gianni Pedrizzetti, Lukas Stoiber, Felix Hennig, Christoph Knosalla, Christoph Schmitz, David Schickling, Lon Annest, Sebastian Kelle
Journal: Circulation (2018)

Introduction: After an acute coronary syndrome many patients with ischemic cardiomyopathy (ICM) suffer from heart failure with reduced ejection fraction (HFrEF). Beside surgical ventricular reconstruction (SVR) by open-chest-surgery as an option to improve myocardial function by restoring the shape and size of the heart in HFrEF patients, first results demonstrated a significant reduction of LV volumes and LVEF using the Revivent TC TM System compared to optimal medical therapy (OMT) in patients with aneurysms in the anterior region of the LV. Objectives: To assess the impact of the Revivent TC™ system (Bioventrix Inc.) as a Less Invasive Ventricular Enhancement (LIVE™) technique to improve systolic and diastolic LV-function in patients with HFrEF compared to treatment of patients with OMT. Methods: We analyzed data from 10 patients and 10 controls with ICM and LVEF ≤ 45% from a multi-center-trial as well as 12 healthy subjects. In total, 10 patients underwent LV reduction with the new LIVE™ technique. The control group patients received OMT only (natural course of disease). Global longitudinal strain (GLS) as advanced, quantitative CMR measurement has been performed both at baseline and 12 months to quantitatively assess LV function. In addition, hemodynamic forces (HF) as an equivalent to intraventricular pressure gradients derived from CMR-data have been evaluated. Results: After 12 months follow-up, LVEF improved after using the Revivent TM System (27.8 ± 10.6 % vs. 31.5 ± 10.9 %), but not in controls (31.8 ± 8.2 % vs 31.3 ± 6.7 %). Minimal invasive treated patients showed a significant reduction in HF (33.6 ± 9.4 vs. 28.5 ± 10.5, p=0.04) and improved GLS (-9.4 ± 3.5 % vs. -11.4 ± 4.7 %; p=0.08). No change was observed in controls (31.5 ± 7.3 vs. 31.9 ± 6.9, p=0.37 and -12.8 ± 2.8 % vs. -12.6 ± 2.1 %; p=0.38) (see Figure). Conclusion: We demonstrate an improvement of LV strain and hemodynamic forces 12 months after using the Revivent TC TM System in HFrEF-patients compared to OMT. The impact on outcome and exercise capacity of HFrEF-patients has to be proven in larger trials with longer follow-up.