tbuckley/cabot-search huggingface dataset:
Abstract 14430: 5-year Outcomes After Transcatheter &amp; Surgical Aortic Valve Replacement in Advanced Chronic Kidney Disease Patients
Authors: Haig Pakhchanian, Rahul Raiker, Osama Boustany, Deepak Acharya, Amrita Mukherjee, Kwan S Lee, Arka Chatterjee
Journal: Circulation (2021)

Introduction: Advanced chronic kidney disease (CKD4,5) patients are known to have increased morbidity and mortality when undergoing surgical procedures. While short term outcomes among patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR) have been studied, research assessing long term outcomes are scant. Therefore, the goal was to assess 5-year outcomes for these patients undergoing TAVR or SAVR. Methods: A retrospective cohort study was done using TriNetX, a national federated real time database of 69 million records. Patient cohorts were identified if they met the criteria for CKD and underwent TAVR or SAVR up until May 2016 for 5 year follow up. A 1:1 matched propensity score analysis was conducted, adjusting for comorbidities and demographics, to calculate adjusted Risk Ratios (aRR) with 95% confidence intervals (CI) for complications of interest. Kaplan Meir (KM) analysis was done to calculate survival probability in 5 years among the 2 cohorts. Results: In a matched sample of 355 patients in each cohort, the TAVR did not show any significant differences in mortality (RR[CI]): (1.07[0.89-1.28]) compared to the SAVR Group. However, KM analysis revealed a significantly lower 5-year survival probability compared to the SAVR group (p&lt;0.035). There were no statistically significant differences among the 2 cohorts in other assessed long-term complications such as stroke (0.67[0.42-1.05]) and new pacemaker placement (1.31[0.81-2.17]). However, redo TAVR/SAVR was higher in the TAVR cohort than the SAVR cohort (3.1[1.54-6.23]). Conclusions: 5-year mortality appears to be similar in advanced CKD patients but repeat TAVR/SAVR were much higher suggesting decreased longevity of TAVR valves in this population.
Abstract 14405: Impact of Educational Attainment on All-Cause and Cardiovascular Mortality: Findings From a National Study of US Adults
Authors: Najah Khan, Zulqarnain Javed, Isaac Acquah, Madiha Khan, Mohamad Taha, Kobina Hagan, Safi U Khan, Ryan Chang, Javier Elizondo, Miguel Cainzos-Achirica, Khurram Nasir
Journal: Circulation (2021)

Introduction: Education is an important determinant of cardiovascular disease (CVD). However, the extent to which educational attainment impacts the risk of all-cause and cardiovascular (CV) mortality on a population level is relatively understudied. Methods: We used data from 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of education (&lt; High School (HS), HS/General Education Development (GED), Some College, and &gt; College) in adults with and without CVD. Cox proportional hazards models were used to examine the association between educational attainment and all-cause and CV mortality. Results: Final sample comprised of 256,991 participants (mean age=46.3), representing ~230 million adults annually, of which 8% had ASCVD. Overall, 14.8% of participants had &lt;HS education and 27.3%, 19.9% and 38.0% had HS/GED, Some College, and &gt; College education, respectively. During a median follow-up of 4.5 (IQR: 2.5-6.8) years (1179 million person-years), all-cause and CV AAMRs were approximately 1.5 and 2 fold higher, respectively, for &lt;HS vs. &gt;College education in the CVD population and 2 fold higher in the non-CVD population ( Figure 1 ). In fully adjusted models, &lt; HS (reference= &gt;College) was associated with 20% increased risk of all-cause (HR 1.20, 95% CI: 1.07-1.35) and 40% increased risk of CV mortality (HR 1.41, 95% CI: 1.10-1.81) in the CVD population, compared to 40-45% increased risk of mortality in the non-CVD population (all-cause mortality HR 1.39, 95% CI: 1.29-1.49; CV mortality HR 1.45, 95% CI: 1.20-1.75). Similar trends were seen by race/ethnicity (data not shown). Conclusions: Lower education is an independent predictor of all-cause and CV mortality in both CVD and non-CVD populations. Efforts for integration of educational attainment into existing CV risk prediction algorithms are needed to mitigate observed socioeconomic disparities in mortality.
Abstract 14410: Predicting Intubation and Ventilation Needs Upon Admission for Intensive Care Patients With Congestive Heart Failure
Authors: Ayush Sangari, Aditya Sood, Anish Sangari, Nitish Sood, Kushagara Maini
Journal: Circulation (2021)

Introduction: Congestive heart failure (CHF) is one of the most common diagnoses for patients admitted to an intensive care unit (ICU), and intubation or ventilation may be necessary to combat severe associated respiratory symptoms. Current guidelines give high-level recommendations to intubate patients with a Glasgow Coma Scale (GCS) score of 8 or lower. However, prior studies have shown that a large portion of patients who were ultimately intubated had GCS scores greater than 8, demonstrating the need for a better tool to predict the necessity of intubation. The present study sought to build machine-learning (ML) models that could predict the need for intubation or ventilation for CHF patients upon ICU admission. Methods: 5,623 patients (of which 1,058 were intubated and 2,816 were ventilated) in the eICU Collaborative Research Database who underwent screening using the Acute Physiology and Chronic Health Evaluation and were diagnosed with CHF were used to train (50%) and test (50%) the ML models. Gender, age, treatment status, readmission status, medication status upon admission, GCS motor score upon admission, and GCS eyes score upon admission were used as feature inputs for the ML models, which were classic three-layer neural networks. For intubation, the ML model performance was compared against using the common heuristic of intubating patients with a GCS score of 8 or less. Results: The ML model for intubation upon admission prediction had an accuracy of 84.8% and an area under the receiver operating characteristic curve (AUC) of 0.79. Meanwhile, using the aforementioned heuristic for intubation prediction yields an accuracy of 85.7% (AUC n/a). A second ML model was trained to predict the need for ventilation upon admission and had an accuracy of 71.2% and an AUC of 0.80. Conclusion: This newly developed ML model for intubation demonstrates relative success in predicting intubation needs for patients with CHF upon ICU admission. In addition, this model performs similarly to currently accepted guidelines. Further improvement and a larger dataset could better train the model to provide more accurate predictions. Such predictions could help support medical decision-making and resource allocation planning.
Abstract 14429: Clinical and Laboratory Correlates of Impaired Cholate Clearance in the Adult Fontan
Authors: Yuli Y Kim, Joshua Saef, Greg Everson, Steve Helmke, Jessica Carducci, Andrew C Glatz, Sara L Partington, Emily Ruckdeschel, Jack Rychik, Maarouf Hoteit
Journal: Circulation (2021)

Introduction: The dual cholate test is a noninvasive, flow-dependent assay measuring hepatic clearance of bile acid, cholate. A measure of liver function, cholate clearance has been shown to be decreased in the Fontan. We aim to explore the association between clinical features, cardiac/liver testing, laboratory tests and cholate clearance in a cohort of Fontan patients. Methods: Single center, prospective study of Fontan patients ≥ 18 years. Hepatic clearance of orally administered d4-cholate and intravenously administered 13C-cholate were measured in peripheral venous samples and calculated as portal hepatic filtration rate (HFR), systemic HFR, shunt fraction (systemic HFR/portal HFR), and disease severity index (DSI). Subjects were grouped according to shunt fraction (abnormal &gt;30%) and/or DSI (abnormal &gt;18.3). Kruskall-Wallis and Fisher exact tests were performed to analyze between-group differences. Results: Twenty-four Fontan patients were enrolled (50% female, median age 30.3 [interquartile range IQR 25.0 - 36.5] years, median cardiac index 2.91 [IQR 2.50 - 3.24] ml/mg/m2). Median total bilirubin was 0.95 [IQR 0.6 - 1.2] mg/dL, AST 29.5 [IQR 21.0 - 38.3] U/L, ALT 26.5 [IQR 20.8 - 36.3] U/L, alkaline phosphatase 75.5 [IQR 68.3 - 94.8] U/L, albumin 4.6 [IQR 4.3 - 4.7] g/dL, alpha fetoprotein 2.0 [1.9 - 3.0] ng/mL, platelets 177 [IQR 142.8 - 189.3] 10 3 /μL. There were no subjects with abnormal shunt fraction and normal DSI (Table). Conclusions: Oxygen saturation, alkaline phosphatase, and alpha fetoprotein correlate with abnormal cholate clearance whereas cirrhosis on imaging and Fontan pressures trended towards an association. Larger studies are warranted to explore these associations with cholate clearance to elucidate the nature of Fontan associated liver disease.
Abstract 9891: Are CAC Scores Less Valuable for Patients of Low Socioeconomic Status? <i>A Dallas Heart Study Analysis</i>
Authors: Mark Berlacher, Taylor Triana, Elaine C Wu, Shreya Rao, Tiffany Powell-wiley, Ambarish Pandey, Parag H Joshi, Amit Khera
Journal: Circulation (2021)

Background: Low socioeconomic status (SES) is associated with atherosclerotic cardiovascular disease (ASCVD) and possible underestimation of risk by the pooled cohort equations (PCE). Whether coronary artery calcium (CAC) scores can improve risk discrimination in those with low SES is unknown. Methods: Individuals from the Dallas Heart Study free of ASCVD and with CAC scanning were evaluated. Low SES was defined as an annual income &lt;$16,000 or an educational attainment level ≤11 years. Unadjusted and adjusted analyses assessing the relationships between SES and 1) CAC scores and 2) ASCVD events (fatal or non-fatal MI or stroke) were performed. The incremental predictive value of CAC in those at low and higher SES was assessed using c-statistics (PCE alone vs PCE + CAC). Results: Among 2246 individuals (mean age 44 yrs, 55% women, 45% Black), 115 ASCVD events occurred over a median of 12.5 years. Low SES by income (n=451) was associated with increased risk of ASCVD after adjustment for risk factors (HR 2.16, 95% CI 1.37-3.42), but was not independently associated with CAC. Higher CAC scores (0, 1-99, ≥100) tracked with increased 10-year ASCVD event rates in those at low (5, 10, and 22%) and higher SES (0.002, 4, and 11%), with low SES groups carrying greater ASCVD risk for every stratum of CAC, including with CAC=0. In multivariable models compared with CAC=0, those with CAC 1-99 and ≥100 had a greater risk of ASCVD events for individuals at higher SES [HR 3.40 (1.5-7.8), and 4.8 (1.9-12.6)], but not for those with low SES [HR 1.00 (0.4-2.4), and 1.6 (0.6-4.6)], (p-interaction CAC x SES=0.002). Similar results were found for low SES defined by education. The addition of CAC to PCE improved risk discrimination for individuals at higher SES, but not for individuals at low SES (Table 1). Conclusion: Individuals at low SES have significantly increased risk of ASCVD, however, CAC scores are not independently associated with ASCVD in this population and may be less useful in risk discrimination.
Abstract 8859: Hematopoietic <i>Calr</i> Frameshift Mutation Exacerbates Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Tetsuro Yokokawa, Tomofumi Misaka, Yusuke Kimishima, Keiji Minakawa, Koichi Sugimoto, Kazuhiko Nakazato, Kazuhiko Ikeda, Yasuchika Takeishi
Journal: Circulation (2021)

Introduction: Calreticulin ( CALR ) frameshift is the second frequent driving mutation in myeloproliferative neoplasms (MPNs). MPNs are complicated with pulmonary hypertension (PH), but the mechanistic relevance of the CALR mutations on PH has not yet been clarified. Methods and Results: We generated a 10-bp deletion knock-in mice with murine Calr exon 9 mimicking the human CALR mutations. To investigate whether the hematopoietic CALR mutation contributes to PH, a bone marrow transplantation (BMT) was applied using the donor BM cells from Calr knock-in mice or control wild-type (WT) mice. Four weeks after BMT, the recipient mice transplanted with BM cells from Calr knock-in mice (Del-R) and WT mice (WT-R) were exposed to chronic hypoxia. Three weeks after starting chronic hypoxia exposure, the right ventricular systolic pressure and right ventricle/left ventricle-plus-septum weight ratio in the Del-R mice were significantly increased compared to the WT-R mice. Lung histology showed an acceleration of pulmonary arterial muscularization and medial wall thickness in Del-R mice after chronic hypoxia. Increases in macrophage infiltration was similarly observed in both WT-R and Del-R mice after chronic hypoxia. Endothelin-1 expression and STAT3 phosphorylation were significantly upregulated in the lung of Del-R mice compared to the WT-R mice in response to chronic hypoxia. Using Calr Del/CAG-EGFP double transgenic mice, we visualized the accumulations of donor-derived macrophages in pulmonary arterial regions. BM-derived macrophages carrying the Calr mutation showed increases in endothelin-1 expression, indicating that BM-derived macrophages with the Calr mutation played important roles in the pulmonary arterial remodeling. Conclusion: The frameshifted Calr mutations presented a novel mechanism of PH through BM-derived macrophages accompanied by upregulation of endothelin-1.
Abstract 9855: Bayesian Multivariate Genetic Analysis of Lipids Improves Translational Insight
Authors: Sarah M Urbut, Margaret Sunitha Selvaraj, Akhil Pampana, Lillian Dattilo, Benjamin Neale, Christopher J ODonnell, Gina Peloso, Pradeep Natarajan
Journal: Circulation (2021)

Introduction: Genome-wide association studies (GWAS) of blood lipids have yielded several translational insights for coronary artery disease. Hypothesis: We tested the hypothesis that novel Bayesian methods leveraging genetic correlation can improve insights from lipid genetics analyses. Methods: We used published lipids GWAS results from 297,626 participants of the Million Veterans Program (MVP), and generated summary statistics for 276,096 participants of the UK Biobank. We employed a multivariate adaptive shrinkage (mashR) model to each dataset. MashR allows the effect of a SNP to be modeled as a mixture of multivariate normal distributions across lipid levels (LDL-C, HDL-C, Total Cholesterol, and triglycerides) and an empirical Bayes approach to appropriately nudge the posterior estimates of the effect in accordance with the overall patterns observed in the data. Results: In addition to reproducing all 318 loci significantly associated with lipids in MVP, we identified 4,689 novel loci associated with lipids using mashR. We observed a high degree of agreement between MVP and UK Biobank, with over 95% of UKBB replicated in MVP and an additional 1246 identified. In genetic prioritization analyses, mashR shows improvement in the detection of known Mendelian genes and the consistency of ranks among subgroups compared with univariate results. Our approach improves the estimate of enrichment parameters of known genomic features similar to established GWAS variants. Finally, combining these joint estimates with tools for incorporating the genetic correlation structure, mashR improves the proportion of variation explained by lipid polygenic risk scores by up to 58% (se 0.015) when compared to univariate substrates across lipid traits. This improvement holds across both European and non-European individuals. We show that much of this gain in power arises from improved precision of the posterior estimates where the ratio of original standard error over posterior marginal variance reflects an increased ‘effective sample size’. Conclusions: Our framework shows that Bayesian multivariate genetic analysis markedly improves power for genomic discovery, better identifies causal genes, and improves polygenic risk prediction for complex traits.
Abstract 12647: Linagliptin Reduces Arterial Stiffness and Arterial Inflammation in Persons With Early Type 2 Diabetes: a Double-blind, Randomized Controlled Trial
Authors: Stefanie A de Boer, Hiddo J Heerspink, Joop D Lefrandt, Arie M van Roon, Luis E Juàrez Orozco, Andor W Glaudemans, Pieter W Kamphuisen, Riemer H Slart, Douwe J Mulder
Journal: Circulation (2016)

Introduction: Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral antidiabetic drugs. Recent experimental studies have suggested beneficial vascular effects, but clinical evidence is limited. Hypothesis: The primary objective was to evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a measure of arterial stiffness and secondarily, on arterial 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake as a measure of arterial inflammation in type 2 diabetes. Methods: A total of 45 treatment naive type 2 diabetes patients (median age 63 (IQR 54-66) years, 61% male, mean HbA1c 6.3±0.4 (%)) without cardiovascular disease were randomized (1:1) to linagliptin 5 mg or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4, 26 weeks of treatment and at 30 weeks (washout). Arterial inflammation was quantified by FDG uptake as the pre-scan glucose corrected maximal standardized uptake value corrected for background (TBR). TBRs were calculated for the carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries, and averaged for the total aortic tree ( mean TBR). Results: PWV decreased in the linagliptin group and was stable placebo (Figure A). The generalized linear model analysis showed a mean group difference of linagliptin compared to placebo of 0.91 m/s [95% CI 0.06-1.76](p=0.035) at 26 weeks. PWV returned to baseline after washout. mean TBR decreased in the linagliptin group compared with placebo by 0.18 [0.04-0.32] (p=0.015) after 26 weeks (Figure B). Linagliptin compared with placebo decreased HbA1c (p&lt;0.001), fasting plasma glucose (p=0.002), and triglycerides (p=0.019). Conclusions: Linagliptin reduces aortic PWV as a measure of arterial stiffness and arterial FDG uptake as a measure of arterial inflammation compared with placebo after 26 weeks of treatment in early type 2 diabetes patients.
Abstract 13496: Impact of Serum Albumin Levels on Long-term Outcomes in Patients Undergoing Percutaneous Coronary Intervention
Authors: Hideki Wada, Tomotaka Dohi, Katsumi Miyauchi, Jun Shitara, Hirohisa Endo, Shinichiro Doi, Ryo Naito, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Takatoshi Kasai, Satoru Suwa, Hiroyuki Daida
Journal: Circulation (2016)

Background: Numerous studies have reported that lower serum albumin on heart failure is associated with increased adverse events. However, the relationship between albumin and long-term outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) is not well known. Methods: We studied 2,860 all-comer patients with CAD who underwent their first PCI and available data of pre-procedural serum albumin between 2000 and 2011. Patients were assigned to tertiles based upon pre-procedural albumin levels. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death and acute coronary syndrome (ACS). Results: The mean albumin level was 4.0±0.5 g/dL. Patients with a lower albumin levels were older and had a higher prevalence of ACS and chronic kidney disease (CKD). Patients with a higher albumin values were likely to be higher LVEF and had a higher prevalence of statin use. During a median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of MACE among the albumin tertile groups (albumin &lt;3.8g/dl: 44.3% vs. 3.8-4.1g/dl: 38.0% vs. &gt;4.1g/dl: 22.9%; log-rank p&lt;0.0001). After adjustment for established cardiovascular risk factors including age, ACS, BMI and CKD, serum albumin levels were significantly associated with incidence of MACE (HR 1.67 per each 1g/dl decrease, 95%CI 1.32-2.08, p&lt;0.0001) and all-cause mortality (HR 1.75, 95%CI 1.30-2.33, p=0.0002). Conclusions: Pre-PCI low serum albumin level was associated with worse long-term outcomes, independent of traditional risk factors. Assessing the albumin levels may have implications for risk stratification in patients with CAD undergoing PCI.
Abstract 13491: Mitral Valve Annular Dilatation &amp; Augmented Valve Closing Force to Tract Papillary Muscle as a Possible Mechanism of Late-systolic Mitral Valve Prolapse: Pre- &amp; Post-operative Echocardiographic Study With Speckle Tracking Analysis
Authors: Shota Fukuda, Jae-Kwan Song, Keitaro Mahara, Yukio Abe, Jeong Yoon Jang, Hiroshi Kuwaki, Atsushi Hayashi, Takeshi Onoue, Soshi Hei, Mai Iwataki, Byung Joo Sun, Yun Jeong Kim, Masaaki Takeuchi, Masataka Eto, Yosuke Nishimura, Yasuyuki Sasaki, Shuichiro Takanashi, Robert A Levine, Yutaka Otsuji
Journal: Circulation (2016)

Introduction: Stable papillary muscle (PM) position and contraction enable constant PM tip distance from mitral valve (MV) annulus, which can contribute to constant MV coaptation height during systole (Figure A). Hypothesis: In patients with late-systolic MV prolapse (L-MVP), superior shift of MV coaptation toward left atrium (LA) during systole may be linked to abnormal PMs superior shift, which can be related to augmented MV closing force by MV annular dilatation. Methods: In 15 controls and 20 with L-MVP, MV coaptation height from its annulus was measured at early- and late-systole by echocardiography to evaluate systolic superior shift of MV coaptation. Distances of PMs tip and MV annulus from external reference point around the apex were monitored by 2 points speckle tracking, and systolic shift of PMs tip toward MV annulus was measured (Figures B and C). MV closing force was calculated as MV annular area х (systolic blood pressure - 10). Echocardiography was repeated after MV plasty in 5 L-MVP patients. Results: Systolic superior shift of MV coaptation (3.3±0.9 vs 1.4±0.5 mm/m 2 ) and PMs tip (2.9±1.3 vs 1.3±0.4 mm/m 2 ) relative to MV annulus were greater in L-MVP compared to controls (p&lt;0.001) (Figures C and D). Systolic superior shift of MV coaptation was independently determined by systolic superior shift of PMs tip (β=0.66, p&lt;0.001), which was related to augmented MV closing force with MV annular dilatation (β=0.72, p&lt;0.001). Systolic superior shift of PMs tip (4.2±2.0 to -0.5±1.2 mm/m 2 , p=0.007) and MV coaptation (4.2±1.7 to 0.9±0.3 mm/m 2 , p=0.006) disappeared after surgical MV plasty with reduction in MV annulus and MV closing force in 5 patients with L-MVP. Conclusions: Systolic superior shift of MV coaptation in patients with L-MVP was associated with systolic superior shift of PM tip. Disappearance of these abnormalities after surgical MV plasty suggests that primarily augmented MV closing force with MV annular dilatation acting on PM traction may promote L-MVP.