tbuckley/cabot-search huggingface dataset:
Abstract 14549: Outcome of Radiofrequency Catheter Ablation of Cavo-tricuspid Isthmus Dependent Flutter in Patients With Adult Congenital Heart Disease
Authors: Stephanie Jou, Isaac L Goldenthal, Angelo B Biviano, Elaine Wan, Amardeep S Saluja, Jose Dizon, John P Morrow, Geoffrey Rubin, Marc Waase, Frederick Ehlert, Marlon S Rosenbaum, Hasan Garan, Hirad Yarmohammadi
Journal: Circulation (2020)

Introduction: Both typical cavo-tricuspid isthmus (CTI) dependent (or its equivalent) and atypical atrial flutter (AFL) are common in adults with congenital heart disease (CHD) either due to its inherent cardiac anatomy or as a result of prior surgical procedures. Radiofrequency catheter ablation is routinely used as a therapeutic option. Hypothesis: Patients with CHD will have an improvement in systemic ventricular ejection fraction and a decreased incidence of atrial arrhythmias after ablation. Methods: A retrospective study was conducted on 99 patients with CHD who underwent ablation for clinical AFL at a single institution between 2010 and 2019. Of these patients, 62 had CTI-AFL. The 2 patients with unspecified CHD were excluded. CHD was divided into 3 categories according to the American College of Cardiology Task Force 1 of the 32nd Bethesda Conference - simple, moderate severity, and great complexity lesions. Outcomes of ablation at 1 year follow up were assessed. Results: Typical counterclockwise CTI-AFL was seen in 50 patients. The mean age was 49.1±13.6 years old with 29 (48.3%) females. Of the 60 patients, 35% (n=21) had simple lesions, 51.7% (n=31) had moderate lesions, and 13.3% (n=8) had great complexity lesions. The mean left or systemic ventricular ejection fraction (EF) significantly improved on follow-up echo among patients with simple CHD (49.1±13.1 to 56.5±4.7%, p=0.018) and moderate CHD (49.5±14.9 to 54±8.5%, p=0.02), but did not change among patients with great complexity CHD (52.5±6 to 52.5±9.25%, p=0.9). There was a significantly increased incidence of atrial fibrillation (9.5% vs. 16.1% vs. 50%, p=0.04) post ablation among simple, moderate, and great complexity lesions, respectively, but no significant difference in the recurrence rate of atrial flutter (p=0.3). Conclusions: Patients who underwent CTI-AFL ablation showed an improvement in EF in patients with simple and moderate CHD. There was also a significantly increased incidence in the development of atrial fibrillation post ablation in CHD with great complexity compared to simple or moderate CHD.
Abstract 14313: Machine Learning for Prediction of Low Density Lipoprotein Cholesterol in Fasting and Non-fasting Patients With and Without HIV Infection
Authors: Mariam N Rana, Chang Kim, Chris T Longenecker, Sadeer Al-Kindi
Journal: Circulation (2020)

Background: Low-density lipoprotein cholesterol (LDL-C) is commonly estimated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) using predefined equations which assume fixed or varying relationships between these parameters and may under- or overestimate LDL-C. Machine learning (ML) algorithms allow prediction of complex non-linear relationships. We, therefore, sought to investigate the utility of ML to predict LDL-C in comparison with two widely-used methods (Friedewald and Hopkins). Methods: We identified 7397 direct LDL-C (4716 HIV, 2060 uninfected controls) measurements in the Women's Interagency HIV Study (WIHS), a prospective study of women with and without HIV undergoing serial assessments. We trained and optimized 5 ML methods (linear regression, random forest, gradient boosting machine, support vector machine, and neural networks) to predict LDL-C using TC, HDL-C, and TG in 80% of the measurements and tested model performance in a holdout test set (20% of the measurements). Results: Overall, the support vector machine model had the best performance characteristics, outperforming Friedewald’s and Hopkins methods with higher R 2 , lower root mean square error and lower mean absolute error. The support vector machine model performance remained superior in participant subgroups with and without HIV and those with non-fasting measurements. Model performance parameters for the test dataset are shown in the Figure. Conclusions: A support vector machine learning model predicts directly measured LDL-C more accurately than Friedewald and Hopkins methods, especially in non-fasting patients with HIV. Further studies are needed to provide external validation.
Abstract 15422: Distribution of 10- and 30-year Predicted Risks for Heart Failure in the United States: NHANES 2015 to 2018
Authors: Nilay S Shah, Hongyan Ning, Sanjiv J Shah, Clyde Yancy, John T Wilkins, Donald M Lloyd-jones, Sadiya Khan
Journal: Circulation (2020)

Introduction: Heart failure (HF) poses a significant health burden with prevalence projected to increase by 46% by 2030 in the United States. Targeted implementation and dissemination of clinical and public health preventive measures across the life course will be informed by describing population distributions of short- and long-term predicted HF risk. Methods: Among nonpregnant middle-aged (30-59 years) adults without prevalent CVD from the National Health and Nutrition Examination Surveys 2015-18, continuous 10-year (10Y) and 30-year (30Y) HF risk estimates were calculated using short- and long-term risk equations derived in the Cardiovascular Lifetime Risk Pooling Project. High estimated 10Y risk was classified as ≥5%, and high 30Y risk as ≥20%. Participants were categorized by combined 10Y and 30Y estimated risk categories overall and stratified by sex, race, age, and body mass index. Distributions were compared using chi-square tests. Results: In 1495 NHANES participants (representing 53,022,413 Americans) with mean age 45 years (SE 0.3), median 10Y risk was 0.8% and 30Y risk was 11%. Approximately 4% of individuals were estimated to have high 10Y predicted risk of HF. Of those who were classified as low 10Y risk, 23% had high 30Y predicted risk. Distributions differed significantly by sex, race, age, and BMI (P&lt;0.01, Figure ). Black males more frequently were classified as high 10Y or 30Y risk compared to other race-sex groups. Older individuals and those with BMI ≥30 kg/m 2 had a higher frequency of low 10Y but high 30Y risk. Conclusions: More than one-fourth of middle-aged U.S. adults have elevated short- or long-term predicted risk for HF. While the majority of middle-aged US adults are at low 10Y risk for HF, a large proportion among this subgroup are at high 30Y HF risk. Application of both short- and long-term HF risk prediction may mitigate the growing morbidity and mortality related to HF and identify strategies to target those at-risk earlier in the life course.
Abstract 14608: Prognostic Value of Diuretic Resistance in Patients Admitted for Acute Decompensated Heart Failure With Reduced, Mid-range, or Preserved Left Ventricular Ejection Fraction
Authors: Takanari Kimura, Takahisa Yamada, Tetsuya Watanabe, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kunpei Ueda, Daisuke Sakamoto, Shota Ito, Takehiro Kougame, Yongchol Chang, Masatake Fukunami
Journal: Circulation (2020)

Background: Diuretic resistance is associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). However, little information is available on the prognostic significance of diuretic resistance in ADHF patients, relating to reduced, mid-range, or preserved left ventricular ejection fraction (LVEF). Methods: We studied 400 consecutive patients who were admitted for ADHF and survived to discharge. Diuretic resistance (DR) was defined by furosemide dose per body weight (BW) at discharge. Patients were classified by DR, and high dose group (higher DR) was defined by furosemide dose of &gt; median value of DR (0.580). The endpoint was a composite of all-cause mortality and unplanned hospitalization for worsening heart failure. Results: There were 139 patients with heart failure with reduced LVEF (HFrEF, LVEF&lt;40%), 86 with mid-range LVEF (HFmrEF, 40%≤LVEF&lt;50%) and 175 with preserved LVEF (HFpEF, LVEF≥50%). There was no significant difference in DR among the three groups (HFrEF; median 0.541 [IQR 0.360-0.786] mg/kg vs HFmrEF; 0.606 [0.398-0.820] mg/kg vs HFpEF; 0.624 [0.380-0.935] mg/kg, p=NS). During follow-up of 2.4±1.6 years, 195 patients reached the endpoint (HFrEF, n=67, HFmrEF, n=44, and HFpEF, n=84). In multivariate Cox analysis, DR was significantly associated with the endpoint independently of age, estimated glomerular filtration rate, plasma brain natriuretic peptide level and LVEF only in HFpEF patients (p&lt;0.0001). Kaplan-Meier analysis showed that the risk of the endpoint was significantly higher in the patients with higher DR in HFpEF patients, but not in HFrEF or HFmrEF patients (Figure). Conclusions: In this study, higher DR was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF.
Abstract 15942: Oral Anticoagulation as Compared to Oral Anticoagulation Plus Single Antiplatelet Therapy in Stable Coronary Artery Disease With Af: A Meta-analysis
Authors: Igor Vaz, Ashish Kumar, Mariam Shariff, Rajkumar P Doshi, Rafael Duarte
Journal: Circulation (2020)

Introduction: There are limited data on the appropriate antithrombotic therapy in patients with stable coronary artery disease (CAD) and concurrent atrial fibrillation (AF). The efficacy of using a single antiplatelet (SAP) in addition to oral anticoagulation (OAC) as compared to OAC alone remains controversial, with the earlier regimen associated with increased risk of major bleeding. Methods: A systematic electronic search of the PubMed, EMBASE and Cochrane databases was performed to identify relevant publications. Inclusion criteria were randomized controlled studies (RCTs) and observational studies comparing OAC+SAPT to OAC alone in patients with stable CAD and concurrent AF. All-cause mortality, stroke and myocardial infarction (MI) were the endpoints analyzed. We used the inverse variance method with random-effect model to calculate the hazard ratio (HR) with 95% confidence interval (CI). Statistical heterogeneity was calculated using Higgins I2 statistics. All statistical analysis was performed using RevMan Version 5.3. Results: The final analysis included two RCTs and 3 observational studies comparing OAC+SAPT versus OAC alone in patients with stable CAD and AF. There was no difference in the rate of mortality between the two treatment strategies [HR: 1.13, 95%CI: 0.88-1.46, I2= 71%] [Figure, PANEL A]. Subgroup analysis based on RCTs and observation studies reported similar results. Additionally, there was no difference in the rate of stroke [HR: 1.24, 95%CI: 0.83-1.85, I2= 0%] [Figure, PANEL B]or MI [HR: 0.57, 95%CI: 0.29-1.14, I2= 0%] [Figure, PANEL C] between the two treatment strategies Conclusion: OAC+SAPT as compared to OAC alone in patients with stable CAD and AF was associated with similar rates of all-cause mortality, stroke and MI.
Abstract 16676: Heightened Platelet Function: An Unrecognized Component of the Covid Hypercoagulability State
Authors: Kevin Bliden, Amit Rout, Rahul Chaudhary, Jaime Barnes, Sahib Singh, Saroj Timilsina, Udaya Tantry, Paul A Gurbel
Journal: Circulation (2020)

Introduction: Thrombo-inflammatory syndrome (TIS) characterized by a pathophysiological state of hypercoagulability, heightened platelet function, and inflammation has been observed in patients with acute myocardial infarction, and HIV. Hypothesis: The incidence of TIS is observed at a high rate in COVID-19 patients and worsens with symptom severity Methods: Blood samples from COVID-19 positive hospitalized patients (n=24) was collected for coagulation and platelet function analysis using point-of-care thromboelastography, TEG6s (Haemonetics, Corp) and routine labs were collected to measure markers of inflammation, coagulation, and organ damage (Table). Disease severity was grouped according to oxygen supplementation requirements and comparisons were made using unpaired t-test and chi-squared tests. Thrombo-inflammation was defined as the presence of both hypercoagulability by TEG [Clot initiation (R) &lt; 4.6, fibrin clot strength (FCS) &gt;32mm, and platelet fibrin clot strength (PFCS) &gt;69] and D-dimer &gt;ULN. Results: Ninety- five percent of COVID positive patients had at least one co-morbidity with the incidence of hypertension (71%), diabetes (50%), and obesity (42%) being the most frequent. A total of 63% (16/24) of patients had TIS, the incidence was significantly increased with escalating disease severity (p=0.03). A significant stepwise (p&lt;0.05) increase in FCS, D-Dimer, WBC count, lactate dehydrogenase, and procalcitonin was observed with worsening respiratory function (table). MA-ADP a measure of platelet function was in the high normal range for 81 % of patients. Conclusions: Thrombo-inflammatory is observed with most COVID patients, importantly heightened platelet function is a component of the syndrome and raises the question if antiplatelet therapy is needed in select COVID patients. Selective assessments with TEG6s may facilitate antithrombotic personalization.
Abstract 16286: Absence of Fxyd1 is Associated With a Female-specific Pro-inflammatory and Hypercholesterolemic Environment: Implications for Atherosclerosis
Authors: Seyed Mojtaba Moosavi, David van Reyk, Belinda Di Bartolo, Owen Tang, Kristen J Bubb, Gemma A Figtree
Journal: Circulation (2020)

Introduction: Bioavailability of nitric oxide (NO) is often compromised in early atherosclerosis, driving disease onset. This is usually due to dysfunctional endothelial nitric oxide synthase (eNOS). We have found that the transmembrane protein, FXYD1, is highly concentrated in the caveolae sub-cellular region and is closely associated with eNOS. Our preliminary data suggest that FXYD1 protects eNOS from redox-dependent inactivation. So, we hypothesise that FXYD1 may protect against atherosclerosis. Hypothesis: We aimed to test the role of FXYD1 in a murine model of atherosclerosis Methods: We produced a novel mutant mouse line by cross-breeding FXYD1 heterozygote (FXYD1 +/- ) and apolipoprotein E knock out (ApoE -/- ) mice. FXYD1 -/- /ApoE -/- and FXYD1 +/+ /ApoE -/- littermates were fed a high fat/high cholesterol diet from 6-8 weeks of age for 16 weeks. At sacrifice, blood was taken, and plasma was separated for analysis of cholesterol and pro-inflammatory cytokines using ELISA. The thoracic aorta was isolated and formalin-fixed to assess atherosclerotic plaque development using oil red O stain. Immunoblotting for eNOS expression was performed in heart lysates. Results: Plasma total cholesterol was significantly increased in FXYD1-/-/ApoE-/- female mice (n = 14 compared to FXYD1+/+/ApoE-/- mice (n = 21; p&lt;0.05)). Circulating IL-1β levels were also significantly increased in female FXYD1-/-/ApoE-/- vs. FXYD1+/+/ApoE-/- mice. Despite this, there was no effect on plaque size as determined by oil red O stain of fixed aortae. eNOS protein expression was decreased in heart tissue from FXYD1-/-/ApoE-/- vs. FXYD1+/+/ApoE-/- female mice which may lead to lower NO generation. All of the FXYD1-mediated changes were specific to female mice as we detected no differences in these parameters in littermate males. Conclusions: FXYD1-/- atherosclerotic female mice have higher circulating lipids and pro-inflammatory cytokines, but this does not appear to alter plaque development in the short term. Ongoing studies will determine the effect on plaque stability and role of FXYD1 in lipidomics. FXYD1 appears to have an anti-inflammatory role and may also be involved in cholesterol metabolism or handling. This could provide a novel therapeutic angle for females.
Abstract 13287: The Clinical Value of Serum Albumin in Predicting Long-term Bleeding Events in Patients Who Underwent Percutaneous Coronary Intervention
Authors: Takuya Ando, Takeshi Shimizu, Joh Akama, Fumiya Anzai, Yuuki Muto, Yusuke KIMISHIMA, Takatoyo Kiko, Akiomi YOSHIHISA, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2020)

Background: It has been known that East Asian people, including Japanese, has a high bleeding risk (HBR) than Western. Therefore, risk stratification is important to detect HBR patients among patients who underwent percutaneous coronary intervention (PCI). The aim of the present study was to investigate the association between serum albumin level and bleeding events in patients who underwent PCI. Methods and Results: Consecutive 1027 patients who underwent PCI and had been discharged from our institution were enrolled. We divided the patients into three groups based on serum albumin levels at discharge: the first tertile (≤3.7 g/dL, n=358), second tertile (3.8-4.1 g/dL, n=308) and third tertile (≥4.2 g/dL, n=361). Clinical characteristics of three groups were as follows: mean age (the first, second and third tertile; 72.9, 69.3 and 63.4 years, P&lt;0.001), body mass index (23.4, 24.4 and 24.9 kg/m 2 , P&lt;0.001), prevalence of male sex (70.7%, 78.6% and 87.1%, P&lt;0.001), chronic kidney disease (53.8%, 39.3% and 27.1%, P&lt;0.001), anemia (27.9%, 11.3% and 7.2%, P&lt;0.001), atrial fibrillation (21.2%, 12.0% and 11.6%, P&lt;0.001), peripheral artery disease (16.5%, 12.5% and 8.8%, P=0.021), stroke (23.2%, 17.9% and 9.6%, P&lt;0.001), heart failure (54.1%, 28.1% and 21.7%, P&lt;0.001), and use of anticoagulants (17.3%, 10.0% and 10.7%, P=0.007). In contrast, combination of antiplatelets did not differ among groups. In the Kaplan-Meier analysis (mean follow-up 1742 days), accumulated bleeding events progressively increased from the third tertile to the first tertile (Figure). The multivariable Cox proportional hazard analysis revealed that the first tertile (vs. third tertile) was independently associated with bleeding events in patients who underwent PCI (hazard ratio 3.080, 95% confidence interval 1.362-6.961, P=0.007). Conclusion: In patients who underwent PCI, low serum albumin level is independently associated with long-term bleeding events.
Abstract 14035: Renal Tubular Secretion and Cardiac Distribution of Dofetilide is Dependent on MATE1 Function
Authors: Muhammad Erfan Uddin, Yan Jin, Alice A Gibson, Ingrid M Bonilla, Cynthia A Carnes, Shuiying Hu, Alex Sparreboom
Journal: Circulation (2020)

Introduction: Dofetilide is a delayed rectifier potassium channel inhibitor used to treat patients with atrial fibrillation and flutter, and its use is associated with a risk of QT prolongation and Torsades de Pointes . The mechanisms involved in dofetilide’s renal tubular secretion and its uptake into cardiomyocytes remain unknown. Previously reported drug-drug interaction (DDI) studies suggest the involvement of organic cation transporters. Here, we investigated the contribution of organic cation transporters (OCT2 and MATE1) to the pharmacokinetics of dofetilide to gain insight into its DDI potential. Hypothesis: Based on known DDIs with dofetilide, we hypothesize that OCT2 and/or MATE1 play a key role in the inter-individual variability in pharmacokinetics and pharmacodynamics of dofetilide. Methods: In vitro and ex vivo transport kinetics of dofetilide were determined in HEK293 cells stably transfected with OCT2 or MATE1, and in isolated cardiomyocytes, respectively. In vivo studies were performed in wild-type, OCT2-, and MATE1-deficient mice (n=5) receiving dofetilide (5 mg/kg, p.o., 2.5 mg/kg, i.v.), with or without several contraindicated drugs. Dofetilide concentrations in plasma and urine were determined by UPLC-MS/MS. Results: In vitro studies demonstrated that dofetilide is a good substrate of MATE1 but not OCT2. Deficiency of MATE1 was associated with increased plasma concentrations of dofetilide and with a significantly reduced urinary excretion (3-fold in females and 5-fold in males, respectively). Dofetilide accumulation in cardiomyocytes was increased by 2-fold in MATE1-deficient females, and pre-incubation with the MATE1 inhibitor cimetidine significantly reduced dofetilide uptake in wild-type cardiomyocytes. Several contraindicated drugs listed in the dofetilide prescribing information, including cimetidine, ketoconazole, increased dofetilide plasma exposure in wild-type mice by &gt;2.8-fold. Conclusion: Renal secretion of dofetilide is mediated by MATE1 and is highly sensitive to inhibition by many widely used prescription drugs that can cause clinically relevant DDIs. Deficiency of MATE1 also increases accumulation in the heart which may contribute to individual variation in response to dofetilide.
Abstract 16543: Severe Thrombocytopenia is Common in Adults Undergoing Venoarterial Extracorporeal Membrane Oxygenation and is Predictive of Hemorrhage
Authors: Tia C Kohs, Vikram Raghunathan, Patricia Liu, Ramin Amirsoltani, Michael Oakes, Owen J McCarty, Sven Olson, David Zonies, Joseph J Shatzel
Journal: Circulation (2020)

Introduction: Extracorporeal membrane oxygenation (ECMO) is used to provide circulatory support and facilitate gas exchange via cardiopulmonary bypass. The relationship between ECMO and the incidence of severe thrombocytopenia (platelet count &lt;50 x 10 9 /L) and subsequent clinical consequences are ill defined. We aimed to identify the risk factors for the development of thrombocytopenia and its clinical implications. Methods: This is a single-center retrospective cohort study of adults who received venoarterial (VA) ECMO. We examined consecutive platelet counts while on ECMO. Univariate logistic regression was used to determine if mean platelet count, platelet count range, or severe thrombocytopenia were predictors of overall survival, hemorrhage and thrombosis. A multivariate logistic regression model was used to identify factors that contribute to the development of the aforementioned patient outcomes. Results: In our cohort, 33 patients were included with a mean age of 55 years and duration of ECMO of 5.9 days. All patients received heparin, 33.3% received antiplatelet therapy and 45.5% developed severe thrombocytopenia. In univariate, analysis the development of severe thrombocytopenia increased the odds of major bleeding by 450% (OR 5.500, 95% CI 1.219 - 24.813, P -value 0.027), and the odds of surviving hospitalization decreased 84.1% (OR 0.159, 95% CI 0.033 - 0.773, P -value 0.023). Multivariate logistic regression controlling for additional clinical variables found no significant association between the development of severe thrombocytopenia and rates of thrombosis, hemorrhage, or overall survival. Platelet count decreased over time while on ECMO. Conclusions: Nearly half of the patients requiring VA-ECMO developed severe thrombocytopenia, which was associated with an increased risk of hemorrhage and in-hospital mortality. Additional studies are required to clarify the clinical implications of severe thrombocytopenia in ECMO patients.